Doctors Are Optimistic About Axovant’s Experimental Alzheimer’s Drug

Alzheimer’sAxovant, a drug company created by former hedge fund manager Vivek Ramaswamy, has become a battleground stock because some critics can’t believe the company’s experimental Alzheimer’s drug, RVT-101, could possibly justify a $1.8 billion market capitalization when GlaxoSmithKline had previously deep-sixed the drug and sold it to Axovant for just $5 million – in addition to a sizeable 12.5% royalty.

There’s a new opportunity to take a look at Axovant’s data today as the company presents a new analysis of the old Glaxo data today at the Alzheimer’s Association International Conference here in Washington D.C. The short version: Doctors almost unanimously view the drug as a promising, if small, advance.

“These data area as good as any of the other marketed drugs had,” says Steven H. Ferris, the Gerald D. and Dorothy R. Friedman Professor at New York University’s Alzheimer’s Disease Center. “ It’s worth moving forward.”

What Axovant is presenting is called a “completers analysis” and it is done to see if looking only at the patients who actually stay in the study gives results similar to looking at all patients who were enrolled, called “intent-to-treat.” The data were presented at a press conference this afternoon and will be show to a medical audience later in the day.

In this case, it does. On the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-Cog), there is a 1.8 point reduction at 48 weeks in the completers analysis, compared to 1 .9 point reduction in the original study. On the Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory (ADCS-ADL), there is a 2.34 point benefit at 48 weeks, compared to a 2.27 point benefit in the earlier analysis. “The take home message is that they’re very very similar,” says Lawrence Friedhoff, Axovant’s chief development officer.

Now there is a downside here: the ADAS-Cog was one of the study’s original main goals, but the ADCS-ADL was not. Instead, Glaxo researchers picked another scale, the Clinical Dementia Rating Sum of the Boxes. On that endpoint, the result was not statistically significant, meaning that the trial failed. That’s likely part of the reason that Glaxo killed the program.

What Axovant hoping that a much larger study will confirm the results on the ADAS-Cog and ADCS-ADL. If this happens, the Food and Drug Administration has said it would consider approving RVT-101. This is no sure thing – picking endpoints that were significant and ignoring ones that were not is a bit like drawing bullseyes around arrows after you shot them. But it’s certainly possible, and many long time researchers say that they think it’s about as good as it gets in Alzheimer’s.

“I [would] not say it absolutely works,” says Mary Sano, associate dean for clinical research at the Mount Sinai Hospital in New York. “I would say taking it forward makes sense.” She notes that in many Alzheimer’s drugs that have failed after mid-stage studies succeeded, companies were not so much hoping a result would be repeated as hoping that the new trial would perform better than the first. “They are not talking about changing an outcome measure or a design,” she says. “So it’s not based on an extrapolation of other data.

There’s also reason to believe that the drug could work. It hits a brain receptor called the serotonin receptor 5HT6. This causes an increase in a neurotransmitter called acetylcholine. The existing Alzheimer’s drug Aricept also works by increasing acetylcholine by blocking an enzyme that eats it up. Aricept blocks the drain that gets rid of acetylcholine, while RVT-101 aims to turn up the faucet. Lundbeck is developing a drug that aims to do the same thing.

Samuel Gandy of Mount Sinai Hospital writes via email that 5HT6 inhibitors seem to have “an authentic pro-cognitive effect.” They won’t do more than improve symptoms temporarily but “there are plenty of patients who could benefit.”

“I think the biology makes sense,” says Ronald Petersen, an Alzheimer’s researcher at the Mayo Clinic. “I’m not sure it gets me overly excited, but any kind of new treatment in Alzheimer’s will probably be well received.”

Any excitement about RVT-101 has to be tempered by the fact that 99% of Alzheimers drugs fail in clinical trials. This is a tough area. But the consensus is that this drug has as good a chance of reaching patients as any other Alzheimer’s medicine, and that any case against Axovant that depends on RVT-101 being essentially chemical vaporware is underestimating the medicine’s chances.

Source: Forbes