Since Allergan’s Namenda FDA nod in late 2003, the world hasn’t seen an approved Alzheimer’s disease new drug for 17 years. That drought was broken Saturday, not by a Western biopharma bigwig, but by a little-known Chinese firm.
China’s drug regulator on Saturday revealed (Chinese) that it had granted conditional approval for Shanghai Green Valley Pharmaceuticals’ oligomannate (GV-971) to help improve cognitive function in patients with mild to moderate Alzheimer’s disease.
As commercial production and launch of the drug is expected by year-end, the Chinese company is also planning a global phase 3 trial with sites in the U.S., Europe and other parts of Asia in early 2020 to support regulatory filings around the world, the company said.
The news immediately drew worldwide attention, and suspicion ensued. Is it possible that a discovery coming out of China—whose biotech industry is just taking off—could succeed where seasoned researchers from the likes of Biogen and Eli Lilly have failed miserably?
Oligomannate, a seaweed-derived compound, was invented by Geng Meiyu’s team at the Shanghai Institute of Materia Medica at the Chinese Academy of Sciences. Its development was supported by Ocean University of China and Green Valley, and the approval is based on a phase 3 trial involving 818 Chinese patients.
In that study, patients on oligomannate scored better on a standard clinical scale called ADAS-Cog that’s used to evaluate cognitive function in Alzheimer’s patients. ADAS-Cog scores range from zero to 70, and higher scores indicate greater dysfunction.
According to results Geng presented at last year’s Clinical Trials on Alzheimer’s Disease Conference in Barcelona, a statistically significant improvement between the drug and placebo was observed as early as week four and continued over the course of the trial. After 36 weeks, patients in the oligomannate arm had improved their ADAS-Cog scores by a median 2.54 points more than placebo patients had.
“I have been doing research on Alzheimer's disease for 50 years, participated in multiple global multi-center studies of multiple drugs, and have never found a satisfactory treatment for Alzheimer's disease,” Zhang Zhenxin, a principal investigator of the phase 3 trial and professor of neurology at Peking Union Medical College Hospital in Beijing, said in a statement. “The result of the 9-month trial of oligomannate is exciting.”
However, skeptics pointed to the fact that oligomannate has only one subjective measure—ADAS-Cog—to back its case. As for the trial’s secondary efficacy measures, the drug only showed a “non-significant trend” for improvement on CIBIC-plus, another widely used assessment tool in Alzheimer’s studies, and demonstrated no difference against placebo in two other measurements known as ADCS-ADL and NPI. And it doesn’t yet have more objective data on physiologic changes, such as levels of toxic clumps of amyloid beta and tau proteins.
In the FDA’s draft guidance (PDF) for developing Alzheimer’s drugs released last year, the U.S. agency specifically said “a finding on a single test unsupported by consistent findings on other tests would be less persuasive” compared with beneficial effects demonstrated across multiple tests in patients with early clinical stages of Alzheimer’s.
In a recently published Cell Research study, Geng’s team showed in mice that oligomannate works by modulating gut microbiota and hence inhibiting inflammation in the nervous system, reducing beta amyloid buildup and tau tangles.
Green Valley’s reputation also came under question after the approval news emerged. As Chinese local media noticed, the company was the protagonist of a marketing scam exposed by China’s state-run China Central Television in 2008. At that time, regulators found the company had been promoting a ganoderma-based drug as an agent that could stop cancer growth, progression and recurrence after surgery, without specific approvals.
The company obviously has a lot of convincing to do. As part of the conditional nod, China’s National Medical Products Administration is requiring the company to conduct further postmarketing studies to confirm the drug’s long-term efficacy.