Merck Serono related Press Releases

NICE Recommends Use Of Cetuximab (Erbitux(R)) For UK Bowel Cancer Patients

Calisha Myers — Wed, 03 Jun 2009 11:32:26 -0400

NICE Recommends Use Of Cetuximab (Erbitux(R)) For UK Bowel Cancer Patients

The National Institute for Health and Clinical Excellence (NICE) has today published a Final Appraisal Determination (FAD) recommending the use of the drug cetuximab (Erbitux®) in combination with chemotherapy as a 1st-line treatment for patients with metastatic (advanced) colorectal cancer (mCRC) who have met specific additional criteria1* - presenting the possibility of potentially curative surgery.2 The treatment is recommended for patients in whom the cancer has spread only to the liver and who have 'wild-type' (unmutated) KRAS‡ tumours.1 Up to 65% of patients have wild-type KRAS tumours.3

Don Cowling, Managing Director of Merck Serono UK, the manufacturer of cetuximab said: "NICE's FAD for cetuximab for use in advanced colorectal cancer is the second positive recommendation for the drug that NICE has published in the last twelve months. In June 2008, NICE issued a recommendation for cetuximab use in the treatment of locally advanced squamous cell cancer of the head and neck♦. We are delighted that this therapy will now also be available to appropriate colorectal cancer patients on the NHS."

The evidence supporting NICE's decision includes the CRYSTAL† study, published in the New England Journal of Medicine in April 2009, which demonstrated the efficacy of cetuximab in mCRC patients with wild-type KRAS tumours. This followed the presentation at the ASCO-GI conference earlier this year of an article outlining the potential economic savings that could result from routinely testing mCRC patients for their KRAS status to determine which patients would be most likely to benefit from treatment with cetuximab.3,4

Bowel cancer is the third most common cancer in the UK, with more than 36,000 people diagnosed each year.5

The final NICE guidance is scheduled to be published in July and will be implemented within three months of publication. The full NICE FAD for the use of Erbitux® in the treatment of advanced colorectal cancer can be found at http://www.nice.org.uk.

* For full details of criteria, visit NICE website (see above)

About KRAS

The KRAS gene codes for a protein involved in the EGFR pathway - a complex pathway involved in the development and progression of cancer. In KRAS wild-type tumours, the KRAS protein is only activated in response to certain stimuli, such as EGFR signalling. Erbitux® works by blocking the EGFR signalling pathway, preventing KRAS activation, and subsequent tumour growth. In mutant KRAS tumours, the KRAS protein is permanently activated (regardless of EGFR signalling), therefore the inhibitory effect of Erbitux® is diminished in these cases.

♦Cetuximab in combination with radiotherapy is recommended by NICE as a treatment option only for patients with locally advanced squamous cell cancer of the head and neck whose Karnofsky performance-status score is 90% or greater and for whom all forms of platinum-based chemoradiotherapy treatment are contraindicated

†CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer

About Erbitux

Erbitux® is a first-in-class IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumour cells and the spread of tumours to new sites. It is also believed to inhibit the ability of tumour cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumours, which appears to lead to an overall suppression of tumour growth. The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a response to therapy. Infusion-related reactions occur with mild to moderate symptoms in more than 10% of patients and with severe symptoms in more than 1% of patients.

Erbitux has already obtained market authorisation in 76 countries. It has been approved for the treatment of colorectal cancer in 75 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 71 countries:

- December 2003 (Switzerland), February 2004 (USA), June 2004 (EU) and followed by other countries: for use in combination with irinotecan in patients with EGFR-expressing mCRC (metastatic colorectal cancer) who have failed prior irinotecan therapy.

- April 2006 (EU) and followed by other countries: for use in combination with radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). In further countries, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.

- July 2008 (EU): license was updated for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin-and irinotecan-based therapy and who are intolerant to irinotecan.

- July 2008 (Japan): for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy

- In November 2008 (EU): license was updated for the use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone Systems, Bristol-Myers Squibb Company and Merck jointly develop and commercialise Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer.

References

1. National Institute for Health and Clinical Excellence. Final Appraisal Determination: Cetuximab for the first-line treatment of metastatic colorectal cancer. June 2009

2. Folprecht G et al.: Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 2005; 16:1311-131

3. Van Cutsem E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408-17

4. Shankaran V, et al. Economic implications of Kras testing in metastatic colorectal cancer (mCRC). American Society of Clinical Oncology Gastrointestinal Cancers Symposium Abstract 298. 2009. http://www.asco.org

5. Cancer Research UK website: http://info.cancerresearchuk.org/cancerstats/types/bowel/ (accessed April 2009)

Source
Merck Serono

Results at ASCO Congress 2009 Highlight Merck Serono's Leadership in Personalizing Cancer Care

Calisha Myers — Thu, 07 May 2009 08:41:38 -0400

Results at ASCO Congress 2009 Highlight Merck Serono's Leadership in Personalizing Cancer Care

70 abstracts accepted for inclusion in the ASCO annual meeting

DARMSTADT, Germany--(BUSINESS WIRE)--Merck Serono, a leader in personalizing cancer care, continues to drive the global effort to ensure patients receive therapies tailored to their cancer. This approach will be the focus of the forthcoming American Society of Clinical Oncology (ASCO) meeting in Orlando, Florida taking place from May 29 to June 2 2009. Seventy abstracts were accepted for inclusion.

At the meeting, Merck Serono, its partners and independent researchers will be presenting new data on Erbitux® (cetuximab) from its major CRYSTAL, FLEX and EXTREME studies among many others, including data in several potential new disease areas and new information on the use of markers in predicting clinical response. The efficacy of Erbitux in combination with a broad range of standard chemotherapy regimens will also be discussed.

