Pfizer's once-a-day calcium channel blocker Norvasc (amlodipine) was approved by FDA on July 31 for monotherapy or combination treatment of hypertension, chronic stable angina and vasospastic angina. Norvasc was given a "1S" designation by FDA, indicating a new molecular entity given a non-priority review. Pfizer filed its computer-assisted NDA (19-787) for Norvasc in December 1987. Norvasc was recommended for approval for all three indications by FDA's Cardio-Renal Drugs Advisory Committee in June 1991 ("The Pink Sheet" June 10, 1991, p. 3). Among other once-a-day calcium channel blockers, only Pfizer's Procardia XL is indicated for both hypertension and angina. Norvasc has been "approvable" since April. Norvasc's labeling appears to bear out Pfizer's assertions that it would have the "cleanest labeling" of any drug in its class. The only warning and precaution statements in Norvasc labeling are class-oriented, and some appear to differentiate Norvasc. A precaution against acute hypotension notes that "since the vasodilation induced by Norvasc is gradual in onset, acute hypotension has rarely been reported after oral administration of Norvasc." Labeling notes that coadministration with digoxin, phenytoin, warfarin, indomethacin, and cimetidine did not have significant pharmacokinetic effects. In public comments on the drug, Pfizer has highlighted Norvasc's safety (and potential activity) in patients with congestive heart failure. Norvasc labeling, however, qualifies the safety data. The "Precautions" section of labeling states that "although hemodynamic studies and a controlled trial in NYHA Class II-III heart failure patients have shown that Norvasc did not lead to clinical deterioration as measured by exercise tolerance, left ventricular ejection fraction, and clinical symptomatology, studies have not been performed in patients with NYHA Class IV heart failure. In general, all calcium channel blockers should be used with caution in patients with heart failure." Pfizer plans to file a supplemental NDA for CHF treatment in mid-1993. Discontinuation from Norvasc treatment due to side effects in the 11,000-patient database was not significantly different on drug versus placebo, labeling states. Dose-related side effects seen with Norvasc include edema, dizziness, flushing and palpitation, labeling states. "For several adverse experiences that appear to be drug and dose related, there was a greater incidence in women than men," labeling states. These side effects include edema, flushing, palpitations and somnolence. FDA's approval letter notes that Pfizer will meet with the Cardio-Renal Drug Products Division at the end of August "to decide what, if any, clinical trials could be conducted that would confirm or deny [this] observation." Pfizer said it will launch Norvasc "early in the fourth quarter," which is in line with the company's prediction at a July 30 securities analysts meeting that Norvasc would be launched this fall ("The Pink Sheet" Aug. 3, p. 12). FDA's longer-than-average 55-month review of Norvasc appears to have worked out well for Pfizer. The company has been able to focus marketing efforts on Procardia XL, which was submitted to FDA only six months before Norvasc. Since its approval in September 1989, Procardia XL has grown to be the number one cardiovascular product in the U.S. and is on track for $1 bil. in sales this year. The Norvasc approval caps off a string of new products following Procardia XL, including the antibiotic Zithromax (azithromycin) and the anti-depressant Zoloft (sertraline) launched earlier this year. The Norvasc patent expires in 2006, Pfizer said. At the July 30 meeting, Pfizer outlined a plan to prevent cannibalization of Procardia XL sales by promoting Norvasc for mild-to-moderate hypertension ("The Pink Sheet" Aug. 3, p. 12). Pfizer also will face the challenge of promoting both products in the ever-more-crowded cardiovascular market. In addition to numerous recent launches, Norvasc will compete against two other July 31 approvals: Lederle's beta blocker Zebeta and Ivax' generic version of Searle's/Knoll's once-a-day calcium channel blocker Calan SR/Isoptin SR (see related stories, this issue).
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Advanz Pharma would have had to show that the European Commission’s decision to revoke Ocaliva’s conditional marketing approval risked causing serious and irreparable harm, according to lawyers from Van Bael & Bellis.
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