Merck related Press Releases

Celera Genomics Group-an Applera Corp. Business Grants License to Merck for Cancer Targets

Maureen Martino — Thu, 10 Apr 2008 10:54:51 -0400

Celera Genomics Group-an Applera Corp. Business Grants License to Merck for Cancer Targets

/10/2008

ALAMEDA, Calif. -- Celera, an Applera Corporation business, today announced a two year exclusive license agreement with Merck & Co., Inc. providing Merck with access to up to ten cancer targets for the development of RNA interference-(RNAi) based therapeutics. These therapeutic targets are over-expressed on the surface of several different tumor cell types and were identified using Celera's proteomics discovery platform.

RNAi-based therapeutics selectively catalyze the destruction of the RNA transcribed from an individual gene, enabling a novel approach to discovering drugs with the potential to produce highly specific, potent and long-lasting effects.

“This new agreement combines the strength of our novel proteomics target discovery and validation capability with Merck's expertise in developing RNAi based therapeutics,” said Steve Ruben, Ph.D., vice president of proteomic research at Celera. “This new relationship extends our ongoing therapeutic development collaborations and may lead to the development of tests that have the potential to become part of routine clinical practice in the pursuit of targeted medicine.”

Under the terms of the agreement, Merck will pay Celera a license fee for the exclusive access to the ten targets, in addition to the payment of development and commercial milestones plus royalties on selected targets that it advances successfully. Merck also has the option to extend the exclusivity period or add additional targets. Financial terms of the agreement were not disclosed. Celera will be able to develop and commercialize related companion diagnostics, or theranostics, that are specific to certain therapeutic candidates arising from Merck’s program.

About Applera Corporation and Celera

Applera Corporation consists of two operating groups. Celera is a diagnostics business delivering personalized disease management through a combination of products and services incorporating proprietary discoveries. Berkeley HeartLab, a subsidiary of Celera, offers services to predict cardiovascular disease risk and optimize patient management. Celera also commercializes a wide range of molecular diagnostic products through its strategic alliance with Abbott and has licensed other relevant diagnostic technologies developed to provide personalized disease management in cancer and liver diseases. Applied Biosystems serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA and RNA), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. Applied Biosystems’ products also serve the needs of some markets outside of life science research, which we refer to as “applied markets,” such as the fields of: human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, such as testing required for food and pharmaceutical manufacturing. Applied Biosystems is headquartered in Foster City, CA, and reported sales of approximately $2.1 billion during fiscal 2007. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.applera.com, or by telephoning 800.762.6923. Information about Celera is available at http://www.celera.com.

Applera Forward-Looking Statement

Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," "expect," "intend," "anticipate," "should," "planned," and "potential," among others. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera Corporation notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) uncertain suitability of cell surface proteins discovered by Celera as targets for RNAi therapeutics; (2) the risk that products developed under this license agreement, if any, will not advance as anticipated, or may not receive required regulatory clearances or approvals; (3) the uncertainty that any products developed under this license agreement will be accepted and adopted by the market, including the risk that these products will not be competitive with products offered by other companies, or that users will not be entitled to receive adequate reimbursement for these products from third party payors such as private insurance companies and government insurance plans; and (4) other factors that might be described from time to time in Applera Corporation’s filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

Copyright© 2008. Applera Corporation. All rights reserved. Applied Biosystems is a registered trademark and Applera and Celera are trademarks of Applera Corporation or its subsidiaries in the U.S. and/or certain other countries.

Experimental Weight-loss Drug Cuts Appetite, Burns More Energy, Study Suggests

Maureen Martino — Thu, 10 Jan 2008 07:49:23 -0500

Experimental Weight-loss Drug Cuts Appetite, Burns More Energy, Study Suggests

The first clinical studies of an experimental drug have revealed that obese people who take it for 12 weeks lose weight, even at very low doses. Short-term studies also suggest that the drug, called taranabant--the second drug designed to fight obesity by blocking cannabinoid receptors in the brain -- seems to cause people to consume fewer calories and burn more, researchers report in the January issue of Cell Metabolism, a publication of Cell Press. Cannabinoid receptors are responsible for the psychological effects of marijuana (Cannabis sativa), and natural "endocannabinoids" are important regulators of energy balance.

"The effects of marijuana on appetite have been known for millennia from its medicinal and recreational use," said study author Steven Heymsfield of Merck Research Laboratories. "The ingredient responsible stimulates cannabinoid receptors. When you block the cannabinoid system with an antagonist like taranabant, you suppress appetite." However, the drug, developed by Merck, also comes with an increased risk of adverse side effects at higher doses, the study shows, including mild to moderate gastrointestinal and psychiatric effects.

The first proof of concept that so-called cannabinoid 1 receptor (CB1R) inverse agonists might offer an obesity therapy came from studies of another drug, developed by Sanofi-Aventis, called rimonabant. That drug is now in use for weight loss in several European countries as an adjunct to diet and exercise but has not received FDA approval for use in the United States.

Taranabant is a structurally novel, highly selective, potent CB1R inverse agonist, Heymsfield's team said. Preclinical studies in animals showed that it can cause weight loss at doses that block just 30 percent of cannabinoid receptors. To extend those findings to humans in the new studies, the researchers first used positron emission tomography (PET) imaging to identify a dose that would bind about 30 percent of cannabinoid receptors in the human brain. They found that 4 to 6 milligrams of taranabant was enough to achieve that goal.

A multicenter, double-blind, placebo-controlled clinical trial including 533 obese patients showed that the drug induces significant weight loss at doses ranging from 0.5 to 6 milligrams. "That was surprising," Heymsfield said. "We didn't expect weight loss at all doses."

The researchers then conducted separate food intake and energy expenditure studies in overweight and moderately obese people who took a single 4- or 12-milligram dose of taranabant. Those studies showed that people taking 12 milligrams of the drug consumed 27 percent fewer calories than those taking a placebo. People taking the drug also expended more energy while at rest and appeared to burn more fat.

The studies also found that higher doses of the drug caused two types of adverse events, Heymsfield said. These negative side effects included gastrointestinal upset, including nausea and vomiting, as well as increased irritability. Marijuana is often used to combat the nausea associated with chemotherapy drugs, Heymsfield noted, and it also tends to make people mellower. "Here, again, [these drugs] have the opposite effect."

A larger, phase III clinical trial of taranabant is now underway to further explore its effects, Heymsfield said. "All we have here is 12 weeks; we don't yet know what will happen at six months or a year."

The researchers include Carol Addy, Merck Research Laboratories, Boston, MA; Hamish Wright, Merck Research Laboratories, Rahway, NJ; Koen Van Laere, Division of Nuclear Medicine, University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium; Ira Gantz, Merck Research Laboratories, Rahway, NJ; Ngozi Erondu, Merck Research Laboratories, Rahway, NJ; Bret J. Musser, Merck Research Laboratories, Rahway, NJ; Kaifeng Lu, Merck Research Laboratories, Rahway, NJ; Jinyu Yuan, Merck Research Laboratories, Rahway, NJ; Sandra M. Sanabria-Bohorquez, Imaging Research, Merck Research Laboratories, West Point, PA; Aubrey Stoch, Merck Research Laboratories, Rahway, NJ; Cathy Stevens, Merck Research Laboratories, Rahway, NJ; Tung M. Fong, Merck Research Laboratories, Rahway, NJ; Inge De Lepeleire, MSD Europe, Inc., Brussels, Belgium; Caroline Cilissen, MSD Europe, Inc., Brussels, Belgium; Josee Cote, Merck Research Laboratories, Rahway, NJ; Kim Rosko, Merck Research Laboratories, Rahway, NJ; Isaias N. Gendrano III, Merck Research Laboratories, Rahway, NJ; Allison Martin Nguyen, Epidemiology, Merck Research Laboratories, Upper Gwynedd, PA; Barry Gumbiner, Merck Research Laboratories, Rahway, NJ; Paul Rothenberg, Merck Research Laboratories, Rahway, NJ; Jan de Hoon, Center for Clinical Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium; Guy Bormans, Division of Nuclear Medicine, University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium; Marleen Depre, Center for Clinical Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium; Wai-si Eng, Imaging Research, Merck Research Laboratories, West Point, PA; Eric Ravussin, Division of Health and Performance Enhancement, Pennington Biomedical Research Center, Baton Rouge, LA; Samuel Klein, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO; John Blundell, Institute of Psychological Sciences, University of Leeds, Leeds, UK; Gary A. Herman, Merck Research Laboratories, Rahway, NJ; H. Donald Burns, Imaging Research, Merck Research Laboratories, West Point, PA; Richard J. Hargreaves, Imaging Research, Merck Research Laboratories, West Point, PA; John Wagner, Merck Research Laboratories, Rahway, NJ; Keith Gottesdiener, Merck Research Laboratories, Rahway, NJ; John M. Amatruda, Merck Research Laboratories, Rahway, NJ; and Steven B. Heymsfield, Merck Research Laboratories, Rahway, NJ.

Merck Sells Pennsylvania Chemicals Plant

Maureen Martino — Wed, 02 Jan 2008 10:25:51 -0500

Merck Sells Pennsylvania Chemicals Plant

PHILADELPHIA, Jan. 1 -- PRWT Services, Inc., a minority-owned business enterprise, today announced that it has, through its wholly-owned subsidiary, Cherokee Pharmaceuticals LLC, acquired the Cherokee chemical manufacturing plant in Riverside, PA, from Merck & Co., Inc. of Whitehouse Station, NJ. Cherokee has also entered into a five-year supply agreement with Merck for an estimated value of $100-200 million annually.

