FDA Urged To Ban High Dose Alzheimer’s Med
7 CommentsBy Ed Silverman // May 18th, 2011 // 9:47 am
In a petition filed today, a consumer watchdog group and a Johns Hopkins University professor are urging the FDA to immediately ban the highest dose of Pfizer’s Aricept due to “serious adverse effects and its lack of effectiveness.” Specifically, they cite higher rates of toxicity with the 23mg dose, which was approved by the agency for patients with moderate to severe Alzheimer’s. The FDA is also being asked to warn docs and patients against taking the 20mg dose - or two 10mg pills a day.
“When clinicians consider whether to initiate a therapeutic trial of a largely ineffective drug, the risk of harm should be a prominent consideration,” says Thomas Finucane, professor of medicine in the Division of Gerontology and Geriatric Medicine at Johns Hopkins, in a statement. “The clearly increased risk of harm from Aricept 23mg compared to Aricept 10mg is so great, coupled with the lack of any evidence of improved benefit, that I believe it should not have been approved for sale to the families and caregivers of Alzheimer patients.”
The petition, which was also filed by Public Citizen, argues 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. Improvement shown in the fourth test for the 23mg dose was only two points higher on a 100-point scale, which Public Citizen’s Sid Wolfe argues is unimportant.
At the same time, the petition maintains 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. Vomiting, for instance, occurred more than 3.5 times as often in patients taking the 23mg dose than in those given the 10mg dose. Overall, patients stopped taking the 23 mg dose because of adverse events more than twice as often as those taking the 10mg dose.
We have asked Pfizer, which licensed the med from Eisai, for comment and will update you accordingly. Meanwhile, here is the petition.
industry insider
There’s a straightforward explanation for the toxicity of the 23mg dose of Aricept. Per the PI, Aricept exhibits non-linear pharmacokinetics at doses above 10mg. In plain English, this means that above 10mg there is the possibility for significant drug accumulation in the body, which in turn can lead to drug toxicity.
pharma gal
Anyone have insights into why the FDA did not request additional study data before approving this drug, given the hightened concern for safety at the agency? Will the FDA follow through with the Johns Hopkins University recommendation?
Salient point
Treatment options for Alzheimer’s are extremely limited & it’s becoming a very common disease. Although it’s not the business of this petition to suggest alternatives, FDA can’t pull Aricept 23 off the market without asking itself what choices a doctor would be left with in situations where 10 is not sufficient. Just having one significant difference may be enough to justify the higher dose in these circumstances.
I’d be willing to bet a fair amount of money that the next old school blockbuster drug will be one that’s truly effective in treating AD. Aricept is just a default.
Concerned
Regardless of the lack of options for Alzheimer’s does not mean that there should be a medication on the market that lacks efficacy and increases toxicity. How is it justified to continue to have this medication on the market when the “efficacy” is equal to the dose that is less than twice of that?
industry insider
Here’s a puzzler to me. Any good Phase II dose ranging study would have gone up to 3-4 times the marketed dose in the ORIGINAL clinical trials for Aricept. This means Eisai probably tested doses up to around 40mg/day, and probably had some notion about the 23mg dose even before the original NDA for 10mg was approved. Of course all of that data is proprietary, but any good Phase II study design would have bracketed the 23mg dose year ago in the original studies.
Typically in Phase II you try to determine two things– the MED (minimal effective dose) and the MTD (maximum tolerated dose). By definition, therefore, they should have tested somewhere close to or even exceeding 40mg/day of Aricept.
Kurt
I am a pharmacist and the 23mg dose of Aricept has changed my father’s quality of life tremendously. He wasn’t talking, now he is… he couldn’t feed himself, now he is… he wasn’t walking, now he is. His experience may be more positive than most, but it has been wonderful for him, my mother, and our family. It won’t cure his disease, but it gives us some more precious time to interact with him in a more meaningful way.
Gassa
How can you take a dose of a pill off the market?
And the problem cited above occurs with most medicine — just look at over-the-counter allergy meds for example.
Make the package insert easier to understand regarding dosing and let the doctor determine the best dose for each patient.
After all, Public Citizen is not taking pharmacogenetics into account.