The FDA has not yet issued any hold orders to Cassava, but the company expects that its time is coming after rivals Denali and Cortexyme received theirs.
Cassava Sciences has warned that the U.S. Food and Drug Administration might order a clinical hold on its studies for Alzheimer’s drug simufilam in 2022 after learning that two of its competitors had received hold orders for similar research efforts.
In its 10-K annual report filing dated February 28, the biotechnology firm warned investors that its operations and business could suffer down the line if it is unsuccessful in lifting the anticipated FDA hold in time. The regulator has not yet issued any such letter to Cassava, but the company expects that its time is coming after rivals Denali Therapeutics and Cortexyme received theirs.
The FDA typically issues a clinical hold order to suspend an active trial if it needs more information about the drug candidate’s mode of action, safety, efficacy and other deficiencies. If a company gets this letter, it will be unable to enroll new participants, and those who are already in the trial might be taken off the investigational drug.
Cassava said that if it does receive such a directive, it will cooperate with the regulator fully and expeditiously in order to get simufilam’s research and development schedule back on track. However, it cautioned that if it fails to satisfy the FDA’s requirements or is unable to address the concerns immediately, its business could suffer, and its investigational new drug (IND) application might be marked as “Inactive”, leading to further losses.
“The grounds for imposition of a clinical hold are complex, variable and somewhat arbitrary. If we are issued a clinical hold, FDA will expect us to address the cited deficiencies and submit a detailed, written response. A clinical hold may require us to spend significant resources over many months to address the root causes of FDA’s concerns. Our response may not be adequate to lift such clinical hold, or we may disagree with FDA’s assessments of deficiencies. To the extent we are not successful in lifting an FDA clinical hold, our results of operations and business will be materially adversely affected,” Cassava said in its filing.
In January, the FDA issued a full clinical hold on Cortexyme’s IND for atuzaginstat, which it is evaluating for the treatment of Alzheimer’s and other neurodegenerative diseases. Cortexyme immediately launched a cost-cutting strategy to rationalize operations while awaiting results to ensure enough cash flow to sustain its pipeline up to 2024.
In the same month, the regulator sent a formal clinical hold letter to another company that focuses on Alzheimer’s treatment, Denali Therapeutics. The hold order involved the investigational drug DNL919, for which the FDA sought additional data, specifically information relating to preclinical toxicology assessments. The FDA also suggested that changes be implemented on its informed consent form, investigator brochure and trial protocol.
Cassava’s latest warning covers other issues that might later affect its operations and revenues. The company said that physicians and patients themselves might not accept and use its drugs, even with FDA approval. It also said that it might not succeed in developing its neurodegeneration product candidates, adding that it does not have the capabilities to manufacture or commercialize its product candidates. Much of its lack of confidence might be pointed to the fact that nearly every attempt at drug approval for Alzheimer’s disease has failed.
“Despite billions of dollars invested by NIH and the biopharmaceutical industry in research programs to develop novel therapeutics for Alzheimer’s disease, the FDA has not approved any new drugs for Alzheimer’s disease. Since 2003, many new types and classes of drugs have been developed and tested in Alzheimer’s disease, and virtually all of these scientific programs have failed in clinical testing,” noted Cassava in the same filing. Cassava did note the exception of Biogen’s aducanumab (Aduhelm), which was approved by the FDA in 2021.