Willie F. Johnson, Chairman & CEO of PRWT, said: "The acquisition of the Cherokee plant is consistent with PRWT's vision of growing the company by expanding into new markets, services, and lines of business. By establishing a presence in the Life Sciences market, PRWT can now participate in an industry with tremendous growth potential and establish a strategic supplier relationship with Merck, one of the premier pharmaceutical companies in the world." Mr. Johnson also acknowledged PRWT's employees who have established a culture of excellence at PRWT that gave Merck the confidence to complete this historic deal.

The Cherokee plant is a state-of-the-art API manufacturing facility of products/antibiotics for humans and animals. All 400 employees working at the plant will be offered jobs and are expected to transfer their employment from Merck to PRWT effective January 1, 2008. PRWT also intends to make considerable capital investments in the Cherokee plant to support the growth of the business and increase the number of jobs available in the local community.

Justin Noll, the Cherokee plant manager, stated, "We are genuinely excited about the sale of the plant and becoming part of PRWT. Not only will it be good for the employees, but also for the community at large. We are looking forward to being a stand-alone company and a company which will have great potential for expansion."

The sale of the site is part of Merck's global restructuring of its manufacturing operations (announced November 2005) to create a global manufacturing network that is better aligned to Merck's current and anticipated future product demand.

"The sale of the Cherokee plant, along with the supplier relationship Merck has established with Cherokee Pharmaceuticals, is another important step in the realigning of our manufacturing operations," said Larry Naldi, Senior Vice President, Science & Technology, Merck Manufacturing Division. "The completion of this sale also enables Merck to continue to have a presence in the local community through its interactions with Cherokee."

About PRWT Services, Inc.

PRWT is a nationally recognized African-American owned business headquartered in Philadelphia, PA. Founded in 1988, PRWT provides business process outsourcing (BPO) services to state and local governments across the country. PRWT is one of America's largest minority-owned businesses and has been ranked in the top 100 by Black Enterprise magazine for the past seven years. In 2000, PRWT entered a new line of business by acquiring U.S. Facilities, Inc. (USF), a facilities management company headquartered in Philadelphia, PA. Since being acquired by PRWT, USF has won several multi- million-dollar contracts in the federal and municipal markets. For more information, visit http://www.prwt.com.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit http://www.merck.com.

PRESS RELEASE: Idera Pharmaceuticals, and Merck Forge $400 Million Cancer Drug Deal

Maureen Martino — Wed, 19 Dec 2007 10:20:11 -0500

Idera Pharmaceuticals, and Merck Forge $400 Million Cancer Drug Deal

CAMBRIDGE, Mass. -- Idera Pharmaceuticals announced today that it has entered into a worldwide licensing and collaboration agreement with Merck KGaA of Darmstadt, Germany, for the research, development and commercialization of Idera’s Toll-like Receptor 9 (TLR9) agonists for the treatment of cancer.

Under the agreement, Idera has agreed to exclusively license the therapeutic oncology applications, excluding cancer vaccines, of its lead TLR9 agonists, IMO-2055 and IMO-2125. In addition, Idera and Merck KGaA have agreed to engage in a research collaboration to identify a specified number of novel, follow-on TLR9 agonists, which will be derived using Idera’s chemistry-based approach and for which Merck will have the exclusive right to use in oncology applications other than cancer vaccines.

“Merck is committed to the development of innovative approaches to cancer therapy on a global basis and we expect that this collaboration with Idera will help us move toward that goal,” said Vincent Aurentz, Executive Board Member and Head of Portfolio Management and Business Development for the Merck Serono division. “We believe that TLR9 agonists represent a novel mechanism of action with great potential and we look forward to advancing their development for various oncology indications.”

Under the terms of the agreement, Merck KGaA has agreed to pay an upfront license fee of $40 million (about EUR 28 million based on current exchange rates) to Idera. In addition, Idera is eligible to receive milestone payments of up to $381 million, based on current exchange rates, (EUR 264 million), depending on success in achieving clinical development and commercialization, as well as royalties on sales of any products developed and commercialized by Merck KGaA using IMO-2055, IMO-2125 or the follow-on TLR9 agonists. The contract will take effect and the upfront fee will be paid following, and subject to, regulatory clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

“Idera has chosen to collaborate with Merck KGaA for the application of our TLR9 agonists in oncology because of its proven capabilities and success in developing novel therapies for cancer and their commitment to global research, development and commercialization in this area,” said Sudhir Agrawal, D. Phil., Chief Executive Officer and Chief Scientific Officer of Idera. “This collaboration adds Merck KGaA’s experience and resources to the development of our TLR9 agonists in oncology and provides us with additional capital to advance our internal TLR-targeted drug discovery and development programs. We look forward to working closely with Merck KGaA to realize the potential of TLR9 agonists in cancer therapy.”

About IMO-2055

IMO-2055 is a novel DNA-based agonist of TLR9. IMO-2055 has been evaluated at multiple-dose levels for safety and immunological activity in Phase 1 trials involving healthy volunteers and patients with refractory solid tumors. IMO-2055 is currently in a Phase 1b trial in combination with Tarceva® and Avastin® in patients with advanced non-small cell lung cancer and is being evaluated at two dose levels in a Phase 2a trial in patients with renal cell carcinoma. IMO-2055 also is being evaluated in combination with chemotherapy agents in a Phase 1 trial in patients with refractory solid tumors.

About IMO-2125

IMO-2125 is a second DNA-based TLR9 agonist and is of a class designed to induce high levels of interferon-alpha and other cytokines and chemokines. IMO-2125 presently is being evaluated in a Phase I trial in patients with chronic hepatitis C virus infection who have not responded to standard treatment. This indication is not included in the agreement with Merck KGaA.

About TLRs

Toll-like Receptors (TLRs) function in human immune cells as the sensors of pathogens. They recognize different microbial products present in pathogens such as bacteria, viruses and parasites, and mount an appropriate immune response against the foreign invaders. TLRs have also been shown to recognize endogenous ligands in autoimmune diseases. TLRs have become attractive targets for developing immune modulators to treat a number of diseases, including cancers and infectious, respiratory and autoimmune diseases, and for use as vaccine adjuvants.

About Merck KGaA

Merck of Darmstadt, Germany, is a global pharmaceutical and chemical company with sales of EUR 6.3 billion in 2006, a history that began in 1668, and a future shaped by 30,962 employees in 61 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

About Idera Pharmaceuticals, Inc.

Idera Pharmaceuticals is a drug discovery and development company that is developing drug candidates to treat cancer and infectious, respiratory, and autoimmune diseases, and for use as vaccine adjuvants. Idera’s proprietary drug candidates are designed to modulate specific TLRs, which are a family of immune system receptors. Idera’s pioneering DNA chemistry expertise enables it to identify drug candidates for internal development and creates opportunities for multiple collaborative alliances. Internal programs include IMO-2125, a lead candidate for treating infectious diseases, and discovery-stage compounds for autoimmune diseases. Idera has identified DNA-based compounds which have been shown to act as antagonists to TLRs 7 and 9 in preclinical studies and are being evaluated in preclinical disease models of lupus, collagen-induced arthritis and multiple sclerosis. Idera is collaborating with Novartis International Pharmaceutical, Ltd. for the discovery, development, and commercialization of TLR9 agonists for the treatment of asthma and allergy indications. Idera is also collaborating with Merck & Co., Inc. for the use of Idera’s TLR7, 8 and 9 agonists in combination with Merck & Co.’s therapeutic and prophylactic vaccines in the areas of oncology, infectious diseases, and Alzheimer’s disease. Merck & Co. of the U.S. is not related to Merck KGaA of Germany. For more information, visit www.iderapharma.com.

Idera Forward Looking Statements

This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera’s actual results to differ materially from those indicated by such forward-looking statements, including whether the collaboration with Merck KGaA will be successful and whether the Company will receive any of the milestone payments provided for under the collaboration; whether products based on Idera’s technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company’s products receive approval, they will be successfully distributed and marketed; whether the results of preclinical studies will be indicative of results that may be obtained in clinical trials; whether the Company’s collaborations with Novartis and Merck & Co. will be successful; whether Idera’s cash resources will be sufficient to fund the Company’s operations, including product development and clinical trials; and such other important factors as are set forth under the caption "Risk Factors" in Idera’s Quarterly Report on Form 10-Q filed on November 13, 2007, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.

PRESS RELEASE: Merck Announces Voluntary Recall of Certain Lots of PEDVAXHIB and COMVAX

Maureen Martino — Thu, 13 Dec 2007 10:37:06 -0500

Merck Announces Voluntary Recall of Certain Lots of PEDVAXHIB and COMVAX

WHITEHOUSE STATION, N.J., Dec. 12, 2007 - Merck & Co., Inc. announced today that the Company has initiated a voluntary recall of 11 lots of its Haemophilus influenzae type B vaccine, PEDVAXHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)], and two lots of its combination Haemophilus influenzae type B/ hepatitis B vaccine, COMVAX [Haemophilus b Conjugate (Meningococcal Protein Conjugate)]. The recall is specific to these 13 lots and does not affect any other vaccines manufactured by Merck. The affected doses of PEDVAXHIB and COMVAX were distributed starting in April 2007.

Merck is conducting this recall because it can not assure sterility of these specific vaccine lots. The potential contamination of these specific lots was identified as part of the Company's standard evaluation of its manufacturing processes. Sterility tests of the vaccine lots that are the subject of this recall have not found any contamination in the vaccine.