Elmar Schnee, member of the Merck Executive Board and President of the Merck Serono division, explains "By tailoring Erbitux treatment to patients who will most likely benefit from therapy, we enhanced the efficacy, the patient benefit and the health economic performance."

As reported in the major Erbitux trials in metastatic colorectal cancer (mCRC), CRYSTAL and OPUS, introducing KRAS testing enhanced the patients' chances to remain tumor-free (to 32% and 43%, respectively).1,2 Importantly, the value of the personalized medicine approach has also been validated through survival results in colorectal, lung and head and neck cancers.1-5

Erbitux was highlighted twice by ASCO in 20086 as a major clinical oncology research advance in both mCRC and non-small cell lung cancer (NSCLC). ASCO stated that KRAS status as a predictive marker of response in mCRC will, "help guide treatment for each patient, increasing efficacy while eliminating unnecessary adverse effects." In EGFR-expressing NSCLC, the increase in overall survival achieved by adding Erbitux to chemotherapy in the FLEX trial was recognized as an advance in this difficult-to-treat cancer which is usually resistant to treatment or diagnosed at a late stage.

Merck Serono has an ongoing commitment to the advancement of oncology treatment and is also investigating, amongst other potential cancer treatments, the use of Stimuvax® (L-BLP25 cancer vaccine) in the treatment of NSCLC, and cilengitide, its novel integrin inhibitor for glioblastoma, NSCLC and squamous cell carcinoma of the head and neck.

References

1. Van Cutsem E, et al. N Engl J Med 2009;360:1408-17.
2. Bokemeyer C, et al. J Clin Oncol 2009;27(5):663-71.
3. Pirker R, et al. Lancet 2009;373(9674):1525-31.
4. Bonner JA, et al. N Engl J Med 2006;354(6):567-78.
5. Vermorken JF, et al. 2008;359(11):1116-27.
6. Winer E, et al. J Clin Oncol 2009;27(5):812-26.

For more information on Erbitux in colorectal, head & neck and non-small cell lung cancer, please visit: www.globalcancernews.com.

About Erbitux
Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.

The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in 76 countries. It has been approved for the treatment of colorectal cancer in 75 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 71 countries:

December 2003 (Switzerland), February 2004 (USA), June 2004 (EU) and followed by other countries: for use in combination with irinotecan in patients with EGFR-expressing mCRC (metastatic colorectal cancer) who have failed prior irinotecan therapy. In addition, Erbitux is also approved for single-agent use in further countries
April 2006 (EU) and followed by other countries: for use in combination with radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). In further countries, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy
July 2008 (EU): license was updated for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin-and irinotecan-based therapy and who are intolerant to irinotecan
July 2008 (Japan): for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy
In November 2008 (EU): license was updated for the use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone Systems, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT® (tegafur-uracil) - an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.

Merck is also investigating among other cancer treatments the use of Stimuvax® (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Bellevue, Washington, USA.

In addition, Merck is developing cilengitide, which is the first in a new class of investigational anti-cancer therapies called integrin inhibitors to reach Phase III of development; it is currently being investigated for the treatment of glioblastoma, SCCHN and NSCLC. Integrin inhibitors are thought to work by targeting the tumor and its vasculature.

About Merck Serono
Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®, cetuximab), multiple sclerosis (Rebif®, interferon beta-1a), infertility (Gonal-f®, follitropin alpha), endocrine and metabolic disorders (Saizen® and Serostim®, somatropin), (Kuvan®, sapropterin dihydrochloride) as well as cardiometabolic diseases (Glucophage®, metformin), (Concor®, bisoprolol), (Euthyrox®, levothyroxine). Not all products are available in all markets.

With an annual R&D expenditure of around € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

For more information, please visit www.merckserono.com or www.merck.de

About Merck
All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to http://www.subscribe.merck.de to register online, change your selection or discontinue this service.

Merck is a global pharmaceutical and chemical company with total revenues of € 7.6 billion in 2008, a history that began in 1668, and a future shaped by 32,700 employees in 60 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.

Merck Serono Launches Glucophage(R) Powder (Metformin Hydrochloride) in First European Countries

Calisha Myers — Tue, 05 May 2009 09:45:32 -0400

Merck Serono Launches Glucophage(R) Powder (Metformin Hydrochloride) in First European Countries

- Innovative Powder Formulation of Metformin Designed to Facilitate Adherence by Increasing Patient Choice in the Treatment of Type 2 Diabetes, Now Available in France and the United Kingdom

FELTHAM, England, May 5 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, today announced that Glucophage(R) Powder for Oral Solution in Sachets, (metformin hydrochloride in 500mg, 850mg and 1000mg strengths) indicated for the first-line treatment of type 2 diabetes mellitus, is now licensed in France and the United Kingdom(1), the first European countries to launch this new formulation of Glucophage(R). Launches in other European countries are expected to take place in the coming months, once individual marketing authorisations are granted.

Bioequivalent to the existing Glucophage(R) tablets(2), the new powder formulation is packaged in individual sachets of 500mg, 850mg and 1000mg(1). Glucophage(R) powder can be easily dissolved in water to produce a clear to slightly opalescent solution.(2)

"Adherence to therapy is increasingly being recognised by physicians as a key condition to achieve glycaemic control for patients with diabetes," said Roberto Gradnik, Executive Vice President Commercial Europe at Merck Serono. "We are pleased to provide this innovative powder formulation of Glucophage(R) to patients seeking a convenient alternative to tablets which may facilitate their adherence to treatment."

