Cassava defends Alzheimer's science after citizen petition raises 'grave concerns' about clinical studies

Small Alzheimer’s disease biotech Cassava Sciences is defending its work after a citizen petition filed with the FDA questioned the scientific integrity of the company's clinical trials for simufilam and asked the agency to put them on hold.

The whistleblower petition, dated August 18th but posted aftermarket yesterday, details “grave concerns about the quality and integrity of the laboratory-based studies surrounding this drug candidate and supporting the claims for its efficacy.” While the data in the petition comes from publicly available information, the whistleblower is not named and the document is signed by lawyer Jordan Thomas from Labaton Sucharow on behalf of his clients. 

The claims sent Cassava’s shares tumbling 30% to $82 as the markets opened Wednesday, compared to a prior close of $117. Cassava President and CEO Remi Barbier dismissed the petition as "bogus" in a statement to Fierce Biotech. 

Cassava is developing simufilam as a different approach to treating Alzheimer’s disease. The therapy does not try to clear amyloid from the brain, which many competing drugs aim for, but instead tries to stabilize a scaffolding protein called filamin A. The biotech recently reached an agreement with the FDA to conduct a phase 3 trial.

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The petition claims that no other lab has confirmed the link between filamin A and Alzheimer’s disease or its effect on models for the disease. Other concerns allege data anomalies and manipulation, including image alteration. The petition also questions Cassava’s use of postmortem human brain tissue to conduct experiments to test the efficacy of simufilam.

Using the data, Cassava has collected $250 million in public fundraising and secured $5 million in grants from the National Institutes of Health, according to the petition.

The whistleblower report asks the FDA to audit Cassava’s studies and regulatory submissions and pause ongoing trials. Moreover, the petition asks the scientific journals that have previously published Cassava’s studies to review and retract them.

Cassava went through the petition’s claims one by one in a Wednesday statement, calling them “false and misleading.” Addressing the use of postmortem tissue, the biotech said that the brain cannot be biopsied, therefore “translational medicine can rely on postmortem tissue.” The collection of this tissue was done through a standard pathologist procedure, and this method is used in cancer and other fields.

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Barbier told Fierce Biotech that the company is unaware of who is behind the petition, calling it a "well-coordinated sneak attack."

"Cassava Sciences stands behind its science, its scientists and its scientific collaborators, and is responding to ensure the facts are known and respected," Barbier said. "As a science company, we champion facts that can be evaluated and verified. This helps people make informed choices. It is important for stakeholders to separate fact from fiction, which is why we wish to address allegations head-on."

Days after the petition was launched, Cassava noted that the company and the FDA came to an agreement on the late-stage trial for simufilam through a Special Protocol Assessments arrangement.

“The SPAs underscore alignment with FDA on key scientific, clinical and regulatory requirements of the company’s phase 3 program of simufilam in Alzheimer’s disease,” the statement said.

Barbier said that no clinical holds have been placed on any of the company's studies and Cassava is not aware of any pending regulatory investigations. 

"It’s all Wall Street shenanigans," he said. 

Cassava's statement also suggests that citizen’s petitions like this can be launched by anyone regarding safety or efficacy concerns for drugs that the FDA is considering for approval, "which is not the case for Cassava Sciences’ simufilam." The therapy has not yet been submitted for marketing authorization and remains in clinical trials. 

The FDA, for its part, responded to say the petition had been accepted and assigned a docket number but did not comment on the merits of the complaint. 

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"I’ve never heard of a citizen’s petition for a pre-phase 3 drug," Barbier said. He stressed that the FDA's acceptance does not suggest the agency agrees with the claims. "I'm confident FDA will dismiss it."

Interest in Alzheimer’s disease therapies has exploded since the FDA approved Biogen’s therapy Aduhelm in early June. Small biotechs like Cassava have suddenly found themselves in the spotlight, with every tiny data point sending investors into a frenzy. Even the Big Pharmas like Eli Lilly have caught the wave as they revisit programs once considered lackluster.

Editor's Note: This story was updated at 11:55 a.m. ET on Sept. 25, 2021, to add comments from CEO Remi Barbier.