The potential for contamination of any individual vaccine is low, and, if present, the level of contamination would be low. However, because the Company cannot assure the sterility of these specific lots of vaccine, it is conducting this recall.

Merck is working closely with the U.S. Food and Drug Administration (FDA) and the U.S. Centers for Disease Control and Prevention (CDC) to inform affected healthcare providers of this recall. We are also in the process of communicating with public health authorities and healthcare providers in the U.S. and in other countries where these lots were distributed, as appropriate.

"We are taking this action because we are committed to ensuring the quality of our vaccines," said Mark Feinberg, M.D., Ph.D., vice president, Medical and Policy Affairs, Merck Vaccines and Infectious Diseases. "We know that our vaccines can play an important role in the nation's public health system, and we are committed to resolving this issue as quickly as possible to ensure that our vaccines are readily available."

Physicians are advised not to administer any vaccine from the vaccine lots being recalled. Individuals who received vaccine from these lots should complete their immunization series with a Haemophilus b conjugate-containing vaccine not affected by this recall, but do not need to be revaccinated to replace a dose they received from a recalled lot. The efficacy of the vaccine was not affected.

Select safety and additional information about PEDVAXHIB
PEDVAXHIB is indicated for routine vaccination against invasive disease caused by Haemophilius influenzae type b in infants and children two to 71 months of age. PEDVAXHIB should not be used in infants younger than six weeks of age.

PEDVAXHIB is contraindicated in patients with hypersensitivity to any component of the vaccine or the diluent; persons who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine.

As with any vaccine, the use of PEDVAXHIB may not result in a protective antibody response in all vaccinees; PEDVAXHIB may not induce protective antibody levels immediately following vaccination.

The most frequently reported (>1 percent) adverse reactions, without regard to causality, were fever (>101F), irritability, sleepiness, injection-site pain/soreness, injection-site erythema (<2.5 cm diameter), injection-site swelling/induration (<2.5 cm diameter), unusual high-pitched crying, prolonged crying (>4 hours), diarrhea, vomiting, crying, pain, otitis media, rash, and upper respiratory infection.

Select safety and additional information about COMVAX
COMVAX [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] is indicated for vaccination against invasive disease caused by Haemophilus influenzae type b and against infection caused by all known subtypes of hepatitis B virus in infants six weeks to 15 months of age born to HBsAg-negative mothers.

COMVAX [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] is contraindicated in patients with hypersensitivity to yeast or any component of the vaccine. Patients who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine. In clinical trials, the most common nonserious adverse experiences observed in ≥1 percent of children receiving COMVAX [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] included injection-site reactions, somnolence, irritability, crying, and fever (≥101F); for a listing of adverse reactions, please see the Prescribing Information.

As with other vaccines, COMVAX [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] may not induce protective antibody levels immediately following vaccination and may not result in a protective antibody response in all individuals given the vaccine.

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

PRESS RELEASE: Merck Reviews Progress on Strategic Plan at 2007 Annual Business Briefing

Maureen Martino — Tue, 11 Dec 2007 15:27:23 -0500

Merck Reviews Progress on Strategic Plan at 2007 Annual Business Briefing

Merck's Pipeline Continues to Progress with Seven Products in Phase III Development
Company Expects to File Applications for Expanded Indications on GARDASIL and ISENTRESS in 2008
Merck Intends to Initiate a Sequenced Phase III Program for Anacetrapib in 2008
Successful Early Launches of GARDASIL, JANUVIA, JANUMET and ISENTRESS Reflect Better Alignment of Product Development and Commercialization Efforts; Replicable Model to Reduce Time to Market of New Medicines and Vaccines
Company Remains on Track to Deliver Long-Term, Double-Digit Compound Annual EPS Growth from 2005 to 2010, Excluding Certain Items

WHITEHOUSE STATION, N.J., Dec. 11, 2007 - Merck & Co., Inc. today hosted its Annual Business Briefing and reviewed the progress the Company has achieved under a strategic plan designed to re-engineer the way Merck develops and distributes medicines and vaccines worldwide. Since 2005, Merck's senior management team has been developing and implementing a new operating model under which customer focus drives drug discovery, development and marketing at the Company, Merck Chairman, President and Chief Executive Officer Richard T. Clark told investors and analysts today at the Merck Annual Business Briefing.

"We are realizing the benefits of the successful execution of our strategy. We have created a model for success that encompasses every aspect of our business, including R&D, manufacturing and commercialization," Mr. Clark said. "As a result, Merck has a sustainable business model that will allow us to realize the goals we set for 2010 and to position the Company for future success."

During his presentation, Mr. Clark highlighted some of the goals the Company has met or expects to meet by 2010, including:

Launched seven new drugs and vaccines in the past two years, many of them first- or best-in-class
Compound annual revenue growth of 4 percent to 6 percent from 2005 to 2010, including 50 percent of all joint-venture revenue
Double-digit compound annual earnings per share (EPS) growth from 2005 to 2010, excluding certain items
Plan to return product gross margin to pre-ZOCOR levels in 2008
Reduced clinical development cycle times relative to the pharmaceutical sector
"The changes we have made and are continuing to make at Merck are designed to be sustained over the long term. They represent a true model for success," Mr. Clark said. "We have not focused only on short-term successes, but we are making the necessary investments to ensure the success of this Company beyond the year 2010."

Merck's Late-Stage Pipeline Continues to Grow
Building on the seven U.S. Food and Drug Administration (FDA) approvals Merck has received in the past two years, the Company anticipates regulatory action will be taken in 2008 on two New Drug Applications (NDA) for EMEND for Injection and CORDAPTIVE, the proposed brand name for MK-0524A. Also in 2008, the Company anticipates making two additional NDA filings with the FDA for MK-0524B, simvastatin combined with laropiprant and extended-release niacin, and MK-0364, taranabant, an investigational medication for the treatment of obesity, said Peter S. Kim, Ph.D., president of Merck Research Laboratories.

Additionally, Dr. Kim said, the Company anticipates making two supplemental filings with the FDA in 2008: one for GARDASIL, Merck's vaccine for the prevention of cervical cancer, for an expanded indication for adult women through age 45, and one for ISENTRESS, a first-in-class integrase inhibitor for the treatment of HIV-1 infection, for an expanded indication for use in treatment-naïve patients.

During his presentation, Dr. Kim also detailed the following seven drug candidates currently in Phase III development:

MK-0524B is a drug candidate that combines the novel approach to raising HDL-cholesterol (HDL-C) and lowering triglycerides from extended-release niacin combined with laropiprant with the proven benefits of simvastatin in one combination product. The candidate already is in Phase III development, and Merck continues to anticipate filing an NDA for MK-0524B in 2008.
MK-0364, taranabant, is a highly selective cannabinoid-1 receptor inverse agonist that in early clinical studies has demonstrated weight loss versus placebo. The Company previously announced the initiation of a targeted Phase III program in 2006. Merck anticipates filing an NDA in 2008.
MK-0974, an investigational oral calcitonin gene-related peptide receptor antagonist, utilizes a new mechanism for the treatment of migraines that has demonstrated efficacy at least comparable to triptans in early clinical studies. The drug candidate entered Phase III development during 2007. The Company anticipates filing an NDA in 2009.
MK-7418, rolofylline, is a Phase III investigational drug being evaluated for the treatment of acute heart failure. Merck acquired the drug candidate as part of the 2007 acquisition of NovaCardia, Inc. and anticipates filing an NDA with the FDA in 2009.
MK-8669, deforolimus, is a novel mTOR (mammalian target of rapamycin) inhibitor being evaluated for the treatment of cancer. The drug candidate is being jointly developed and commercialized with ARIAD Pharmaceuticals, Inc. under an agreement reached in mid-2007. The Company anticipates filing an NDA in 2010.
HEPLISAV, a novel investigational hepatitis B vaccine, currently is being evaluated in a Phase III clinical trial in adults and in patients undergoing dialysis treatment. Merck is jointly developing HEPLISAV with Dynavax Technologies Corporation under an agreement reached in late 2007. Merck anticipates filing an NDA in 2010 for adults.
MK-0822, odanacatib, is a highly selective inhibitor of cathepsin K enzyme, which is being evaluated for the treatment of osteoporosis. The Phase III program began in mid-2007. Merck anticipates filing an NDA with the FDA in 2012.

Dr. Kim also provided an update on the development of MK-0859, anacetrapib, an inhibitor of the cholesterol ester transfer protein (CETP) that in early clinical trials has shown promise in lipid management by raising HDL-C and reducing LDL-cholesterol (LDL-C) without raising blood pressure.

"In clinical studies, inhibition of CETP raises plasma HDL-C levels and decreases LDL-C levels, which represents a potential therapeutic intervention to reduce the risk of coronary artery disease," Dr. Kim said. "The safety and tolerability profile of anacetrapib was comparable to placebo in clinical studies conducted to date. In 2008, we plan to initiate a sequenced Phase III program to obtain additional clinical experience in patients before initiating an outcomes study."

As of Dec. 11, 2007, Merck's updated pipeline chart includes 25 distinct candidates in Phase I and 15 in Phase II. In addition, there are seven candidates currently in Phase III, one submission currently under FDA review, and another that has received an approvable letter and is awaiting further regulatory action. In its pipeline review, Merck does not include backup candidates; additional indications for candidates in the same therapeutic area; or additional claims, line extensions or formulations for existing products.

New Commercial Model More Effective and Efficient
Kenneth C. Frazier, executive vice president and president, Global Human Health, provided an update on the early successes of Merck's ongoing endeavor to align the Company's product research, development and marketing efforts.