The International Diabetes Federation (IDF) estimates that diabetes currently affects 246 million people worldwide, representing roughly 6% of the adult population; this number is expected to rise to 380 million by 2025. Type 2 diabetes constitutes about 85% to 95% of all diabetes cases in developed countries and accounts for an even higher percentage in developing countries. The IDF recommends that, metformin remains a drug of choice for first-line therapy of type 2 diabetes.(3)

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) advise that metformin therapy should be initiated concurrently with lifestyle intervention at diagnosis of type 2 diabetes.(4) However the current therapeutic indication for Glucophage(R) remains the treatment of type 2 diabetes mellitus, particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycaemic control.(5)

References

1. In the United Kingdom, Glucophage powder for Oral Solution in Sachets is available in 500mg and 1000mg strengths only.

2. Summary of Product Characteristics (SmPC) Glucophage Powder 500mg and 1000mg 12th March 2009

3. International Diabetes Federation, Global Guideline for Type 2 Diabetes, http://www.idf.org/webdata/docs/IDF%20GGT2D.pdf

4. Nathan DM et al., Medical Management of Hyperglycemia in Type 2 Diabetes: a Consensus Algorithm for the Initiation and Adjustment of Therapy, Diabetes Care 2009, 32:193-203

5. National Institute for Clinical Excellence (NICE). Type 2 diabetes. The management of type 2 diabetes (update). NICE clinical guideline 66, corrected December 2008. Accessed via http://www.nice.org.uk/nicemedia/pdf/CG066NICEGuidelineCorrectedDec08.pdf

About Glucophage(R) (metformin hydrochloride)

Glucophage(R) has been approved worldwide as a first line treatment of Type 2 diabetes. It belongs to the biguanide class of molecules, which decrease glucose production by the liver. A primary objective of type 2 diabetes treatments is to correct the dual effects of tissue unresponsiveness to insulin (insulin resistance) and insulin deficiency arising from impaired functioning of the beta cells in the pancreas that make insulin. Metformin corrects insulin resistance by making tissues, such as the liver and muscle, responsive to insulin. This way, patients get less "in-house" glucose production in the liver and better glucose uptake into muscle, where it is stored as glycogen or burnt off to produce energy. The net result is restoration of normal glucose levels.

The wealth of evidence documented in some 5,600 scientific publications since 1957, the year of metformin's introduction into clinical practice, led the International Diabetes Federation (IDF) to recommend metformin as the 1st line therapy of choice for the treatment of type 2 diabetes in its global guidelines, issued in 2005. A landmark study, the United Kingdom Prospective Diabetes Study (UKPDS) has shown metformin to be effective at lowering blood glucose and reducing the risk of long term complications (eg heart attacks and strokes).

Merck Serono is a world market leader in oral diabetes medications. More than six million patients in over 100 countries around the globe currently benefit from various products of the Glucophage(R) family.

Glucophage(R) Powder for Oral Solution in Sachet is a new formulation manufactured under license from Dainippon Sumitomo Pharma Co., Ltd. Osaka, Japan.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon beta-1a), infertility (Gonal-f(R), follitropin alpha), endocrine and metabolic disorders (Saizen(R) and Serostim(R), somatropin), (Kuvan(R), sapropterin hydrochloride) as well as cardiometabolic diseases (Glucophage(R), metformin), (Emcor(R) and Concor(R), bisoprolol), (Euthyrox(R), levothyroxine). Not all products are available in all markets.

With an annual R&D expenditure of around EUR 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.6 billion in 2008, a history that began in 1668, and a future shaped by 32,700 employees in 60 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.

Ambrx and Merck Serono Expand Collaboration Through ARX424 Multiple Sclerosis Drug Development Alliance

Calisha Myers — Tue, 24 Feb 2009 10:37:27 -0500

Ambrx and Merck Serono Expand Collaboration Through ARX424 Multiple Sclerosis Drug Development Alliance

SAN DIEGO, Feb. 24 /PRNewswire/ -- Ambrx Inc, and Merck Serono, a division of Merck KGaA, Darmstadt, Germany, today announced a global strategic collaboration to develop and commercialize Ambrx's ARX424 preclinical product candidate for the treatment of multiple sclerosis. ARX424 was created by Ambrx through the application of its proprietary protein optimization technology, ReCODE(TM).

This second collaboration between the two companies follows a previous agreement announced in 2007 to develop ARX201, Ambrx's long-acting growth hormone product, currently in Phase II of clinical development.

Under the terms of the agreement, Merck Serono will receive worldwide exclusive development and commercialization rights for ARX424. Merck Serono will make an initial payment to Ambrx, and Ambrx is eligible to receive undisclosed clinical, regulatory and commercial milestone payments based upon the successful development and commercialization of potential products resulting from this collaboration, as well as undisclosed royalties on the associated worldwide net sales. Ambrx also retains the option to convert its right to receive royalties in the U.S. to a profit and loss sharing option. If the option is exercised, Ambrx and Merck Serono will share global development expenses, US commercialization expenses as well as profit. In addition, Merck Serono will make an undisclosed equity investment in Ambrx. Additional terms of the collaboration were not disclosed.

"This second collaboration with Ambrx not only demonstrates their robust research and development capability, it also strengthens our partnership to deliver innovative products to the market to help improve the quality of life of patients," said Vincent Aurentz, Executive Vice President Portfolio Development at Merck Serono.

"We are pleased to expand our productive relationship with Merck Serono, a company ideally suited to harness the potential of our growth hormone and multiple sclerosis product candidates given their franchises in these areas," said Stephen Kaldor, Ph.D., Ambrx President and Chief Executive Officer. "While we are operating from a strong cash position, we felt it appropriate that Merck Serono make an equity commitment as part of this transaction to further strengthen and align our interests going forward."

