FDA related Press Releases

PRESS RELEASE: FDA Announces Steps to Improve Advisory Committee Processes

Maureen Martino — Fri, 16 Nov 2007 11:59:15 -0500

FDA Announces Steps to Improve Advisory Committee Processes

The Food and Drug Administration is announcing several steps to strengthen its advisory committee processes in ways consistent with recommendations of the Institute of Medicine. The measures include proposed new guidance or procedures on advisory committee voting, on disclosing information on conflicts of interest, and on security and appropriate conduct for participants at meetings. Other improvements include greater clarity to FDA’s advisory committee Web site, which can be found at http://www.fda.gov/oc/advisory/default.htm.

“One of FDA’s strengths is that we routinely enlist the nation’s leading experts to give us public advice on complex medical and scientific issues,” said Randall Lutter, Ph.D., deputy commissioner for policy. “The new steps we’re taking further enhance the transparency and reliability of our advisory committee processes.”

A draft guidance document being issued today recommends advisory committees adhere to a process of simultaneous voting, in which all members vote at once. The results of the vote would be announced immediately. How each member voted would be part of the public record. The draft guidance document is available at http://www.fda.gov/oc/advisory/votingguidance.html.

A second draft guidance issued recently lays out recommended changes to the process of public disclosure of financial interests that create conflicts of interest for advisory committee members. The new draft guidance makes the process more transparent and consistent by having all advisory committee members publicly disclose interests for which a waiver is granted. The draft guidance also includes redesigned disclosure and waiver templates that are clearer and easier for the general public to understand. The draft guidance document and redesigned templates are available at http://www.fda.gov/oc/advisory/waiver/ACdisclosure1007.html.

FDA also has formalized operating procedures designed to ensure appropriate security and promote proper decorum and public conduct at advisory committee meetings. They are intended to help ensure that meetings proceed in an orderly fashion and that the work of the committees is not impeded, but that the right of free speech is also protected.

In addition, FDA has improved its Web page on advisory committees by providing better access to information about waivers granted for conflicts of interest. This Web page provides current information about upcoming advisory committee meetings and other updated information related to FDA's advisory committee processes. The Web site is at http://www.fda.gov/oc/advisory/default.htm.

Finally, the FDA has recently posted the names of outside experts that it has named to a new risk communication advisory committee to make recommendations to FDA about how best to communicate the risks and benefits of FDA regulated products. More information about this advisory committee and the list of members can be found at http://www.fda.gov/bbs/topics/NEWS/2007/NEW01739.html.

FDA’s policies on advisory committees continue to be informed by new studies on conflicts of interest. The agency asked a consultant, Eastern Research Group, to study 16 recent advisory committees. The report highlights the difficulty of assembling highly qualified experts who are free of conflicts and finds that those who have received waivers appear to be significantly more qualified than those who have not received waivers. The full report is available online at http://www.fda.gov/oc/advisory/ERGCOIreport.pdf.

So far this year the agency has convened 47 meetings of expert independent advisory committees to advise FDA on topics such as new gene therapies and the safety of children’s cough and cold medicines.

PRESS RELEASE: FDA Sends Sanofi Warning Letter for Ketek Study

Maureen Martino — Thu, 25 Oct 2007 09:37:24 -0400

FDA Sends Sanofi Warning Letter for Ketek Study

ROCKVILLE, Md., Oct. 24, 2007--The FDA posted on its web site a letter to Sanofi-aventis regarding a study with the antibiotic Ketek.

DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration
Rockville MD 20857

WARNING LETTER
VIA EMAIL AND
CERTIFIED MAIL
RETURN RECEIPT REQUESTED

Gregory Irace
Chief Executive Officer
Sanofi-Aventis U.S. LLC.
55 Corporate Drive
Bridgewater, NJ 08807
Ref: 07-HFD-45-1002

Dear Mr. Irace:

This Warning Letter is to inform you of objectionable conditions found during the U.S. Food and Drug Administration's (FDA) investigation into Aventis Pharmaceuticals' (hereafter referred to as Aventis) role as sponsor of study HMR3647Al3014 (study 3014) entitled "Randomized, Open-Label, Multicenter Trial of the Safety and Effectiveness of Oral Telithromycin [Ketem] and Amoxicillin-Clavulanic Acid [Augmentin] in Outpatients with Respiratory Tract Infections in Usual Care Settings" of the investigational drug, Ketek (telithromycin). We note that the issues addressed in this letter pertain to the time period prior to the merger of Sanofi-Synthelabo and Aventis Pharmaceuticals in August 2004. FDA notes that the legal name of the current firm is Sanofi-Aventis and that Sanofi-Aventis is the current sponsor of the Ketek New Drug Application (NDA).

This investigation is a part of FDA's Bioresearch Monitoring Program which is designed to evaluate the conduct of research and to ensure that the rights, safety, and welfare of the human subjects of those studies have been protected. Another objective of the program is to ensure that data submitted in support of New Drug Applications are scientifically valid and accurate.

In July 2002, Aventis submitted to FDA the clinical study results obtained from study 30 14 in support of NDA 21,144. Subsequent FDA data validation inspections of several clinical investigators participating in study 3014 revealed multiple and significant violations of FDA regulations codified at 21 CFR 3 12 that affected the integrity of data submitted to NDA 21,144. As a result of these findngs, FDA requested in its January 24, 2003 Approvable Letter that Aventis provide information on its sponsor monitoring and auditing of clinical investigator sites for study 3014. Aventis submitted this information to the FDA in July 2003 (preliminary response) and October 2003 (final response). FDA obtained additional information related to Aventis's oversight of study 3014 in a subsequent investigation.

