In a sign of just how tough neuroscience is, Biogen is cutting a clutch of programs from its Alzheimer’s disease, amyotrophic lateral sclerosis and schizophrenia pipelines.
The company revealed the pipeline cuts in its second quarter earnings call Wednesday morning, with CEO Michel Vounatsos detailing a few extras during a call with investors. Vounatsos said the therapies were being terminated due to a “lower quality of success.”
On the block is BIIB076, an anti-tau antibody for Alzheimer’s that had been in phase 1 development as of November 2021 in partnership with Neurimmune. The therapy was being tested in healthy volunteers and those with the neurodegenerative disease, according to an oral presentation abstract posted at the end of last year.
A spokesperson for Biogen said that BIIB076 was terminated due to “ongoing portfolio prioritization efforts,” not due to any clinical trial data that raised red flags. Further questions on the future of BIIB076 were directed to Neurimmune. A spokesperson for the biotech said that “BIIB076 is capable of engaging with its target and we will evaluate options for further development.”
With this tau therapy out of the running, Biogen will shift focus on to BIIB080, which is currently in phase 1. The therapy is being developed in a collaboration with Ionis Pharmaceuticals. A phase 2 is expected to get underway this year, Priya Singhal, head of Global Safety & Regulatory Sciences and interim head of Research & Development at Biogen, told investors.
Singhal also pointed to a pending readout for the star of Biogen’s Alzheimer’s portfolio: lecanemab, which has pushed aside the controversially approved treatment Aduhelm in terms of priority this year. The company was recently granted a priority review under the accelerated pathway for that therapy earlier in July.
The phase 3 Clarity trial is expected to read out in the fall, a study that could serve as a confirmatory study to support a full approval in Alzheimer’s disease rather than the more limited accelerated approval that Biogen and partner Eisai have applied for. A complete regulatory filing for lecanemab is expected in the first quarter of 2023 pending the results from the Clarity trial.
Biogen has its hopes pinned on the late-stage read-out. Singhal would not speculate on how the application could change if the data is mixed. But she pointed to other data collected so far on lecanemab and the broader amyloid theory, which is also being tested by Eli Lilly’s donanemab and Roche’s gantenerumab. Both of the Big Pharmas are expecting major late-stage readouts in the coming months as well.
“So really this is a bigger question about these readouts and what they mean for the anti-amyloid hypothesis in early Alzheimer's disease,” Singhal said.
Roche’s Genentech unit, which is leading development of gantenerumab, just notched a disappointing failure with another candidate, crenezumab in early Alzheimer’s disease, dealing a blow to the amyloid theory.
Biogen also has a broader clinical plan to test lecanemab in pre-symptomatic patients and as a maintenance treatment, plus an open-label study. Eisai is leading the clinical development this time around after Biogen took the lead on Aduhelm.
Biogen will also walk away from the schizophrenia treatment BIIB104, which is getting the ax after a phase 2 trial called Tally failed to meet its endpoint. The company said that due to a “consistent lack of efficacy” on both the primary and secondary endpoints relating to cognition and functioning, the therapy would be discontinued. Adverse events were mild to moderate in severity, according to the earnings report.
Biogen has yet to release the results of the Tally trial, but Singhal said the data would be presented at an upcoming medical meeting. The therapy did show pharmacological exposure, but ultimately the effect just wasn’t there.
“We believe that we have tested the hypothesis very well here and that it's time to reconsider the data, look at it very carefully, think about other applications, but ensure that we allocate resources to the programs with higher probability of success,” she said.
Also at the end of its clinical journey is BIIB100, which had been tested in a phase 1 study for patients with amyotrophic lateral sclerosis in a partnership with Karyopharm. This termination was previously announced as part of a larger cull in June.
The spokesperson said this decision was again due to portfolio prioritization. The small molecule drug was an outsider in Biogen’s ALS program, tackling a different target called XPO1. Biogen still has tofersen, which was recently featured at the European Network to Cure ALS meeting in Scotland in June. The therapy, which targets the SOD1 gene, was found to slow decline on several measures of clinical and respiratory function, strength, and quality of life.
“We've embarked upon a very focused and disciplined prioritization of the R&D portfolio, but it is dependent on internal inflection points, as well as external scientific insights,” Singhal said, speaking to the pipeline cuts.
Vounatsos said that at the same time, Biogen is expanding its pipeline too, although he did not provide specifics.
“There is inherent risk in neuroscience, and it's natural that we always try to increase [our] success and select based on trigger point and science insight and this is what Priya is doing,” he said.