About Merck Serono

Merck Serono has leading brands serving patients with cancer (Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon beta-1a), infertility (Gonal-f(R), follitropin alfa), endocrine and cardiometabolic disorders (Glucophage(R), metformin); (Concor(R), bisoprolol); (Euthyrox(R), levothyroxine); (Saizen(R) and Serostim(R), somatropin). Not all products are available in all markets.

With an annual R&D expenditure of around euro 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of euro 7.6 billion in 2008, a history that began in 1668, and a future shaped by 32,800 employees in 59 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.

For more information, please visit www.merckserono.com or www.merck.de

About Ambrx

Ambrx Inc. is a clinical stage biopharmaceutical company with a broad biologics platform that allows it to create best-in-class protein therapeutics, including improved versions of native proteins and therapeutic antibodies. Its most advanced product candidate, ARX201, is a long-acting human growth hormone drug candidate partnered with Merck Serono that has successfully completed initial clinical trials. The company has further validated its biologics platform through substantial partnerships with Eli Lilly and Company and Merck & Co. Ambrx is advancing a robust portfolio of product opportunities spanning multiple therapeutic areas that are highly optimized for efficacy, safety, and ease of use. For additional information, call 858.875.2400 or visit www.ambrx.com.

Media Contact
Heidi Chokeir, Ph.D.
Russo Partners
T (619) 528-2217
M (858) 380-6584
heidi.chokeir@russopartnersllc.com

Source: Ambrx Inc.

Merck Serono's Oral Investigational Treatment Cladribine Tablets for Multiple Sclerosis Significantly Reduced Relapse Rate

Calisha Myers — Fri, 23 Jan 2009 14:31:31 -0500

Merck Serono's Oral Investigational Treatment Cladribine Tablets for Multiple Sclerosis Significantly Reduced Relapse Rate in Two-Year Phase III Pivotal Trial

GENEVA, Switzerland, January 23 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today that the CLARITY(1) Phase III pivotal trial of its proprietary oral formulation of cladribine (cladribine tablets) met the two-year primary endpoint of clinical relapse rate reduction in patients with relapsing-remitting multiple sclerosis (MS).

The two cladribine tablet treatment groups of the study, assessing different dose regimens, demonstrated a statistically significant reduction in the annualized rate of relapses compared to placebo. Patients from the lower total dose group experienced a 58% relative reduction in annualized relapse rates with respect to placebo (0.14 versus 0.33 for the placebo group; p<0.001). Patients from the higher total dose group experienced a 55% relative reduction in annualized relapse rates with respect to placebo (0.15 versus 0.33; p<0.001).

Overall, the frequencies of adverse events were low in the cladribine tablet treatment groups and were comparable to that observed in the placebo group. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the cladribine tablet treatment groups. With the exception of lymphopenia, the most frequently reported adverse events in the three study groups were headaches and nasopharyngitis.

"We believe the CLARITY data mark an important milestone in the assessment of investigational oral treatments for multiple sclerosis and that cladribine tablets have the potential to make a real difference in the lives of patients," said Elmar Schnee, President of Merck Serono. "Based on the successful completion of the CLARITY study, we plan to submit cladribine tablets for registration to the EMEA and to the FDA for mid-2009."

Secondary endpoints of the CLARITY study were also met, including reduction of lesion activity as measured by magnetic resonance imaging (MRI), proportion of subjects relapse-free and disability progression. Full study results will be submitted for presentation at an upcoming scientific meeting.

The CLARITY study was a two-year (96 weeks), randomized, double-blind, placebo-controlled, international trial. It enrolled 1,326 patients with relapsing-remitting MS according to the revised McDonald criteria(2). Study participants were randomized to one of three different treatment groups consisting of two different dose regimens of cladribine tablets or matching placebo tablets (1:1:1 ratio). Cladribine tablets were given in two or four treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days, which means study patients took cladribine tablets for only 8 to 20 days during the year. In the second year, two treatment courses were administered to all patient groups. The primary endpoint of the CLARITY study was the qualifying relapse rate at 96 weeks. Secondary endpoints included MRI endpoints(3), proportion of subjects relapse-free and disability progression at 96 weeks. Out of the 1,326 randomized patients, 90% of patients treated with cladribine tablets completed the study (92% in the lower total dose group and 89% in the higher total dose group) compared to 87% in the placebo group.

About cladribine tablets

Merck Serono's proprietary oral formulation of cladribine (cladribine tablets) is currently being evaluated in Phase III as a treatment for patients with relapsing forms of multiple sclerosis (MS). Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS.

The clinical development program for cladribine tablets includes:

- The CLARITY (CLAdRIbine Tablets Treating MS OrallY) extension study: a two-year placebo-controlled extension of the CLARITY study, designed to provide data on the long-term safety and efficacy of extended administration of cladribine tablets for up to four years

- The ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS). This trial was announced in September 2008.

- The ONWARD (Oral Cladribine Added ON To Rebif New Formulation in Patients With Active Relapsing Disease) study: a Phase II placebo-controlled trial designed primarily to evaluate the safety and tolerability of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy. This trial was announced in January 2007.

Cladribine tablets have been granted a fast track designation by the US Food and Drug Administration based on the need for an oral therapy in a subset of patients with relapsing forms of multiple sclerosis.

About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including cladribine tablets, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono also is taking a leading role in developing an understanding of the role of genetics in MS.

About multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory condition of the nervous system and is the most common, non-traumatic, disabling neurological disease in young adults. The World Health Organization estimates that up to 2.5 million people suffer from MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American affiliates operate in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®, cetuximab), multiple sclerosis (Rebif®, interferon beta-1a), infertility (Gonal-f®, follitropin alfa), endocrine and cardiometabolic disorders (Glucophage®, metformin); (Concor®, bisoprolol); (Euthyrox®, levothyroxine); (Saizen® and Serostim®, somatropin). Not all products are available in all markets.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.1 billion in 2007, a history that began in 1668, and a future shaped by 32,458 employees in 59 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.