In his presentation, Mr. Frazier said that the successful launches and strong global uptake of GARDASIL, JANUVIA and JANUMET are the result of a replicable model that continues to evolve. He said that the Merck model is not only proving more cost efficient but is allowing Merck to reduce the time it takes to get new medicines and vaccines into markets around the world.

As part of this effort, Merck Global Human Health, aligned with Merck Research Laboratories and Merck Manufacturing, is utilizing the latest technologies and broadening its engagement with customers, physicians and scientific leaders to get needed medicines and vaccines through the development pipeline and to patients sooner, Mr. Frazier said.

The strong sales of Merck's new products, coupled with continued strong growth from in-line products, especially SINGULAIR, should allow Merck to offset the impact of the loss of U.S. marketing exclusivity for FOSAMAX and other products, Mr. Frazier said. He also said that the Company has achieved a nearly fourfold increase in global vaccine sales since 2005 and remains on track to double sales in emerging markets to $2 billion by 2010.

Merck Reaffirms 2007 and 2008 Financial Guidance
During his presentation, Executive Vice President and Chief Financial Officer Peter N. Kellogg reaffirmed Merck's previously disclosed financial outlook for 2007 and 2008.

"With our 2007 and 2008 guidance, it is clear that our products are driving a healthy top line despite lapping the ZOCOR expiry and the upcoming FOSAMAX exposure," Mr. Kellogg said. "We are very pleased with our results in 2007, and we anticipate continued strong financial performance from our key franchises in 2008.

"As I previously noted on Dec. 4, our financial guidance in 2008 represents the next step in our journey to reach our stated 2010 top- and bottom-line goals. Despite the loss of marketing exclusivity for FOSAMAX in the United States in February 2008, the Company anticipates solid earnings growth in 2008," Mr. Kellogg added.

He continued, "As we disclosed in 2005, Merck's new and in-line pharmaceutical products and vaccines are expected to drive revenue at a compound annual growth rate of 4 percent to 6 percent from 2005 through 2010, including 50 percent of the revenues from the joint ventures from which Merck derives equity income. We also expect that we can fully support our expanding pipeline with mid-single-digit compound annual growth in research funding over the same period. The productivity generated by our ongoing cost management initiatives allows Merck to fully capitalize on the promise of our expanding product portfolio while maintaining marketing and administrative expense at 2006 levels."

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements set forth in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

PRESS RELEASE: Merck Anticipates Earnings per Share Growth in 2008

Maureen Martino — Tue, 04 Dec 2007 11:35:35 -0500

Merck Anticipates Earnings per Share Growth in 2008; Reaffirms Long-Term, Double-Digit Compound Annual EPS Growth from 2005 to 2010, Excluding Certain Items

Full-Year 2007 Anticipated non-GAAP EPS Range of $3.08 to $3.14, Excluding Certain Items; 2007 GAAP EPS Range of $1.45 to $1.51
Full-Year 2008 Anticipated non-GAAP EPS Range of $3.28 to $3.38, Excluding Certain Items; 2008 GAAP EPS Range of $3.96 to $4.06
Merck Continues to Anticipate Compound Annual Revenue Growth (Including 50 Percent of Joint Venture Revenue) of 4 Percent to 6 Percent from 2005 to 2010
Company Remains on Track to Deliver Long-Term, Double-Digit Compound Annual EPS Growth from 2005 to 2010, Excluding Certain Items
Merck Expects Strong Growth of SINGULAIR and New Franchises Including JANUVIA, ISENTRESS and GARDASIL

WHITEHOUSE STATION, N.J., Dec. 4, 2007 - Merck & Co., Inc. today updated its 2007 financial guidance and, for the first time, provided 2008 guidance. Merck's senior management will host a conference call to discuss the details of the Company's financial guidance at 8:30 a.m. EST.

"Since 2005, we have been changing every aspect of our business in order to position Merck for sustained revenue and earnings growth," said Richard T. Clark, chairman, president and chief executive officer. "These changes – combined with our current and recently launched products, anticipated new product introductions and cost-savings initiatives – will help position Merck to deliver compound annual double-digit earnings growth, excluding certain items, by 2010 from that 2005 base.

"The 2007 and 2008 guidance that we are providing today helps position the Company to meet its long-term performance targets. In 2007, we have made strides to remove a significant amount of uncertainty related to legal concerns through the U.S. VIOXX product liability settlement agreement announced on Nov. 9, 2007, as well as the anticipated resolution of other litigation. In 2008 the Company expects continued growth in newer franchises, including the on-going global launches of GARDASIL, JANUVIA, JANUMET and ISENTRESS as well as other potential new product introductions. Many of the investments that we are making today to grow our pipeline and to re-engineer our business are enabling us to deliver sustained revenue and earnings growth beyond 2010 and we look forward to discussing our progress at our Annual Business Briefing for investors on Dec. 11," Mr. Clark added.

2007 Guidance
The Company reaffirms its full-year 2007 non-GAAP (generally accepted accounting principles) earnings per share (EPS) guidance range of $3.08 to $3.14, excluding certain items and anticipates a 2007 GAAP EPS range of $1.45 to $1.51. The Company has included in its full-year 2007 GAAP guidance:

The previously disclosed pretax charge of $4.85 billion for the U.S. VIOXX product liability litigation settlement. As previously disclosed, the Company has established a reserve solely for future legal defense costs related to the VIOXX litigation which was $720 million as of Sept. 30, 2007. The Company continues to evaluate that reserve.
A previously disclosed pretax charge of approximately $700 million associated with its global restructuring program.
A pretax charge of $670 million in connection with the anticipated resolution of investigations, the first of which was disclosed beginning in 2002, of civil claims by federal and state authorities relating to certain past marketing and selling activities, including nominal pricing programs and samples. The resolution of these matters is still subject to execution of definitive agreements.
An anticipated fourth-quarter, pretax gain of approximately $450 million relating to insurance proceeds which the Company was awarded (or agreed to receive pursuant to negotiated settlements) in the previously disclosed arbitration with the Company's upper level excess product liability insurance carriers relating to coverage for costs incurred in the VIOXX product liability litigation.
A reconciliation of 2007 EPS as reported in accordance with GAAP to non-GAAP EPS, which adjusts for certain items, is provided in the table that follows.

Full-Year 2007
GAAP EPS $1.45 to $1.51
EPS impact of items* $1.63
Non-GAAP EPS, which adjusts for items listed below1 $3.08 to $3.14

* Amount calculated as follows (In millions except
per share amount): Full-Year 2007
U.S. VIOXX product liability settlement charge $4,850
Costs related to the global restructuring program 700
Civil governmental investigations charge 670
Insurance arbitration gain (450)
Net reduction before income taxes $5,770
Income tax benefits on above items (2,200)
Reduction in net earnings 3,570
EPS impact of items $1.63

1 Merck is providing information on earnings per share in 2007 and 2008, adjusted for certain items, because of the nature of these items and the impact they have on the analysis of underlying business performance and trends. Management believes that providing this information enhances investors' understanding of the Company's performance. This information should be considered in addition to, but not in lieu of, earnings per share prepared in accordance with GAAP.

2008 Guidance
Merck anticipates a full-year 2008 non-GAAP EPS range of $3.28 to $3.38, excluding certain items and a 2008 GAAP EPS range of $3.96 to $4.06. The 2008 GAAP guidance includes:

A pretax charge of approximately $100 million associated with its global restructuring program.
An estimated minimum gain from distributions associated with the AstraZeneca limited partnership. As previously disclosed, pursuant to the provisions of the Company's agreements with AstraZeneca, the Company expects to receive certain payments from AstraZeneca in the first half of 2008. The resulting estimated pretax minimum gain from those payments is $2.5 billion. The resulting minimum gain does not reflect the potential gain associated with the "non-PPI" asset option that Merck holds. The Company intends to make a decision on the "non-PPI" asset option in the first quarter of 2008.
A reconciliation of 2008 EPS as reported in accordance with GAAP to non-GAAP EPS, which adjusts for certain items, is provided in the table that follows.

Full-Year 2008
GAAP EPS $3.96 to $4.06
EPS impact of items* $(0.68)
Non-GAAP EPS, which adjusts for items listed below $3.28 to $3.38

* Amount calculated as follows (In millions except
per share amount): Full-Year 2008
Costs related to the global restructuring program $100
Minimum gain on distributions from AstraZeneca (2,500)
Net increase before income taxes $(2,400)
Income tax expense on above items 915
Increase in net earnings (1,485)
EPS impact of items $(0.68)

Details on the 2007 and 2008 guidance can be found on pages 6-7 and 8-9, respectively, of this release.

Commenting on the Company's financial prospects, Peter N. Kellogg, Merck's executive vice president and chief financial officer, said "Our guidance in 2008 represents the next step in our journey to reach our stated 2010 top- and bottom-line goals. Despite the loss of marketing exclusivity for FOSAMAX in the United States in February 2008, the Company anticipates solid earnings growth in 2008.

"As we disclosed in 2005, Merck's new and in-line pharmaceutical products and vaccines are expected to drive revenue at a compound annual growth rate of 4 percent to 6 percent from 2005 through 2010, including 50 percent of the revenues from the joint ventures from which Merck derives equity income. We also expect that we can fully support our expanding pipeline with mid-single-digit compound annual growth in research funding over the same period. The productivity generated by our ongoing cost management initiatives allows Merck to fully capitalize on the promise of our expanding product portfolio while we expect marketing and administrative expense to return to the 2006 level in 2010," Mr. Kellogg added.

