FDA Sued For Dosage of Alzheimer’s Medication

FDA Sued For Dosage of Alzheimer’s Medication

September 6th, 2012 // 1:38 pm @ jmpickett

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A public watchdog has filed a lawsuit against the FDA for allowing a high dosage of the Aricept medication for Alzheimer’s disease to remain on the market. In its suit, Public Citizen charges the pill has not demonstrated “greater efficacy than the lower doses, but has more severe — and potentially life-threatening – side effects.” Aricept, which is made by Eisai and sold by Pfizer, was approved by the agency for patients with moderate to severe Alzheimer’s.

The lawsuit comes more than a year after the watchdog filed a citizen’s petition asking the agency to ban the 23mg dose and to warn doctors and patients against taking a 20mg dose – or combining lower 5m or 10mg pills. The petition also sought similar warnings on the generic version. The agency, however, has not acted on the petition and so Public Citizen maintains the agency violated the law (here is the lawsuit).

The petition argued that the only clinical trial submitted to the FDA for approval of the 23mg dose compared it to the 10mg dose, but failed to prove the higher dose was more effective. And in three of four tests, there was no significant difference between the doses on a cognitive or functional level. At the same time, the petition maintained the 23mg dose increased side effects such as a slowed pulse rate, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and anorexia compared with the 10mg dose.

There is allegedly more to the story, however. As we reported previously, two years ago, the FDA approved a higher dose of Aricept just a few months before the drug was due to lose patent protection. At the time, Pfizer (PFE) sold two versions of Aricept – a 5 mg dose and a 10 mg dose – but wanted to sell the 23 mg pill. The move was designed to provide an advantage over forthcoming generics that would allow patients to combine two 10 mg pills more cheaply.

As we wrote, Pfizer and the FDA agreed that approval would be granted if the 23 mg dose was superior to the existing 10 mg dose on both a cognitive and a global functioning measure. However, an article earlier this year in BMJ charged the approval was made “only over the objections of the FDA’s medical and statistical reviewers” and, therefore, “breached the FDA’s own regulatory standard” and led to “incomplete and distorted messages” about the drug (back story).

The FDA documents indicate the higher dose did improve cognitive functioning, but not overall functioning, which would suggest the cognitive difference was actually not meaningful. The BMJ paper previously charged that the primary FDA medical reviewer recommended the application to market a 23mg dose should have been denied, but the recommendation was rejected by Rusty Katz, the director of the FDA’s Division of Neurology Products.

At the time that we reported about the BMJ paper, an Eisai spokeswoman told us that “we can’t comment on the FDA process… A Phase III used for submission showed a statistically significant improvement in cognition compared with the 10 mg dosage, but not global improvement when copmared with the 10 mg dosage.” Meanwhile, we have asked the FDA for comment and will update you accordingly.