For more information, please visit http://www.merckserono.net or http://www.merck.de

1. CLARITY: CLAdRIbine Tablets Treating MS OrallY

2. The McDonald criteria are diagnostic criteria for MS. In April 2001 an international panel in association with the National Multiple Sclerosis Society (NMSS) of America recommended revised diagnostic criteria for MS. They make use of advances in MRI imaging techniques and are intended to replace the Poser criteria. The new criteria facilitate the diagnosis of MS in patients who present with signs and symptoms suggestive of the disease. The McDonald criteria for the diagnosis of multiple sclerosis were revised in 2005 to simplify and speed diagnosis, while maintaining adequate sensitivity and specificity.

3. The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

Merck Serono and Apitope Announce Licensing Agreement on Novel Peptide Therapeutics for the Treatment of Multiple Sclerosis

Calisha Myers — Tue, 13 Jan 2009 11:02:18 -0500

Merck Serono and Apitope Announce Licensing Agreement on Novel Peptide Therapeutics for the Treatment of Multiple Sclerosis

- Merck Serono and Apitope to Collaborate on Development and Commercialization of ATX-MS-1467, Apitope's Peptide Therapeutic for the Treatment of Multiple Sclerosis (MS)

GENEVA, Jan. 13 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today the signature of a research, development and commercialization agreement with Apitope Technology (Bristol) Ltd., a wholly owned subsidiary of Apitope International NV. Under this agreement, Apitope has granted exclusive worldwide rights to Merck Serono to develop and commercialize Apitope's product ATX-MS-1467. This peptide therapeutic has completed an initial clinical study in patients with multiple sclerosis (MS). It is designed to induce immunological tolerance of the body's T-cells to key autoantigens involved in the pathogenesis of MS.

ATX-MS-1467 is a novel peptide-based therapeutic derived from Apitope's proprietary technology platform. Under the terms of the agreement, Apitope will receive an upfront payment and will initially be responsible for the further development of ATX-MS-1467, for which Merck Serono will fund the costs. Merck Serono will be responsible for all development activities from the beginning of Phase II clinical trials. Merck Serono will also provide committed funding to Apitope for research on other novel therapeutic peptides for the treatment of MS.

Under the terms of the agreement, Apitope is eligible to receive up to EUR 154 million in upfront, development and commercialization milestone payments, in addition to royalties on the net sales of products resulting from the collaboration.

"This partnership with Apitope strengthens our position as a leader in the field of innovative research and development in multiple sclerosis," said Bernhard Kirschbaum, Executive Vice President Research and Development at Merck Serono. "ATX-MS-1467 represents a novel, targeted approach and may have the potential to complement existing MS drugs by offering a novel mode of action. By applying our existing stratified medicine approaches, we will also identify those MS patients who should benefit most from this potential treatment."

"We are very pleased that ATX-MS-1467 has attracted a major pharmaceutical partner such as Merck Serono with extensive experience and leadership in the development of therapies for multiple sclerosis," said Keith Martin, CEO of Apitope. "We view this collaboration as confirmation of Apitope's ability to develop early-stage first-in-class therapies for autoimmune diseases. In addition to continuing to build our in-house diagnostic platform in MS, we look forward to progressing ATX-MS-1467 with Merck Serono."

ATX-MS-1467 consists of four short peptides that are derived from myelin basic protein, a key autoantigen in MS. It is specifically designed to target up to 70% of MS patients who have a specific genetic profile.

About multiple sclerosis

About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif(R) (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including oral cladribine, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono is also taking a leading role in developing an understanding of the role of genetics in MS.

About Apitope

Apitope International NV is a biopharmaceutical company with headquarters in Hasselt, Belgium, and a subsidiary in Bristol, England. The Company is developing novel products to revolutionize the diagnosis and treatment of chronic autoimmune and allergic disorders. Apitope's therapeutic peptide technology platform is based on established scientific evidence showing that soluble, synthetic peptides can reinstate tolerance and selectively attenuate pathological immune responses. The ApitopesTM (Antigen Processing Independent epiTOPES) inhibit the immune system's harmful attack on the body while preserving normal immune responses to harmful antigens, such as infections. Apitope's portfolio includes novel peptide therapies for MS as well as other autoimmune diseases and common allergies. Apitope is also developing novel diagnostic products for the early detection of autoimmune diseases such as MS and rheumatoid arthritis (RA). Apitope is backed by LRM; Vesalius Biocapital; Fast Forward, VINNOF; Hasselt University; The Wellcome Trust; the Daniels family, Wyvern Seedcorn Fund and the University of Bristol; Innovator Capital Limited advised on the recent funding rounds.

For more information, please go to http://www.apitope.com

About Merck Serono

Merck Serono has leading brands serving patients with cancer (Erbitux(R)), multiple sclerosis (Rebif(R)), infertility (Gonal-f(R)), endocrine and cardiometabolic disorders (Glucophage(R), Concor(R), Euthyrox(R), Saizen(R), Serostim(R)), as well as psoriasis (Raptiva(R)).