This anticipated performance, together with Merck's ongoing inventory and capital management programs, which contribute to ensuring strong cash flow, supports the Company's commitment to maintaining its dividend at current levels and also is expected to continue to provide opportunities for share repurchases.

Elements of Long-Term Guidance
Merck continues to expect the initial phase of the cost reduction program, announced in 2005, to yield cumulative pretax savings of $4.5 billion to $5.0 billion from 2006 through 2010 and as previously stated, a significant portion of the total restructuring savings through 2010, or approximately $2 billion, will result from the implementation of the manufacturing supply strategy. The Company now anticipates that these savings in manufacturing should enable Merck's gross margin starting in 2008 to return to levels consistent with those seen in the period prior to the loss of U.S. market exclusivity for ZOCOR.

As part of the Company's global restructuring program announced in November 2005, Merck remains on track to eliminate 7,000 positions by the end of 2008. Since the inception of the program through Sept. 30, 2007, approximately 6,000 positions have been eliminated.

The Company expects the pretax costs of the restructuring to be approximately $700 million in 2007 and approximately $100 million in 2008. Through the end of 2008, when the initial phase of the restructuring program will be substantially complete, the cumulative pretax costs of the restructuring activities announced in November 2005 are expected to be approximately $2.2 billion. Approximately 70 percent of the cumulative pretax costs are non-cash relating primarily to accelerated depreciation for those facilities scheduled for closure.

Merck anticipates capital expenditures of approximately $1.1 billion in 2007. Capital expenditures for 2008 are estimated to be $1.6 billion. As Merck continues its initiatives in managing capital, the total reduction over the 2005 to 2008 period is expected to be $1.3 billion versus the Company's expectations for long-range capital spending at the end of 2004.

Conference Call
The Company will host a conference call to discuss the Company's financial guidance. Investors are invited to a live webcast of Merck's conference call today at 8:30 a.m. EST by visiting the Newsroom section of the Merck Web site (www.merck.com/newsroom/webcast/). Institutional investors and analysts can participate in the call by dialing (706) 758-9927. Journalists are invited to listen by calling (706) 758-9928. A replay of the conference call will be available starting at 10 a.m. EST today through 5 p.m. EST on Dec. 11. To listen to the replay, dial (706) 645-9291 or (800) 642-1687 and enter ID # 21484042.

Merck Financial Guidance for 2007
Worldwide sales will be driven by the Company's major products, including the impact of new studies and indications. Sales forecasts for those products for 2007 are as follows:

PRODUCT WORLDWIDE
2007 SALES
SINGULAIR (Respiratory) $4.1 to $4.3 billion
COZAAR/HYZAAR (Hypertension) $3.2 to $3.4 billion
Vaccines (as recorded by Merck & Co., Inc.) $4.2 to $4.6 billion
FOSAMAX (Osteoporosis) $2.9 to $3.1 billion
ZOCOR (Cholesterol modifying) $0.7 to $0.9 billion
Other reported products* $5.6 to $5.9 billion

* Other reported products comprise: AGGRASTAT, ARCOXIA, CANCIDAS, COSOPT, CRIXIVAN, EMEND, INVANZ, ISENTRESS, JANUVIA, JANUMET, MAXALT, PRIMAXIN, PROPECIA, PROSCAR, STOCRIN, TIMOPTIC/TIMOPTIC XE, TRUSOPT, VASOTEC/VASERETIC and ZOLINZA.

Under an agreement with AstraZeneca (AZN), Merck receives revenue at predetermined percentages of the U.S. sales of certain products by AZN, most notably NEXIUM. In 2007, Merck anticipates that these revenues will be approximately $1.6 to $1.8 billion.
Equity income from affiliates includes the results of the Merck and Schering-Plough collaboration and SP-MSD, combined with the results of Merck's other joint venture relationships. Equity income from affiliates is expected to be approximately $2.8 to $3.0 billion for 2007.
Product gross margin (PGM) percentage is estimated to be approximately 76 to 76.5 percent for the full-year 2007. This guidance excludes the portion of the restructuring costs that will be included in product costs and will affect reported PGM in 2007.
Marketing and administrative expense is anticipated to increase between 2.5 and 3.5 percentage points over the full-year 2006 level. The marketing and administrative expense guidance excludes the charges taken in 2006 and 2007 related solely to future legal defense costs of VIOXX and FOSAMAX litigation. In addition, marketing and administrative guidance excludes the financial impact from the U.S. VIOXX product liability settlement agreement, the civil governmental investigations charge, as well as the insurance arbitration gain.
Research and development expense (which excludes joint ventures) is anticipated to increase between 13 and 15 percentage points over the full-year 2006 level. The full-year 2007 guidance includes the third-quarter acquired research charge associated with the NovaCardia acquisition. The full-year 2006 level includes the second-quarter 2006 acquired research expense relating to GlycoFi but excludes the fourth-quarter 2006 acquired research expense relating to the Sirna Therapeutics acquisition. The full-year 2006 level excludes the portion of the restructuring costs that is reported in research and development expense.
As part of the Company's restructuring of its operations, additional costs related to site closings, position eliminations and related costs will be incurred in 2007. The aggregate 2007 pretax expense related to these activities is estimated to be approximately $700 million.
The consolidated 2007 tax rate is estimated to be approximately 24 to 26 percent. This guidance does not reflect the tax rate impact of the U.S. VIOXX product liability settlement charge, restructuring costs, the civil governmental investigations charge and the insurance arbitration gain. The effective tax rate to be applied to these items is at a higher level than the underlying effective tax rate guidance.
Merck plans to continue its stock buyback program in 2007. As of Nov. 30, 2007, $5.7 billion remains under the current buyback authorizations approved by Merck's Board of Directors.
Given these guidance elements, Merck anticipates full-year 2007 non-GAAP EPS of $3.08 to $3.14, excluding certain items, and 2007 GAAP EPS in the range of $1.45 to $1.51.

Merck Financial Guidance for 2008
Worldwide sales will be driven by the Company's major products, including the impact of new studies and indications. Sales forecasts for those products for 2008 are as follows:

PRODUCT WORLDWIDE
2008 SALES
SINGULAIR (Respiratory) $4.6 to $4.8 billion
COZAAR/HYZAAR (Hypertension) $3.2 to $3.4 billion
Vaccines (as recorded by Merck & Co., Inc.) $4.8 to $5.2 billion
FOSAMAX (Osteoporosis) $1.1 to $1.4 billion
Other reported products* $7.5 to $7.9 billion

Under an agreement with AstraZeneca (AZN), Merck receives revenue at predetermined percentages of the U.S. sales of certain products by AZN, most notably NEXIUM. In 2008, Merck anticipates that these revenues will be approximately $1.5 to $1.7 billion. A decision on the "non-PPI" asset option that Merck holds has not been made however, it is not anticipated that the decision will have a material impact on this AZN guidance. The Company intends to make a decision in the first quarter of 2008.
Equity income from affiliates includes the results of the Merck and Schering-Plough collaboration and SP-MSD, combined with the results of Merck's other joint venture relationships. Equity income from affiliates is expected to be approximately $3.0 to $3.3 billion for 2008. This equity income guidance range includes the impact of the reduction of the AZLP priority return and the buyout of the Astra USA products which are anticipated to occur in April 2008. There is a summary document previously posted on www.merck.com/finance that provides additional details on the Merck and AstraZeneca relationship.
Product gross margin (PGM) percentage is estimated to be approximately 77 to 78 percent for the full-year 2008. This guidance excludes the portion of the restructuring costs that will be included in product costs and will affect reported PGM in 2008.
Marketing and administrative expense is anticipated to be approximately $7.8 to $8.0 billion.
Research and development expense (which excludes joint ventures) is anticipated to be approximately $4.7 to $4.9 billion.
As part of the Company's restructuring of its operations, additional costs related to site closings, position eliminations and related costs will be incurred in 2008. The aggregate 2008 pretax expense related to these activities is estimated to be approximately $100 million.
The consolidated 2008 tax rate is estimated to be approximately 24 to 26 percent. This guidance does not reflect the tax rate impact of the anticipated gain on distributions from AstraZeneca or restructuring costs. The effective tax rate to be applied to the AstraZeneca gain and the Company's restructuring costs is at a higher level than the underlying effective tax rate guidance.
Merck plans to continue its stock buyback program in 2008. As of Nov. 30, 2007, $5.7 billion remains under the current buyback authorizations approved by Merck's Board of Directors.
Given these guidance elements, Merck anticipates full-year 2008 non-GAAP EPS of $3.28 to $3.38, excluding certain items, and 2008 GAAP EPS in the range of $3.96 to $4.06.

Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements set forth in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

PRESS RELEASE: GlaxoSmithKline Obtains Exclusive U.S. OTC Marketing Rights to MEVACOR from Merck

Maureen Martino — Tue, 27 Nov 2007 10:42:21 -0500

GlaxoSmithKline Obtains Exclusive U.S. OTC Marketing Rights to MEVACOR from Merck Following FDA Approval, Agreement will Broaden Access to Cholesterol-Reducing Medicine

PHILADELPHIA and WHITEHOUSE STATION, N.J., Nov. 26 -- GlaxoSmithKline, Philadelphia, PA, USA (GSK) and Merck & Co., Inc., Whitehouse Station, NJ, USA (Merck), announced today that they have entered into an agreement for over-the-counter (OTC) marketing rights for MEVACOR(R) (lovastatin). Under the agreement, GSK will have exclusive rights to market non-prescription MEVACOR in the United States. Terms of the agreement are confidential but include milestone and royalty payments from GSK to Merck.