From our review of these records, we conclude that Aventis did not adhere to the applicable statutory requirements and FDA regulations governing the conduct of clinical investigations. We wish to emphasize the following:

1. Failure to secure investigator compliance with the investigational plan and applicable FDA regulations [21 CFR 312.56(b)].

Under FDA regulations, a sponsor who discovers that an investigator is not complying with the signed investigator agreement [Form FDA 15721, the general investigational plan, or the requirements of applicable FDA regulations shall promptly either secure compliance or discontinue shipment of the drug to the investigator, terminate the investigator's participation, and notify FDA. Our investigation found that despite several clinical monitoring visits from Aventis's designated monitors, PPD Development (hereafter referred to as PPD), and Aventis's own audits documenting serious protocol violations and regulatory noncompliance by multiple clinical investigators, these violations persisted. We were unable to find evidence that Aventis promptly secured compliance or terminated participation of these clinical investigators and notified FDA. For example: a. Review of PPD monitoring records, Aventis Quality Assurance (QA) audit records, and email communications between PPD and Aventis disclosed that Aventis knew of pervasive problems at the clinical investigator site of Dr. Maria Anne Campbell aka Anne Kirkman Campbell (hereafter referred to as Dr. Kirkman Campbell), a solo practitioner in rural Alabama who had never previously conducted an FDA-regulated study, but randomized 407 subjects into Study 3014 over a 3 month time period (i.e., November 2001-January 2002.)

FDA's October 2002 routine data validation inspection of this investigator raised numerous concerns with her conduct of study 3014, including potential fabrication of study subjects, fabrication of study data, and enrollment of ineligible subjects. FDA investigated Dr. Kirkman Campbell and found that she falsified Case Report Forms (CRFs) that were submitted to the sponsor and falsified documentation to support the existence of a fictitious subject. Dr. Kirkman Campbell subsequently pled guilty to one count of mail fraud in connection with this fictitious subject and was sentenced to 57 months in federal prison.

While study 3014 was ongoing, PPD conducted monitoring visits of Dr. Kirkman Campbell on November 29,2001, after 65 subjects were enrolled; on February 18-21,2002, after all 407 subjects were enrolled; on April 1-5,2002, after all the subjects completed the study, and on October 8-10,2002, to prepare the site for the upcoming FDA inspection. In addition, Aventis conducted a quaIity assurance (QA) audit at this site on January 17-18,2002.

Our review found that PPD identified significant problems at Dr. Kirkman Campbell's site and subsequently informed Aventis of its findings and concerns. We note that Aventis failed to promptly secure compliance from Dr. Kirkman.

PRESS RELEASE: OIG Releases Report of FDA’s Oversight of Clinical Trials

Maureen Martino — Fri, 28 Sep 2007 10:46:14 -0400

OIG Releases Report of FDA’s Oversight of Clinical Trials, Concludes Improvement of Information Systems and Processes is Needed

WASHINGTON, Sept. 28, 2007—Weaknesses in the Food and Drug Administration’s (FDA) information systems and management processes hinder the agency’s ability to oversee clinical trial inspections. So concludes Inspector General Daniel R. Levinson of the Office of Inspector General (OIG) for the Department of Health and Human Services (HHS) in a report released today: “FDA’s Oversight of Clinical Trials.”

To protect human subjects, federal law requires that all new drugs and medical devices undergo clinical trials to demonstrate their safety and efficacy prior to receiving FDA approval. FDA inspects clinical trials to determine whether sponsors, clinical investigators, and institutional review boards responsible for conducting or overseeing clinical trials for investigational products are complying with relevant regulations.

FDA oversees clinical trials through a variety of mechanisms that include protocol reviews and onsite inspections through its Bioresearch Monitoring Program (BiMo). The OIG report focused exclusively on BiMo inspections, an important mechanism for protecting human subjects once a clinical trial is underway.

OIG concluded that the FDA does not have a mechanism to identify all clinical trials and Institutional Review Boards (IRBs), which approve, monitor, and review research involving human subjects. Moreover, it lacks a comprehensive database for tracking its inspections of clinical trials. Previous OIG reports found similar weaknesses. “Data limitations hinder the FDA’s ability to ensure that participants are protected
from unreasonable risks,” said Daniel R. Levinson, HHS Inspector General. “Accurate record-keeping is critical to maintaining the safety of clinical trial patients.”

FDA inspected about 1 percent of clinical trial sites from fiscal year (FY) 2000 to FY 2005, OIG concluded after reviewing multiple data sources. Of these inspections, 75 percent were surveillance inspections, which generally target completed trials and often focus on verifying the quality of data from clinical trials. FDA also inspected few IRBs.

In 1998, a series of OIG reports concluded that IRBs lacked the time and expertise to sufficiently monitor the research. And a 2000 report found that data integrity concerns, rather than human subject protection, drove FDA’s oversight of clinical investigators.
.
OIG identified steps that FDA could take to improve its system for overseeing clinical trials, which are:

• Develop a comprehensive internal database of all clinical trials,
• Create a registry of IRBs,
• Create a cross-center database that allows complete tracking of FDA inspections,
• Seek legal authority to provide oversight that reflects current clinical trial practices; and
• Establish a mechanism to provide feedback to FDA district office staff on their inspection reports and findings.

