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FDA Approves Imbruvica for Treatment of Children with Chronic Graft Versus Host Disease

August 26, 2022

The U.S. Food and Drug Administration approved the use of AbbVie’s Imbruvica for the treatment of pediatric patients one year and older with chronic graft versus host disease after failure of one or more lines of systemic therapy

Photo: Susan Stewart, executive director of BMT InfoNet

The approval marks the first approved treatment option for children under 12 years of age suffering from chronic graft versus host disease (cGVHD). The approval is based on positive results from the iMAGINE phase 1/2 clinical trial. Imbruvica was the first treatment approved in the United States in 2017 for adult patients with cGVHD after failure of one or more lines of systemic therapy

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. cGVHD impacts major organs, including the skin, eyes, mouth and liver as the most commonly affected. 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. Additionally, cGVHD is the most common cause of morbidity after an allogeneic transplant. Steroids are the current standard treatment for pediatric cGVHD.

Imbruvica is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. Imbruvica the Bruton’s tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, Imbruvica may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.

“For a substantial fraction of children who develop moderate or severe chronic graft versus host disease after blood or marrow transplantation, treatment options supported by methodical, formal study in children are limited,” said Paul Carpenter, attending physician at Seattle Children’s Hospital and a study principal investigator. “Now, healthcare professionals have another effective treatment option for both pediatric and adult patients living with this disease after failure of one or more lines of systemic therapy. Additionally, having an oral suspension formulation designed for children is a helpful alternative.”

iMAGINE is an open-label, multi-center, single-arm trial of Imbruvica for the treatment of pediatric and young adult patients aged one year to less than 22 years with moderate or severe cGVHD as defined by NIH Consensus Criteria. The study included 47 patients who required additional therapy after failure of one or more prior lines of systemic therapy. Patients aged 12 years and older were treated with Imbruvica 420 mg orally once daily, and patients aged one year to less than 12 years were treated with Imbruvica 240 mg/m2 orally once daily. Primary endpoints included pharmacokinetics (PK) and safety, and secondary endpoints included overall response rate (ORR; CR/PR) per 2014 NIH criteria, overall survival, and duration of response (DOR).

The iMAGINE study demonstrated an Overall Response Rate (ORR) through week 25 of 60 percent  in patients median age 13 years with relapsed/refractory (R/R) moderate to severe cGVHD. The median duration of response was 5.3 months. Safety was consistent with the established profile for Imbruvica, with observed adverse reactions (ARs) consistent with those observed in adult patients with moderate to severe cGVHD. The most common ARs (occurring in 20 percent or more of patients), including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.

“In some ways, children struggling with cGVHD have been an ‘orphan population’ in relation to having treatment options available. Although there has been progress in approved treatment options for adults with cGVHD, the safety and efficacy of these have not been well studied in children,” said Susan Stewart, executive director of BMT InfoNet, a non-profit advocacy organization for bone marrow, stem cell and cord blood transplant patients. “This FDA approval of Imbruvica gives children and their families struggling with this very difficult disease newfound hope.”

Author: Rare Daily Staff

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