MEVACOR was introduced in the United States in 1987 by Merck as the first in a class of cholesterol-reducing medicines known as "statins". The U.S. patent for MEVACOR expired in 2001.

Commenting on the agreement, JP Garnier, chief executive officer, GlaxoSmithKline said, "This new partnership with Merck will enable GSK to address the important public health issue of high cholesterol and help patients better manage their health. OTC Mevacor will be a dynamic new addition to our fast-growing over-the-counter business and is further evidence of GSK's ability to partner in new OTC switch opportunities."

"With MEVACOR, Merck pioneered the development of cholesterol-lowering medicines known as "statins" which are recognized worldwide and remain the standard of care today," said Richard T. Clark, chief executive officer, Merck. "We are pleased to be able to partner with GSK as a way to bring MEVACOR directly to consumers in the United States."

Application for OTC MEVACOR to be reviewed by FDA

The new drug application (NDA) for OTC MEVACOR will be reviewed by the U.S. Food and Drug Administration (FDA) in a joint meeting of the Nonprescription Drugs Advisory Committee (NDAC) and the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) on December 13. The NDA, filed by Merck, is seeking approval of OTC MEVACOR 20 mg taken once daily to help lower cholesterol. OTC MEVACOR 20 mg is proposed for use in women age 55 and older and men age 45 and older with moderately elevated cholesterol and one or more heart disease risk factors.

About prescription MEVACOR

MEVACOR is a prescription medicine that is approved in the United States for the treatment of elevated cholesterol levels that lifestyle changes alone cannot control and to reduce the risk of first heart attack, unstable angina and coronary revascularization procedures in healthy men and women with average or moderately elevated cholesterol levels.

According to the prescribing information, MEVACOR should not be used by anyone allergic to any of its components, people with liver disease, or by women who are pregnant, breast-feeding or likely to become pregnant. It is recommended that liver function tests be performed in all patients prior to daily use of MEVACOR 40 mg or more.

Muscle pain or weakness in patients taking prescription MEVACOR should be reported to a doctor because these could be signs of a serious side effect. Patients should tell their doctors about other medications they are taking in order to avoid possible drug interactions.

The most common adverse events reported with MEVACOR 20 mg taken once a day were diarrhea, flatulence, headache and myalgia.

About GSK

GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline at www.gsk.com.

Nicorette, NicoDerm CQ and alli trademarks are either owned by and/or licensed to GSK or associated companies. Xenical is a registered trademark of the Roche Group.

About GSK Consumer Healthcare

OTC MEVACOR would be marketed in the United States by GSK Consumer Healthcare, a GSK division with a well-established record of bringing informed access to OTC medicines.

In 1996, GSK Consumer Healthcare launched the first OTC nicotine replacement therapies, Nicorette and NicoDerm CQ, together with an innovative Committed Quitters behavioral support program. Through increased access to GSK's smoking cessation brands and support, more than five million adults in the United States have quit smoking.

In 2004, GSK Consumer Healthcare acquired the OTC marketing rights to orlistat in the United States from the Roche Group (orlistat 120 mg is marketed as the prescription product Xenical(R) by Roche). In June 2007, GSK Consumer Healthcare launched alli in the United States, the first FDA-approved OTC weight control medicine. alli (orlistat 60mg) provides overweight adults a proven weight loss medicine and a comprehensive, tailored, behavioral support program.

GSK's education programs provide consumers with information and the tools to support them through the behavioral modifications that are essential for their success with OTC medicines and that require long-term lifestyle changes.

GSK forward-looking statement

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2006.

About Merck

Merck forward-looking statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

DESCRIPTION

MEVACOR* (Lovastatin) is a cholesterol lowering agent isolated from a strain of Aspergillus terreus. After oral ingestion, lovastatin, which is an inactive lactone, is hydrolyzed to the corresponding beta-hydroxyacid form. This is a principal metabolite and an inhibitor of 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG- CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol.

Lovastatin is [1S-[1alpha(R*),3alpha,7beta,8beta (2S*,4S*), 8abeta]]- 1,2,3,7, 8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H- pyran-2-yl)ethyl]-1-naphthalenyl 2-methylbutanoate. The empirical formula of lovastatin is C24H36O5 and its molecular weight is 404.55.

Lovastatin is a white, nonhygroscopic crystalline powder that is insoluble in water and sparingly soluble in ethanol, methanol, and acetonitrile.

Tablets MEVACOR are supplied as 20 mg and 40 mg tablets for oral administration. In addition to the active ingredient lovastatin, each tablet contains the following inactive ingredients: cellulose, lactose, magnesium stearate, and starch. Butylated hydroxyanisole (BHA) is added as a preservative. Tablets MEVACOR 20 mg also contain FD&C Blue 2 aluminum lake. Tablets MEVACOR 40 mg also contain D&C Yellow 10 aluminum lake and FD&C Blue 2 aluminum lake.

CLINICAL PHARMACOLOGY

The involvement of low-density lipoprotein cholesterol (LDL-C) in atherogenesis has been well-documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological and clinical studies have established that high LDL-C and low high-density lipoprotein cholesterol (HDL-C) are both associated with coronary heart disease. However, the risk of developing coronary heart disease is continuous and graded over the range of cholesterol levels and many coronary events do occur in patients with total cholesterol (total-C) and LDL-C in the lower end of this range.

MEVACOR has been shown to reduce both normal and elevated LDL-C concentrations. LDL is formed from very low-density lipoprotein (VLDL) and is catabolized predominantly by the high affinity LDL receptor. The mechanism of the LDL-lowering effect of MEVACOR may involve both reduction of VLDL-C concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-C. Apolipoprotein B also falls substantially during treatment with MEVACOR. Since each LDL particle contains one molecule of apolipoprotein B, and since little apolipoprotein B is found in other lipoproteins, this strongly suggests that MEVACOR does not merely cause cholesterol to be lost from LDL, but also reduces the concentration of circulating LDL particles. In addition, MEVACOR can produce increases of variable magnitude in HDL-C, and modestly reduces VLDL-C and plasma triglycerides (TG) (see Tables I-III under Clinical Studies). The effects of MEVACOR on Lp(a), fibrinogen, and certain other independent biochemical risk markers for coronary heart disease are unknown.

MEVACOR is a specific inhibitor of HMG-CoA reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol.

Pharmacokinetics

Lovastatin is a lactone which is readily hydrolyzed in vivo to the corresponding beta-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the beta-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of lovastatin.

Following an oral dose of 14C-labeled lovastatin in man, 10% of the dose was excreted in urine and 83% in feces. The latter represents absorbed drug equivalents excreted in bile, as well as any unabsorbed drug. Plasma concentrations of total radioactivity (lovastatin plus 14C-metabolites) peaked at 2 hours and declined rapidly to about 10% of peak by 24 hours postdose. Absorption of lovastatin, estimated relative to an intravenous reference dose, in each of four animal species tested, averaged about 30% of an oral dose. In animal studies, after oral dosing, lovastatin had high selectivity for the liver, where it achieved substantially higher concentrations than in non- target tissues. Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. As a consequence of extensive hepatic extraction of lovastatin, the availability of drug to the general circulation is low and variable. In a single dose study in four hypercholesterolemic patients, it was estimated that less than 5% of an oral dose of lovastatin reaches the general circulation as active inhibitors. Following administration of lovastatin tablets the coefficient of variation, based on between-subject variability, was approximately 40% for the area under the curve (AUC) of total inhibitory activity in the general circulation.

Both lovastatin and its beta-hydroxyacid metabolite are highly bound (>95%) to human plasma proteins. Animal studies demonstrated that lovastatin crosses the blood-brain and placental barriers.

The major active metabolites present in human plasma are the beta- hydroxyacid of lovastatin, its 6'-hydroxy derivative, and two additional metabolites. Peak plasma concentrations of both active and total inhibitors were attained within 2 to 4 hours of dose administration. While the recommended therapeutic dose range is 10 to 80 mg/day, linearity of inhibitory activity in the general circulation was established by a single dose study employing lovastatin tablet dosages from 60 to as high as 120 mg. With a once- a-day dosing regimen, plasma concentrations of total inhibitors over a dosing interval achieved a steady state between the second and third days of therapy and were about 1.5 times those following a single dose. When lovastatin was given under fasting conditions, plasma concentrations of total inhibitors were on average about two-thirds those found when lovastatin was administered immediately after a standard test meal.

In a study of patients with severe renal insufficiency (creatinine clearance 10-30 mL/min), the plasma concentrations of total inhibitors after a single dose of lovastatin were approximately two-fold higher than those in healthy volunteers.

In a study including 16 elderly patients between 70-78 years of age who received MEVACOR 80 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age (see PRECAUTIONS, Geriatric Use).

Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors. The increase in AUC for lovastatin and lovastatin acid is presumably due, in part, to inhibition of CYP3A4.

The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Potent inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS, Drug Interactions).

Lovastatin is a substrate for cytochrome P450 isoform 3A4 (CYP3A4) (see PRECAUTIONS, Drug Interactions). Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4. In one study**, 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with and 30 and 90 minutes following a single dose of 80 mg lovastatin on the third day. This regimen of grapefruit juice resulted in a mean increase in the serum concentration of lovastatin and its beta-hydroxyacid metabolite (as measured by the area under the concentration-time curve) of 15-fold and 5-fold, respectively [as measured using a chemical assay -- high performance liquid chromatography.] In a second study, 15 subjects consumed one 8 oz glass of single-strength grapefruit juice (one can of frozen concentrate diluted with 3 cans of water) with breakfast for 3 consecutive days and a single dose of 40 mg lovastatin in the evening of the third day. This regimen of grapefruit juice resulted in a mean increase in the plasma concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity [using an enzyme inhibition assay both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 1.34-fold and 1.36-fold, respectively, and of lovastatin and its beta- hydroxyacid metabolite [measured using a chemical assay -- liquid chromatography/tandem mass spectrometry -- different from that used in the first** study] of 1.94-fold and 1.57-fold, respectively. The effect of amounts of grapefruit juice between those used in these two studies on lovastatin pharmacokinetics has not been studied.

