Thousands of Children are Waiting for FDA’s Approval of IMBRUVICA for Pediatric Graft-Versus-Host Disease


Every year almost half of the fourteen thousand patients who have received bone marrow or stem cell transplants will develop chronic graft-versus-host disease (cGVHD). Currently, there are no options approved by the FDA for any child under the age of twelve with cGVHD.

According to a recent PRNewswire press release, AbbVie announced a submission to the FDA to allow IMBRUVICA®  (ibrutinib) prescribing information to include adolescent and pediatric patients. AbbVie’s application to the FDA was the result of analyzing three years’ successful data from its IMAGINE Phase 1/2 clinical trial. The trial reported a seventy-eight percent response rate which is in line with adult dosing of IMBRUVICA.

The U.S. FDA approved IMBRUVICA in 2017 as the first treatment for adults with cGVHD who had failed systemic therapies.

If AbbVie’s application is accepted, cGVHD patients who are one year or older and also had little success with systemic therapy would have the option of managing their cGVHD with an oral formulation.

Dr. James Dean, AbbVie’s Medical Director, commented that the liquid form of the drug, rather than a capsule, is significant. The ease of administration enables children to overcome the challenges of swallowing tablets or capsules.

The Origin of cGVHD

Graft-versus-host disease occurs when transplanted stem cells in the bone marrow or peripheral blood are viewed by the body as foreign substances. This causes the immune system to attack the “invader” and can contribute to the patient’s death.

About the IMAGINE Trial

The trial enrolled fifty-nine patients ages one to nineteen with either the onset of cGVHD, relapsed cGVHD, or refractory disease (resistance to treatment). The primary goal of the study was safety and drug absorption, metabolism, distribution, and excretion (pharmacokinetics). The response rate was a secondary goal of the study.

In Part A of the study, patients who are one to twelve years old with moderate to severe cGVHD were administered either oral suspension (liquid) or a capsule of IMBRUVICA. Dosing began at 120 mg/m2  once each day. After fourteen days, if no grade 3 toxicity occurred, the dosage was raised to 240 mg/m2  in order to reach a recommended dose for pediatric patients.

Response rates of seventy percent and fifty-eight percent, respectively, were reported as being sustained after a period of twenty weeks.

Safety matched previously established profiles. Observed adverse events were consistent with observed events previously established for IMPRUVICA.

If a recommended dose was established in part A, enrollees ages one to twelve were allowed to enroll in the Part B segment of the trial.

Part B enrolled patients twelve to twenty-two years old who had either moderately severe or severe cGVHD and were either recently diagnosed or were not successfully treated with systemic therapy. These patients received 420mg of oral IMBRUVICA each day.

Safety and pharmacokinetics were primary endpoints for Part B, as well as overall response rate according to the 2014 NIH standards, response duration, overall survival, and reported outcomes expressed by patients.

About cGVHD

The disease affects major organs such as the eyes, skin, mouth, and liver. Approximately thirty-five percent of the eight thousand patients who received allogeneic stem cell transplants each year will acquire cGVHD, a major cause of morbidity being surpassed only by allogeneic transplants.

Currently, steroids are considered to be the treatment of choice for pediatric cGVHD.

About IMBRUVICA (ibrutinib)

The drug is administered once daily. It is an oral medication jointly developed by Pharmacyclics LLC and Janssen Biotech. The drug is engineered to block Bruton’s tyrosine kinase protein (BTK). The protein is required by both normal as well as abnormal B cells in order for the B cells to multiply. IMBRUVICA may be able to move and block abnormal B cells from their damaging environment in the bone marrow and lymph nodes of the patient.

One hundred countries have approved IMBRUVICA and 250,000 patients around the world have been treated with the drug. Over fifty clinical trials have been conducted to evaluate IMBRUVICA’s safety and efficacy. The drug has been indicated to treat six diseases for adult patients. Five of which are hematologic cancers.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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