– Approval for the treatment of cGVHD is the sixth U.S. disease indication for the medication and the first therapy specifically approved for adults with cGVHD after failure of one or more lines of systemic therapy
– This indication — the first for IMBRUVICA outside of cancer — underscores the potential utility of ibrutinib’s unique mechanism of action beyond oncology

NORTH CHICAGO, IL, USA I August 2, 2017 I AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® (ibrutinib) for the treatment of adult patients with chronic graft-versus-host-disease (cGVHD) after failure of one or more lines of systemic therapy.1 With this approval, IMBRUVICA becomes the first and only therapy specifically approved for adults with cGVHD, a serious and debilitating potential consequence of stem cell or bone marrow transplant.2 IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

“Stem cell and bone marrow transplants can be life-saving treatment options for people with blood cancers or marrow failure syndromes; however, nearly half of transplant patients subsequently develop chronic graft-versus-host-disease, or cGVHD, in which the donor’s immune cells damage the patient’s normal organs and their quality of life,” said David Miklos, M.D., Ph.D., Associate Professor of Medicine (Blood and Marrow Transplantation), Stanford University, and lead investigator of the IMBRUVICA cGVHD clinical study.* “With IMBRUVICA, we observed sustained responses lasting five months or longer across multiple organs affected by this debilitating condition for 48 percent of all patients. This approval represents a major advance and provides physicians with a new option for adults with steroid refractory cGVHD.”

The approval in cGVHD is based on findings from an open-label, multi-center, single-arm Phase 1b/2 trial (PCYC-1129), which evaluated the safety and efficacy of ibrutinib in 42 patients with cGVHD that failed to respond to first-line corticosteroid therapy and required additional therapy (median age of 56; range: 19 to 74 years old; 52 percent male; 93 percent Caucasian). The most common underlying malignancies leading to transplantation for the study population were acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The median time since cGVHD diagnosis was 14 months, and the median number of prior cGVHD treatments was two (range: one to three treatments). The majority of patients (88 percent) had at least two organs affected at baseline, including mouth (86 percent), skin (81 percent) and gastrointestinal tract (33 percent).1

“The FDA’s approval of IMBRUVICA in chronic graft-versus-host-disease after failure of one or more lines of systemic therapy addresses an area of high unmet medical need for patients and marks the first approved use for the therapy outside of blood cancers,” said Lori Styles, M.D., Senior Medical Director and GVHD program clinical lead at Pharmacyclics LLC, an AbbVie company. “This approval is an indicator of what is possible with IMBRUVICA, and we remain excited about the clinical utility of IMBRUVICA in other disease areas. We continue to explore the full potential of this therapy and believe our comprehensive clinical trial program will help advance patient care.”

Investigators assessed responses per the 2005 National Institute of Health Consensus Panel Response Criteria with modification. Responses were seen across involved organs for cGVHD (i.e., skin, mouth, gastrointestinal tract and liver). Overall response rate (ORR) was achieved in 67 percent of patients, 21 percent of which were complete responders (CR) and nearly half (45 percent) were partial responders (PR). The rate of sustained response for at least 20 weeks was 48 percent for all patients.1

The most common adverse events (AEs) of all Grades (occurring in ≥20 percent of cGVHD patients treated with IMBRUVICA) included fatigue, bruising, diarrhea, thrombocytopenia, stomatitis, muscle spasms, nausea, hemorrhage, anemia and pneumonia. Atrial fibrillation occurred in one patient (2 percent), which was Grade 3. Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were fatigue and pneumonia. Adverse reactions leading to dose reduction occurred in 26 percent of patients.1

The risks associated with IMBRUVICA as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome and embryo fetal toxicities.1

IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, including in cGVHD. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.3

IMBRUVICA is now approved for six indications overall, including adult patients with cGVHD that failed to respond to one or more lines of systemic therapy, as well as adults with certain types of non-Hodgkin’s lymphomas, including CLL/small lymphocytic lymphoma (SLL), including patients with 17p deletion; patients with mantle cell lymphoma (MCL) who have received at least one prior therapy; patients with Waldenström’s macroglobulinemia (WM); and patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. Accelerated approval was granted for the MCL and MZL indications based on ORR. Continued approval for the MCL and MZL indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 In addition to IMBRUVICA being the first therapy specifically approved for adult patients with cGVHD after failure of one or more lines of systemic therapy, it also was the first therapy specifically approved for adults with MZL and WM.

About Graft-Versus-Host-Disease
Chronic graft-versus-host-disease (cGVHD) is a severe, potentially life-threatening consequence of stem cell or bone marrow transplant.2 GVHD is a condition where the bone marrow recipient’s tissues are attacked by bone marrow donor immune cells after they undergo an allogeneic stem cell or bone marrow transplant.2 GVHD can be acute or chronic; cGVHD typically begins three or more months following a transplant and can last several years.2 The effects of GVHD can be seen throughout the body, affecting almost any organ and manifesting through rashes and skin thickening, joint pain and stiffness, eye dryness and irritation, diarrhea, jaundice, mouth sores and ulcers, and severe lung dysfunction.2 The incidence of cGVHD has continued to increase over time, and approximately 30-70 percent of post allogenic transplant patients will develop cGVHD.4,5  

IMBRUVICA® (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells as well as other serious, debilitating conditions.1,6 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.

IMBRUVICA is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host-disease (cGVHD).1

  • IMBRUVICA was first approved for adult patients with MCL who have received at least one prior therapy in November 2013.
  • Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for adult CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
  • IMBRUVICA was approved for adult patients with WM in January 2015.
  • In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for adult patients with previously treated CLL/SLL.
  • In January 2017, IMBRUVICA was approved for adult patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
  • In August 2017, IMBRUVICA was approved for adult patients with cGVHD that failed to respond to one or more lines of systemic therapy.

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

1 IMBRUVICA U.S. Prescribing Information, August 2017. 
2 The Leukemia and Lymphoma Society. Graft Versus Host Disease. Available from: http://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/graft-versus-host-disease. Accessed July 2017.
3 U.S. Food and Drug Administration. Fact Sheet: Breakthrough Therapies. Available from: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed July 2017.
4 Arai, et al. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant: 21 (2015) 266-274.
5 Grube, et al. Risk Factors and Outcome of Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation—Results from a Single-Center Observational Study. Biol Blood Marrow Transplant: 2016; 22 (11): 1781-1791.
6 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed July 2017.