The US Food and Drug Administration (FDA) has granted approval to Janssen Pharmaceutical Companies of Johnson & Johnson and AbbVie’s Imbruvica (imbrutinib) for pediatric patients with chronic graft-versus-host disease (cGVHD). This is Imbruvica’s first approval for a pediatric indication.
The drug, which is available as a new oral suspension formulation, is intended for the treatment of pediatric patients one year of age and older with cGVHD who have failed one or more lines of systemic therapy, such as corticosteroids.
The milestone approval makes it the first FDA-approved treatment for young patients in this age group (one year to under 12 years of age) who previously had no approved treatment options for the life-threatening disease. It is also the first approval for the liquid form of the drug.
Imbruvica got its first FDA approval for cGVHD in 2017 for individuals 12 years of age and older.
cGVHD is a life-threatening complication that can occur after an allogeneic transplant involving stem cells or bone marrow where the newly transplanted donor cells attack the recipient’s body.
Symptoms of the condition can include development of scar tissue in the skin and joints, skin rash, mouth sores, dry eyes, liver inflammation and lung damage. It is estimated that 52 to 65 percent of children who receive such transplants develop cGVHD.
The drug is approved in more than 100 countries and has been used to treat more than 250,000 patients worldwide, according to the press release from Johnson & Johnson announcing the latest approval. The company added that there are more than 50 company-sponsored clinical trials, including 18 Phase III studies, and more than 11 years having been devoted to evaluating the drug’s efficacy and safety.
The liquid form of the drug is notable as it allows it to be dissolved and administered in a drink. The new formulation, which is administered once a day, helps children who have trouble swallowing capsules or tablets, said Paul Carpenter, MD, lead investigator of the trial evaluating Imbruvica in pediatric patients, in a statement.
The latest FDA nod makes Imbruvica the only Bruton’s tyrosine kinase inhibitor (BTKi) with 12 FDA approvals across seven indications that include cGVHD and five hematologic cancers, including mantle cell lymphoma and chronic lymphocytic leukemia (CLL).
Imbruvica is a small molecule BTKi. Bruton’s tyrosine kinase promotes the growth of both normal and abnormal B cells (such as cancer cells), allowing them to multiply and spread. The drug also targets interleukin-2-inducible T-cell kinase (ITK), which is involved in T cell proliferation and differentiation.
The approval for the new indication was based on results from the Phase I/II iMAGINE study, which showed an overall response rate (ORR) of 60 percent through week 25 in patients one to 19 years of age with moderate to severe cGVHD. According to the trial results, safety was consistent with the established profile for Imbruvica, with observed adverse events (AEs) in pediatric patients consistent with those observed in adult patients with moderate to severe cGVHD.
Imbruvica’s approval addresses a significant unmet need in young patients with cGVHD given the limited treatment options.
“The pediatric cGVHD community is a prime example of an underserved patient population with high unmet medical needs for whom Janssen is committed to developing life-saving therapies,” said Craig Tendler, MD, Global Head of Late Development, Diagnostics & Medical Affairs, Hematology & Oncology Janssen Research & Development, LLC.
Dr. Tendler said, “cGVHD has life-threatening implications for children, and we are deeply proud of the opportunity to make an impact for these young patients with Inbruvica and their families.”
The only other approved cGVHD treatment for younger patients is Bristol Myers Squibb’s rheumatoid arthritis drug Orencia, which received an FDA nod as a preventative for cGVHD in individuals two years of age and older.