Hmm.   Is this good news or not?

The FDA (Food and Drug Administration) has just approved aducanumab (Aduhelm) for Alzheimer’s.  Of course, if you are Biogen, this is great news.  But, since the data is – how do I say this?- less than emphatic- will this really help patients?

For those of you with some medical/biotech background, you may recognize that Aduhelm is a monoclonal antibody (MAB).   The MAB targets amyloid (the protein) that forms the clumps in brains of Alzheimer’s patients [some researchers believe this is a biomarker for the disease], to which it attaches (the immune response) and flushes the agglomerated mass out of the brain.

There are risks associated with the treatment.  Some 40% of the patients who received a high dose of the antibody manifested brain swelling or bleeding.  This is why 6% of the patients on the trial discontinued their treatment.

(NOTE:  The FDA employed the accelerated approval pathway- a process by which drugs can be brought to the market before definitive proof is displayed that there is a clinical benefit to its administration.  Most of the time this process is used for cancer treatment therapy.)

There were three trials (3482 patients), each demonstrating a dose and time dependent effect – lowering the level of amyloid beta plaques.  (The three trial results were 59% [Engage], 71% [Emerge], and 61% [Prime]).  However, there is no clear link between a lowered amyloid beta plaque level and severity of Alzheimer’s. Nor is there medical consensus on the role that amyloid plays in Alzheimer’s- actually, there is no good evidence whatsoever that reducing amyloid levels yields meaningful changes in the clinical course of the disease.

Yes, it is unclear if aducanumab does, indeed, alleviate cognitive impairment for Alzheimer’s patients. (Theoretically, Aduhelm is limited to those patients with mild memory and thinking problems, where it is expected to slow cognitive decline.  I say theoretically because the FDA only makes recommendations; once a drug is available, physicians can use the drug as they see fit.)

Some Alzheimer’s patients swear by the drug-  but the proof is lacking.  Let us not forget that Biogen shelved the drug a few years ago because it was not happy with the clinical evaluations.  Or, that the Peripheral and Central Nervous Systems Drug Advisory Committee [5 to 0, 6 abstentions] had determined in November thought there was evidence of pharmacodynamic effects of the drug- but then [8 to 1, 2 abstentions] declared it was not effective in treating Alzheimer’s and [7 to 0, 4 abstentions] that Biogen failed to provide evidence that is was an effective Alzheimer’s treatment.

(NOTE:  Three folks have already resigned from the Advisory Committee because the FDA approved the drug without advisory approval.)

This is exactly why the FDA has prescribed a phase 4 clinical trial for the drug.  Should the drug not manifest clear clinical advantage, the approval could be withdrawn.

And, that also means that many physicians may be reticent in prescribing the drug.  (By the way, Aduhelm is administered via intravenous infusion, over the course of an hour, on a monthly basis.) Moreover, that is NOT related to the annual cost for the drug ($ 56,000)- which won’t help matters.  (NOTE:  Medicare has already announced it will cover the cost for the drug, via its Part B drug program.)

(By the way, the Institute of Clinical and Economic Review [ICER] has calculated the fair price of the drug to be somewhere between $ 2500 and $ 8300; with better success rates, it would raise that valuation to $ 11100 to $ 23100.  In other words, Biogen has decided to price the drug at virtually thrice its value .)

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