An experimental drug from Eisai and Biogen significantly slowed the decline of people with Alzheimer’s disease in a large Phase 3 clinical trial, a surprise finding that could revitalize a research field accustomed to disappointing study results.
The positive data that the companies released Tuesday could renew faith in a central hypothesis for the root cause of the disease, as well as raise hopes that similar drugs from Eli Lilly and Roche could succeed as well in now ongoing trials.
Eisai and Biogen’s lecanemab works by blocking a form of a protein known as amyloid, accumulations of which in the brain have been linked to the characteristic loss of memory, orientation and function in Alzheimer’s.
The drug, an experimental antibody, is the latest in a long line of treatments testing the so-called amyloid hypothesis that clearing out those plaques might slow the disease’s progression.
Yet the chances of success had appeared slim. Many prior attempts to treat Alzheimer’s with amyloid-blocking drugs failed, with once-promising treatments like Pfizer, Johnson & Johnson and Elan’s bapineuzumab and Lilly’s solanezumab scrapped after years of testing and millions of dollars spent.
Even Biogen’s amyloid-busting drug Aduhelm, which last year became the first Alzheimer’s drug approved in 17 years, was backed by conflicting data, resulting in an anemic rollout and renewed questions around the amyloid hypothesis.
Lecanemab could change the narrative, however. Phase 3 results showed it slowed patients’ cognitive decline by 27% compared to a placebo after 18 months, greatly raising its chances of approval. All secondary study goals were met as well.
The outcome has led analysts to raise their expectations for Lilly’s and Roche’s drugs. Both companies expect to report data from large late-stage trials in the coming months, and saw significant stock gains on news of lecanemab’s success.
Lilly’s share price climbed 8% and Roche’s Swiss-listed shares rose 4% Wednesday. Shares of other biotechs developing Alzheimer’s treatments, like Prothena and AC Immune, benefited as well.
“We believe the positive Phase 3 data for lecanemab will serve as an overall catalyst for companies working in the [Alzheimer’s disease] space,” Mizuho Securities analyst Graig Suvannavejh wrote in a Wednesday note to clients.
The commercial prospects for each could rise, too. While access to Aduhelm has been restricted significantly by restrictive coverage decisions from Medicare and other insurers, the positive lecanemab data “should resume the possibility of class reimbursement,” wrote RBC Capital Markets analyst Brian Abrahams.
Donanemab, which the Food and Drug Administration is now reviewing for a potential accelerated approval, was able to slow patients’ decline by 32% in a smaller Phase 2 trial, although the benefit over a placebo diminished by the trial’s end at 76 weeks.
While comparing drugs across trials can be difficult, Lilly’s medicine resulted in a higher rate of a type of brain swelling that’s been observed in testing of amyloid-blocking therapies. In lecanemab’s Phase 3 trial, 13% of patients had evidence of this brain swelling, called ARIA-E, compared to 27% of those who received donanemab in Lilly’s Phase 2 trial.
Lilly’s Phase 3 trial is due to read out results in early 2023 but, before that, the company expects data from a smaller study testing the drug’s ability to clear brain plaques compared to Aduhelm. That data will likely only be helpful for its accelerated approval application, with full approval contingent on a positive result in the larger study.
Biogen and Eisai, as well as Lilly, are due FDA decisions on accelerated approval of their respective drugs in early 2023. In announcing the results from the lecanemab Phase 3 trial, Biogen and Eisai said they will use the results to apply for full approval by the end of March.
“Assuming approval, lecanemab will be a first mover within this next wave of [amyloid-blocking] antibodies,” Stifel analyst Paul Matteis wrote in a note to clients.
Roche’s gantenerumab, meanwhile, was due to complete a Phase 3 trial in early disease this month, so results could come soon. The drug has had a mixed, and lengthy, history in clinical study. Two previous Phase 3 trials were stopped because there were no signs treatment was helping patients receiving the drug. But, because of reported reductions in brain amyloid, the drug gained a Breakthrough Therapy designation from the FDA, helping to sustain further research.
Gantenerumab will likely have similar safety concerns as donanemab, was one-third of patients in extension studies from those two terminated trials showed signs of brain swelling.