FDA concurred with four of the OIG’s recommendations but did not address the provision of feedback regarding inspection reports and findings. FDA’s full response to OIG's recommendations is included as an appendix to the report.

PRESS RELEASE: FDA Clears Genetic Lab Test for Warfarin Sensitivity

Maureen Martino — Tue, 18 Sep 2007 11:36:52 -0400

FDA Clears Genetic Lab Test for Warfarin Sensitivity

The U.S. Food and Drug Administration today cleared for marketing a new genetic test that will help physicians assess whether a patient may be especially sensitive to the blood-thinning drug warfarin (Coumadin), which is used to prevent potentially fatal clots in blood vessels.

One-third of patients receiving warfarin metabolize it quite differently than expected and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The Nanosphere Verigene Warfarin Metabolism Nucleic Acid Test detects some variants of both genes.

"Today’s action offers physicians the first FDA cleared genetic test for warfarin sensitivity, which is another step in our commitment to personalized medicine,” said Daniel Schultz, M.D., director, FDA’s Center for Devices and Radiological Health. “With this test, physicians may be able to use genetic information along with other clinical information to treat their patients.”

Warfarin can be a difficult drug to use because the optimal dose varies depending on many risk factors, including a patient's diet, age, and the use of other medications. Rapidly achieving the correct dose is important. Patients who receive doses that are higher than needed to correctly thin the blood are at risk of life-threatening bleeding. Those who receive doses that are too low may remain at risk of life-threatening blood clots.

Warfarin is the second most common drug, after insulin, implicated in emergency room visits for adverse drug events.

In August, FDA approved updated labeling for Coumadin, the brand name version of warfarin, explaining that people with variations of the genes CYP2C9 and VKORC1 may respond differently to the drug. Manufacturers of generic warfarin are adding similar information to their products' labeling.

Physicians and other health care professionals who prescribe warfarin regularly check to see if the drug is working properly by ordering a test called the PT or prothrombin time that evaluates the blood's ability to clot properly. The results are measured in seconds and compared with the expected value in healthy people, known as the International Normalized Ratio or INR.

The Nanosphere test is not intended to be a stand-alone tool to determine optimum drug dosage, but should be used along with clinical evaluation and other tools, including INR, to determine the best treatment for patients.

FDA cleared the test based on results of a study conducted by the manufacturer of hundreds of DNA samples as well as on a broad range of published literature. In a three site study, the test was accurate in all cases where the test yielded a result; 8 percent of the tests could not identify which genetic variants were present.

The new test was cleared for use on the Verigene System, a clinical laboratory test system. Both products are manufactured by Nanosphere Inc., Northbrook, Ill.

PRESS RELEASE: Cephalon Warns Doctors Over Pain Drug Deaths Says FDA

Maureen Martino — Thu, 13 Sep 2007 15:14:55 -0400

Cephalon Warns Doctors Over Pain Drug Deaths Says FDA

FRAZER, Pa., Sept. 13 -- Cephalon, Inc. today communicated with healthcare professionals to clarify the appropriate patient selection, dosing and administration for FENTORA(R) (fentanyl buccal tablet) [C-II]. The company is sharing this information with the medical community to reinforce the appropriate prescribing and use of the medication.

The letter, issued in collaboration with the U.S. Food and Drug Administration (FDA), was in response to recently reported serious adverse events, including some deaths in patients who were not appropriate candidates for FENTORA. These events appear to have occurred as a result of improper use in patients who were not already taking opioids around-the-clock (opioid nontolerant); improper dosing of the medication; and/or improper substitution of FENTORA for other fentanyl-based medications.

The letter has been sent to physicians, pharmacists, managed care organizations, and other healthcare professionals and it emphasizes the need to adhere to the FENTORA prescribing information, including the following:

-- FENTORA is indicated only for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. -- FENTORA must only be prescribed to patients who are routinely taking around-the-clock opioids. FENTORA should not be prescribed to patients for acute pain, postoperative pain, headache/migraine, or sports injuries. -- Only one tablet per episode should be taken once a dose is established and patients must wait at least four hours before taking another dose of FENTORA. -- FENTORA is not bioequivalent to or a generic version of ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II]; therefore, FENTORA should not be substituted for ACTIQ or any other fentanyl-containing pain medication.

Cephalon also is proactively working with the FDA to emphasize the appropriate patient selection, dosing and administration in the FENTORA label and Risk Minimization Action Plan (RiskMAP). Healthcare professionals and patients may contact Cephalon Medical Services at 1-800-895-5855 or visit www.fentora.com for additional prescribing information.

PHYSICIANS AND OTHER HEALTHCARE PROVIDERS MUST BECOME FAMILIAR WITH THE IMPORTANT WARNINGS IN THIS LABEL.

FENTORA contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. FENTORA can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing FENTORA in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the

highest potential for abuse and risk of fatal overdose due to respiratory depression.

FENTORA is indicated only for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer. Because life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients, FENTORA is contraindicated in the management of acute or postoperative pain. This product is not indicated for use in opioid nontolerant patients.

