Drug Pipeline Series: Approvals --- Oct16-Oct23, 2006

FDA Approves Once-Daily JANUVIA™, the First and Only DPP-4 Inhibitor Available in the United States for Type 2 Diabetes
Merck & Co., Inc. announced that the U.S. Food and Drug Administration (FDA) approved JANUVIA™ (sitagliptin phosphate), the first and only DPP-4 inhibitor available in the United States for the treatment of type 2 diabetes. JANUVIA has been approved as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones (TZDs), to improve blood sugar (glucose) control in patients with type 2 diabetes when diet and exercise is not enough. The recommended dose of JANUVIA is 100 mg once daily. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
JANUVIA belongs to a new breakthrough class of prescription medications called dipeptidyl peptidase-4 (DPP-4) inhibitors that improves blood sugar control in patients with type 2 diabetes. JANUVIA enhances a natural body system called the incretin system, which helps to regulate glucose by affecting the beta cells and alpha cells in the pancreas. Through DPP-4 inhibition, JANUVIA works only when blood sugar is elevated to address diminished insulin due to beta-cell dysfunction and uncontrolled production of glucose by the liver due to alpha-cell and beta-cell dysfunction.

FDA Approves New, Once-a-Day COREG CR™ for the Treatment of Three Key Cardiovascular Conditions
GlaxoSmithKline and Flamel Technologies announced FDA approval of once-a-day Coreg CR™ (carvedilol phosphate) extended-release capsules, for the treatment of three cardiovascular conditions:
* High blood pressure, also known as hypertension. * A heart attack that has reduced how well the heart pumps (known medically as post-myocardial infarction left ventricular dysfunction). * Mild to severe heart failure.
COREG CR will utilize Flamel's proprietary Micropump® technology, which controls the delivery of carvedilol helping to maintain appropriate amounts of medicine in the body over a 24-hour span. This technology allows COREG CR to be dosed once daily, in contrast to immediate-release COREG (carvedilol) tablets, which patients must take twice daily. GlaxoSmithKline plans to begin shipping COREG CR in the first quarter of 2007.
COREG CR is a third generation "beta blocker," which is a class of medicines that work by slowing heart rate and lowering the force with which it pumps. Studies of COREG CR indicate it is generally well tolerated with a low incidence of adverse events. COREG CR, a once-a-day medicine, is approved to treat the same conditions as twice-a-day COREG, which has established a significant role in the treatment of heart disease.

FDA Approves Allegra® (fexofenadine hydrochloride) Oral Suspension for Treatment of Seasonal Allergy Symptoms and Chronic Idiopathic Urticaria
Sanofi-aventis U.S. announced that the U.S. Food and Drug Administration (FDA) has approved Allegra® (fexofenadine hydrochloride) Oral Suspension for the twice-daily treatment of symptoms associated with seasonal allergies in pediatric patients, 2 to 11 years of age, and for the treatment of chronic idiopathic urticaria in children 6 months to 11 years of age. This approval makes available a safe and effective seasonal allergy treatment option that is non-impairing to pediatric populations as young as 2 years old.
Seasonal allergic rhinitis is a common chronic condition in children. Symptoms of seasonal allergies include nasal drainage, sneezing, watery eyes and itchy nose, eyes and throat. Studies indicate that seasonal allergy inflammation as well as the impairing side effects of older antihistamines can be disruptive to a child and may affect cognitive skills and function. Allegra Oral Suspension has also been approved for the treatment of chronic idiopathic urticaria (CIU) in twice-daily 30 mg doses for pediatric patients 2 to 11 years of age and twice-daily 15 mg doses for pediatric patients 6 months to 2 years of age. CIU is a rare and bothersome condition characterized by hives lasting more than 6 weeks from an unknown cause. Its symptoms are caused by a reaction to an unknown trigger in the upper layers of the skin.

