Skip to main content

AbbVie Seeks New Indication for IMBRUVICA (ibrutinib) in Pediatric Patients with Chronic Graft Versus Host Disease (cGVHD)

NORTH CHICAGO, Ill., Feb. 28, 2022. AbbVie today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for IMBRUVICA (ibrutinib) for the treatment of pediatric and adolescent patients one year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. A New Drug Application (NDA) was also submitted for an oral suspension formulation of IMBRUVICA to provide an alternative administration option for pediatric patients. If approved, this represents AbbVie's first pediatric indication for IMBRUVICA.

cGVHD is a life-threatening complication for about 14,000 patients each year after receiving a donor stem cell or bone marrow transplantation.1,2 Nearly half of these transplant patients develop cGVHD, and there are currently no FDA-approved treatment options for children under 12.3 The applications seek to update the IMBRUVICA U.S. Prescribing Information primarily based on the analysis of three years of data from the Phase 1/2 iMAGINE clinical trial, including use of a new oral suspension formulation of the treatment.

"We are committed to this work with IMBRUVICA in the hopes of providing the first FDA-approved BTKi treatment option for younger patients with cGVHD, including a new oral suspension formulation," said James Dean, M.D., Ph.D., IMBRUVICA Global Development Lead and Executive Medical Director at AbbVie. "For young children, the availability of a liquid oral suspension versus an oral capsule or tablet can be significant to enable them to take the recommended dose and address challenges swallowing capsules or tablets."

The iMAGINE clinical trial enrolled 59 patients 1-19 years of age with relapsed/refractory (R/R) or new-onset moderate/severe cGVHD. The primary endpoints of the study were pharmacokinetics (PK) and safety; secondary endpoints included overall response rate. Results showed an overall response rate of 78 percent with IMBRUVICA and that PK data was consistent with adult dosing of IMBRUVICA. After 20 weeks, sustained response rates were observed in 70 percent and 58 percent of treatment-naive and R/R responders, respectively. Safety was consistent with the established profile for IMBRUVICA, with observed adverse events (AEs) consistent with those observed in adult patients with moderate to severe cGVHD. The most common Grade ≥3 AEs (≥ 5% of subjects) overall were pyrexia (8.5%), neutropenia (6.8%), stomatitis (6.8%), hypoxia (6.8%), osteonecrosis (6.8%), alanine aminotransferase increased (5.1%), hypokalemia (5.1%), and pneumothorax (5.1%).

"It is important to empower patients and their families with evidence-based knowledge and I am encouraged by the results from the iMAGINE clinical trial of IMBRUVICA," said Dr. Paul A. Carpenter, attending physician at Seattle Children's Hospital and study principal investigator. "Results show that PK and safety were consistent with the known profile of IMBRUVICA and that of cGVHD. Efficacy results, including sustained response rates, were also encouraging."

In 2017, IMBRUVICA was first approved as a single-agent therapy for adult patients with cGVHD who have experienced failure of prior systemic therapy, becoming the first FDA-approved treatment for adults with cGVHD. IMBRUVICA could be the first FDA-approved BTKi treatment option for pediatric and adolescent patients with cGVHD.

About cGVHD

cGVHD occurs when donated peripheral blood or bone marrow stem cells view the recipient's body as foreign and the donated cells launch an immune attack on the body.4 cGVHD impacts major organs, with the skin, eyes, mouth and liver being most common.5 About 35 percent of the estimated 8,000 patients who undergo life-saving allogeneic Hematopoietic Stem Cell Transplant (HSCT) per year develop cGVHD that requires systemic treatment.4 Additionally, cGVHD is the most common cause of morbidity after allogeneic transplant.6 Steroids are the current standard treatment for pediatric cGVHD.7

About the iMAGINE Study

iMAGINE (PCYC-1146-IM) is an interventional single group treatment Phase 1/2 study, which enrolled 59 pediatric patients with chronic graft versus host disease (cGVHD). In the two-part study, Part A patients ages one to <12 years with moderate or severe cGVHD after failure of one or more lines of systemic therapy received IMBRUVICA oral suspension or capsule starting at 120mg/m2 once daily. To determine the Recommended Pediatric Equivalent Dose (RPED), dosage was escalated to 240mg/m2 after 14 days if no Grade 3 or higher related toxicity was observed. In Part B, patients 12 to <22 years of age with moderate or severe cGVHD who were newly diagnosed or had failed one or more lines of systemic therapy were given 420mg IMBRUVICA orally once daily. Once the RPED was determined in Part A, patients 1 to <12 years of age with new-onset or relapsed/refractory cGVHD could be enrolled in Part B. Primary endpoints included pharmacokinetics (PK) and safety, and secondary endpoints included overall response rate (ORR; CR/PR) per 2014 NIH criteria, overall survival, duration of response (DOR), and patient reported outcomes.

About IMBRUVICA

IMBRUVICA (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc. IMBRUVICA blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, to multiply and spread. By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.8,9,10

IMBRUVICA is approved in more than 100 countries and has been used to treat more than 250,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 ongoing or completed Phase 3 studies, over 11 years evaluating the efficacy and safety of IMBRUVICA.

IMBRUVICA was first approved by the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include adults with CLL/small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p) and adults with Waldenström's macroglobulinemia (WM), as well as adult patients with previously treated mantle cell lymphoma (MCL)*, adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, as well as adult patients with previously treated chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.11

*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

Since 2019, the National Comprehensive Cancer Network (NCCN), recommends ibrutinib (IMBRUVICA) as a preferred regimen for first-line treatment of CLL/SLL, with Category 1 status for previously untreated patients without del17p. Additionally, IMBRUVICA is a preferred treatment regimen for previously untreated patients with del17p. Since January 2020, the NCCN Guidelines recommend IMBRUVICA as a category 2A preferred regimen for the treatment of relapsed/refractory MCL. Since September 2020, the NCCN Guidelines recommend IMBRUVICA with or without rituximab as a Category 1 preferred regimen for both untreated and previously treated WM patients.12.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio.

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2021 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

IMBRUVICA is a registered trademark of Pharmacyclics LLC.

Posted: February 2022

More news resources

Subscribe to our newsletter

Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.