Notable Approval: FDA approves first treatment for children aged 4-11 years with APDS, a rare genetic disorder of the immune system Action

https://clinicaltrials.gov/study/NCT02435173?utm_medium=email&utm_source=govdelivery Notable Approval: FDA approves first treatment for children aged 4-11 years with APDS, a rare genetic disorder of the immune system Action FDA has approved Joenja (leniolisib) tablets as the first treatment for activated phosphoinositide 3-kinase delta syndrome (APDS) in children 4-11 years who weigh at least 27 kg. Joenja was first approved in 2023 for the same indication in patients 12 years and older at a dose of 70 mg orally twice a day. Children 4-11 years take a weight-based dosage (40, 50, or 70 mg) orally twice a day, approximately 12 hours apart. https://clinicaltrials.gov/study/NCT05438407?utm_medium=email&utm_source=govdelivery Disease or Condition Activated PI3K delta syndrome (APDS) is a rare genetic disorder that impairs cells of the immune system. These cells are necessary to recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. People with APDS develop recurrent infections, particularly in the sinuses, ears, and respiratory tract. They also develop enlarged lymph nodes, tonsils, spleen, and other organs that can cause obstruction in the airway and gastrointestinal tract. Individuals with this condition often have low numbers of white blood cells, including red cells and platelets. Patients with APDS are more prone to develop blood cell cancers, like lymphoma. APDS is caused by mutations in the PIK3CD or PIK3R1 genes that encode a protein called phosphoinositide-3 kinase delta (PI3K delta), which is important for the normal development and function of white blood cells in the body. Effectiveness For the original approval for patients 12 years and older with APDS, the efficacy of Joenja was evaluated in the placebo-controlled portion of Study 2201 (NCT02435173). This was a 12‑week blinded, randomized, placebo-controlled study of 31 patients 12 years and older with confirmed APDS-associated genetic PI3K delta mutations, with a documented variant in either PIK3CD or PIK3R1. During the study, 21 patients received 70 mg of Joenja and 10 received placebo twice a day for 12 weeks. The co‑primary efficacy endpoints were improvement in lymphoproliferation (lymph node reduction) and the normalization of immunophenotype as measured by the percentage of naïve B cells out of total B cells. By day 85 of the study, patients taking Joenja saw a reduction in lymph node size and a 37 percent improvement in naïve B cells counts compared to placebo, indicating a correction of the underlying immune defect. For the approval for patients aged 4-11 years, safety and pharmacokinetic data were established from a single-arm, open-label study (Study LE 3301). In this study, 8 patients received the recommended Joenja dosage based on body weight. The pharmacokinetic data demonstrated no clinically significant difference between patients younger or older than 12 years. Safety Information The most common side effects of Joenja in children aged 4-11 were stomach pain, respiratory tract infection, diarrhea, headache, cough, nausea, rhinitis, and alopecia. Patients with moderate-to-severe liver impairment should not use Joenja. See full prescribing information for additional information on risks associated with Joenja. Designations Joenja received orphan drug designation, rare pediatric disease designation, and priority review.