Clinical Studies in Adults

MEVACOR has been shown to be highly effective in reducing total-C and LDL- C in heterozygous familial and non-familial forms of primary hypercholesterolemia and in mixed hyperlipidemia. A marked response was seen within 2 weeks, and the maximum therapeutic response occurred within 4-6 weeks. The response was maintained during continuation of therapy. Single daily doses given in the evening were more effective than the same dose given in the morning, perhaps because cholesterol is synthesized mainly at night.

In multicenter, double-blind studies in patients with familial or non- familial hypercholesterolemia, MEVACOR, administered in doses ranging from 10 mg q.p.m. to 40 mg b.i.d., was compared to placebo. MEVACOR consistently and significantly decreased plasma total-C, LDL-C, total-C/HDL-C ratio and LDL- C/HDL-C ratio. In addition, MEVACOR produced increases of variable magnitude in HDL-C, and modestly decreased VLDL-C and plasma TG (see Tables I through III for dose response results).

MEVACOR was studied in controlled trials in hypercholesterolemic patients with well-controlled non-insulin dependent diabetes mellitus with normal renal function. The effect of MEVACOR on lipids and lipoproteins and the safety profile of MEVACOR were similar to that demonstrated in studies in nondiabetics. MEVACOR had no clinically important effect on glycemic control or on the dose requirement of oral hypoglycemic agents.

Expanded Clinical Evaluation of Lovastatin (EXCEL) Study

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a double-blind, randomized, placebo-controlled, primary prevention study, demonstrated that treatment with MEVACOR decreased the rate of acute major coronary events (composite endpoint of myocardial infarction, unstable angina, and sudden cardiac death) compared with placebo during a median of 5.1 years of follow-up. Participants were middle-aged and elderly men (ages 45-73) and women (ages 55-73) without symptomatic cardiovascular disease with average to moderately elevated total-C and LDL-C, below average HDL-C, and who were at high risk based on elevated total-C/HDL-C. In addition to age, 63% of the participants had at least one other risk factor (baseline HDL-C <35 mg/dL, hypertension, family history, smoking and diabetes).

AFCAPS/TexCAPS enrolled 6,605 participants (5,608 men, 997 women) based on the following lipid entry criteria: total-C range of 180-264 mg/dL, LDL-C range of 130-190 mg/dL, HDL-C of Less Than or Equal To 45 mg/dL for men and Less Than or Equal To 47 mg/dL for women, and TG of Less Than or Equal To 400 mg/dL. Participants were treated with standard care, including diet, and either MEVACOR 20-40 mg daily (n= 3,304) or placebo (n= 3,301). Approximately 50% of the participants treated with MEVACOR were titrated to 40 mg daily when their LDL-C remained >110 mg/dL at the 20-mg starting dose.

MEVACOR reduced the risk of a first acute major coronary event, the primary efficacy endpoint, by 37% (MEVACOR 3.5%, placebo 5.5%; p<0.001; Figure 1). A first acute major coronary event was defined as myocardial infarction (54 participants on MEVACOR, 94 on placebo) or unstable angina (54 vs. 80) or sudden cardiac death (8 vs. 9). Furthermore, among the secondary endpoints, MEVACOR reduced the risk of unstable angina by 32% (1.8 vs. 2.6%; p=0.023), of myocardial infarction by 40% (1.7 vs. 2.9%; p=0.002), and of undergoing coronary revascularization procedures (e.g., coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 33% (3.2 vs. 4.8%; p=0.001). Trends in risk reduction associated with treatment with MEVACOR were consistent across men and women, smokers and non-smokers, hypertensives and non-hypertensives, and older and younger participants. Participants with Greater Than or Equal To 2 risk factors had risk reductions (RR) in both acute major coronary events (RR 43%) and coronary revascularization procedures (RR 37%). Because there were too few events among those participants with age as their only risk factor in this study, the effect of MEVACOR on outcomes could not be adequately assessed in this subgroup.

Atherosclerosis

In the Canadian Coronary Atherosclerosis Intervention Trial (CCAIT), the effect of therapy with lovastatin on coronary atherosclerosis was assessed by coronary angiography in hyperlipidemic patients. In the randomized, double- blind, controlled clinical trial, patients were treated with conventional measures (usually diet and 325 mg of aspirin every other day) and either lovastatin 20-80 mg daily or placebo. Angiograms were evaluated at baseline and at two years by computerized quantitative coronary angiography (QCA). Lovastatin significantly slowed the progression of lesions as measured by the mean change per-patient in minimum lumen diameter (the primary endpoint) and percent diameter stenosis, and decreased the proportions of patients categorized with disease progression (33% vs. 50%) and with new lesions (16% vs. 32%).

In a similarly designed trial, the Monitored Atherosclerosis Regression Study (MARS), patients were treated with diet and either lovastatin 80 mg daily or placebo. No statistically significant difference between lovastatin and placebo was seen for the primary endpoint (mean change per patient in percent diameter stenosis of all lesions), or for most secondary QCA endpoints. Visual assessment by angiographers who formed a consensus opinion of overall angiographic change (Global Change Score) was also a secondary endpoint. By this endpoint, significant slowing of disease was seen, with regression in 23% of patients treated with lovastatin compared to 11% of placebo patients.

In the Familial Atherosclerosis Treatment Study (FATS), either lovastatin or niacin in combination with a bile acid sequestrant for 2.5 years in hyperlipidemic subjects significantly reduced the frequency of progression and increased the frequency of regression of coronary atherosclerotic lesions by QCA compared to diet and, in some cases, low-dose resin.

The effect of lovastatin on the progression of atherosclerosis in the coronary arteries has been corroborated by similar findings in another vasculature. In the Asymptomatic Carotid Artery Progression Study (ACAPS), the effect of therapy with lovastatin on carotid atherosclerosis was assessed by B-mode ultrasonography in hyperlipidemic patients with early carotid lesions and without known coronary heart disease at baseline. In this double-blind, controlled clinical trial, 919 patients were randomized in a 2 x 2 factorial design to placebo, lovastatin 10-40 mg daily and/or warfarin. Ultrasonograms of the carotid walls were used to determine the change per patient from baseline to three years in mean maximum intimal-medial thickness (IMT) of 12 measured segments. There was a significant regression of carotid lesions in patients receiving lovastatin alone compared to those receiving placebo alone (p=0.001). The predictive value of changes in IMT for stroke has not yet been established. In the lovastatin group there was a significant reduction in the number of patients with major cardiovascular events relative to the placebo group (5 vs. 14) and a significant reduction in all-cause mortality (1 vs. 8).

Eye

There was a high prevalence of baseline lenticular opacities in the patient population included in the early clinical trials with lovastatin. During these trials the appearance of new opacities was noted in both the lovastatin and placebo groups. There was no clinically significant change in visual acuity in the patients who had new opacities reported nor was any patient, including those with opacities noted at baseline, discontinued from therapy because of a decrease in visual acuity.

A three-year, double-blind, placebo-controlled study in hypercholesterolemic patients to assess the effect of lovastatin on the human lens demonstrated that there were no clinically or statistically significant differences between the lovastatin and placebo groups in the incidence, type or progression of lenticular opacities. There are no controlled clinical data assessing the lens available for treatment beyond three years.

Clinical Studies in Adolescent Patients

Efficacy of Lovastatin in Adolescent Boys with Heterozygous Familial Hypercholesterolemia

In a double-blind, placebo-controlled study, 132 boys 10-17 years of age (mean age 12.7 yrs) with heterozygous familial hypercholesterolemia (heFH) were randomized to lovastatin (n=67) or placebo (n=65) for 48 weeks. Inclusion in the study required a baseline LDL-C level between 189 and 500 mg/dL and at least one parent with an LDL-C level >189 mg/dL. The mean baseline LDL-C value was 253.1 mg/dL (range: 171-379 mg/dL) in the MEVACOR group compared to 248.2 mg/dL (range: 158.5-413.5 mg/dL) in the placebo group. The dosage of lovastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter.

MEVACOR significantly decreased plasma levels of total-C, LDL-C and apolipoprotein B (see Table IV).

The mean achieved LDL-C value was 190.9 mg/dL (range: 108-336 mg/dL) in the MEVACOR group compared to 244.8 mg/dL (range: 135-404 mg/dL) in the placebo group.

Efficacy of Lovastatin in Post-menarchal Girls with Heterozygous Familial Hypercholesterolemia

In a double-blind, placebo-controlled study, 54 girls 10-17 years of age who were at least 1 year post-menarche with heFH were randomized to lovastatin (n=35) or placebo (n=19) for 24 weeks. Inclusion in the study required a baseline LDL-C level of 160-400 mg/dL and a parental history of familial hypercholesterolemia. The mean baseline LDL-C value was 218.3 mg/dL (range: 136.3-363.7 mg/dL) in the MEVACOR group compared to 198.8 mg/dL (range: 151.1-283.1 mg/dL) in the placebo group. The dosage of lovastatin (once daily in the evening) was 20 mg for the first 4 weeks, and 40 mg thereafter.

