On November 13, 2013, FDA approved Imbruvica® (ibrutinib) for the treatment of patients with mantle cell lymphoma ("MCL"), a rare and aggressive form of non-Hodgkin lymphoma or blood cancer. Imbruvica® will be co-marketed by Pharmacyclics, Inc. ("Pharmacyclics") based in Sunnyvale, Calif. and Janssen Biotech, Inc. ("Janssen") based in Raritan, N.J and will be sold as a single agent oral capsule.

Imbruvica® has been approved for patients with MCL who have received at least one prior therapy and works by blocking a specific protein called Bruton's tyrosine kinase ("BTK"). Non-clinical studies have shown that blocking BTK inhibits malignant B-cell survival. The recommended dose of Imbruvica® is 560 mg (four 140 mg capsules) once daily. About six percent of all non-Hodgkin lymphoma cases in the U.S. are classified as MCL. MCL is often diagnosed in an advanced stage after it has already spread to the lymph nodes, bone marrow and other organs.

Imbruvica® was approved as part of the Breakthrough Therapy Designation ("BTD") program that facilitated its development, review, and approval. Imbruvica® was granted three BTDs by FDA, including relapsed or refractory MCL, and is the second drug with a BTD to receive FDA approval.

With the passage of The Food and Drug Administration Safety and Innovation Act ("FDASIA") in July 2012, FDA could designate a drug as breakthrough therapy at the request of the sponsor, if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. Under the BTD program, FDA can approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is "reasonably likely" to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. The approval of Imbruvica® comes just more than four months after the New Drug Application ("NDA") submission was completed in late June 2013.

Imbruvica®'s accelerated approval was based on an open-label, multi-center, single-arm Phase 2 study, where 111 patients with MCL who had received at least one prior therapy were given Imbruvica® daily until their disease progressed or side effects became intolerable. The results showed nearly 66 percent of participants had their cancer shrink or disappear after treatment (overall response rate). Based on investigator assessment, the median duration of response was 17.5 months. An improvement in survival or disease-related symptoms has not been established. Janssen and Pharmacyclics are continuing an extensive clinical development program for Imbruvica®, including Phase 3 study commitments in patients suffering from relapsed or refractory MCL.

The Warnings and Precautions for Imbruvica® include hemorrhage, infections, myelosuppression, renal toxicity, second primary malignancies and embryo-fetal toxicity. The most common side effects (adverse reactions in 20 percent or more of patients in the clinical trial) reported in participants receiving Imbruvica® were low levels of platelets in the blood (thrombocytopenia), diarrhea, a decrease in infection-fighting white blood cells (neutropenia), anemia, fatigue, musculoskeletal pain, swelling (edema), upper respiratory infection, nausea, bruising, shortness of breath (dyspnea), constipation, rash, abdominal pain, vomiting, and decreased appetite. Other clinically significant side effects include bleeding, infections, kidney problems and the development of other types of cancers.

FDA also granted Imbruvica® priority review, since the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. FDA further designated Imbruvica® as an orphan-product intended to treat a rare disease. Orphan diseases are characterized by high unmet need and small patient populations affecting 200,000 individuals or fewer in the U.S.

Imbruvica® is the third drug approved to treat MCL. Velcade® (bortezomib) (2006), marketed by Millennium Pharmaceuticals, Inc., and Revlimid® (lenalidomide) (2013), marketed by Celgene Corporation, are also approved to treat the disease. Imbruvica® has been submitted to FDA for the treatment of previously treated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).