October 6, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Hamilton, Bermuda-based Axovant Sciences Ltd. announced today that its first patients had been screened for its confirmatory Phase III study of Alzheimer’s drug RVT-101. In addition, Axovant announced the U.S. Food and Drug Administration (FDA) had granted the study a Special Protocol Assessment (SPA).
Axovant was founded by 30-year-old Vivek Ramaswamy, a former hedge-fund manager. He founded Roivant Sciences in May of 2014, then spun off Axovant in October.
The clinical trial, dubbed MINDSET, is an international, multi-center, double blind, placebo-controlled 24-week trial. It will compare 35-mg, once-daily oral disease of RVT-101 to placebo in about 1,150 patients with mild-to-moderate Alzheimer’s disease on a stable dosage of donepezil therapy. It will evaluate patients using the Alzheimer’s Disease Assessment Scale, a cognitive subscale (ADAS-cog) and the Alzheimer’s Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL).
“It’s a very exciting day for our business. We are actually launching the global Phase III study for RVT-101,” said Ramaswamy in an interview with Forbes recorded at the Forbes 30 Under 30 Summit. “This is a major milestone for the company. We said we were going to start it in the fourth quarter and here we are in the first week of the fourth quarter, and we have started that study with a small group of people, including some of the top Alzheimer’s disease drug developers that really made this possible.”
Axovant is at least mildly controversial among investors because the company has a $1.8 billion market capitalization. Some analysts are skeptical about the company’s value based on a drug it bought from GlaxoSmithKline for $5 million. The skepticism seems to revolve around why GSK would unload a drug for so little — although it does have a 12.5 percent royalty on the drug if it gets approved — if the company thought it stood a chance of being successfully developed.
In July, Axovant presented a second look at GSK’s data at the Alzheimer’s Association International Conference held in Washington, DC. Axovant presented what is known as a “completers analysis,” which evaluates only patients who stayed in the study compared to the results that evaluated all patients, which is dubbed “intent-to-treat.”
“These data are as good as any of the other marketed drugs had,” said Steven Ferris to Forbes at the time. Ferris is the Geraldine D. and Dorothy R. Friedman Professor at New York University’s Alzheimer’s Disease Center. “It’s worth moving forward.”
In the completers analyses, there was a 1.8 point drop at 48 weeks on the ADAS-Cog subscale, compared to 1.9 point drop in the original study. On the ADCS-ADL, there was a 2.34 point improvement at 48 weeks, compared to a 2.28 point benefit.
Essentially the comparison found them to be identical. In the original GSK study, ADCS-ADL was not used. Instead, they selected the Clinical Dementia Rating Sum of the Boxes, which did not show improvement, which is likely why GSK gave up on the drug.
Axovant hopes that a larger study will confirm the results shown on ADAS-Cog and ADCS-ADL. If so, then the FDA may approve the drug. Some critics suggest that is cherry-picking data, although others have suggested that, when it comes to drugs for Alzheimer’s, that’s about the best you can hope for currently.
RVT-101 works on a brain receptor called the serotonin receptor 5HT6, similar to the Alzheimer’s drug Aricept. Aricept prevents the removal of acetylcholine, while RVT-101 stimulates its production. This doesn’t cure Alzheimer’s, but has some temporary improvement in symptoms.
“I think the biology makes sense,” said Ronald Petersen, an Alzheimer’s researcher at the Mayo Clinic in an interview with Forbes. “I’m not sure it gets me overly excited, but any kind of new treatment in Alzheimer’s will probably be well received.”
Drug development for Alzheimer’s disease is a wasteland of failed trials. Approximately 123 drugs for Alzheimer’s have failed in the past. On the other hand, a successful drug could create annual sales of more than $3 billion worldwide.
