The aducanumab saga continues. The Food and Drug Administration has delayed a decision on licensing by three months, pushing the deadline from March to June 7. In a press release, the drug’s sponsor, Biogen, said the FDA had requested more information, and in response Biogen submitted “additional analyses and clinical data.” The FDA considered the addition to be a major amendment to the biologics licensing application, necessitating more review time.

The aducanumab tale was already full of surprises, going from futility on its two Phase 3 trials to their resurrection (Mar 2019 news; Oct 2019 news; Dec 2019 conference news). Biogen submitted a licensing application to the FDA last year, and has also applied for marketing approval in Europe and Japan (Jul 2020 news; Aug 2020 news). The FDA application ran into headwinds at an advisory committee meeting, prompting speculation the application would be rejected (Nov 2020 news; Nov 2020 news).

It is unclear what additional data Biogen submitted. The company declined to share details with Alzforum. Biogen continues to gather data on aducanumab’s safety and effectiveness in the EMBARK open-label extension trial. This type of data is not placebo-controlled, and is not usually used as the basis for licensing decisions.

Researchers were mystified, as well. “I have no idea what the FDA delay of the Biogen aducanumab decision means, nor do any of my colleagues who usually have insightful opinions on such matters,” David Knopman at the Mayo Clinic in Rochester, Minnesota, wrote to Alzforum. Russell Swerdlow at Kansas University Medical Center in Kansas City wrote, “It will be interesting to see how any new data impacts the very negative FDA statistical analysis.”

Bruno Imbimbo of Chiesi Pharmaceuticals in Parma, Italy, wondered if the recent change in FDA leadership, where Janet Woodcock took over as acting commissioner from Steven Hahn, would affect the licensing decision. “Based on the enormous impact the FDA’s final decision on aducanumab will have on the U.S. health care system, I believe the three-month postponement of the feedback is a positive development of this delicate scientific and patient health care story,” Imbimbo wrote to Alzforum.

Industry analysts speculated that the delay might raise the odds of approval. “Based on our analysis of prior Prescription Drug User Fee Act (PDUFA) extensions, we think minor delays typically lead to an approval,” analysts at New York-based financial analysis firm Jefferies told the industry press. If so, aducanumab could be approved based on data not seen by the advisory committee. Biogen shares jumped 9 percent the day of the announcement, but have now dropped back to previous levels.—Madolyn Bowman Rogers


  1. We do not know which information FDA requested of Biogen. I do not believe the new data from the ongoing open-label extension trial on aducanumab represent significant information because of the uncontrolled nature of the study. Rather, I can speculate that, based on the criticism raised by the Aducanumab Advisory Committee of November 6, 2020, the FDA may have requested “additional analyses and clinical data.” Apparently, this information is quite significant since the FDA considered it a Major Amendment to the application, which requires additional time for review.

    As of January 20, the FDA Acting Commissioner is Dr. Janet Woodcock, whose FDA experience goes back to 1986. We can speculate that she will favor within-agency discussion of aducanumab and the interaction with Biogen. Based on the enormous impact that the final FDA’s decision on aducanumab will have on the health care system in the U.S., I believe this three-month postponement is a positive development in this delicate scientific and patient health care story.

  2. The three-month delay is a political win-win-win for the FDA, Biogen, and the indefatigable advocacy groups. The agency has had the necessary information to decide since November, but is either conflicted or carefully timing an announcement. Their current request for data from open-label studies, while facilitating “patient engagement opportunities” as they did with the Alzheimer’s Association in January, makes the agency appear even more deliberative and sensitive to stakeholders.

    But data from an open-label extension study tells little about safety and less about effectiveness, since participants who had intolerable adverse events and those declining rapidly washed out earlier, leaving mainly the healthier non-decliners, and those with the wherewithal to continue monthly infusions. In the meantime, hosting patient testimonials and being in regular contact with Alzheimer’s Association officers allows the FDA to better include advocates in their decision.

    Perhaps more important, postponing an unavoidably controversial decision forces the upcoming FDA political leadership to own it, and gives the current acting officers a finesse. Will the Biden-appointed FDA commissioner be Joshua Sharfstein or Janet Woodcock? Will Janet return as COVID-19 czar or go back to the Center for Drug Evaluation and Research (CDER)? Will Patrizia Cavazzoni be permanent CDER director? These directors’ views may differ substantially when it comes to applying FDA regulatory concepts such as “adequate and well-controlled studies,” “safe and effective,” “potential for efficacy,” “breakthrough therapy,” and drugs for “unmet medical needs.” There may be little upside for the current FDA staff to make this decision now.

    Biogen, for its part, gets to continue its lobbying and publicity events with WEF/Davos, ADI, the Alzheimer’s Association, and Us Against Alzheimer’s. The company has more time to work with physicians and KOLs, and promote medical education events. And the advocacy groups have three more months to show patients that they are working hard for them, and still stand ready to share credit if aducanumab is approved. Finally, there is virtually no cost to this delay. There is only Biogen’s opportunity cost of three months of sales.

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News Citations

  1. Biogen/Eisai Halt Phase 3 Aducanumab Trials
  2. ‘Reports of My Death Are Greatly Exaggerated.’ Signed, Aducanumab
  3. Exposure, Exposure, Exposure? At CTAD, Aducanumab Scientists Make a Case
  4. Biogen Asks FDA To Approve Aducanumab
  5. FDA Accepts Aducanumab Application for Priority Review
  6. FDA Advisory Committee Throws Cold Water on Aducanumab Filing
  7. Aducanumab Still Needs to Prove Itself, Researchers Say

External Citations

  1. press release
  3. industry press

Further Reading