MEVACOR significantly decreased plasma levels of total-C, LDL-C, and apolipoprotein B (see Table V).

The mean achieved LDL-C value was 154.5 mg/dL (range: 82-286 mg/dL) in the MEVACOR group compared to 203.5 mg/dL (range: 135-304 mg/dL) in the placebo group.

The safety and efficacy of doses above 40 mg daily have not been studied in children. The long-term efficacy of lovastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.

INDICATIONS AND USAGE

Therapy with MEVACOR should be a component of multiple risk factor intervention in those individuals with dyslipidemia at risk for atherosclerotic vascular disease. MEVACOR should be used in addition to a diet restricted in saturated fat and cholesterol as part of a treatment strategy to lower total-C and LDL-C to target levels when the response to diet and other nonpharmacological measures alone has been inadequate to reduce risk.

Primary Prevention of Coronary Heart Disease

In individuals without symptomatic cardiovascular disease, average to moderately elevated total-C and LDL-C, and below average HDL-C, MEVACOR is indicated to reduce the risk of:

Coronary Heart Disease

MEVACOR is indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total-C and LDL-C to target levels.

Hypercholesterolemia

Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. MEVACOR is indicated as an adjunct to diet for the reduction of elevated total-C and LDL- C levels in patients with primary hypercholesterolemia (Types IIa and IIb***), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate.

Adolescent Patients with Heterozygous Familial Hypercholesterolemia

MEVACOR is indicated as an adjunct to diet to reduce total-C, LDL-C and apolipoprotein B levels in adolescent boys and girls who are at least one year post-menarche, 10-17 years of age, with heFH if after an adequate trial of diet therapy the following findings are present:

General Recommendations

Prior to initiating therapy with lovastatin, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure total-C, HDL-C, and TG. For patients with TG less than 400 mg/dL (<4.5 mmol/L), LDL-C can be estimated using the following equation:

LDL-C = total-C - [0.2 x (TG) + HDL-C]

For TG levels >400 mg/dL (>4.5 mmol/L), this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. In hypertriglyceridemic patients, LDL-C may be low or normal despite elevated total-C. In such cases, MEVACOR is not indicated.

The National Cholesterol Education Program (NCEP) Treatment Guidelines are summarized below:

++ Some authorities recommend use of LDL-lowering drugs in this category if an LDL-C level of <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical judgment also may call for deferring drug therapy in this subcategory.

+++ Almost all people with 0-1 risk factor have a 10-year risk <10%; thus, 10-year risk assessment in people with 0-1 risk factor is not necessary.

After the LDL-C goal has been achieved, if the TG is still Greater Than or Equal To 200 mg/dL, non-HDL-C (total-C minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category.

At the time of hospitalization for an acute coronary event, consideration can be given to initiating drug therapy at discharge if the LDL-C is Greater Than or Equal To 130 mg/dL (see NCEP Guidelines above).

Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the total-C be used to monitor therapy.

Although MEVACOR may be useful to reduce elevated LDL-C levels in patients with combined hypercholesterolemia and hypertriglyceridemia where hypercholesterolemia is the major abnormality (Type IIb hyperlipoproteinemia), it has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDL or IDL (i.e., hyperlipoproteinemia types I, III, IV, or V).***

Children treated with lovastatin in adolescence should be re-evaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult goals for LDL-C.

CONTRAINDICATIONS

Hypersensitivity to any component of this medication.

Active liver disease or unexplained persistent elevations of serum transaminases (see WARNINGS).

Pregnancy and lactation (see PRECAUTIONS, Pregnancy and Nursing Mothers). Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Moreover, cholesterol and other products of the cholesterol biosyn

PRESS RELEASE: Merck and Vertex Pharmaceuticals MK-0457 Trials Halted on Heart Risk

Maureen Martino — Wed, 21 Nov 2007 09:40:28 -0500

Merck and Vertex Pharmaceuticals MK-0457 Trials Halted on Heart Risk

CAMBRIDGE, Mass. -- Vertex Pharmaceuticals Incorporated and Merck & Co., Inc. today provided an update to their collaborative Aurora kinase research and development program, which is targeting the treatment of cancer. Merck has suspended enrollment in clinical trials of the lead investigational Aurora kinase inhibitor in the collaboration, MK-0457 (VX-680), pending a full analysis of all efficacy and safety data for MK-0457. The decision was based on preliminary safety data, in which a clinical safety finding of QTc prolongation was observed in one patient. Merck and Vertex have a broad research and development program underway to evaluate Aurora kinase inhibitors as novel approaches to targeted cancer treatment. As part of Merck’s strategy to develop multiple drug candidates in different tumor types and treatment combinations, Merck plans to initiate in early 2008 a Phase 1 trial of VX-689 in patients with advanced and/or refractory solid tumors.

MK-0457 is being investigated in a Phase 2 trial in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) containing the T315I mutation, as well as an ongoing Phase 1 clinical trial in patients with advanced leukemias. Patients currently enrolled in these trials may continue to be treated with MK-0457, with additional monitoring for QTc prolongation. A recently initiated Phase 1 trial of MK-0457 in combination with dasatinib in patients with CML or Ph+ALL has also been suspended. In addition, development of the Aurora kinase inhibitor MK-6592 (VX-667) has been discontinued after the compound did not meet pharmacokinetic objectives in a Phase 1 clinical study.

About Merck Oncology

Merck Oncology focuses on all aspects of cancer care -- prevention, treatment, and supportive care. Through strong internal research capabilities, selective alliances and acquisitions, and enabling technologies such as the Molecular Profiling platform of Rosetta, Merck Oncology is looking to lead in the discovery, development and delivery of targeted anticancer therapies customized for patient subpopulations. Merck Oncology conducts research at sites in Boston, Seattle, West Point, Japan and Italy.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, inflammation, autoimmune diseases, cancer, pain and bacterial infection. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline. Vertex's press releases are available at www.vrtx.com.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

Safe Harbor Statement

This press release may contain forward-looking statements, including statements that (i) Merck and Vertex expect to continue to evaluate the clinical potential of Aurora kinase inhibitors, with the goal of developing multiple drug candidates in different tumor types and treatment combinations, and (ii) Merck expects to initiate a Phase 1 clinical trial of VX-689 in early 2008. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause the actual results of studies to vary materially. Those risks and uncertainties include, among other things, the risk that planned studies will not be commenced due to unanticipated scientific developments or business constraints, that observed outcomes in clinical investigations of smaller numbers of patients will not be reflected in clinical trials involving larger numbers of patients, that unexpected and adverse outcomes in ongoing clinical and nonclinical studies will occur, and other risks listed under Risk Factors in Vertex's Form 10-K filed with the Securities and Exchange Commission on March 1, 2007. Vertex disclaims any obligation to update the information contained in this press release as new data become available.

PRESS RELEASE: Nicholas Piramal Announces Drug Discovery and Development Agreement with Merck

Maureen Martino — Mon, 19 Nov 2007 12:27:18 -0500

Nicholas Piramal Announces Drug Discovery and Development Agreement with Merck

Mumbai, India 19 November 2007: Nicholas Piramal India Limited and Merck & Co., Inc., which operates in India through its subsidiary, MSD Pharmaceuticals Private Ltd, today announced a research and development collaboration agreement to discover and develop new drugs for two selected targets provided by Merck.

NPIL will be responsible for carrying out an integrated drug discovery program from hits to leads through pre-clinical candidate selection, followed by Investigational New Drug (IND )-enabling non-clinical studies and human clinical trials demonstrating proof-of-concept primarily for Oncology. Merck will have an option to advance the most promising drug candidates into late stage clinical trials and to commercialize these drug candidates. NPIL will be eligible to receive milestone payments associated with progress in the development of drug candidates of up to $175 million per target, plus royalties on sales of any products resulting from the collaboration.

Commenting on the collaboration agreement, Dr. Swati Piramal, Director - Strategic Alliances & Communications, NPIL said: “The Merck-Nicholas Piramal research collaboration is a major step in bringing the cross-border synergies to drug development which should have cost, quality and time advantages and should benefit patients worldwide in reducing the burden of disease.”

"Merck is excited to collaborate with a company with the discovery and development capabilities of NPIL," said Merv Turner, Ph.D., Senior Vice President, Worldwide Licensing and External Research at Merck. "This agreement furthers our strategy of building global alliances that expand and advance Merck's pipeline, especially in countries such as India with rapidly expanding drug discovery competencies"

About Nicholas Piramal India Limited:
Nicholas Piramal India Limited ("NPIL") is one of India's largest pharmaceutical companies with a growth track record of 30% Revenues CAGR since 1988. The Company is currently ranked fourth in the Indian market with a diverse product portfolio spanning nine therapeutic areas. NPIL's had consolidated Revenues of US $ 602 million in 2006-07. The Company has R&D capabilities in Discovery Research, Custom Chemical Synthesis, Process Innovation, and Drug Delivery Systems. It has world-class USFDA-approved formulations and API facilities without any 483s.

NPIL has a long track record of successful collaboration with innovator companies. Since early-2000, the Company has made significant investments in Discovery Research and Custom Manufacturing Operations (CMO) for Innovator Companies. Nicholas Piramal has a global CMO footprint across North America, Europe & Asia, and is committed to respecting Intellectual Property.

NPIL is listed in India on the Bombay Stock Exchange and National Stock Exchange. For further information, please mail investorrelations@nicholaspiramal.co.in
or visit www.nicholaspiramal.com.

About Merck & Co, Inc:
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines, but also help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. Merck operates in India through its subsidiary, MSD Pharmaceuticals Private Ltd.