The US Food and Drug Administration (FDA) has granted its third breakthrough product designation and the first for an entirely unapproved product, the product's sponsor, Jenssen, announced today.
What is breakthrough product designation? It's not entirely clear yet. The designation was created under the 2012 FDA Safety and Innovation Act, and is intended to give special regulatory advantages to products intended to treat-often in combination with other products-patients with life-threatening or otherwise serious diseases for which there are no or few treatment options.
FDASIA defined eligibility for the pathway as a product that is "intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints."
The designation opens up new incentives for companies, giving their application access to faster reviews. This is particularly important for combination therapies, which might not otherwise be eligible for priority review status or other incentives despite their intended use. The principal benefit, as explained by its advocates, is that novel combination therapies involving already-approved products will now be better able to obtain those faster review times, further assisting patients.
The review category has already seen two products accepted, both from Massachusetts-based Vertex Pharmaceuticals. The first, a combination of Kalydeco (ivacaftor) and an experimental compound known as VX-809, is intended to treat additional forms of cystic fibrosis. The second, just for Kalydeco, is also intended to treat additional variants of cystic fibrosis. At present, the drug is only approved to treat one variation of the disease which specifically afflicts patients with the G551D mutation.
While FDA has touted the pathway at numerous junctures, some companies have made it clear that they don't know what the precise benefit will be.
"The implications of Breakthrough Therapy Designation cannot be determined at this time," Vertex said in a statement in January 2013. "Vertex is working with FDA and other global regulatory agencies to determine any potential implications of the Breakthrough Therapy Designations to its ongoing and planned development activities, and subsequent regulatory submissions, for ivacaftor monotherapy and the combination regimen of VX-809 with ivacaftor."
Janet Woodcock, FDA's director of the Center for Drug Evaluation and Research (CDER), has meanwhile hinted that products might be able to obtain approval based on just a single, robust phase I clinical trial.
"We expect many of these would come available very quickly with Phase 1 data," Bloomberg reported Woodcock as saying in January 2013.
In light of the confusion around the pathway, FDA Commissioner Margaret Hamburg told an audience of biotechnology executives that a guidance document on the topic is forthcoming.
Hamburg also noted that the agency has received 31 breakthrough designation requests. Nine have been granted, 10 denied, and one withdrawn. The rest are awaiting agency decisions.
Third Breakthrough Product Revealed
But FDA is banned from disclosing which products have sought breakthrough status, and it is up to the companies to release that information. Now, Johnson & Johnson subsidiary Janssen has announced that it holds one of those nine applications to have obtained approval.
That designation has been extended to the company's ibrutinib, an investigation oral Bruton's tyrosine kinase (BTK) inhibitor intended for use as a monotherapy with patients with chronic lymphocytic leukemia or small lymphocytic lymphoma with deletion of the short arm of chromose 17 (del17p).
"Ibrutinib continues to demonstrate promise for patients living with B-cell malignancies, and we are pleased that the FDA has recognized its potential for people living with CLL and the del17p mutation," said Peter Lebowitz, therapeutic area head of global oncology for Janssen. "This third Breakthrough Therapy Designation reflects the potential importance of ibrutinib for patients diagnosed with a 17p deletion chromosomal abnormality in CLL/SLL, and we are committed to working with Pharmacyclics and the FDA to expedite development and review of ibrutinib as quickly as possible."
As with Vertex, Janssen added that "The implications of Breakthrough Therapy Designation cannot be determined at this time."
"Janssen and Pharmacyclics are working with the FDA to determine any potential implications of the Breakthrough Therapy Designation to the ongoing and planned development activities," the company added.
The designation was first given to the company in February 2013.