Another high-profile attempt to produce an Alzheimer’s treatment has failed.
An unusual biotech company called Axovant Sciences (NASDAQ: [[ticker:AXON]]) reported today that its drug intepirdine did not show a meaningful difference between the patients taking a combination of intepirdine and donepezil (Aricept) and the patients taking only donepezil, which is one of just a handful of drugs approved to help slow down the cognitive decline that Alzheimer’s patients suffer.
The Phase 3 study was called MINDSET. After 24 weeks, Axovant took two measures. It reported the topline results this morning. The improvement in cognition for the intepirdine patients wasn’t statistically significant (.36 points on a standard test known as ADAS-Cog, with a p value of .22). And there was “essentially no difference” (0.09 points on a test called ADCS-ADL, with a p value of .83) between the intepirdine/donezepil patients and the donezepil patients in the activities of daily living, according to Axovant. Interpirdine was generally well tolerated, Axovant reported.
“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 Axovant CEO David Hung.
The Alzheimer’s Association estimates there are 5 million Americans with Alzheimer’s disease, which could triple by mid-century. There is also financial urgency to develop a drug to address the disease, which takes its toll on family members and other unpaid caregivers who themselves suffer health consequences and lost productivity.
On a conference call this morning, Hung said the company would move on with other studies in its pipeline, including the study of intepirdine in a different form of neurodegeneration called Lewy body dementia. He held out hope that a higher dose of intepirdine—70 mg instead of MINDSET’s 35mg dose—could yield a “more robust effect” than it did in MINDSET, potentially hitting a second biological target in the brain.
Axovant shares fell more than 70 percent during trading on Tuesday.
Hung joined Axovant earlier this year after selling his San Francisco-based Medivation to Pfizer (NYSE: [[ticker:PFE]]) for $14 billion, in large part for Medivation’s prostate cancer drug. But Medivation had also been stung in Alzheimer’s development, first touting a drug called dimebon only to see it fail in a large Phase 3 study. (Pfizer was Medivation’s partner at the time.)
Before intepirdine was Axovant’s, it belonged to GlaxoSmithKline, which tested it against Alzheimer’s but shelved it after it fared poorly in clinical trials.
Along came Axovant founder and young hedge-fund manager Vivek Ramaswamy, who used the drug to launch a grander plan: Find deep discounts on the pharmaceutical industry’s dusty shelves and develop them quickly with loads of new cash. He has repeated the trick with companies formed around women’s health, dermatology, rare diseases, and urology and has created a holding company, Roivant Sciences, to house them all.
Axovant bought intepirdine from GSK in 2014 for $5 million and parlayed the attention into a massive $315 million IPO in 2015, despite misgivings about the drug’s spotty track record. Intepirdine, a once-a-day pill, blocks 5-HT receptor 6, which is supposed to boost the levels of the neurotransmitter acetylcholine that plays a role in cognition. There has been an open question as to whether the approach would have an impact on Alzheimer’s, particularly since a rival 5-HT6-blocking pill from Lundbeck, idalopirdine, failed two Phase 3 trials earlier this year.
Axovant has pointed to promising results from GSK’s clinical tests when intepirdine was paired with patients already taking donepezil. But the earlier misgivings have come full circle. As with other Alzheimer’s drugs that seemed promising in smaller-scale studies, intepirdine returned a gloomier picture once tested in a large population. MINDSET enrolled more than 1,300 people with mild to moderate Alzheimer’s, which means they were already displaying obvious symptoms. Half the participants have been taking intepirdine along with donepezil. The other half have been taking donepezil and a placebo.
In 2014, an overview of Alzheimer’s drug development put the failure rate at nearly 100 percent. The numbers have only gotten worse since then.
Unlike some Alzheimer treatments that have failed in recent years, intepirdine’s developers did not seek to change the underlying cause of the disease. Instead, they had a more modest goal of boosting the cognition of people with the disease, at least when used in combination with donepezil. Donepezil and memantine (Namenda) were approved in 1996 and 2003, respectively.
