The Lynx Group

Breakthrough Therapy Designation Program: Reviewing the First-Year Experience

June 2014, Vol 5, No 5

Chicago, IL—The US Food and Drug Administration (FDA) introduced the concept of a breakthrough therapy designation in 2012 to help expedite patient access to new therapies for the treatment of serious or life-threatening diseases. A new study published in association with the 2014 American Society of Clinical Oncology meeting reviewed the first-year experience of the breakthrough therapy program for cancer therapies.

Of the 14 oncology agents that earned the breakthrough therapy designation, 2 are now approved by the FDA, both for hematologic malignancies. These are obinutuzumab (Gazyva), approved in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia, and ibrutinib (Imbruvica) for the treatment of mantle-cell lymphoma.

“The breakthrough therapy program is still in its early stages, and some of the designations have been granted to drugs in later stages of development. These products were not able to take advantage of all the benefits of BT [breakthrough therapy]. In the future, if BT designations are granted in earlier stages of drug development, it is possible that drug development and review process could be even further streamlined,” wrote the FDA Office of Media Affairs in an e-mail to Value-Based Cancer Care.

“We are delighted now to have an additional tool to help expedite the development and approval of products with the BT designation. We will continue to use our existing tools and the new BT authority to make our expedited drug development process even more effective, with the goal of benefitting patients with unmet medical needs,” the e-mail response continued.

The FDA’s Office of Hematology and Oncology Products (OHOP) received 50 requests for a breakthrough therapy designation between the program’s inception on October 30, 2012, and October 31, 2013. OHOP, together with the review division and the Medical Policy Council, completed the assessment of 43 of the 50 requests. In all, 14 requests were granted a breakthrough therapy designation, 29 were denied, and 7 were withdrawn by the sponsors.

Of the 14 granted breakthrough therapy designations, 3 submitted marketing applications to the FDA within 3 months of receiving the des­ignation, and 2 (obinutuzumab and ibrutinib) received FDA approval approximately 5 to 6 months after submission.

“It is too early to determine the long-term impact of this program on development and approval of oncology products,” wrote lead investigator Yangmin M. Ning, MD, PhD, Acting Deputy Director of Safety, FDA’s Division of Oncology Products 1, Silver Spring, MD, and colleagues.

Quality of the Evidence Is Key
Of the 29 submissions that were denied by the FDA, 24 included preliminary clinical evidence showing no substantial improvement compared with existing therapies for their intended use, and 5 had limited clinical data that precluded reliable assessments. Other reasons for denial included reliance on a novel biomarker or a surrogate end point without sufficient evidence of benefit to the patient, and post-hoc analysis of failed trials identifying a subset of patients who may benefit.

The FDA website for expedited review programs states that many of the denials for breakthrough therapy designation represent “the triumph of hope over evidence.”

In the e-mail, the FDA Office of Media Affairs stated, “Some companies with denied requests for BT designation may resubmit more mature data and request the designation again, particularly if the request was submitted prematurely. The denial of a BT designation would not stop the development program for a drug.”

Related Articles

Subscribe to
Value-Based Cancer Care

Stay up to date with personalized medicine by subscribing to recieve the free VBCC print publication or weekly e‑Newsletter.

I'd like to recieve: