IMBRUVICA™ (ibrutinib) capsules now approved in the U.S. for Mantle Cell Lymphoma patients who have received at least one prior therapy

Posted: 13 November 2013 | | No comments yet

Janssen Biotech, Inc. [“Janssen”] today announced the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA™ (ibrutinib) capsules for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.1 This indication is based on overall response rate (ORR). An improvement in survival or disease-related symptoms has not been established.

IMBRUVICA is one of the first medications to receive FDA approval via the Breakthrough Therapy Designation pathway. Its approval comes just more than four months after the New Drug Application (NDA) submission was completed in late June 2013. IMBRUVICA is being jointly developed and commercialized by Janssen and Pharmacyclics, Inc.

“Mantle cell lymphoma is a rare, aggressive type of B-cell lymphoma,” said Michael Wang, M.D., Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center and lead investigator for the pivotal registration trial PCYC-1104. “With IMBRUVICA, we now have a once-daily oral therapy that has been shown to affect the disease. I’m proud to have been involved in this study.”

MCL is an orphan disease. Orphan diseases are characterized by high unmet need and small patient populations affecting fewer than 200,000 people.2 In the U.S., approximately 2,900 new cases of MCL are diagnosed each year3 with a median age at diagnosis of 65.4 MCL typically involves the lymph nodes, but can spread to other tissues, such as the bone marrow, liver, spleen and gastrointestinal tract.5 This challenging disease is associated with poor prognoses.5

“The approval of IMBRUVICA is great news for MCL patients who have received prior therapy and the physicians who treat them,” said William Hait, M.D., Ph.D. global head, research and development, Janssen Research & Development, LLC. “The Breakthrough Therapy Designation helped turbo-charge our timelines – it’s a remarkable process. It’s an excellent example of collaboration between the FDA, Janssen and Pharmacyclics.”

“Breakthrough Therapy Designation is intended to speed up the development and review of treatments to help address serious or life-threatening diseases. It is gratifying to see this early example of the new Breakthrough Therapy Designation pathway meeting its intention – getting promising treatments to patients who are waiting for new options,” said Dr. Ellen Sigal, chair and founder of Friends of Cancer Research, a think tank and advocacy organization based in Washington, DC.ɫ

IMBRUVICA was granted three Breakthrough Therapy Designations by the FDA, including relapsed or refractory MCL. IMBRUVICA was approved under the FDA’s Subpart H regulation.6 Janssen and Pharmacyclics are continuing an extensive clinical development program for IMBRUVICA, including Phase 3 study commitments in this patient population. Additionally, IMBRUVICA has been submitted to the FDA for the treatment of previously treated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

IMBRUVICA works by blocking a specific protein called Bruton’s tyrosine kinase (BTK). 1 Non-clinical studies have shown that blocking BTK inhibits malignant B-cell survival.1

The safety and efficacy of IMBRUVICA in patients with MCL who have received at least one prior therapy were evaluated in an open-label, multi-center, single-arm Phase 2 study of 111 treated patients. The primary endpoint was investigator-assessed overall response rate (ORR). Based on investigator assessment, the ORR was 65.8 percent (95% CI 56.2, 74.5%) and the median duration of response was 17.5 months (95% CI 15.8, not reached).1 This endpoint was based on responses assessed according to the revised International Working Group (IWG) for non-Hodgkin’s lymphoma (NHL) criteria.1

The Warnings and Precautions for IMBRUVICA include hemorrhage, infections, myelosuppression, renal toxicity, second primary malignancies and embryo-fetal toxicity.

The most commonly occurring side effects (adverse reactions in 20 percent or more of patients in the clinical trial) were thrombocytopenia*, diarrhea (51%), neutropenia*, anemia*, fatigue (41%), musculoskeletal pain (37%), peripheral edema (swelling of hands and feet, 35%), upper respiratory tract infection (34%), nausea (31%), bruising (30%), dyspnea (shortness of breath, 27%), constipation (25%), rash (25%), abdominal (stomach) pain (24%), vomiting (23%) and decreased appetite (21%). [*NOTE: Treatment-emergent decreases (all grades) of platelets (57%), neutrophils (47%) and hemoglobin (41%) were based on laboratory measurements and adverse reactions.]

The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were: pneumonia (7%), abdominal pain (5%), atrial fibrillation, diarrhea (5%), fatigue (5%), and skin infections (5%). Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111).

The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.

The recommended dose of IMBRUVICA is 560 mg (four 140 mg capsules) once daily.1

The IMBRUVICA MCL study was published online in The New England Journal of Medicine in June 2013.7


IMBRUVICA is commercially available immediately. Janssen Biotech is striving to make the process of obtaining IMBRUVICA and navigating insurance benefits easy for patients by offering comprehensive access services and support for eligible patients. The YOU&i Access™ program is designed specifically for patients who are prescribed IMBRUVICA and provides personalized attention coupled with access services designed to make obtaining medication simple and convenient for patients and those involved in their care.

This includes a YOU&i Access™ Instant Savings program, which provides co-pay support and benefits information to eligible commercially-insured patients. Patients can access the program by contacting 1-877-877-3536, option 1 or by visiting

  1.  IMBRUVICA Prescribing Information, November 2013
  2. National Organization for Rare Disorders. “Rare Disease Information”. Available from: Accessed September 2013.
  3. ©2013 DR/ Decision Resources, LLC. All rights reserved. Reproduction, distribution, transmission or publication is prohibited. Reprinted with permission.
  4. Humala K,Younes A. Current and emerging new treatment strategies for mantle cell lymphoma. Leukemia & Lymphoma. 2013; 54(5): 912–921.
  5. Leukemia and Lymphoma Society. Mantle Cell Lymphoma Facts. Available from: Accessed August 2013.
  6. The U.S. Food and Drug Administration. CFR – Code of Federal Regulations Title 21. Available from: Accessed August 2013.