Early in 2020, Biogen will re-open study of aducanumab, a drug that targets brain amyloid, for the treatment of Alzheimer’s disease.
On December 5, at the Clinical Trial in Alzheimer’s Disease (CTAD) meeting in San Diego, California, Biogen scientists discussed the data supporting their reversal of March 2019 announcement to end study of aducanumab. The decision was driven by results from late-study changes in dosing in the ENGAGE and EMERGE studies (see reporting from STAT).
By the time Biogen implemented the amendment, 200 more patients had enrolled in ENGAGE than EMERGE, affecting how high doses were distributed throughout each trial. The change allowed 51% of EMERGE patients to receive the highest dose for the full 14 weeks, versus 29% prior. ENGAGE saw 47% of patients receive the full dose compared to only 22% before the protocol amendment. At the time of the futility analysis, fewer individuals were on this highest dose. However, by the time the trial was discontinued the above numbers were reached and data was more favorable when analyzed driving Biogen’s renewed confidence in aducanumab.
“The results are encouraging,” said PMC Co-Director Dr. Jason Karlawish, who reviewed the results at CTAD. “They reinvigorate the need to study anti-amyloid therapies. I’m keen to learn how changes in brain amyloid tracked with changes in measures of patient well-being, and how having certain Alzheimer’s risk genes related to the experience of side-effects and response to the drug.”
The Cambridge pharmaceutical giant’s presentation marked another zenith in a roller coaster ride of dashed expectations and renewed hope.
After independent analyses in March 2019 declared the drug unlikely to work, Biogen announced in late October at meeting with investors that it would seek FDA approval in light of new data from patients excluded from earlier analyses that showed the drug’s effectiveness over longer periods of time in higher doses. The news shocked investors, excited former study participants and patients, and elicited cautious optimism from scientists, all while rocketing the company’s stock prices back to near pre-failure levels.
“In many senses, the aducanumab data that we are discussing today sort of characterizes — is almost a caricature — of the course we have had in the field,” Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center in Rochester, Minnesota told Bloomberg.
Some researchers still debate about the need for another trial or further evidence to prove Biogen’s claims around the drug.
“The data presented provided compelling evidence that aducanumab may be effective, but there are still some key additional analyses which would be helpful in further supporting efficacy,” PMC Co-Director Dr. David Wolk said. “Whether there is enough evidence in light of the incomplete trial for the FDA to approve without additional data collection in a new trial is difficult to say at this point.”
Until the need for a completely new clinical trial is determined, only participants previously in any of the prior aducaumab studies will be invited into a re-dosing trial, likely beginning in March. There are inclusion/exclusion criteria that must be met for these participants. Coordinators will reach out to these participants with more information about when this process will begin.
Ultimately it will be up to the FDA to declare the drug’s effectiveness.
“Obviously there is a tremendous need in Alzheimer’s, and we’ll just have to see about data,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research said in an interview with Bloomberg ahead of the conference.
Biogen said it plans to file for FDA approval in early 2020.
Currently, there are no treatments to reverse or slow the effects of Alzheimer’s, the sixth-leading cause of death in the U.S. The FDA has approved several drugs that aid with symptoms of the disease.