About Merck

For more information, please visit http://www.merckserono.net or http://www.merck.de

Merck Serono and Apitope Technology Announce Licensing Agreement on Novel Peptide Therapeutics

Calisha Myers — Tue, 13 Jan 2009 09:46:50 -0500

Merck Serono and Apitope Technology Announce Licensing Agreement on Novel Peptide Therapeutics for the Treatment of Multiple Sclerosis; Apitope Eligible to Receive up to EUR 154 Million

GENEVA, Switzerland, January 13 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today the signature of a research, development and commercialization agreement with Apitope Technology (Bristol) Ltd., a wholly owned subsidiary of Apitope International NV. Under this agreement, Apitope has granted exclusive worldwide rights to Merck Serono to develop and commercialize Apitope's product ATX-MS-1467. This peptide therapeutic has completed an initial clinical study in patients with multiple sclerosis (MS). It is designed to induce immunological tolerance of the body's T-cells to key autoantigens involved in the pathogenesis of MS.

ATX-MS-1467 consists of four short peptides that are derived from myelin basic protein, a key autoantigen in MS. It is specifically designed to target up to 70 % of MS patients who have a specific genetic profile.

About multiple sclerosis

About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including oral cladribine, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono is also taking a leading role in developing an understanding of the role of genetics in MS.

About Apitope

For more information, please go to http://www.apitope.com

About Merck Serono

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Euthyrox®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).

About Merck

For more information, please visit http://www.merckserono.net or http://www.merck.de

Source: Merck Serono

Merck Serono: Study Published in JCO Shows Erbitux Enhances Efficacy in mCRC Patients with KRAS Wild-Type Tumors in 1st-Line Set

Calisha Myers — Mon, 05 Jan 2009 10:41:21 -0500

Merck Serono: Study Published in JCO Shows Erbitux Enhances Efficacy in mCRC Patients with KRAS Wild-Type Tumors in 1st-Line Setting

·Results of OPUS trial support new standard of care for mCRC patients with KRAS wild-type tumors

DARMSTADT, Germany, Jan. 05, 2009 - A study published today in the Journal of Clinical Oncology demonstrates that the addition of Erbitux® (cetuximab) to standard oxaliplatin-based chemotherapy (FOLFOX-4) in previously untreated metastatic colorectal cancer (mCRC) patients with KRAS wild-type tumors results in significantly higher efficacy than chemotherapy alone. The OPUSa study demonstrated a remarkably high response rate (RR) of 61%, clearly exceeding that seen in patients treated with chemotherapy alone (RR 37%, p=0.011).

"This study is very exciting as it is one of the first to demonstrate the role of KRAS as a biomarker in the treatment of mCRC," commented Professor Carsten Bokemeyer, lead investigator of the OPUS trial, Universitaetsklinikum Eppendorf, Hamburg, Germany. "By testing the KRAS status of a patient's tumor we can now provide a tailored treatment approach - and, as these data demonstrate, for the approximately 65% of mCRC patients with wild-type KRAS tumors, this means the possibility of significantly improved outcomes through treatment with Erbitux."

OPUS was a randomized, multi-center, Phase II trial (n=337) comparing the efficacy and safety of Erbitux combined with FOLFOX versus FOLFOX alone in the 1st-line treatment of epidermal growth factor receptor (EGFR)-expressing mCRC. The primary objective was response rate. In the intention to treat (ITT) population, 46% of patients receiving Erbitux in combination with FOLFOX experienced a response, compared to 36% of patients treated with chemotherapy alone (p=0.064). In a retrospective efficacy analysis (n=233) it was shown that 61% of patients with KRAS wild-type tumors responded when treated with Erbitux plus chemotherapy, compared to 37% of patients in the chemotherapy alone arm (p=0.011). In addition, the risk of disease progression in the Erbitux plus chemotherapy arm decreased by 43% (hazard ratio 0.57, p=0.0163) and the complete (R0) resection rate more than doubled (9.8% vs. 4.1%) compared with those in the chemotherapy alone arm. Due to small patient numbers these resection data should be interpreted with caution, however, in the metastatic disease setting, complete resection provides the only hope for cure for patients.

Safety and tolerability were also studied in the OPUS trial, and the Erbitux plus FOLFOX combination was found to be generally well-tolerated with no evidence to suggest that Erbitux increased the frequency or severity of the known toxicities of oxaliplatin-based chemotherapy. Moreover, the incidence and severity of skin reactions, infusion-related reactions and mucositis were consistent with the known safety profile of Erbitux.

"The publication of these important data represents another step towards the new era for mCRC treatment," said Dr Frank T. Weber, Senior Vice President and Head of Medical Science and Innovation, Merck Serono. "The enhanced efficacy that Erbitux provides patients with KRAS wild-type tumors in the 1st-line - as demonstrated by the high response rates in the OPUS study - clearly supports the role of Erbitux as a new standard of care for these patients."

Alongside the Phase III CRYSTALb trial, results from the OPUS trial formed the basis for the recently granted license extension of Erbitux in Europe to include the 1st-line treatment of patients with EGFR-expressing, KRAS wild-type mCRC.

More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths.1 Approximately 25% of patients present with metastatic disease.2 Five-year survival rates for patients with mCRC are as low as 5%.3 Approximately 65% of mCRC patients have KRAS wild-type tumors.4

a OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC b CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer

References 1. Parkin DM, et al. CA Cancer J Clin 2005;55:72??. 2. Cunningham D and Findley M. Eur J Cancer 1993;29A(15):2077?. 3. Macdonald JS. CA Cancer J Clin 1999;49(4):202??. 4. Van Cutsem E, et al. ESMO 2008; Abstract No: 710.

For more information on Erbitux in colorectal, head & neck and non-small cell lung cancer, please visit: www.globalcancernews.com.

About Erbitux Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.