Schering-Plough Announces FDA Approval of NOXAFIL® (Posaconazole) for Treatment of Oropharyngeal Candidiasis (OPC)
Schering-Plough Corporation reported that the U.S. Food and Drug Administration (FDA) has approved NOXAFIL® (posaconazole) Oral Suspension for the treatment of oropharyngeal candidiasis (OPC), including infections refractory to itraconazole and/or fluconazole. OPC is a fungal infection of the mouth and throat caused by the yeast Candida. NOXAFIL is a novel triazole antifungal agent discovered and developed by Schering-Plough Research Institute.
This approval follows the Sept. 15 FDA approval of NOXAFIL for prophylaxis (prevention) of invasive Aspergillus and Candida infections in patients 13 years of age and older who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy. Invasive fungal infections are a leading cause of death in these high-risk populations.

FDA Approves REYATAZ® (atazanavir sulfate) 300 mg Single Capsule Formulation in Combination Therapy for Adults With HIV-1 Infection
Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration (FDA) has granted approval of a new 300 mg single capsule formulation of REYATAZ® (atazanavir sulfate) for the treatment of HIV-1 infection in adults as part of combination therapy. Taken once daily along with ritonavir and food as part of a anti-HIV drug regimen, the REYATAZ 300 mg single capsule formulation can replace two REYATAZ 150 mg capsules for: patients who have previously received anti-HIV medicines, patients who will be receiving tenofovir disoproxil fumarate, and patients who have never taken anti-HIV medicines that require SUSTIVA® (efavirenz) as part of their anti-HIV drug regimen. The REYATAZ single capsule formulation will be available in the United States within seven business days.
REYATAZ is an anti-HIV drug that blocks the action of the HIV protease enzyme, which is needed for the virus to multiply. REYATAZ is a prescription medicine used in combination with other medicines to treat people who are infected with HIV. REYATAZ has been studied in 48-week trials in both patients who have taken or have never taken anti-HIV medicines. REYATAZ does not cure HIV, a serious disease, or help prevent passing of HIV to others. Since REYATAZ was initially approved by the FDA in 2003, approximately 129,000 patients in the United States have been treated with the drug. Bristol-Myers Squibb will continue to produce the currently available REYATAZ 200 mg, 150 mg, and 100 mg once-daily capsules.

Taxotere® Receives U.S. FDA Approval for the Treatment of Patients With Head and Neck Cancer
Sanofi-aventis announced that following a priority review of a supplemental new drug application (sNDA), the U.S. Food and Drug Administration (FDA) has approved Taxotere® (docetaxel) Injection Concentrate in combination with cisplatin and fluorouracil for the induction treatment of patients with inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN). This approval follows a positive opinion for the same use granted by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) in September of this year.
The FDA based its decision on results from the EORTC 24971/TAX 323 phase III, open-label, randomized study, which enrolled 358 patients with SCCHN.
Patients receiving the Taxotere®-based regimen also had a significantly longer progression-free survival of 11.4 months, compared with 8.3 months (p=0.0077) for the patients receiving a standard therapy. Patients treated with the Taxotere®-based regimen (Taxotere®, cisplatin and fluorouracil) prior to radiation (with or without a surgical component) had a significantly longer median overall survival compared to a standard treatment of cisplatin and fluorouracil (18.6 vs 14.2 months), with a 29 percent risk reduction of death (p=0.0055), a benefit of more than four months improvement in median survival. In the study, induction chemotherapy (also called neoadjuvant therapy) was the first step in treating the disease prior to radiation therapy or surgical intervention.

FDA Approves AstraZeneca's SEROQUEL® For Bipolar Depression Treatment
AstraZeneca announced that the U.S. Food and Drug Administration (FDA) has approved SEROQUEL® (quetiapine fumarate) for the treatment of patients with depressive episodes associated with bipolar disorder. SEROQUEL already is approved for the treatment of acute manic episodes associated with bipolar I disorder** and for the treatment of schizophrenia. SEROQUEL is now the first and only single medication approved by the FDA to treat both depressive and acute manic episodes associated with bipolar disorder.