Regulatory Focus™ > News Articles > 2019 > 6 > FDA Drafts Guidance on Heart Failure Treatment Endpoints

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Posted 27 June 2019 | By Zachary Brennan 

FDA Drafts Guidance on Heart Failure Treatment Endpoints

2868 As heart failure afflicts 6.5 million in the US, the Food and Drug Administration (FDA) on Thursday released draft guidance on the agency’s current thinking on developing drugs to treat heart failure.

While noting that there are no effective treatments for heart failure with preserved ejection fraction (HFpEF), which represents about 50% of heart failure cases, FDA says up front that the 7-page draft has two purposes: to make clear that an effect on symptoms or physical function (even without a favorable effect on survival or risk of hospitalization) can be a basis for approving a new heart failure drug, and to provide sponsors with recommendations on assessing mortality effects.

The agency also notes how after some heart failure drugs (e.g., milrinone and flosequinan) were found to increase mortality, FDA asked sponsors to assess mortality effects and some sponsors and stakeholders reported that favorable effects on mortality and morbidity were now required for a new heart failure drug’s approval. But FDA clarifies that its “intent was not to require demonstration of improved survival—although that would be an important outcome—but rather to provide reasonable assurance that the drug did not increase mortality.”

FDA also clarifies that mortality data can serve as either a primary efficacy endpoint or as a safety endpoint. And when approval is based on an improvement of symptoms or function, FDA will consider three other factors to determine if additional mortality data are necessary:
  • The mortality and other safety findings of pharmacologically similar drugs
  • Planned duration of exposure
  • The mortality and other safety findings of the drug in a closely related population in which at least a subset of the patients had heart failure or were at risk of heart failure
“FDA believes there should be further discussion about whether the nature, magnitude, and clinical importance of a symptomatic benefit, considered with the demonstrated risks, could justify deferral or omission of outcome studies to assess mortality,” the draft says.

The draft also discusses efficacy endpoints related to how patients feel and function, hospitalization and outpatient intervention, biomarkers and surrogate endpoints, and brief discussions of developing drugs to treat acute heart failure and pediatric considerations.

In addition to the draft guidance, FDA will hold a public workshop on 26 July to discuss clinical endpoints for trials in heart failure that could be used to support approval of such drugs. The workshop will focus on endpoints related to symptoms and physical function.

Treatment for Heart Failure: Endpoints for Drug Development: Draft Guidance for Industry


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