That’s when the last Alzheimer’s drug — Allergan’s Namenda —was approved in the U.S. That 16-year drought ended Nov. 2 when Chinese regulatory authorities gave conditional approval to Shanghai Green Valley Pharmaceuticals’ Oligomannate as a new drug for the treatment of “mild to moderate Alzheimer’s disease (AD) and improving cognitive function,” per the company’s news release.
The news was initially overlooked here in the U.S. One biopharma analyst —Marc Goodman with SVBLeerink — attributes it to the rush of quarterly earnings news that drew the attention of the investment world. But now people are both excited and skeptical.
“Introducing a new treatment option with a different mechanism helps increase the treatment options for AD patients in China, but we still think that more data are needed to better understand the long-term treatment efficacy and underlying biology,” Goodman wrote in a research note on Friday.
How does the drug work? Oligomannate (GV-971) basically remodels gut microbiota and suppresses the accumulation of MoA phenylalanine/isoleucine and other, related neuroinflammation to limit the progression of Alzheimer’s, Goodman explained.
Trial results showed that the drug statistically improved cognitive function in mild-to-moderate Alzheimer’s patients as early as week four and the benefit was sustained at each follow-up assessment visit. The mean difference between GV-971 and placebo groups in ADAS-Cog12 Score (which is a standard cognitive measure commonly used in Alzheimer’s studies) was 2.54. The result was sustained from the first month of treatment to the end of 9 months of treatment. The study also found that GV-971 was safe and well-tolerated among patients and the side effects were comparable to those in the placebo arm.
In fact, Goodman noted that the treatment effect of GV-971 in ADAS-cog12 (-2.5 vs placebo) at week 36 was comparable to approved drugs like Namenda, which is the current standard of care for Alzheimer’s Disease patients.
But there are questions in the data. He writes:
GV-971 did not separate from [placebo] in all secondary endpoints including ADCS-ADL, NPI, and CIBIC+, all of which are also well-validated in AD and are commonly used efficacy endpoints in AD trials; (2) The [placebo] arm had an unusually high response (appears to indicate [placebo] patients had improvement on ADAS-cog12), and there is a significant drop of [placebo] response during the last 12 weeks, which resulted in a better separation by the end of 36-week treatment period, and there is, as of yet, no clear explanation for the[placebo] effect trend.
While excitement is warranted, cautiousness is also prudent given the history of failed Alzheimer’s trials. Goodman warns investors that the team at SVBLeerink views Alzheimer’s trials as the “most risky in all biopharma therapeutic areas.”
Meanwhile, Green Valley Pharmaceuticals is gearing up for a multi-center global Phase 3 clinical trial (entitled GREEN MEMORY) in the U.S., Europe and Asia in early 2020 so that the company can submit a global regulatory filing for the drug.