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FDA: Symptom improvement alone may be basis of approval for HF drugs
The FDA announced it has issued draft guidance on drug development for HF treatments, which indicates that an effect on physical function or symptoms without favorable effects on hospitalization or survival can be a basis for approval.
The draft guidance also mentions the necessity to address mortality in clinical trials that assess drugs for the treatment of HF, according to a statement from the FDA.
“Despite the availability of drugs and devices to treat heart failure, it remains a cause of significant disability, has major effects on physical function and quality of life and is a leading cause of death,” Ellis Unger, MD, director of the Office of Drug Evaluation I for the Center for Drug Evaluation and Research at the FDA, said in the statement. “The FDA is hoping to stimulate drug development in this area as new drugs are needed for the treatment of this serious condition.”
The FDA will be holding a public workshop July 26 to bring stakeholders together to discuss useful clinical endpoints in HF trials to support the approval of drugs by the FDA, according to the statement.
The draft guidance document can be found on the FDA website. Comments can be submitted online or sent to the FDA until Aug. 27, 2019.
Disclosure: Unger is an employee of the FDA.
Perspective
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HF results in substantial symptoms, functional limitations, hospitalization risks, mortality and health care expenditures.
The traditional focus of clinical trials of medications and devices leading to FDA approval as treatments for HF have generally involved demonstration of reduction in CV mortality and/or HF hospitalizations.
Patients with HF, while valuing reductions in hospitalization and mortality, also consistently note that improving functional status, decreasing symptoms and improving overall health status are highly valued by them as well. It is increasingly recognized that patient-reported outcomes need to receive greater focus in clinical trials, regulatory decisions and clinical care.
This new draft guidance from the FDA is highly welcomed in that it provides useful guidance and clarifications regarding categories of efficacy that may lead to drug approval. Specifically, it makes clear that a drug that was demonstrated to provide clinically relevant improvements in symptoms or functional status for HF patients, even if it did not reduce hospitalization or enhance survival, could be approved.
More controversial and needing further discussion is whether a therapy that improves symptoms but actually decreases survival could be considered for approval. The use of biomarkers and surrogates as the sole basis for approval is mentioned but may be problematic and could result in unintended consequences.
Additional input and guidance are needed to define the magnitude of symptom improvement and functional status improvements that would be consider of sufficient magnitude to support demonstration of effectiveness to the FDA’s satisfaction.