By Lisa Seachrist

Washington Editor

WASHINGTON — Less than a month after initiating a post-marketing clinical study to examine neurotoxicity of the diet drug Redux (dexfenfluramine hydrochloride capsules), its maker and marketer have pulled the drug off the market in light of news it is associated with heart valve abnormalities.

Interneuron Pharmaceuticals Inc. and Wyeth-Ayerst Laboratories announced the withdrawal of Redux at the request of the FDA after the agency determined that approximately 30 percent of patients taking the drug — most often in combination with the diet drug phentermine — suffered from aortic regurgitation or mitral valve abnormalities.

Simultaneously, Wyeth-Ayerst, of King of Prussia, Pa., is withdrawing the weight loss medication Pondimin (fenfluramine hydrochloride). Wyeth-Ayerst is a division of American Home Products Corp., of Madison, N.J.

The decision cuts off a royalty stream that garnered $14 million for Lexington, Mass. -based Interneuron in 1997.

Interneuron's stock (NASDAQ: IPIC) lost nearly 10 percent of its value on the news, closing at $16.875 per share, down $1.688. American Home Products (NYSE:AHP) was off $3.688 to $73.25.

"This information came as quite a surprise on Friday afternoon," said William Boni, Interneuron's vice president for communications. "The epidemiologic signal is strong enough that the only prudent course of action is to withdraw the drug from the market."

The decision to withdraw Redux came on the heels of mounting concerns over the drug's safety. With approval in November 1995, the companies committed to post-market surveillance because of concerns over pulmonary hypertension and neurologic toxicity.

In July, a post-marketing study by researchers at the Mayo Clinic, of Rochester, Minn., found 24 people taking the combination of phentermine and fenfluramine suffered from heart valve disease. At that time, Wyeth-Ayerst added boxed warnings to the labels of both Pondimin and Redux. In late August, the researchers reported their findings in The New England Journal of Medicine.

In light of this evidence, the FDA requested that five centers conduct echocardiograms of patients who were taking Redux and Pondimin either alone or in combination with phentermine, to look for cardiac valve abnormalities in asymptomatic patients. In total, the centers performed echocardiograms on 291 patients.

While the vast majority of the patients were on the combination of phentermine and Pondimin (fenfluramine), 20 had taken Redux either alone or in combination with phentermine. Of those 20, six had abnormal echocardiograms and two of those six were taking Redux alone.

"It is very difficult to interpret this data because there were no baseline echocardiograms to determine if these patients had an underlying condition," Boni said. "But we really have no other choice than to remove the drug from the market."

The move hurts the company, analyst Michael King Jr., of Vector Securities International, told BioWorld Today, "but it isn't a crippling blow."

King pointed out that Interneuron has a deep pipeline of drugs encompassing anxiety, congestive heart failure and stroke. Far more crippling for the company is the potential liability associated with Redux. The company has been named as a defendant — along with other pharmaceutical companies — in a number of legal actions involving the use of Redux and other weight loss drugs.

"The potential cost of that litigation is unanalyzable," King said. "That is why I rate the stock as neutral. [Their stroke drug] will soon be considered by the agency, but all during that time the news about Redux just keeps getting worse and worse."

Interneuron plans to submit a new drug application with the FDA for CerAxon (citicoline) — the company's ischemic stroke therapy — in late October or early November.

In withdrawing Redux, the company also is stopping a Phase IV trial assessing any long-term neurological effects the drug may have, as well as the development of a once-a-day dose for Redux.

Wyeth-Ayerst has sent notification of the withdrawal to 450,000 physicians and pharmacists and will offer an opportunity for patients to return unused product. Wyeth-Ayerst also has formed a panel of experts to evaluate the findings and recommend additional actions. *