What Happens If The Confirmatory Clinical Trial For Biogens Alzheimers Drug Fails?
In one of its most anticipated decisions of 2021, the FDA surprisingly granted marketing clearance to Biogens new drug for Alzheimers disease (AD), Aduhelm (generic name: aducanumab). Adulhelm doesnt cure AD, nor does it appear to reverse it. Rather, it slows disease progression perhaps better than any drug to date. Ordinarily, this step by the FDA would be met with hosannas. However, the development of Adulhelm has been plagued by controversy as has been well described by STATs Matt Herper. The FDAs approval is conditional  Biogen must conduct another large clinical trial to validate the results generated in a subset of patients in only one of its two clinical trials (the second trial failed). (Photo by Nicolaus Czarnecki/MediaNews Group/Boston Herald via Getty Images) MediaNews Group via Getty Images  That is not necessarily a remote possibility. Drugs that act on the central nervous system (CNS) are notorious for giving false positive results due to large placebo effects. In the case of Aduhelm, the key outcome in patients is better cognitive effects in those who received the drug as compared to those who got a placebo. But, patients on placebo always show some benefit in CNS trials complicating such studies. It will be crucial for Biogen to show a more profound and statistically significant effect for Aduhelm over placebo. A positive outcome is certainly not a given and these results will be anxiously awaited. Failure of Aduhelm in this study will have profound consequences, most notably for patients. Aduhelm provides hope for those in the early throes of AD. Failure will presumably result in the FDA pulling the drug from the market. That would mean that those who were on this drug for two years or more would have been exposed to essentially a placebo  but not one that is totally benign as brain swelling has been found in a small number of those on the drug. A much bigger issue will be dealing with those patients who believed that they have benefitted from the drug (remember  placebo effect). A second set of consequences involves the costs to the healthcare system. Biogens list price for Aduhelm is $56,000/patient annually. Its likely that tens of thousands of people in the early stages of AD will be treated with this drug in the coming months. If Aduhelms efficacy is shown to be ephemeral, some billions of dollars will have been spent on a flawed drug. And that doesnt include all the ancillary costs generated such as the PET scans needed to prove the presence of amyloid in the brains of patients (a necessary step before a patient is qualified to take the drug) along with other needed care in the monthly administration of Aduhelm. Some billions of dollars will be spent on Aduhelm before the results of Biogens new trial are available. But, the reputation of the FDA, as well as that of its acting commissioner, Dr. Janet Woodcock, is also on the line. The FDAs own advisory committee voted unanimously AGAINST approving Aduhelm at its review last summer. It is rare for the FDA to approve a drug when such a negative position is taken by its advisors. One has to be sympathetic with the FDAs position. They have been battered by patients and advocacy groups (including the Alzheimers Association) to approve this drug as AD sufferers and their families are desperate for any promising treatment. However, should the Biogen confirmatory study fail, there will be many who will decry the FDA for what will be perceived to be a lowering of standards by the very body that the U.S. expects to protect it from ineffective medicines. Finally, the entire biopharmaceutical industry will be tarnished if Aduhelm needs to be discontinued. Despite the goodwill generated by the industrys stellar performance in battling Covid-19, all will be undone in this scenario. Industry critics will seize on such an event as an example of the FDA being too cozy with biopharma and not being more rigorous in its review of new drugs. Furthermore, critics will also focus on the price of Aduhelm, using it as an example of a greedy industry that needs to be brought under control. We have heard these attacks before. Theres a lot more riding on Biogens next clinical study for Aduhelm. For patients, payers, regulators and those working in the biopharma industry, lets hope it works.