Patients and their caregivers must be instructed that FENTORA contains a medicine in an amount which can be fatal to a child. Patients and their caregivers must be instructed to keep all tablets out of the reach of children. (See Information for Patients and Caregivers for disposal instructions.)

Due to the higher bioavailability of fentanyl in FENTORA, when converting patients from other oral fentanyl products, including oral transmucosal fentanyl citrate (OTFC and Actiq(R)), to FENTORA, do not substitute FENTORA on a mcg per mcg basis. Adjust doses as appropriate. (See DOSAGE AND ADMINISTRATION.)

FENTORA is intended to be used only in the care of opioid tolerant cancer patients and only by healthcare professionals who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.

The concomitant use of FENTORA with strong and moderate cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.

Full prescribing information about FENTORA, including boxed warning, is available from www.FENTORA.com.

About Cephalon, Inc.

Cephalon, Inc. is an international biopharmaceutical company, recently inducted in to the World Economic Forum Community of Global Growth Companies. For 20 years, the company has been dedicated to the discovery, development and commercialization of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon has delivered a seven-year compound annual growth rate (CAGR) through 2006 greater than 75% and 2006 revenue of $1.760 billion. A member of the Fortune 1000, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France.

The company's proprietary products in the United States include: PROVIGIL(R) (modafinil) Tablets [C-IV), FENTORA, TRISENOX(R) (arsenic trioxide) injection, AMRIX(TM) (cyclobenzaprine hydrochloride extended-release capsules), VIVITROL(R) (naltrexone for extended-release injectable suspension), GABITRIL(R) (tiagabine hydrochloride), NUVIGIL(TM) (armodafinil) Tablets [C-IV] and ACTIQ. The company also markets numerous products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855.

In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products,; interpretation of clinical results; manufacturing development and capabilities; market prospects for its products; sales and earnings guidance; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward- looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.

PRESS RELEASE: FDA Advisory Committees Recommend Continued US Marketing Authorization for Trasylol

Maureen Martino — Thu, 13 Sep 2007 10:48:06 -0400

FDA Advisory Committees Recommend Continued US Marketing Authorization for Trasylol

Committees also recommend further changes to US Label for Trasylol and additional safety studies

Leverkusen, Germany; West Haven, CT, USA, September 12, 2007 - Today, the Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to the U.S. Food and Drug Administration (FDA) held a meeting to discuss the risk /benefit profile of Trasylol® (aprotinin injection), a Bayer drug used in coronary artery bypass graft (CABG) surgery. At the close of the meeting, based on the Trasylol data in Bayer’s controlled clinical studies and after considering data from observational studies and public testimony presented at the meeting, the Committees recommended that US marketing authorization for Trasylol should be continued.

The Committees also recommended that Bayer amend the U.S. product label for Trasylol to provide additional prescribing guidance to physicians and also recommended that Bayer conduct additional clinical studies, including randomized controlled trials, to further assess the risk and benefit of Trasylol.

Bayer was pleased to participate in today’s session because it provided a proper forum in which to discuss the complex scientific issues surrounding the risk/benefit profile of Trasylol in detail. Trasylol is the only drug currently approved by the FDA for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.

Patient safety is Bayer’s first and foremost concern. In line with the discussions and guidance received from the Committees today, the company will work with FDA on appropriate U.S. label revisions providing additional prescribing guidance to physicians.

The Committees also recommended that Bayer undertake additional clinical studies, including randomized controlled clinical trials, to further assess risks and benefits of Trasylol. Following the Committees’ recommendation, Bayer will move forward with discussions with the FDA to reach agreement with them regarding further clinical activities.

Bayer is in close contact with other regulatory authorities around the world and will inform them of the outcome of today’s meeting and potential next steps.

Bayer considers the discussion today and the valuable feedback provided by the Committees as important guidance and input that will help the company in clarifying and addressing these critical issues. Bayer continues to believe that the totality of the medical evidence, including the RCTs and other data discussed today demonstrates that Trasylol is safe and effective when used according to the product labeling. Bayer will continue to work closely and cooperatively with all regulatory authorities to address questions regarding safe and effective use of its drugs.

About Trasylol

Important Safety Considerations

Trasylol® administration may cause fatal anaphylactic or anaphylactoid reactions. Fatal reactions have occurred with an initial (test) dose as well as with any of the components of the dose regimen. Fatal reactions have also occurred in situations where the initial (test) dose was tolerated. The risk for anaphylactic or anaphylactoid reactions is increased among patients with prior aprotinin exposure and a history of any prior aprotinin exposure must be sought prior to Trasylol® administration. The risk for a fatal reaction appears to be greater upon re-exposure within 12 months of the most recent prior aprotinin exposure. Trasylol® should be administered only in operative settings where cardio-pulmonary bypass can be rapidly initiated. The benefit of Trasylol® to patients undergoing primary CABG surgery should be weighed against the risk of anaphylaxis associated with any subsequent exposure to aprotinin.
(See CONTRAINDICATIONS, WARNINGS and PRECAUTIONS in the prescribing information.)

Safety Considerations

Trasylol is contraindicated in patients with a known or suspected aprotinin exposure during the last 12 months. Aprotinin may also be a component of some fibrin sealant products.
• In clinical studies, hypersensitivity and anaphylactic reactions were rare (<0.1%) in patients with no prior exposure to Trasylol.

