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

DraftCenter for Biologics Evaluation and Research Center for Drug Evaluation and Research06/28/2019

Description

This guidance has two purposes: 1) to make it clear that an effect on symptoms or physical function, without a favorable effect on survival or risk of hospitalization, can be a basis for approving drugs to treat heart failure; and 2) to provide recommendations to sponsors on the need to assess mortality effects of drugs under development to treat heart failure.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

1
Pediatric population

Specific population with unique safety considerations

Stakeholders

1
Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

2
Accelerated approval

eligible for one or more of FDA's expedited programs

FDA approval

Regulatory milestone for heart failure drugs

Attributes

3
Symptoms

Endpoint for approving drugs

Physical function

Endpoint for approving drugs

Mortality

Primary endpoint for efficacy studies

Technical Details

Substances

10
NT pro-BNP

Biomarker used for prognostic enrichment

digoxin

Specific drug with established safety profile

MRAs

Mineralocorticoid receptor antagonists

ARBs

Angiotensin II receptor blockers with established safety

Sacubitril-valsartan

Approved drug for heart failure

Diuretics

Used to reduce signs and symptoms

Mineralocorticoid receptor antagonists

MRAs

Beta blockers

Pharmacologic class for heart failure; Drug class used in heart failure treatment

Angiotensin receptor blockers

ARBs

ACE inhibitors

Pharmacologic class for heart failure; Class of drugs with well-established safety profiles

Testing Methods

1
6-minute Walk Test

Endpoint influenced by expectation bias requiring blinding

Clinical Concepts

10
Hospitalization

Measure of morbidity and clinical outcome

Diabetes

Therapeutic area standard

Coronary artery disease

Closely related population to heart failure

Mortality

include estimates of acute morbidity and mortality; Deaths included in the public health impact evaluation.

New York Heart Association Class IV

Patient population classification

New York Heart Association Class III

Patient population classification

Heart failure with preserved ejection fraction

HFpEF

Heart failure with reduced ejection fraction

HFrEF

Acute Heart Failure

Discussed briefly in the guidance

Chronic Heart Failure

Primary focus of the guidance

Standards & References

Specifications

2
Left ventricular ejection fraction

Biomarker used to characterize risk

New York Heart Association functional class

Acceptable efficacy endpoint for heart failure

ICH References (2)

ICH E11(R1)

Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population

ICH E11

Clinical Investigation of Medicinal Products in the Pediatric Population.

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Treatment for Heart Failure: Endpoints for Drug Development Guidance for Industry | Guideline Explorer | BioRegHub