December 2015, Vol. 4, No. 6

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FDA Drug Approvals: Earlier Availability for Promising Drugs

2015 Breast Cancer Symposium

It’s no secret that developing cancer drugs is a time-consuming and costly endeavor. Although the FDA review represents only a fraction of the entire time line, accelerated evaluation can still shave years off this process. According to data presented at the 2015 Breast Cancer Symposium, expedited programs allow for intensive FDA guidance through the discovery and testing period, shortening review periods when appropriate.

“These programs have been implemented to ensure that promising therapies for serious conditions are approved and made available quickly,” said Suparna Wedam, MD, Division of Oncology Products 1 at the FDA. “However, these measures are not appropriate for all drugs, only the most promising therapies. Benefits still need to justify the risks.”

For those drugs that do show promise, regulations call for early consultation with the FDA, more expeditious review, and regulatory flexibility. Wedam provided an overview of these expedited programs, including 3 separate designations and an accelerated approval pathway.

Fast Track Designation

As Wedam explained, drugs seeking fast track designation must treat a serious condition and demonstrate, with clinical data, the potential to address an unmet clinical need.

Fast track designation allows for:

  • Increased communication
    “This designation offers more opportunities for frequent interaction with the agency,” said Wedam, “wherever there are concerns regarding clinical trial design, biomarkers, and dose response.”
  • Rolling review
    “Application can be presubmitted,” said Wedam, “and modules come in pieces until the last arrives. When the last module comes in, that’s when the clock starts for final review.”
  • Flexibility on the part of the sponsor
    Problems are identified and addressed sooner rather than waiting until the whole application comes in. If the drug no longer meets qualifying criteria for fast track, designation may be rescinded at any time.

“The sooner in the development program that the designation is requested or granted,” said Wedam, “the more benefit that can be derived from having that designation. The timing is with the Investigational New Drug application or soon after.”

Breakthrough Therapy Designation

This designation is a process designed to expedite the development and review of drugs intended to treat a serious condition. Preliminary clinical evidence indicates that this drug may demonstrate substantial improvement on a clinically significant end point over available therapies. Unlike fast track, clinical evidence must be available at the time of the request.

“Clinical evidence needed is preliminary, not premature,” said Wedam. “It’s not the same standard as needed for approval, as controlled studies are not required.”

According to Wedam, the ideal breakthrough request in oncology features:

  • A novel mechanism, first-in-class drug
  • An indication with no or few effective available therapies
  • Adequate sample size of patients
  • Markedly higher response rate relative to available therapies
  • Substantial duration of response
  • Safety profile that is as good as or better than available therapies
  • Designation early in development in order to receive maximum benefit.

Like fast track, the breakthrough designation offers intensive drug development guidance from the FDA, frequent meetings with focused attention, more timely and informal communications, and FDA organizational commitment.

Priority Review Designation

Priority review designation directs attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.

This designation is requested by the sponsor with the initial New Drug Application or Biologic License Application submission, and if granted, reduces the review goal date by 4 months.

“The benefit is straightforward,” said Wedam. “A shorter review cycle means that we get a safe and efficacious drug out to patients faster.”

Accelerated Approval Pathway

These regulations allow a drug that treats a serious condition and provides meaningful advantage over available therapies and demonstrates an effect on a surrogate end point that is reasonably likely to predict clinical benefit to be approved faster than the traditional pathway.

“Drugs approved based on a surrogate end point will be available to the patient sooner,” said Wedam. “However, there is a level of uncertainty. The effect size may be overestimated and not confirmed in subsequent trials. So that is the risk that we take here.”

Speed Brings Uncertainty

Although speedy drug approvals have become the norm, not the exception, Wedam cautioned that expedited drug development comes with smaller safety databases and increased uncertainty.

“These drugs still need to generate adequate data for safety and efficacy, which require substantial evidence from adequate and well-constructed clinical trials,” she said.

“Every decision we make at FDA requires balancing safety and efficacy,” Wedam concluded. “We know that there is no perfect or benign drug, and the same stands true for expedited drugs.”

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