Trasylol administration increases the risk for renal dysfunction and may increase the need for dialysis in the perioperative period.

• This risk may be especially increased for patients with pre-existing renal impairment or those who receive aminoglycoside antibiotics or drugs that alter renal function.

• The incidence of serum creatinine elevations >0.5 mg/dL above pre-treatment levels was statistically higher in the high-dose aprotinin group (9.0%) compared with placebo (6.6%).

• The incidence of serum creatinine elevations >2.0mg/dL above baseline was slightly higher in the high-dose aprotinin group (1.1% vs. 0.8%).

In clinical trials Trasylol® did not increase the risk of the following perioperative events: myocardial infarction, congestive heart failure, hepatic dysfunction and mortality.

For Trasylol® contraindications, warnings and precautions see prescribing information.

Forward-looking statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

PRESS RELEASE: Ariad Pharmaceuticals Says Reaches Agreement with FDA for Cancer Drug Trial

Maureen Martino — Mon, 10 Sep 2007 10:21:40 -0400

Ariad Pharmaceuticals Says Reaches Agreement with FDA for Cancer Drug Trial

CAMBRIDGE, Mass. -- ARIAD Pharmaceuticals today announced that it has reached agreement on a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA) for its global Phase 3 trial of oral deforolimus in patients with metastatic sarcomas. Based on the SPA, progression-free survival (PFS) will be the primary endpoint of the Phase 3 trial, and overall survival will be a secondary endpoint. The Company expects to begin patient enrollment in the trial later this month.

The SPA is a written agreement between the trial's sponsor and the FDA regarding the design, endpoints, and planned conduct and analysis of a trial to be used in support of regulatory approval. The European Medicines Agency (EMEA) has provided protocol advice consistent with that of the FDA regarding the Phase 3 trial design as part of its Protocol Assistance program. ARIAD and Merck & Co., Inc. have a global collaboration to jointly develop and commercialize deforolimus for use in cancer.

"We are extremely pleased with the outcome of our positive and collaborative discussions with the FDA review staff regarding the design of our Phase 3 trial for oral deforolimus in metastatic sarcomas. Working with leading sarcoma experts and our clinical investigators, we were able to successfully resolve the open issues regarding the trial's endpoints and reach agreement with the Agency on PFS as the primary endpoint," said Camille Bedrosian, M.D., chief medical officer of ARIAD.

ARIAD and Merck plan to conduct a Phase 3 trial of oral deforolimus in patients with metastatic soft-tissue and bone sarcomas following a favorable response to chemotherapy - a period when continued treatment with traditional chemotherapeutic agents has not been established to provide additional clinical benefit. Thus, absent new alternatives, patients would generally not receive other cancer therapies.

This double-blind trial is designed to evaluate approximately 650 patients who will be randomized (1:1) to oral deforolimus or placebo at approximately 125 sites. The trial is 90% powered to detect a 33% increase in median PFS (corresponding to a hazard ratio of 0.75) comparing the oral deforolimus arm with the placebo arm. Two interim analyses are included. Complete patient enrollment and the second interim analysis are expected to take place within approximately two years of the first patient being enrolled.

Pierre F. Dodion, M.D., senior vice president, oncology of ARIAD, added, "FDA agreement on our overall Phase 3 trial design, patient population and endpoints, as well as our newly established partnership with Merck represent important achievements for the global development of deforolimus."

About Sarcoma

Sarcomas are a group of aggressive cancers of connective tissue of the body for which there are currently limited treatment options. Sarcomas can arise anywhere in the body and are divided into two main groups - bone tumors and soft-tissue sarcomas. They are further subdivided based on the type of cell or tissue from which the tumor developed. There are approximately 12,000 new cases of sarcoma diagnosed each year in the United States and approximately 100,000 sarcoma patients overall in the United States. More information about sarcomas is available at http://www.curesarcoma.org and at http://www.sarcoma.net/facts/htm.

About Deforolimus

ARIAD's lead product candidate, deforolimus, is a novel small-molecule inhibitor of the protein mTOR, a "master switch" in cancer cells. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and angiogenesis. Patient enrollment has been completed in multiple Phase 1 and 2 clinical trials of deforolimus in patients with solid tumors and hematologic cancers. The global Phase 3 trial of oral deforolimus in metastatic soft-tissue and bone sarcomas is the subject of a Special Protocol Assessment with the U.S. Food and Drug Administration (FDA). Deforolimus has been designated both as a fast-track product and an orphan drug by the FDA and as an orphan drug by the European Medicines Agency for the treatment of sarcomas. ARIAD has a global partnership with Merck & Co., Inc. to develop and commercialize deforolimus in multiple cancer indications. ARIAD also is collaborating with Medinol Ltd. to develop stents and other medical devices that deliver deforolimus to prevent reblockage at sites of vascular injury following stent-assisted angioplasty.

About ARIAD

ARIAD is engaged in the discovery and development of breakthrough medicines to treat cancer by regulating cell signaling with small molecules. ARIAD is developing a comprehensive approach to patients with cancer that addresses the greatest medical need - aggressive and advanced-stage cancers for which current treatments are inadequate. ARIAD has a global partnership with Merck & Co., Inc. to develop and commercialize deforolimus, ARIAD's lead cancer product candidate. Medinol Ltd. is also developing stents and other medical devices that deliver deforolimus to prevent reblockage at sites of vascular injury following stent-assisted angioplasty. ARIAD has an exclusive license to pioneering technology and patents related to certain NF-(kappa)B treatment methods, and the discovery and development of drugs to regulate NF-(kappa)B cell-signaling activity, which may be useful in treating certain diseases. Additional information about ARIAD can be found on the web at http://www.ariad.com.

