Is FDA in a Bind with the Canadian Approval for the ALS drug?
(Thursday, June 16, 2022)
This week Amylyx’s ALS drug was approved by the Canadian regulators raising speculations that this would make it very hard for FDA to reject this drug despite the negative vote by the FDA’s Advisory Committee which based its recommendation on the underwhelming clinical trial data from the one pivotal trial conducted by the company. But this could set up another bad precedence for FDA. The Canadian approval is based on the same clinical data presented to the FDA; the data that FDA concluded was insufficient, and FDA’s decision was independently supported. Also, Canadian laws, unlike the US, allow conditional approval where the approval can be rescinded at a well-defined later time if the conditions for approval are not satisfied. Such conditional approvals are not provisioned in the US laws. Although there are processes to withdraw approval based on non-completion of post-marketing commitments, such withdrawals are rare and they raise practical issues, particularly, if the drug in question is the only or one of the few drugs available to the patients. Another issue that FDA needs to deal with is the use of surrogate markers via accelerated approval pathway by Amylyx. Since Biogen’s Aduhelm, many questions have been raised about the misuse of the accelerated approval pathway so much so that Adulhelm has limited coverage by the payors and anemic preference by the prescribers despite being the only drug for Alzheimer’s disease. One would think that FDA would be very reluctant to make on another controversial decision that goes against the scientific data presented to it. But there is a silver lining for Amylyx. The company has an ongoing 600-patient Phase 3 clinical trial from which preliminary data may be available. FDA has asked for additional data from the ongoing study. Even the Canadian approval is conditional to Amylyx presenting data from this Phase 3 study by 2024, about 2 years hence. FDA could piggy-back on that rationale and punt its decision to mid-study results or other criteria where the decision is not based on just one unsatisfactory trial. The Congress is currently considering some revision to the accelerated approval pathway which could make it easier for FDA to impose stricter timelines on post-market commitment and quicker withdrawal of approval for drugs approved under the accelerated approval pathway. The political decision is expected in the next few months. FDA could be waiting for that so it can apply those rules on Amylyx. In the current circumstances, either decision from FDA would be highly controversial which would set another bad precedence. But there are some ways for FDA to both approve the product and appear to be balanced and scientific in its decision. FDA needs it and so do all the stakeholders: patients, industry, and the prescribers.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC