ZZ Biotech Hit with Data Manipulation Allegations Regarding Stroke Trial

2023-11-15

临床2期临床结果

Pictured: Doctor looking at brain scan images/iStock, Tippapatt Phase II data supporting ZZ Biotech’s investigational stroke therapy 3K3A-APC might have been doctored to make the candidate appear safer and more effective than it actually is, according to an investigative report by the journal Science, citing a small group of whistleblowers. The whistleblowers produced a 113-page dossier—which has already been submitted to the National Institutes of Health (NIH)—detailing a potentially higher rate of deaths in patients that received the experimental treatment compared to placebo. Those who were given 3K3A-APC also showed worse disability and dependency toward the end of the mid-stage study. Besides the Phase II data, the dossier obtained by Science also alleges that preclinical data had been tampered with, including papers that supported the human testing for 3K3A-APC. Overall, the whistleblowers flagged a total of 35 papers with manipulated data plus two publications in connection with 3K3A-APC’s Phase II trial, according to Science. Underpinning these data manipulation allegations is a “culture of intimidation” at the lab of Berislav Zlokovic, co-founder of Houston-based ZZ Biotech and chairman of its scientific advisory board. According to the whistleblowers, Zlokovic allegedly routinely pressured his scientists to tweak the data in favor of 3K3A-APC. Zlokovic would allegedly tell his scientists to “change lab notebooks” after experiments so that they “only contained the desired results,” according to Science. The University of Southern California (USC), where Zlokovic works as a professor of physiology and neuroscience, said that it will conduct a confidential review of the dossier and investigate its merits. Zlokovic declined to comment to Science but his lawyer said in a statement that the professor knows some of the dossier’s contents “to be completely incorrect.” In acute ischemic stroke, 3K3A-APC’s development is being supported by the NIH’s National Institute of Neurological Disorders and Stroke, which has awarded USC a $30 million grant to conduct a Phase III trial. The first tranche of this grant, amounting to $4 million, was disbursed in May 2022. 3K3A-APC is a genetically engineered variant of the activated protein C (APC) molecule, which is a serine protease with known anticoagulant and cell-protective activity. This mechanism of action allows the candidate to reduce bleeding and inflammation in the brain following a stroke episode, as well as prevent cell death in the neurons, glia and other cells in the brain. In its Phase II RHAPSODY study, 3K3A-APC treatment led to a significant reduction in intracranial hemorrhage rates versus placebo, as well as a substantial, but not significant, reduction in the total hemorrhage volume. The mid-stage trial also documented an estimated toxicity rate of 7%. Beyond stroke, 3K3A-APC is currently in a Phase II study for amyotrophic lateral sclerosis and is about to enter mid-stage development for diabetic wound healing, according to ZZ Biotech’s website. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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