Ibrutinib Receives Breakthrough Designations for Mantle Cell Lymphoma and Waldenström's Macroglobulinemia

Paul Stoffels, MD

The investigational agent ibrutinib was granted “Breakthrough Therapy Designations” by the FDA as a singular therapy for a pair of B-cell malignancies: relapsed or refractory mantle cell lymphoma (MCL) and Waldenström’s macroglobulinemia.

Ibrutinib is a tyrosine kinase inhibitor that selectively inhibits the Bruton’s tyrosine kinase enzyme. This enzyme is associated with the regulation of apoptosis, cell adhesion, and cell migration and helps the microenvironment of the tumor survive. Currently, ibrutinib is being investigated in a number of hematologic malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Waldenström’s macroglobulinemia, and multiple myeloma.

The drug is being co-developed and co-commercialized through a collaborative agreement between Janssen Biotech, Inc. part of the Janssen Pharmaceutical Companies of Johnson & Johnson, and Pharmacyclics.

A breakthrough therapy is a relatively new FDA designation that was enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA). The goal is to further expedite the time necessary for development and review of a new drug “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.”

According to the act, this designation would allow for more meetings to take place during the development process, potentially reduce the number of patients required to enroll in further clinical trials, and subsequently shorten the length of those trials when it is appropriate. Manufacturers of these drugs are still allowed to seek fast-track designation, accelerated approval, and priority review.

“We are pleased that the FDA has granted two Breakthrough Therapy Designations for ibrutinib as the designation represents a major leap forward in accelerating drug development timelines,” said Paul Stoffels, MD, Chief Scientific Officer and Worldwide Chairman of Pharmaceuticals at Johnson & Johnson, in a statement. “We are committed to realizing the full potential of ibrutinib for patients with mantle cell lymphoma, Waldenström’s macroglobulinemia, as well as other B-cell malignancies, and will work with Pharmacyclics and the FDA to ensure the clinical development program for ibrutinib continues to move forward as quickly as possible.”

Ibrutinib’s two breakthrough designations are among the first as a result of the act. The first breakthrough designations were announced in January for two cystic fibrosis treatments from Vertex Pharmaceuticals: ivacaftor (Kalydeco) monotherapy, and a combination of ivacaftor and the investigational compound VX-809.