This press release contains "forward-looking statements," including statements related to the design, conduct and timing of the Phase 3 clinical trial of deforolimus in metastatic sarcoma. Forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, the costs associated with our research, development, manufacturing and other activities, the conduct and results of pre-clinical and clinical studies of our product candidates, difficulties or delays in obtaining regulatory approvals to market products resulting from our development efforts, our reliance on partners, including Medinol and Merck, and other key parties for the successful development, manufacturing and commercialization of products, the adequacy of our capital resources and the availability of additional funding, patent protection and third-party intellectual property claims relating to our and any partner's product candidates, the timing, scope, cost and outcome of legal and patent office proceedings concerning our NF-(kappa)B patent portfolio, the potential acquisition of or other strategic transaction regarding the minority stockholders' interests in our 80%-owned subsidiary, ARIAD Gene Therapeutics, Inc., future capital needs, key employees, markets, economic conditions, prices, reimbursement rates, competition and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this document is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.

PRESS RELEASE: GTC Obtains FDA Fast Track Designation for ATryn

Maureen Martino — Fri, 07 Sep 2007 11:39:58 -0400

GTC Obtains FDA Fast Track Designation for ATryn and Permission to Submit a Rolling BLA

FRAMINGHAM, Mass. -- GTC Biotherapeutics announced today that the US Food and Drug Administration, or FDA, has designated ATryn® a “fast track product” entitled to accelerated FDA review for the hereditary antithrombin deficiency indication. The FDA has also granted GTC permission to submit the associated Biologics License Application, or BLA, for ATryn® on a rolling basis. Fast track designation is provided to those products that are intended to treat serious or potentially life threatening conditions for which there is an unmet medical need. The BLA requesting marketing approval for ATryn® will be submitted as sections are completed rather than waiting for all sections to be submitted together, enabling FDA review to begin sooner. GTC anticipates filing the initial sections with the FDA in the fourth quarter and completing the rolling submission after all clinical data is gathered, analyzed, and available for the BLA, which is planned to be by the end of the first quarter of 2008.

ATryn® is GTC’s recombinant form of human antithrombin, a protein with anticoagulant and anti-inflammatory properties that is normally present in human plasma. ATryn® is being investigated in a Phase III comparative study for the treatment of hereditary antithrombin deficiency, or HD, patients at risk for developing deep vein thrombosis or thromboembolism while undergoing surgical procedures or childbirth. Top line data from this study is planned to be available late in the fourth quarter.

ATryn® is produced in the milk of goats that have incorporated the human antithrombin gene such that it is only expressed during lactation. This technology enables an alternative supply of antithrombin that is unconstrained by the limited availability of plasma-sourced material.

ATryn® has been approved for use in the European Union for the treatment of HD patients undergoing surgical procedures, marking the first time that any transgenically produced therapeutic protein had been approved anywhere in the world. LEO Pharma A/S, GTC’s commercial and development partner in Europe, Canada and the Middle East, has initiated a Phase II study of ATryn® in the treatment of patients with disseminated intravascular coagulation, or DIC, associated with severe sepsis. DIC is a large unmet medical with approximately 500,000 patients in the US and EU each year and up to 50% mortality.

About GTC Biotherapeutics

GTC Biotherapeutics develops, produces, and commercializes therapeutic proteins through transgenic animal technology. In addition to ATryn®, GTC is working with LFB Biotechnologies to develop recombinant forms of human factor VIIa and a CD20 monoclonal antibody. GTC’s intellectual property includes a patent in the United States through 2021 for the production of any therapeutic protein in the milk of any transgenic mammal. GTC’s transgenic production platform is particularly well suited to enabling cost effective development of proteins that are difficult to express in traditional recombinant production systems as well as those that are required in large volumes. Additional information is available on the GTC web site, http://www.gtc-bio.com.

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the timing of completion of GTC’s current Phase III study of ATryn® and filing of the associated BLA. Such forward-looking statements are subject to a number of risks, uncertainties and other factors that could cause actual results to differ materially from future results expressed or implied by such statements. Factors that may cause such differences include, but are not limited to, the risks and uncertainties discussed in GTC's most recent Annual Report on Form 10-K and its other periodic reports filed with the Securities and Exchange Commission, including the uncertainties associated with conducting clinical studies, and the risks and uncertainties associated with dependence upon the actions of regulatory agencies. GTC cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this document, and GTC undertakes no obligation to update or revise the statements, except as may be required by law.

