The baffling early June decision by the Food and Drug Administration (FDA) to approve Biogen’s Alzheimer’s disease drug and ignore the recommendation of its Advisory Committee has been covered and chronicled to the level of the COVID-19 pandemic. On another platform, I put in my two cents on how payers may step in to save the FDA from itself.
In this post, I want to weigh in on two aspects of this lamentable episode that affects the biosimilar sector. First is the obvious: An erosion of confidence in the FDA’s ability and incentives in carrying out its mission—ensuring that drugs approved for use in the US are safe and effective. Based on the available evidence, arguments can be made that the risks of aducanumab well outweigh the potential benefits. That is what the FDA’s own staff reviewers thought when giving their assessment for the drug evaluation.
Another unassailable argument can be made for the risk for rewards for Biogen. The projected price point ($56,000) and the potential number of patients for whom it can be prescribed under the broad indication originally approved (though the FDA has backtracked and tried to narrow the indication) could set Biogen up for multibillion product sales for at least 12 years into the future. Now word has come out that FDA has had subsequent discussions with Biogen that seemed to affect the FDA’s final decision. Now, those optics are about as bad as it gets—for the FDA and for Biogen. Acting FDA Commissioner Janet Woodcock has ordered an investigation by the Health and Human Services Inspector General into the process—the result of excellent journalism uncovering these secretive talks by STAT. If I were a provider, patient, or payer who was not yet convinced of the armada of proof of the safety and efficacy of biosimilars, this is a big deal. The FDA approves a product for which safety is an issue and for which its clinical effectiveness is seriously in doubt.
In the case of the FDA’s decision, Patrizia Cavazzoni, MD, went all in on the fact that aducanumab removes amyloid plaque from the brains of patients with mild disease. However, this has not yet been shown, in several clinical trials, to result in any clinical improvement or delayed progression of the Alzheimer’s disease process. In other words, she and her colleagues at FDA believe that removing amyloid plaque is a proxy for a positive outcome, which one day will be confirmed to be true.
Don’t forget that FDA made a similar bet on proxies for clinical outcomes in the biosimilar field: That the similarity in physiochemical structure of biosimilars would result in clinical outcomes that were equivalent to those produced by biosimilars. They’ve cashed in on that bet; it has been backed up with plentiful phase 3 clinical trial evidence and switching studies. Those proxies are particularly important in terms of extrapolated indications, for which there were no late-stage clinical studies.
The second piece to this is Biogen’s role as a player in the biosimilar market. Biogen is a major shareholder in Samsung Bioepis, and will be marketing the latter’s biosimilars like denosumab, ranibizumab, and others in the US. Biogen already markets several biosimilars in Europe, including a version of adalimumab. It is also working with Bio-Thera to bring its tocilizumab biosimilar to market.
If Biogen is found to have had inappropriate communications with the FDA that materially contributed to obtaining approval for aducanumab, then stakeholders may have reason to hold Biogen to a different standard for both new innovator drugs and biosimilars. All we can do is speculate at the moment. The industry is on the precipice of launches of new ophthalmologic biosimilars and of course for the white whale—adalimumab. Potentially damaging questions about a major biosimilar manufacturer and marketer are not at all welcome.