A clinical trial for an Alzheimer’s disease drug approved in China that would otherwise have supported a potential FDA submission has stopped.
Impacted by “multiple negative factors” and after “careful evaluation,” Green Valley Pharmaceuticals has decided to terminate a global phase 3 trial early for its seaweed-derived Alzheimer’s drug oligomannate, or GV-971, according to a statement (Chinese) posted Friday.
Green Valley said it made the choice not out of any safety or efficacy concerns. The company cited the “global geopolitical situation” and a gloomy biotech capital market at the beginning of 2022 as reasons for its failure to raise additional funds to support the trial. What’s more, COVID-19 outbreaks in China hurt GV-971’s sales in its home country, the company said.
The drug was approved to treat mild to moderate Alzheimer’s disease in China in 2019 with great controversy. In its Chinese study against placebo, the drug only hit one goal on a dementia measurement, ADAS-Cog, but failed on three other scores, namely, CIBIC-plus, ADCS-ADL and NPI.
To prove its case and potentially win approvals in Western countries, Green Valley launched the global phase 3 trial, dubbed GREEN MEMORY, with an FDA go-ahead in April 2020, just as COVID started to wreak havoc.
Over the past two years, Green Valley said it overcame multiple hurdles to carry out the trial amid the pandemic and opened 162 trial sites altogether. As of April 26, 1,308 patients had been screened and 439 enrolled, including 257 participants in the U.S.
On Jan. 21, when the study hit 10% of its target enrollment goal, an independent data monitoring committee ran an analysis and concluded it was safe to continue the trial.
Entering 2022, as enrollment accelerated, Green Valley found itself in need of cash. To make matters worse, unpredictable COVID-19 outbreaks in different parts of the world caused increasing loss of participants during follow-ups, further pushing up the cost, Green Valley noted. The company did try to raise additional money, but the biopharma “capital winter” thwarted that effort.
Green Valley could have leveraged sales of GV-971 in China. The drug won national coverage after the company offered a hefty 60% discount to 296 Chinese yuan ($43.60) per box. A typical patient takes about four boxes a month.
But COVID outbreaks in China also impacted the drug’s hospital sales channel. There were also media reports in China that Green Valley sacked its national reimbursement negotiation team because the drug’s price went lower than expected.
All things considered, Green Valley decided to pull the plug on the global phase 3 trial. The company said it’s following ICH-GCP protocols to take several steps to mitigate the consequences. It’s informing patients, ensuring their safe withdrawal from the drug and starting them on standard treatment. The company in January also got an FDA go-ahead for a phase 2 trial for GV-971 in Parkinson's disease.
Meanwhile, two Chinese postmarketing trials evaluating GV-971’s long-term safety and efficacy as well as certain biomarkers remain ongoing. Pointing to China’s 10 million Alzheimer’s patients, Green Valley said it’ll focus on that existing market.
The company remains committed to getting international approvals for GV-971, it added, saying the global clinical program will start again “when condition permits in the future.”
GV-971’s clinical termination marks another setback in the search for an effective Alzheimer’s therapy. It follows Biogen’s decision to practically stop sales support for its much-criticized anti-beta-amyloid antibody Aduhelm after an unfavorable Medicare coverage determination. Now, all eyes are on the pharma's second Alzheimer’s drug, lecanemab, for which its partner Eisai has just wrapped up a rolling submission to the FDA.