PRESS RELEASE: FDA Announces Baraclude Not for HIV/HBV Co-infected Patients Not Also Receiving HAART

Fri, 17 Aug 2007 11:20:20 -0400

FDA Announces Baraclude (entecavir) is Not Recommended for HIV/HBV Co-infected Patients Who Are Not Also Receiving HAART Due to the Potential for the Development of HIV Resistance

ROCKVILLE, Md., Aug. 16 -- FDA and Bristol-Myers Squibb notified healthcare professionals of revisions to the following sections of the Baraclude prescribing information: BOXED WARNINGS, MICROBIOLOGY/Antiviral Activity against HIV (human immunodeficiency virus), WARNINGS/Co-infection with HIV, PRECAUTIONS/Information for Patients, and Patient Package Insert. Baraclude therapy is not recommended for HIV/hepatitis B virus (HBV) co-infected patients who are not also receiving highly active antiretroviral therapy (HAART) due to the potential for the development of HIV resistance.

Read the letter below. The label is attached.

August 2007

IMPORTANT DRUG WARNING

Dear Healthcare Professional:

Bristol-Myers Squibb would like to inform you that therapy with BARACLUDE® (entecavir) is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART) due to the potential for the development of HIV (human immunodeficiency virus) resistance.

Accordingly, the BARACLUDE Full Prescribing Information has been updated to include the following information in the boxed WARNINGS1:

"Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). See WARNINGS: Co-infection with HIV."

In addition, the MICROBIOLOGY section of the BARACLUDE Full Prescribing Information has been revised to include the following additional information:

Antiviral Activity against HIV

"A comprehensive analysis of the inhibitory activity of entecavir against a panel of laboratory and clinical human immunodeficiency virus type 1 (HIV-1) isolates using a variety of cells and assay conditions yielded EC50 values ranging from 0.026 to >10 ?M; the lower EC50 values were observed when decreased levels of virus were used in the assay. In cell culture, entecavir selected for an M184I substitution in HIV reverse transcriptase at micromolar concentrations, confirming inhibitory pressure at high entecavir concentrations. HIV variants containing the M184V substitution showed loss of susceptibility to entecavir."

Consistent with clinical practice guidelines for chronic hepatitis B management,2,3 the WARNINGS section of the BARACLUDE Full Prescribing Information has been updated with the following information:

"Before initiating BARACLUDE therapy, HIV antibody testing should be offered to all patients. BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use."

Other changes in the WARNINGS and PRECAUTIONS sections and PATIENT INFORMATION have been made consistent with the information described above. Please refer to the enclosed BARACLUDE Full Prescribing Information, including boxed WARNINGS, for more information.

Bristol-Myers Squibb remains committed to providing you the most current and accurate information available for our products.

686US07LD21001 08/07

If you have any questions about this new information or require additional medical information, please contact Bristol-Myers Squibb at 1-800-321-1335.

If you have had a patient who experienced an adverse event following, or coincident with the use of BARACLUDE (entecavir), please contact Bristol-Myers Squibb at 1-800-321-1335 or the FDA MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, or by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787).

Please refer to the accompanying Important Information about BARACLUDE and the enclosed BARACLUDE Full Prescribing Information, including boxed WARNINGS.

Sincerely,

Freda C. Lewis-Hall, M.D.

Senior Vice President, US Medical Affairs

Bristol-Myers Squibb

BARACLUDE is a registered trademark of Bristol-Myers Squibb Company.

Enclosure: BARACLUDE Full Prescribing Information

REFERENCES

1. BARACLUDE (entecavir) Full Prescribing Information, Bristol-Myers Squibb Company, Princeton, New Jersey.®

2. Lok AS, McMahon BJ. AASLD practice guidelines: chronic hepatitis B. Hepatology 2007;45:507-39.

3. Department of Health and Human Services. Supplement to the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. April 30, 2007. Available at: http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=7&ClassID=1. Accessed June 27, 2007.

Indication and Important Safety Information about BARACLUDE® (entecavir) Tablets

INDICATION:

BARACLUDE is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-naïve and lamivudine-resistant adult patients with HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver disease, and on more limited data in adult patients with HIV/HBV co-infection who have received prior lamivudine therapy.

IMPORTANT SAFETY INFORMATION:

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.

• Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including BARACLUDE. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

• Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). Before initiating BARACLUDE therapy, HIV antibody testing should be offered to all patients.

• BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use.

• Dosage adjustment of BARACLUDE is recommended for patients with a creatinine clearance <50 mL/min, patients with age-related decreases in renal function, and those on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

• Since entecavir is primarily eliminated by the kidneys, coadministration of BARACLUDE with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

• The safety and efficacy of BARACLUDE in liver transplant recipients are unknown. Renal function must be carefully monitored both before and during treatment with BARACLUDE in a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus.

• Patients should be advised that treatment with BARACLUDE (entecavir) has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

• There are no adequate and well-controlled studies of BARACLUDE administered to pregnant women. BARACLUDE should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits. There are no studies on the effect of BARACLUDE on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV. Women should be instructed not to breast-feed if they are taking BARACLUDE.

• Safety and effectiveness of BARACLUDE in pediatric patients below the age of 16 years have not been established.

The most common adverse events of moderate to severe intensity among patients treated with BARACLUDE in clinical trials included: headache (4%), fatigue (3%), diarrhea (1%), and dyspepsia (1%).

The recommended dose of BARACLUDE is 0.5 mg once daily in nucleoside-naïve adults and 1 mg once daily in lamivudine-refractory adults. BARACLUDE should be administered on an empty stomach (at least 2 hours after a meal and at least 2 hours before the next meal). The optimal duration of treatment with BARACLUDE for patients with chronic hepatitis B infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.

Please see enclosed Full Prescribing Information, including boxed WARNINGS.

