Pediatric Indication and New Dosage Form for Imbruvica
AbbVie’s Imbruvica® (ibrutinib) was approved by the U.S. Food and Drug Administration (FDA) for children as young as one year old who have been treated previously for chronic cases of graft versus host disease (cGVHD) on Aug. 24, 2022. This is the first pediatric indication approved for Imbruvica, a Bruton’s tyrosine kinase (BTK) inhibitor. At the same time, an oral suspension form was approved for patients who cannot swallow capsules easily. A complication of hematopoietic (stem) cell transplants (HCT), cGVHD occurs when immune cells in the donated tissue (the graft) continually attack organs and tissues of the transplant recipient (the host), resulting in inflammation and fiber formation in multiple parts of the body. The skin, gastrointestinal (GI) system, and liver frequently are affected, but many other organs also may be damaged by cGVHD, which can be fatal. Currently, a corticosteroid, the usual prednisone, is the first-line therapy for pediatric cGVHD. In 2020, about 2,500 patients under the age of 18 years had HCTs and about one-quarter of them are estimated to develop cGVHD within three years from the transplant. For children between the ages of one year and 12 years, the recommended dose of Imbruvica to treat cGVHD is based on the child’s body surface area (BSA) at 240mg/m2, but no more than 420mg, once a day. For older patients, the daily dose is 420mg. Imbruvica also is approved for other adult conditions, including several types of cancer. Imbruvica’s revised prescribing information is here.
New Indication for Pemazyre
On Aug. 25, 2022, the FDA approved Pemazyre® (pemigatinib – Incyte) tablets as the first specific drug treatment for adults who have been treated previously formyeloid/lymphoid neoplasms (MLNs) that have rearrangements of fibroblast growth factor receptor 1 (FGFR1) genes. A rapidly progressing group of blood cancers, MLNs affect only a few thousand patients in the United States. Current treatment includes chemotherapy (chemo), but most kinase inhibitors, such as imatinib, typically are not effective. Even after allogeneic HCTs, many patients relapse and the survival rate is low. Pemazyre blocks the activity of FGFR 1, 2 and 3, which are believed to promote cancer growth. In a clinical trial of 28 patients, 22 responded to treatment with it. However, over one-half of participants experienced high phosphate levels in their blood and side effects that included loss of hair and fingernails/toenails, diarrhea, and dry eyes. The recommended dose of Pemazyre for MLNs is 13.5mg once every day until cancer worsens or the patient cannot take the drug any longer. Taking Pemazyre may damage the retinas, so patients should have eye examinations every two months for the first six months and then once every three months while treatment continues. Because it also may elevate blood phosphate to unsafe levels, patients may need to follow a low-phosphate diet, take phosphate-reducing drugs or discontinue Pemazyre if phosphate levels cannot be controlled. Its use is not recommended during pregnancy since it may harm a developing baby. Pemazyre also has the FDA’s Accelerated Approval for adults previously treated for cholangiocarcinoma that has a FGFR2 fusion or another rearrangement that has spread and that cannot be removed by surgery. An FDA-approved test is available to detect FGFR2 abnormalities, but tests for FGFR1 are not yet approved in the U.S. Look here for updated prescribing information for Pemazyre.