On May 10, according to Endpoints News, the international phase III clinical trial of Green Valley Pharma’s Alzheimer’s disease drug GV-971 has been halted (halt).
Image source: Screenshot of Endpoints News report
Five trial sites have so far confirmed the news to Endpoints News. Of these, 4 trial sites indicated that the study was stopped for supply chain reasons, but another trial agency stated that the study was halted not related to the supply chain.
Eric Reiman, a former scientific advisor to Green Valley Pharmaceuticals, told Endpoints News that he was told that “the research stop is related to the financial problems brought on by the pandemic.”
Green Valley Pharma’s clinical trial began in October 2020 and plans to enroll 2,046 patients with mild to moderate Alzheimer’s disease, with completion expected in 2025. As of January this year, trials had been initiated in 10 countries and 154 clinical centers.
A search on Clinicaltrials.gov shows that the status of the clinical trial is still “recruiting”.
Image source: Clinicaltrials.gov
Controversy continues
As a domestic original drug for Alzheimer’s disease, GV-971, a marine oligosaccharide molecule extracted from seaweed, has been controversial since its inception.
In November 2019, the official website of the State Drug Administration issued a conditional approval of the marketing application for the treatment of GV-971, “for the treatment of mild to moderate Alzheimer’s disease, improving cognitive function in patients”. There are 3 joint research and development units for the drug: Ocean University of China, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Shanghai Green Valley Pharmaceutical Company.
Screenshot of the official website of the State Food and Drug Administration
Since it is a conditional approval, the Food and Drug Administration has also put forward supporting requirements: 1. The applicant is required to continue to conduct research on the pharmacological mechanism after listing; 2. To continue to conduct long-term safety and efficacy research 3. Improve the analytical method of oligosaccharides.
In general, more research data needs to be provided.
Since then, more questions about the efficacy and mechanism of GV-971 have emerged.
At the end of 2019, Rao Yi reported the academic fraud of researcher Geng Meiyu of Shanghai Institute of Materia Medica with his real name: “Researcher Geng Mei of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, as the corresponding author Zhang, claims to have invented The drug GV971 can treat Alzheimer’s disease in mice through gut microbiota. This article is impossible to fake.”
Since then, according to China News Weekly, Rao Yi himself responded to the report, saying, “It was not issued, but there was a draft.”
In July 2020, Rao Yi published a newsletter in the journal Cell Research, expressing concern about the article about GV-971 published by Geng Meiyu’s team in 2019. There are two main concerns.
Image source: Cell Research
First, before the publication of this paper, Geng Meiyu’s team had published 12 GV-971 related papers (2003-2013) including in vitro, in vivo studies and review articles, but The 2019 article by Geng Meiyu’s team did not cite these related papers.
Second, according to the arrangement, Geng Meiyu’s previous papers pointed out that GV-971 can help alleviate Alzheimer’s disease, but the specific effects and targets are different, Rao Yi said: “I have never encountered a drug with so many targets that can treat or alleviate the same disease.”
A week later, Geng Meiyu’s team also responded by publishing a newsletter in the same journal: The correlation between the 12 related papers pointed out by Professor Rao Yi and the papers published in 2019 is not strong ;It is very common for a drug to have multiple target pathways to achieve a therapeutic effect, such as metformin.
Image source: Cell Research
In addition, Geng Meiyu’s team stated that they have collected a large amount of data from in vitro and in vivo experiments, which support the idea that GV-971 can affect β-amyloid aggregation, related neurological damage and cognitive decline. .
On December 14, 2021, according to Xinhua News Agency client news, Geng Meiyu v. Rao Yi’s reputation infringement case lost the first instance.
Approved for Parkinson’s trial after coverage
Amid the controversy, on December 3, 2021, GV-971 was included in the National Medical Insurance Directory for the first time.
According to the official account of Green Valley Pharma, the drug has been reduced from 895 yuan per box to 296 yuan per box; based on 4 boxes per month, the patient’s medication cost will be reduced from the original per box The monthly out-of-pocket cost is 3,580 yuan, down to 1,184 yuan, and the average patient’s daily cost is close to 40 yuan (considering the reimbursement level of medical insurance coverage in different regions and the level of medical insurance for different people, the individual responsibility is not calculated separately here).
According to the first published Phase III results of GV-971 published in BMC: The study included 818 patients with mild to moderate AD, the primary endpoint was the ADAS-Cog12 scale, and the follow-up period was 36 week. The study concluded that GV-971 continued to improve cognition throughout the entire observation period of the 36-week trial, showed significant efficacy, and GV-971 was safe and well-tolerated.
GV-971 Phase III Results (Image Source: BMC)
It is worth noting that at the 2019 Suzhou Innovative Drug Conference, Green Valley Pharma has already partially disclosed in the presentation materials, the ADAS-Cog efficacy curve shown in this ppt The trend graph is consistent with the final published paper: the difference between the treatment group and the placebo group began at week 4 (p=0.01), and the trend was similar in the two groups after that, and the scores in the treatment group improved significantly during the last 12 weeks (weeks 24-36). .
The ADAS-Cog Efficacy Curve Trend in Phase III Paper
The 2019 Suzhou Innovative Drug Conference Green Valley Pharma partially disclosed the ADAS-Cog curative effect curve trend graph in the presentation materials
However, the above picture curve changes were questioned when they were first disclosed: The test patients showed a significant effect in the 4th week, and the treatment group and the placebo group basically belonged to the first 6 months. Changes in the same direction, the difference seems to be small, but the patients in the placebo group seem to get worse between 24 and 36 weeks.
Alzheimer’s disease is a chronic degenerative disease. Is there any doubt about such a significant change? In this case, should we observe longer follow-up, or supplement a phase III clinical data?
From the 2019 ppt to the 2021 paper data, this question does not seem to be fully answered for the time being.
In January 2022, GV-971 ushered in a new turn, this time not AD, but Parkinson’s.
According to the official account of “Green Valley Pharmaceutical Technology”, Green Valley received a written notice from the U.S. Food and Drug Administration (FDA) on January 13, 2022, approving the company’s original treatment for Al Mannat sodium capsules (English name: Sodium Oligomannate, code name: GV-971, trade name: Phase 9 Phase 1), a new drug for Zheimer’s disease, has launched an international multicenter Phase II clinical trial (IND 159315) for the treatment of Parkinson’s disease. It will come into effect on December 16, 2021.
Image source: “Green Valley Pharmaceutical Technology” official account
However, the progress of this clinical trial of GV-971 in Parkinson’s disease has not yet been found on Clinicaltrials.gov.
According to Clinicaltrials.gov, there are 7 clinical studies related to GV-971, 2 of which are indicated to be completed, 1 has an unknown status, and 1 has not yet started recruitment (not yet recruiting), the other 3 items are all showing that they are recruiting (recruiting).
Image source: Clinicaltrials.gov
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