Erbitux has already obtained market authorization in 76 countries. It has been approved for the treatment of colorectal cancer in 75 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldova, New Zealand, Nicaragua, Norway, Oman, Pakistan, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Thailand, Ukraine, Uruguay, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. In the European Union, the license was updated in July 2008 for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC (metastatic colorectal cancer) in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan. Apart from the European Union label, Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Iceland, Japan, Lebanon, Liechtenstein, Mexico, Moldova, New Zealand, Nicaragua, Norway, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela.

In addition, Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in 70 countries: Argentina, Australia, Belarus, Brazil, Canada, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldova, New Zealand, Nicaragua, Norway, Oman, Pakistan, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Ukraine, Uruguay, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Lebanon, Mexico, Moldova, Nicaragua, Peru, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy. In the European Union, the license was updated in November 2008 for the 1st-line use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone Systems, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT® (tegafur-uracil) - an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.

About Merck Serono Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).

With an annual R&D investment of around € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

For more information, please visit www.merckserono.net<http://www.merckserono.net/> or www.merck.de<http://www.merck.de/>

About Merck All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to http://www.subscribe.merck.de<http://www.subscribe.merck.de/> to register online, change your selection or discontinue this service.

Merck is a global pharmaceutical and chemical company with total revenues of € 7.1 billion in 2007, a history that began in 1668, and a future shaped by 32,458 employees in 59 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.

Merck Serono's Kuvan(R) Receives Marketing Authorization in Europe

Calisha Myers — Tue, 09 Dec 2008 09:36:41 -0500

Merck Serono's Kuvan(R) Receives Marketing Authorization in Europe

GENEVA, Switzerland, December 9 /PRNewswire/ --

- First Drug to be Approved in Europe for the Treatment of Hyperphenylalaninemia due to Phenylketonuria or BH4 Deficiency

Merck Serono, a division of Merck KGaA, Darmstadt, Germany, today announced that the European Commission has granted marketing authorization for Kuvan(R) for the treatment of hyperphenylalaninemia (HPA) in phenylketonuria (PKU) or BH4 deficient patients. Kuvan, which had previously received Orphan Medicinal Product designation from the European Medicines Evaluation Agency (EMEA), is the first drug approved in Europe for HPA due to PKU or BH4 deficiency.

"To date, there has been no drug treatment available in Europe for patients suffering from PKU, a debilitating inherited condition that can cause serious brain damage in children and transient to lasting impairments in adults if a strict diet is not observed throughout life," said Roberto Gradnik, Executive Vice President Commercial Europe at Merck Serono. "With the approval of Kuvan(R), Merck Serono provides patients access to an efficient treatment to better control their blood phenylalanine levels. This will contribute to improving their quality of life and may ultimately reduce the risk of lasting mental impairment," he added.

There are approximately 35,000 patients diagnosed with hyperphenylalaninemia due to PKU or BH4 deficiency in the European Union.(1) PKU and BH4 deficiency are rare diseases caused by genetic defects in the metabolism of the amino acid phenylalanine (PKU), or in the enzymes responsible for the recycling and synthesis of the cofactor BH4 (BH4 deficiency), resulting in hyperphenylalaninemia, i.e. abnormally high levels of phenylalanine in the blood. Hyperphenylalaninemia can cause serious brain damage in infants and children, and transient to lasting neurocognitive impairment in adult patients.

Until today, the only therapy option for PKU patients in Europe to manage their disease was through a diet highly restricted in phenylalanine (food with high levels of phenylalanine include meat, fish, nuts, dairy products and some vegetable and fruits) associated with daily amino-acid supplementation. Non-adherence to the restrictive diet and adequate control of blood phenylalanine levels can result in a decline in mental and behavioral performance.

"Through the approval of Kuvan(R), Merck Serono confirms its commitment to developing and marketing innovative therapeutic solutions for patients suffering from high medical unmet needs. PKU and BH4 deficiency deserve the attention of the whole healthcare industry and we are pleased to provide patients today with the first therapeutic option to treat these rare diseases," said Richard Douge, Executive Vice President Global Marketing at Merck Serono.

The marketing authorization is supported by data from two international, double-blind, randomized, placebo-controlled Phase III clinical trials in patients with hyperphenylalaninemia due to PKU. The data show that treatment with Kuvan(R) reduces blood phenylalanine levels and increases the proportion of patients with blood phenylalanine levels within target range, resulting in a higher dietary phenylalanine tolerance, which may reduce the need to limit phenylalanine intake in patients' diet. The most frequently reported potentially undesirable effects were headache, runny nose, diarrhea, vomiting, sore throat, cough, abdominal pain, stuffy nose and low levels of phenylalanine in the blood. These adverse events were generally mild to moderate and transient.

The European Commission has granted marketing authorization for the 27 countries(2) of the European Union as well as Iceland, Liechtenstein and Norway. As an Orphan Medicinal Product and the first drug approved for the treatment of HPA, Kuvan(R) will receive 10 years of data protection in the European Union for this therapeutic indication. Launch of Kuvan(R) in Europe is expected to start in the first half of 2009.

Kuvan(R)

Kuvan(R) (INN: sapropterin dihydrochloride, formerly known as Sapropterin and Phenoptin(TM)) is developed by Merck Serono and BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) as an oral therapeutic for the treatment of hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency. Kuvan(R) is the synthetic form of 6R-BH4, a naturally occurring enzyme cofactor that works in conjunction with the enzyme phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe). Clinical data suggest that Kuvan(R) produces significant reductions in blood Phe levels in the subset of patients who are BH4-responsive. Merck Serono estimates that Kuvan(R) could be a potential treatment option for the approximately 35,000 patients in the European Union who have been diagnosed with HPA, due to PKU or BH4 deficiency and are responsive to BH4 treatment.

