Supplemental NDA Submitted to FDA for Ibrutinib in cGVHD

A supplemental new drug application has been submitted to the FDA for ibrutinib to help treat pediatric and adolescent patients with chronic graft versus host disease.

A supplemental new drug application for ibrutinib (Imbruvica) has been submitted to the FDA for pediatric and adolescent patients with chronic graft versus host disease (cGVHD) who are 1 year or older, according to a press release from AbbVie.1

AbbVie has also submitted a new drug application for ibrutinib as an oral suspension formulation as an alternative treatment option for pediatric patients. The application is based on the results from the dose finding phase 1/2 iMAGINE trial (NCT03790332), which aimed to determine the safety of ibrutinib in patients with cGVHD.

“We are committed to this work with [ibrutinib] in the hopes of providing the first FDA-approved [Brutons tyrosine kinase inhibitor] treatment option for younger patients with cGVHD, including a new oral suspension formulation. For young children, the availability of a liquid oral suspension vs an oral capsule or tablet can be significant to enable them to take the recommended dose and address challenges swallowing capsules or tablets,” James Dean, MD, PhD, ibrutinib global development lead and executive medical director at AbbVie, said in the press release.

A total of 59 patients with relapsed/refractory or new-onset moderate to severe cGVHD between the ages of 1 to 19 years were enrolled on the trial. Patients in part A of the study who were 12 years or younger with previous failed lines of therapy received ibrutinib at 120 mg/m2 once daily. To determine the appropriate dose for phase 2, dosing was escalated to 240 mg/m2 after 14 days if patients did not experience grade 3 or higher adverse effects (AEs). In part B, patients 12 to 22 years old who were newly diagnosed or for whom previous treatment had failed received 420 mg of ibrutinib once daily. Patients in part A could enroll in part B only after the recommended pediatric equivalent dose was determined.

The primary end points of the study were pharmacokinetics and safety, and the secondary end point was overall response rate (ORR). Patients had an ORR of 78% and the pharmacokinetic data were consistent with what was seen in trials with adult patients. At the 20-week mark, responders who were treatment-naïve and relapsed/refractory experienced sustained response rates of 70% vs 58%, respectively.

AEs in the trial were consistent with those seen in adult patients. Grade 3 or higher AEs seen in 5% or more of patients were pyrexia (8.5%), stomatitis (6.8%), neutropenia (6.8%), hypoxia (6.8%), osteonecrosis (6.8%), alanine aminotransferase increased (5.1%), hypokalemia (5.1%), and pneumothorax (5.1%).

Ibrutinib was previously approvedin August of 2017 as the first treatment for cGVHD.2 The approval came as a result of a single-arm study of 42 patients who had persistent symptoms despite receiving the standard of care. The data from the trial indicated that 67% of patients experienced improved cGVHD symptoms, and 48% experienced improved symptoms that lasted for 5 months or longer.

AEs seen with this treatment were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, and sores in the mouth. Serious AEs included bleeding, infections, cytopenia, atrial fibrillation, and hypertension.


1. AbbView seeks new indication for Imbruvica (ibrutinib) in pediatric patients with chronic graft versus host disease (cGVHD). News Release. AbbVie. February 28, 2022. Accessed March 1, 2022.

2. FDA approves treatment for chronic graft versus host disease. News Release. FDA. August 2, 2017. Accessed March 1, 2022.