FDA Drug Approvals: Earlier Availability for Promising Drugs

TON November 2015 Vol 8 No 6 - FDA Approvals, News & Updates
Chase Doyle

It is no secret that developing cancer drugs is a time-consuming and costly endeavor. Although the US Food and Drug Administration (FDA) review represents only a fraction of the entire timeline, accelerated evaluation can still shave years off this process. According to data presented at the 2015 Breast Cancer Symposium,1 expedited programs allow for intensive FDA guidance through the discovery and testing period, shortening review periods when appropriate.

“The programs have been implemented to ensure that promising therapies for serious conditions are approved and [made] available quickly,” said Suparna Wedam, MD, Medical Officer, Division of Oncology Products 1, Center for Drug Evaluation and Research at the FDA. However, these measures are not appropriate for all drugs, only the most promising therapies. “The 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. Dr Wedam provided an overview of these expedited programs, including 3 separate designations and an accelerated approval pathway.

Fast Track Designation
As Dr Wedam explained, drugs seeking fast track designation must treat a serious or life-threatening disease or condition, and demonstrate, with clinical or nonclinical data, the potential to address an unmet clinical need.1,2
Fast track designation allows for:

  • Increased communication
    “[This designation] allows more opportunities for frequent interaction with the agency,” said Dr Wedam. “Wherever there are any concerns regarding clinical trial design, biomarkers, and dose-response.”
  • Rolling review
    “Application can be presubmitted,” Dr Wedam explained. “And the modules can come in pieces until the last one [arrives]. When the last module comes in, that’s when the time 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 If the drug no longer meets qualifying criteria for fast track, designation may be rescinded at any time.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, the more benefit that can be derived from having that designation,” said Dr Wedam. “The timing is with the Investigational New Drug (IND) application, or soon after.”

Breakthrough Therapy Designation
This designation is also a process designed to expedite the development and review of drugs intended to treat a serious or life-threatening disease or condition.1,2 Preliminary clinical evidence indicates that this drug must demonstrate substantial improvement over available therapies on ≥1 clinically significant end points. Unlike fast track designation, clinical evidence must be available at the time of the request, which would be with the IND application or soon after, and no later than the end-of-phase 2 meeting.2

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

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

  • A novel mechanism, first-in-class drug
  • An indication with no or few effective available therapies
  • An adequate sample size of patients
  • Markedly higher response rate relative to available therapies
  • Substantial duration of response
  • A 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 designation, the breakthrough therapy 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 provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.1,2

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. “A shorter review cycle means that we get a safe and efficacious drug out to patients faster,” noted Dr Wedam.

Accelerated Approval Pathway
These regulations allow a drug that treats a serious condition, provides meaningful advantage over available therapies, and also demonstrates an effect on a surrogate end point that is reasonably likely to predict clinical benefit to be approved faster than the traditional pathway.1,2

Drugs approved based on a surrogate end point will be available to the patient sooner, explained Dr 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, Dr Wedam cautioned that expedited drug development comes with smaller safety databases and increased uncertainty.

The FDA is continuing to work on these issues with “improved postmarketing pharmacovigilance tools and close attention to conduct and completion of postmarketing trials.”

Dr Wedam said that every decision made at the FDA requires balancing safety and efficacy, noting that there is no perfect or benign drug, and that the same stands true for expedited drugs.

1. Wedam S. FDA drug approvals: getting drugs to patients sooner. Presented at: 2015 Breast Cancer Symposium; September 25-27, 2015; San Francisco, CA.
2. US Department of Health & Human Services; US Food and Drug Administration; Center for Drug Evaluation and Research; Center for Biologics Evaluation and Research. Guidance for industry: expedited programs for serious conditions – drugs and biologics. www.fda.gov/downloads/Drugs/GuidanceComplianceRegula toryInformation/Guidances/UCM358301.pdf. Published May 2014. Accessed October 15, 2015.

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Last modified: November 20, 2015