Under the terms of the agreement with BioMarin, Merck Serono has exclusive rights to market Kuvan(R) in all territories outside North America and Japan. BioMarin has exclusive rights to market Kuvan(R) in the USA and Canada; in the USA, Kuvan received approval from the Food and Drug Administration for the treatment of BH4-responsive PKU in December 2007. In July 2008, Asubio Pharma Co., Ltd. (a subsidiary of Daiichi Sankyo), received marketing approval from the Japanese Ministry of Health, Labour and Welfare for a label extension of Biopten, which contains the same active ingredient as Kuvan(R), for the treatment of patients with PKU.

Hyperphenylalaninemia (HPA)

Disorders of phenylalanine (Phe) metabolism can lead to abnormal elevations of blood Phe levels, also called hyperphenylalaninemia (HPA). Two inborn errors of metabolism, phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency, account for the majority of cases of HPA.

Phenylketonuria (PKU)

PKU, a genetic disorder affecting approximately 50,000 diagnosed patients in the developed world, is caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). PAH is required for the metabolism of phenylalanine (Phe), an essential amino acid found in all protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and brain, resulting in a variety of complications including severe mental retardation and brain damage, mental illness, seizures and tremors, and cognitive problems. As a result of global newborn screening efforts implemented in the 1960s and early 1970s, virtually all PKU patients in developed countries are diagnosed at birth. The only treatment currently available for PKU patients is a highly restrictive and expensive medical food diet that most patients fail to adhere to the extent needed for achieving adequate control of blood Phe levels. The diet restricts consumption of normal foods such as meat, fish and dairy products.

BH4 deficiency

BH4 deficiency is a very rare inborn error of metabolism, and is estimated to account for 1-2 % of cases of HPA. BH4 deficiency is an autosomal recessive genetic condition and can result from deficiencies of any of the five different enzymes involved in BH4 synthesis and regeneration. BH4 is a necessary co-factor for PAH. Therefore, BH4 deficiency impairs PAH activity leading to a biochemical situation similar to PKU, with HPA resulting from deficient conversion of Phe to tyrosine. In addition, since BH4 is also a necessary co-factor for both tyrosine hydroxylase and tryptophan hydroxylase, BH4 deficiency causes deficiencies in the downstream neurotransmitter products of these amino acids including catecholamines and serotonin. Dietary limitation of whole protein or Phe intake is often not necessary with BH4 treatment. However, since BH4 does not cross the blood brain barrier, concomitant therapy with neurotransmitter precursors, i. e. levodopa and 5-hydroxytryptophan, may be necessary to boost central nervous system substrate levels for catecholamine and serotonin synthesis, respectively.

Merck Serono

Merck

Footnotes

(1) Kuvan(R) is a potential treatment option in those PKU and BH4-deficient patients who are responsive to BH4 treatment. According to published literature, 20 to 50 % of PKU patients are responsive to treatment with Kuvan(R).

(2) Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom

For more information, please visit http://www.merckserono.net or http://www.merck.de

http://www.merckserono.net

Distributed by PR Newswire on behalf of Merck Serono International S A

Galapagos NV and Merck Serono Enter New Collaboration Agreements

Calisha Myers — Tue, 18 Nov 2008 11:18:41 -0500

Galapagos NV and Merck Serono Enter New Collaboration Agreements

MECHELEN, BELGIUM--(MARKET WIRE)--Nov 18, 2008 -- Galapagos NV (Euronext: GLPG) announced today new collaboration agreements with Merck Serono, a division of Merck KGaA, Darmstadt, Germany. Total value of the contracts for Galapagos is EUR 1.1 million over one year.

Galapagos' service division BioFocus DPI will provide SoftFocus© compounds for use in Merck Serono's drug discovery programs. In a separate agreement, BioFocus DPI will perform medicinal chemistry services on an undisclosed Merck Serono program; this represents an extension of a long running collaboration which was last expanded in 2005.

"BioFocus DPI has a long relationship with Merck Serono in medicinal chemistry, which we are pleased to extend again this year," said Onno van de Stolpe, CEO of Galapagos. "The purchase of BioFocus DPI's SoftFocus libraries underscores our ability to grow business with clients."

About Galapagos and BioFocus DPI

Galapagos (Euronext Brussels: GLPG; Euronext Amsterdam: GLPGA; OTC: GLPYY) is a drug discovery company with pre-clinical programs in bone and joint diseases and bone metastasis. Its BioFocus DPI division offers a full suite of target-to-drug discovery products and services to pharmaceutical and biotech companies, encompassing target discovery and validation, screening and drug discovery through to delivery of pre-clinical candidates. BioFocus DPI also provides adenoviral reagents for rapid identification and validation of novel drug targets, compound libraries for drug screening as well as ADMET database products to select compounds. Galapagos currently employs about 460 people and operates facilities in six countries, with global headquarters in Mechelen, Belgium. More information about Galapagos and BioFocus DPI can be found at www.glpg.com and www.biofocusdpi.com.

CONTACT

Galapagos NV Onno van de Stolpe, CEO Tel: +31 6 2909 8028 ir@glpg.com

This release may contain forward-looking statements, including, without limitation, statements containing the words "believes," "anticipates," "expects," "intends," "plans," "seeks," "estimates," "may," "will," "could," "stands to," and "continues," as well as similar expressions. Such forward-looking statements may involve known and unknown risks, uncertainties and other factors which might cause the actual results, financial condition, performance or achievements of Galapagos, or industry results, to be materially different from any historic or future results, financial conditions, performance or achievements expressed or implied by such forward-looking statements. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. Galapagos expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation.

This announcement was originally distributed by Hugin. The issuer is solely responsible for the content of this announcement.

Contact: Source: Galapagos NV