PRESS RELEASE: Anesiva Receives FDA Approval for Zingo, a Product to Reduce Pain Associated with Needle Insertion Procedures

Fri, 17 Aug 2007 09:36:01 -0400

Anesiva Receives FDA Approval for Zingo, a New, Innovative Product to Reduce Pain Associated with Needle Insertion Procedures in Children

- Zingo is First Commercial Product for Anesiva -

SOUTH SAN FRANCISCO, Calif., Aug. 17 -- Anesiva, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved Zingo (lidocaine hydrochloride monohydrate) powder intradermal injection system, which provides rapid, topical, local analgesia to reduce the pain associated with venous access procedures, such as IV insertions or blood draws, in children ages three to 18. Zingo is an easy-to-administer, single-use, needle-free system containing 0.5 mg sterile lidocaine powder. It provides a rapid onset of action, allowing intravenous line placement or venipuncture to begin one to three minutes after administration.

"Blood draws and IV insertions are the most frequently reported painful events in hospitalized children. Despite guidelines recommending the use of topical anesthetics prior to venous access procedures, currently available local anesthetics commonly take 20 minutes or longer to act, making their use in today's fast-paced hospital environment difficult. FDA approval of Zingo provides a unique option for healthcare providers who strive to safely and effectively manage children's pain during these procedures," said John P. McLaughlin, chief executive officer of Anesiva. "Anesiva is committed to improving pain management, and the approval of Zingo marks an important step toward reaching this goal. This favorable decision by the FDA to approve Zingo came more than five weeks earlier than our PDUFA date of September 24th, and we are grateful for the efforts put in by the agency and for the cooperative relationship that we enjoyed during this process."

Guidelines and recommendations from the American Academy of Pediatrics, the American Pain Society and the Infusion Nurses Society all call for the use of topical anesthetics prior to venous access procedures.

"Healthcare providers have always faced an uncomfortable trade-off when it comes to the use of topical anesthetics: they can choose speed and convenience or patient comfort," said William T. Zempsky, M.D., associate professor, Department of Pediatrics, University of Connecticut; associate director, Pain Relief Program, Connecticut Children's Medical Center, Hartford, who led the pediatric clinical trials of Zingo. "With Zingo, doctors and nurses can offer the best of both worlds, providing pain control that won't slow the delivery of medical care."

Data from two pivotal, placebo-controlled, Phase 3 clinical studies, which collectively enrolled 1,109 patients across 15 U.S. clinical centers, demonstrated that Zingo, a preparation of powdered lidocaine administered through a needle-free, pre-filled, disposable device, provided statistically significant pain relief in children ages three to 18 undergoing venous access procedures, such as IV line placements. These data indicated that treatment with Zingo quickly and effectively reduced pain when given just one to three minutes prior to the venous access procedure. Zingo was well-tolerated. The most common adverse reactions were redness (erythema), red dots (petechiae) and swelling (edema) at the site of administration.

Venous access procedures, like IV insertions and blood draws, are among the most common interventions performed at a hospital, with more than 18 million pediatric venous access procedures and 400 million total procedures per year in the U.S. Needlesticks are also a source of deep anxiety. An Impulse Research survey conducted last year by Anesiva found that 70 percent of children experience fear and stress during a visit to the doctor or hospital that involves a needlestick procedure, and more than half of all children -- even those older than seven -- cry during these procedures. The problem is compounded in children with chronic illnesses who must undergo frequent IV insertions.

"Pre-treating pain associated with venous access procedures is the right thing to do, and parents should feel comfortable asking how pain can be minimized for their child," said Micke A. Brown, BSN, RN, director of advocacy, American Pain Foundation. "Regular use of topical anesthetics to lessen a painful needlestick can be a nurse's best friend. It allows us to quickly gain patient trust and sets a therapeutic tone that positively affects the hospital experience."

Anesiva will provide updated information on the commercialization plan for Zingo in the coming weeks. In addition, Anesiva is now studying Zingo in a large Phase 3 trial in adults. The company will use the data generated in that trial as the basis for an FDA filing to expand the label to include adults.

There may be opportunities to use the needle-free delivery technology employed in Zingo for the delivery of drugs other than lidocaine. Possible drug candidates include insulin, human growth hormone, erythropoietin, calcitonin, and other medications, excluding vaccines. The company may license the rights to the use of this technology for such other medications to third parties.

About Zingo

Zingo is a ready-to-use, single-use, needle-free system that delivers sterile lidocaine powder into the epidermis of the skin and provides topical, local analgesia in one to three minutes after administration. This rapid onset, which may be especially useful in pediatric populations and busy emergency room settings, means the product can be incorporated into a medical procedure allowing uninterrupted care, an important advantage over current options. In addition to the hospital setting, Zingo may be used in physicians' offices and clinical laboratories.

Conference Call Details

Anesiva will conduct a webcast conference call with the investment community at 8:30 a.m. ET, today, August 17, 2007, 2007 to discuss this announcement. Interested parties can listen to the live audio webcast by dialing (800) 340-6289 (international dial: (706) 634-1538) or by logging on to http://www.anesiva.com and going to the Investor Information page. For those unable to participate via the Internet, a 24-hour replay will be available for seven days after the call by (800) 642-1687 (international dial: (706) 645-9291) and giving the following pass code: 13882358.