Biogen and partner Eisai are throwing in the towel on late-stage tests for their key Alzheimer’s drug aducanumab as independent experts reveal that it just won't make the grade.
Statistically speaking, this was bound to happen: Despite the hype and the hope coming from Biogen, 99% of all trials in Alzheimer’s have failed over the past 15 years, and drugs on the market for the memory-wasting disease are limited in their capacity to curb its effects.
Getting an effective, safe Alzheimer’s drug on the market is the Holy Grail in pharma research, but the disease continues to be an R&D black hole.
The post-mortem reads like this: The aducanumab phase 3 program, involving tests known as EMERGE and ENGAGE in early Alzheimer’s disease (AD), were terminated early for futility based on a recommendation from the data-monitoring committee, which found it unlikely that the primary endpoint would be met at the 18-month primary analysis.
A full breakdown of the results was not made available, but the primary objective of the study was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes score. It wasn’t on track to meet this.
The drug, an amyloid-targeting mAb, was going after a theory in AD that simply has not seen results worthy of approval, with many Big Pharmas—including Eli Lilly, AstraZeneca, Roche, Johnson & Johnson and Pfizer—all throwing billions of dollars at this research area but in return have only been beset by failures and setbacks.
“This disappointing news confirms the complexity of treating Alzheimer’s disease and the need to further advance knowledge in neuroscience. We are incredibly grateful to all the Alzheimer’s disease patients, their families and the investigators who participated in the trials and contributed greatly to this research,” said Michel Vounatsos, CEO at Biogen.
“Biogen’s history has been based on pioneering innovation, learning from successes and setbacks. Driven by our steadfast commitment to patients and our strong business foundation, we will continue advancing our pipeline of potential therapies in Alzheimer’s disease and innovative medicines for patients suffering from diseases of high unmet need.”
Detailed data from the ENGAGE and EMERGE studies “will be presented at future medical meetings to inform ongoing research,” the biotech said in a statement.
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There was also an EVOLVE phase 2 safety test in the works as well as the long-term extension of the PRIME phase1b study of aducanumab: Both will now also be discontinued.
“Initiation of the aducanumab phase 3 secondary prevention trial will be assessed while the data from ENGAGE and EMERGE are further evaluated,” the company added.
A quick-fire flash from analysts at Leerink said: “We expect Biogen’s stock to trade down to $240-260 (around 20%) on this negative news, and we cannot find any near-term catalysts that would help the stock recover back above $300.
“Our model is currently under review as we previously assigned a 35% probability of success for this program despite our many concerns regarding beta amyloid as a target following the failures of multiple other antibodies in recent years.”
Analysts at RBC were more downbeat, saying in a note to clients: “We view this as a transformative failure for BIIB's pipeline; elimination of all Alzheimer’s revenues from our model and reduction in our terminal growth rate would reduce our DCF valuation to ~$240/share (from ~$318/share), though we believe the stock could overshoot, given our view many investors owned BIIB to not miss out on what could have been one of the biggest blockbuster products in the pipeline of large biopharma, and the failure will likely expose the significant risks to BIIB's base MS business (competition, Tecfidera IP) and SMA franchise (competition).
“Given this, we believe as well that appreciation following today's likely sharp downside would be contingent on a more aggressive business development approach to de-risk and diversify the pipeline, which BIIB will now come at from more of a position of weakness.”
AD affects around 5.4 million Americans and will eventually prove fatal, with its prevalence only expected to rise as the population ages.
Biogen has in the past year tried to diversify outside of its focus on aducanumab, recently delving into gene therapies with its $877 million Nightstar buy, but this drug was a central pipeline asset for the Big Biotech, and its failure will way heavily on the company and—given Biogen’s weight within the biotech industry—biotech shares in general.
Biogen was already down 27% premarket on the news, wiping nearly $16 billion off its market cap, as investors reacted badly, with the Nasdaq Biotechnology Index sliding into the red by around 3%, whilst the S&P Biotech was down 1.6%.