Breakthrough Approval

Substantial improvement over available therapy

Breakthrough Therapy Designation is a process that expedite the development and review of drugs which are considered in treating a serious health condition. The preliminary clinical evidence of such drugs indicates that the drug may show substantial improvement over the therapies which are available on a clinically significant endpoint.

The evidence

What makes an improvement significant

Magnitude of the effect

The determination whether the improvement over the available therapy is significant depends on the judgment and the magnitude of the effect caused by the treatment. This magnitude may include the duration of effect and importance of the observed outcome. So, in a way, the preliminary clinical evidence shows a clear benefit over an available therapy.

A clinically significant endpoint

The endpoint of clinically significant for Breakthrough Therapy Designation refers to an endpoint which measures the effect caused on irreversible morbidity or mortality or on symptoms representing serious consequences of the disease.

Qualifying findings

Effects that count as clinically significant

A clinically significant endpoint also refers to the findings that suggest an effect on serious symptoms or on IMM, which includes:

  • Effect on an established surrogate endpoint
  • Effect on intermediate clinical endpoint or on a surrogate endpoint, which is considered reasonably likely for predicting a clinical benefit, that is the accelerated approval standard.
  • Effect on pharmacodynamic biomarkers which do not meet the criteria for acceptable surrogate endpoint. However, it still suggests a strong clinical effect on an underlying disease.
  • Significantly improve in safety profile as compared to available therapy, but with evidence of similar efficacy, for instance a less dose limiting toxicity for oncology agent.
Requesting designation

When FDA suggests a request

BT designation is requested from the drug company and if a sponsor has not requested for the same, then FDA will suggest the sponsor to submit, if

  • The Agency after reviewing the submitted data, including the preliminary clinical evidence, things that the development program can meet the criteria of BT designation.

  • The drug development program which is remaining can be benefited from BT designation.

Timing

When to submit the request

To obtain the features of the designation, it is ideal to submit a BT designation request to FDA before the end of Phase-2 meetings. This is so because, the primary intention of BT designation is to develop an evidence that is needed to support the approval and FDA does not anticipate that these requests will be made when original BLA or NDA or a supplement is submitted. FDA responds to BT designation requests within 60 days of receiving the request.

  1. Phase 1Early development
  2. Before end of Phase 2Ideal time to submit the request
  3. BLA / NDA submissionRequests not anticipated here
What it unlocks

Eligibility after designation

A drug on receiving a Breakthrough Therapy designation is eligible for the following:

  • Features of all Fast-Track designation.
  • An intensive guidance on efficient drug development program, even in Phase 1.
  • Commitment from organization that involves senior managers.
Examples

Drugs with breakthrough approval

Following are some drugs that have received Break Through Approval:

  • Chronic lymphocytic leukaemia
    Obinutuzumab

    OBINUTUZUMAB, which is for treatment of patients with previously untreated chronic lymphocytic leukaemia in combination with chlorambucil.

  • Hepatitis C
    Sofosbuvir

    SOFOSBUVIR, which is for treatment of chronic hepatitis C infection.

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