FDA explains when it will rescind breakthrough designations

Regulatory NewsRegulatory News | 23 June 2022 |  By 

The US Food and Drug Administration (FDA) on Thursday released draft guidance explaining its thought process for rescinding breakthrough therapy designation (BTD) during its evaluation of a drug.
While FDA has long asserted its authority to rescind or withdraw BTDs, the new guidance will add clarity for sponsors as to when the agency might revoke the designation. Since designation was created under the Food and Drug Administration Safety and Innovation Act in 2012, the agency has only rescinded BTDs from products about 35 times, according to the most current quarterly data available. The designation has been withdrawn after granting around 11 times. (RELATED: FDA rescinds two breakthrough therapy designations, Regulatory Focus 8 March 2019)
“The information supporting the granting of BTD for a particular drug may change over time. Some drugs that appear promising in early development may not be shown to be safe or effective in later trials, or the magnitude of a treatment effect suggested by early development may not be observed in later stages of development,” FDA explains in the guidance.
Due to the “resource-intensive nature” of the program, FDA says it may rescind the designation for products that no longer meet the legal criteria for the program.
The agency provides examples of three scenarios in which it might rescind a product’s BTD, including when another drug is approved for an unmet need that was cited in the rationale for granting BTD. FDA notes that other drugs intended for the same unmet medical need that are granted accelerated approval will not typically be considered as reason for rescinding BTD.
The other two scenarios in which FDA says it might rescind BTD include when “emerging data for the designated drug no longer support a finding that ‘preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies,’” and when the drug’s sponsor halts a drug development program for the use the BTD was granted for.
FDA further explains that “Rescinding a BTD may be warranted if a phase 3 trial intended to definitively show the designated drug’s effect fails to meet its primary endpoint, or the extent of benefit is more modest such that the trial does not indicate that the drug may demonstrate a substantial improvement over available therapy. The emergence of additional safety information that alters the benefit-risk assessment of the designated product may also support a decision to rescind BTD.”
The agency adds that it will generally apply greater weight to larger trials and those that “use a well-understood and widely accepted, well-constructed clinical endpoint, and incorporate certain design features,” such as randomization or blinding, noting that the quality of available evidence can play a role in its decision-making.
In other situations, where there is inconsistent clinical evidence from multiple well-designed studies, FDA says the decision to maintain or rescind BTD “may become more challenging.” As such, the agency stresses that the decision will be made on a case-by-case basis, depending “on the facts specific to that drug development program.”
Draft guidance, Federal Register notice


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