In a surprising move, the acting commissioner of the Food and Drug Administration has requested an investigation of the FDA itself, specifically its contacts with Biogen regarding a controversial new Alzheimer’s drug.
In June, the FDA took the rare step of approving the drug Aduhelm, overruling an advisory committee that had urged denial because of doubts about its efficacy. The agency ruled that evidence showing this monoclonal antibody reduces toxic amyloid clumps in the brain met the regulatory threshold for “accelerated approval.” Advocates urged approval in the absence of any drugs offering hope for Alzheimer’s patients.
An inspector general investigation of the interaction between the FDA and Biogen may be the best way for the FDA to demonstrate it acted properly and to reassure the public of its independence. Still, we need to have more contact between FDA officials and drug developers, rather than less, if we want the agency to make informed and scientifically sound judgments about the performance of a new drug or medical device.
The value of more intense collaboration and communication with the FDA is a primary lesson learned in the response to the COVID-19 pandemic. The most startling and promising gain came in the development of vaccines in only one year, rather than taking a decade or more as was typical. We accelerated the utilization of breakthrough messenger-RNA technology in the works for a couple of decades, using it commercially for the first time.
This medical rapid-response capability owes to many factors. Last year, before the real work began, the federal government pledged bold, billion-dollar grants and guaranteed orders of new vaccines. This mitigated risk and attracted developers. Iron-clad legal protections against liability lawsuits against drug companies freed them to explore experimental approaches. World-class research and around-the-clock toil from drugmakers, combined with the intellectual assets of academia, provided the knowledge and data needed for regulatory approval.
But the most important element of all was the unprecedented level of interaction between vaccine developers and the FDA. Prompted by the pandemic, this new and intense dialogue began in the very earliest pretrial stages, and it continued up through the approval process.
Historically, research and development proceeded in a context of rigid and prescribed interactions with the FDA that were often managed so as to avoid seeming to favor a developer. Interactions were sporadic, and long periods could pass without any communication at all. Ask a question, and the FDA would endeavor to give you an answer but not specifically tell you what to do. The COVID-19 vaccine process shows the upside of more, rather than less, FDA guidance.
In the COVID-19 crisis, the FDA was involved continuously with drugmakers in the development and regulation journey toward rapid but rigorous regulatory review. The FDA also was proactive in incorporating new science and new methodologies for tracking and interpreting patient responses and outcomes.
It led to the creation of the “Evidence Accelerator Initiative,” working with the Reagan-Udall Foundation and the Friends of Cancer Research Foundation to form an infrastructure for “real-world evidence” on the natural history and treatment of COVID-19. If that worked for COVID-19, we should encourage the same kinds of collaboration for an Alzheimer’s drug. It should be the norm rather than the exception.
Drugmakers need more specific communications with the FDA and more help from the agency regarding preclinical lab and animal data, the mechanisms of action, and the characteristics of trial patients. This exchange can lead to an even better-informed regulator.
The FDA has an opportunity to institutionalize these gains and embed them into its regulatory approach. The FDA should conduct an “after action” study of this multifaceted effort to combat the pandemic. It then could recommend to Congress any legislation needed to authorize the agency to engage more freely and deeply with developers in guiding the early stages of drug and medical device development. For those fretting about “contamination” or “collusion,” the FDA can set up a Chinese wall between staff who facilitate trials and staff who judge the results.
This would enhance the likelihood of meeting regulatory standards to expedite work on safe diagnostics and therapeutics while preserving the integrity of a science-based review. It might even increase the success rate for winning approvals of safe and effective new therapies that can help millions of patients, which is precisely why the FDA was created.
Dr. Andrew von Eschenbach was commissioner of the FDA from 2006 to 2009. Dr. Robin Smith is the co-founder and CEO of the Cura Foundation.
