PFIZER's ONCE-A-DAY PROCARDIA XL APPROVED BY FDA FOR HYPERTENSION AND ANGINA ON SEPT. 6: COMPANY WILL BEGIN SHIPPING TO TRADE "THIS MONTH"

Pfizer's one-a-day version of nifedipine Procardia XL was approved by FDA on Sept. 6 after a two-and-one-half year review at the agency. Pfizer said that it will begin shipping the product to the trade "this month." Marketing will be handled by the Pfizer Labs division. The once-daily calcium channel blocker makes use of Alza'a GITS sustained release delivery system.

The approval of Procardia XL is timely for Pfizer. The company has increasingly become the subject of merger rumors on Wall Street due to a slow down in sales growth and declining earnings. In addition, Procardia, which generated $364 mil. in sales in 1988, is nearing the end of its patent protection. Pfizer is currently embroiled in a patent dispute with generic manufacturer Chase Chemical.

Pfizer will be launching Procardia XL into a crowded calcium channel blocker market that is also competing with ACE inhibitors in the hypertension area and beta blockers in hypertension and angina. In addition to Searle's one-a-day verapamil Calan SR, branded and generic immediate release verapamil products, Syntex' Cardene (nicardipine) and Marion's Cardizem, Procardia XL will also be going up against Marion's recently launched b.i.d. form of diltiazem, Cardizem SR.

Pfizer Pharmaceutical Products President William Steere noted that Procardia XL will be the only one-a-day calcium channel blocker to have both a hypertension claim and an indication for angina. Both Searle's Calan SR (verapamil), approved in late 1987, and Marion's Cardizem SR (diltiazem), approved in January, are indicated only for hypertension. The immediate release forms of verapamil and diltiazem are approved for angina.

"This controlled release formulation provides remarkably smooth therapeutic control over 24 hours and has a favorable side effects profile and, since the approval of Procardia XL is for both angina and hypertension, it increases the utility of this fine drug," Steere commented.

With Procardia XL, Pfizer may be one of the first companies to try to market an extended release version of an old product as a therapeutic improvement as well as a convenience improvement.

In addition to adding a hypertension claim and reducing the daily dosage from three-times-daily to once-daily, Procardia XL may significantly reduce the side-effect profile of the compound nifedipine. One of the clinical investigators of the nifedipine GITS system, Albert Einstein School of Medicine professor William Frishman, MD, noted in a presentation to securities analysts in 1987 that "the side effects related to the rapid absorption of nifedipine dissipate" with the controlled release version. Frishman reported that reflex tachycardia drops from 7% of patients with nifedipine to 1% with Procardia XL and that palpitations dropped from 8% to 1.5%.

Pfizer's dispute with Chase, which recently received an ANDA approval for nifedipine, involves the generic firm's challenge of Pfizer's 1991 process patent expiration date for Procardia. The chemical composition patent held by Bayer, which discovered nifedipine and licensed U.S. rights to Pfizer, expired in February. The patent case is currently in the discovery phase and could reach trial this fall.

The longer-than-expected review time for the one-a-day product may have been partly a result of FDA concerns over methylene chloride residuals on tablets from Alza's tablet manufacturing process. Pfizer's Minipress XL, which has been at FDA almost as long as Procardia XL, also employs Alza's GITS sustained release delivery system. The Pfizer approval may also be a harbinger of approval for a pending Glaxo product, Volmax, a sustained release version of albuterol.