23.03 Experts Challenge FDA Over Approval For New Dose Of Alzheimer's Drug

In a report published on bmj.com a team of experts argue that the U.S. Food and Drug Administration's (FDA) approval for a new 23 mg dose of Donepezil (a drug for Alzheimer's disease), has "breached the FDA's own regulatory standard" and has resulted in "incomplete and distorted messages" about the medication.

In the first of a new occasional series entitled "not so", Professor Lisa M. Schwartz and Steven Woloshin of the Center for Medicine and the Media at The Dartmouth Institute for Health Policy and Clinical Practice, highlight the distortions, embellishments, and publication bias that mark some new reports, advertising, and medical journal articles.

According to Schwartz and Woloshin, the new 23 mg dose of Donepezil was approved "only over the objections of the FDA's medical and statistical reviewers." Furthermore, they state that it offers "no meaningful added benefit, just more harm."

In the U.S. alone, donepezil produces over $2bn in annual sales. Previously, donepezil was only available in 5 mg and 10 mg doses. However, just before its patent expired, the FDA approved a 23 mg dose for moderate to severe Alzheimer's disease. This new approval thereby extended its patent for three more years.

The FDA and the manufacturer concurred that the 23 mg dose of donepezil would only be approved if it was demonstrated to be superior to the 10 mg dose on both a cognitive and global functioning measure.

Even though donepezil improved cognitive symptoms, overall functioning did not improve, indicating that the cognitive difference was not meaningful. In addition, the 23 mg dose resulted in more adverse effects, including vomiting and nausea.

In an advertisement aimed at doctors, Schwartz and Woloshin highlight a claim that individuals who received the 23 mg dose of donepezil "experienced important clinical benefit on both measures [cognition and overall functioning]."

They state that:

"Nowhere - not in the direct to consumer or the physician advertisements, nor even in the FDA approved label - are the great uncertainties about this drug acknowledged, uncertainties that led the FDA's own medical and statistical reviewers to recommend against approval of the 23 mg drug."

Despite objections of the FDA's medical and statistical reviewers, the FDA approved the new dose which is currently covered by the government and private insurance programs. The new dose is currently, or will be soon, being considered for approval in 16 countries in South America and Asia.

According to Schwartz and Woloshin, Alzheimer's is a terrible disease and "sadly, the available drugs don't work well. But that is no excuse for manipulating vulnerable patients, desperate family members, and their doctors to use a product that is more likely to cause net harm."

"To make good decisions about drugs, doctors and patients need the evidence. The FDA should not forget to give it to them," they conclude.

The researchers highlight that they recently obtained new material stating that the FDA are aware that they made an error in relation to the previous label.

"The offending phrase was in the original label, and we don't recall how it slipped by, but we contracted the company as soon as it was brought to our attention, and they readily agreed to remove it. We are always interested in improving the content and clarity of our labeling, and appreciate being informed of any misleading or inaccurate statements that anyone may notice."

Written by Grace Rattue
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