September 26, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Basel, Switzerland – Axovant Sciences , one of Vivek Ramaswamy’s biotech startups headed by former Medivation founder and chief executive officer David Hung, had bad news today—really, really bad news. The company’s Phase III MINDSET clinical trial of intepirdine in Alzheimer’s disease failed … spectacularly.
Ramaswamy and Axovant acquired the drug for mild-to-moderate Alzheimer’s disease for $5 million from GlaxoSmithKline . The drug showed a favorable safety and tolerability profile, and in a Phase IIb trial, showed immediate and sustained efficacy over placebo. However, the drug had been abandoned by GSK after four failed clinical trials. Ramaswamy felt he could revitalize the drug in a narrower patient population, and convinced investors he could, too.
The MINDSET trial looked at 1,315 patients on a stable background therapy of donepezil (Aricept) who will receive either intepirdine or a placebo. The drug failed to meet its co-primary efficacy endpoints. Patients receiving 35 mg of intepirdine failed to show any improvement in cognition or in measures of activities of daily living at 24 weeks. There was “essentially no difference between the intepirdine and placebo arms in change from baseline in activities of daily living,” the company stated.
Only one secondary endpoint showed any significant improvement of the intepirdine arm versus the placebo arm. That was the Clinician Interview-Based Impression of Change plus caregiver interview, or CIBIC+.
“While we are deeply disappointed by these trial results, we also are saddened for the millions of patients and families impacted by Alzheimer’s disease,” said Hung in a statement. “However, we believe that the fight against Alzheimer’s and other important areas of unmet need in neurology is too important to be derailed by this setback.”
Investors may feel otherwise. Shares cratered at the news, dropping from $26.95 on Sept. 21, plunging 74.23 percent in premarket trading to $6.15.
It also places pressure on many of Ramaswamy’s companies, which are typically built on acquiring big pharma’s castoffs at bargain-bin prices and attempting to recycle them. It’s not completely unprecedented. Lipitor, the bestselling drug ever, was almost abandoned. About a dozen companies have successfully been built on the acquisition of a forgotten drug. However, it’s a high-risk proposition and Alzheimer’s disease has proven to be an extremely difficult nut to crack.
John Carroll, writing for Endpoints News,notes, “The failure here will come as no surprise to longtime investigators in the field. Pfizer and Lundbeck had both tried and failed to amp up cognition with a 5HT6 program, designed to spur release of a neurotransmitter, though Axovant instead that it could beat the odds. If it had, analysts agreed that a new drug now could be worth billions in annual revenue. Instead, the drug isn’t worth the $5 million Ramaswamy paid for it.”
Hung, who was brutally honest about the failure, also tried to shine it up a little bit, saying, “Moreover, we remain committed to advancing our pipeline, which includes our Phase IIb HEADWAY study of intepirdine, and nelotanserin, our highly selective inverse agonist of the 5HT2A receptor in Phase II development, both of which are being evaluated in patients with dementia with Lewy bodies.”
Lewy Body Dementia is a neurodegenerative disease with symptoms similar to Alzheimer’s and Parkinson’s diseases. The trial is expected to have results by the end of the year, and the company also has three other drugs in early development.
There are only four drugs approved to treat symptoms of Alzheimer’s, with Aricept being the bestselling one. Had intepirdine succeeded in the Phase III trial and been approved, it would have been able to piggyback on Aricept’s financial success. None of the current Alzheimer’s drug are viewed to be particularly good drugs, showing modest improvements in cognition and short-term delay of symptoms in a subset of the patient population.
