Biogen has shared the detailed data on aducanumab that it hopes will secure FDA approval in Alzheimer’s disease. The Clinical Trials on Alzheimer's Disease (CTAD) presentation cleared up some questions about the data set without delivering a telling blow for either side of the debate.
Since Biogen shocked the biopharma community by resurrecting aducanumab following a failed futility analysis, observers have tried to gauge the legitimacy of its belief that the positive aspects of the very mixed phase 3 data set represent the drug’s true effects. Biogen fleshed out the data at CTAD while sticking to the core narrative that mid-study modifications and the timing of enrollment explain the divergent results seen in the two trials.
The result was a presentation that is unlikely to have convinced outright skeptics of the merits of taking aducanumab to the FDA but that equally offered enough encouragement to those tantalized by the signs of efficacy.
“When added up this week, investors will feel FDA could be more convinced to approve Adu than before CTAD. That said, the consensus remains fairly skeptical of the package because the statistics and overall rules on getting a drug approved don't appear to be met here and so this comes down to a review and discussion with FDA. We have seen orphan drugs approved when not hitting their primary endpoint but in rare populations. This would be a unique and unprecedented approval if so,” analysts at Jefferies wrote in a note to investors.
Those doubts remain despite the CTAD panel taking a broadly favorable view of the data. Paul Aisen, director of the Alzheimer's Therapeutic Research Institute, called the EMERGE findings a “hugely important result” that represent a “major advance for the field.”
Yet, even Aisen’s upbeat reading of the data was undercut by acknowledgement of the problems with the data set.
“The data is complex. I think the futility decision was highly unfortunate and puts us in the situation of interpreting complex data. But clearly the EMERGE final analysis is positive … and the analysis of all the key secondaries was consistent and positive. As important, the biomarker evidence supports the mechanism, with significant amyloid reduction leading to … reduction in tauopathy,” Aisen said.
To further complicate matters, Aisen accepts that the final ENGAGE data are negative, adding that it is “challenging” to understand the discordant results between the two trials. However, Aisen is convinced by Biogen’s argument that the timing of enrollment is driving the divergence of the EMERGE and ENGAGE results, leading him to reach “an overall positive interpretation of the data.”
Other panelists shared Aisen’s positive take on the data, arguing the results show aducanumab has a clinically meaningful effect on Alzheimer’s symptoms. However, the panel lacked speakers who are skeptical of the amyloid hypothesis, meaning the data got a relatively easy ride and either failed to answer or was never asked some key outstanding questions.
“[The CTAD] doc panel was quite positive but they didn't answer some of the Street questions still outstanding,” the Jefferies analysts wrote.
Some of those questions remain unanswered despite direct questions from the CTAD audience. For example, Samantha Budd Haeberlein, Biogen’s vice president for clinical development, declined to say whether the results varied by geography, meaning it is unclear if the positive aspects of the data are driven by a particular region or are a consequence of broad-based improvements.
Biogen cleared up one big query after the panel, telling investors on a conference call that a key subgroup was “well balanced” in terms of ApoE4 positive and negative patients. The comment lessens fears that an imbalance is behind the more encouraging aspects of the data set, although Biogen is yet to reveal the exact split between ApoE4 positive and negative patients.
That outstanding uncertainty and other remaining questions will likely get a more thorough airing when the data set is reviewed by the FDA. But for now, Biogen has come through another assessment without suffering a terminal blow to its hopes of getting aducanumab to market.
Shares in Biogen closed up 3% following the presentation.