FDA Approves Ibrutinib for Pediatric Patients with Chronic Graft Versus Host Disease, Including a New Oral Suspension

August 24, 2022

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On August 24, 2022, the Food and Drug Administration approved ibrutinib (Imbruvica, Pharmacyclics LLC) for pediatric patients ≥ 1 year of age with chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy. Formulations include capsules, tablets, and oral suspension. 

Efficacy was evaluated in iMAGINE (NCT03790332), an open-label, multi-center, single-arm trial of ibrutinib for pediatric and young adult patients 1 year to less than 22 years old with moderate or severe cGVHD. The trial included 47 patients who required additional therapy after failure of 1 or more lines of systemic therapy. Patients were excluded if single organ genitourinary involvement was the only manifestation of cGVHD.

The median age of patients was 13 years (range, 1 to 19). Selected demographics of the 47 patients were as follows: 70% male, 36% White, 9% Black or African American, 55% other or unreported.

The main efficacy outcome measure was overall response rate (ORR) through Week 25. ORR included complete response or partial responses according to the 2014 NIH Consensus Development Project Response Criteria. ORR by Week 25 was 60% (95% CI: 44, 74). The median duration of response was 5.3 months (95% CI: 2.8, 8.8). The median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI: 4.6, not evaluable).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.

The recommended dosage of Imbruvica for patients 12 years of age and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2 orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.

View full prescribing information for Imbruvica

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. 

The applications for this action were granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Ibrutinib also was granted orphan drug designation. The applications were submitted in response to a pediatric Written Request issued by the FDA.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.