Janssen Research & Development, LLC, and Pharmacyclics, LLC, announced that the FDA has granted Breakthrough Therapy Designations for the investigational oral agent ibrutinib as a monotherapy for two B-cell malignancies: in patients with relapsed or refractory mantle cell lymphoma who have received prior therapy, and in patients with Waldenstrom’s macroglobulinemia.
Enacted as part of the 2012 FDA Safety and Innovation Act, Breakthrough Therapy Designation is intended to expedite the development and review time for a potential new medicine “to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.”1
The FDA Breakthrough Therapy Designation for ibrutinib in patients with mantle cell lymphoma was based on data from clinical and preclinical studies. Ibrutinib has the potential to improve the outcome in this serious and life-threatening disease which has a poor prognosis. Janssen and Pharmacyclics have designed a comprehensive development program of ibrutinib in mantle cell lymphoma which includes the following studies:
A phase III randomized, multicenter registration trial of ibrutinib as a monotherapy vs temsirolimus in patients with relapsed or refractory mantle cell lymphoma who received at least one prior rituximab (Rituxan)-containing chemotherapy regimen, RAY (MCL3001).
A phase III randomized, double-blind, placebo-controlled study of ibrutinib plus bendamustine (Treanda) and rituximab vs placebo plus bendamustine and rituximab in subjects with newly diagnosed mantle cell lymphoma, SHINE (MCL3002).
A phase II single-arm study of ibrutinib as a monotherapy in patients with mantle cell lymphoma who received at least one prior rituximab-containing chemotherapy regimen and who progressed after bortezomib (Velcade) therapy, SPARK (MCL2001).
A phase II single-arm study of ibrutinib as monotherapy in patients with relapsed or refractory mantle cell lymphoma (PCYC-1104).
Janssen Biotech, Inc. and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib. The filing for ibrutinib in mantle cell lymphoma is expected to be made prior to the end of 2013, and discussions with the FDA about filing in Waldenstrom’s macroglobulinemia continue. The implications of Breakthrough Therapy Designation cannot be determined at this time. The companies are working with the FDA to determine any potential implications of the Breakthrough Therapy Designations to the ongoing and planned development activities.
“As an oncology product, ibrutinib receiving the Breakthrough Therapy Designation is an example of progress and hope for patients fighting a range of cancers. This designation shows that the FDA is dedicated to using an ‘all hands on deck approach’ to work on products that show promise in treating serious and life-threatening diseases,” said Ellen Sigal, PhD, Chair and Founder of Friends of Cancer Research, a think tank and advocacy organization based in Washington, DC. “The breakthrough pathway that our organization worked to create is intended to speed up the development and review of treatments that may demonstrate substantial improvement over existing therapies, and ibrutinib is a great example of using this new designation to potentially accelerate patient access to promising treatments.” ■