The US Food and Drug Administration has approved leniolisib (Joenja) to treat activated phosphoinositide 3-kinase delta syndrome in pediatric patients aged 4 to 11 years weighing at least 27 kg, according to a press release from the agency. The treatment has been available for patients aged 12 years and older since its initial approval in 2023.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that impairs immune system cells needed to recognize and attack foreign invaders, including viruses and bacteria. Recurrent sinus, ear, and respiratory tract infections are among the manifestations of APDS. The condition can also cause enlargement of the lymph nodes, tonsils, spleen, and other organs, potentially resulting in airway and gastrointestinal tract obstruction.

APDS is caused by mutations in PIK3CD or PIK3R1, which encode phosphoinositide 3-kinase delta, a protein involved in the normal development and function of white blood cells.

For the original approval in patients aged 12 years and older, efficacy was evaluated in Study 2201, a 12-week, blinded, randomized, placebo-controlled study of 31 patients with confirmed APDS-associated genetic phosphoinositide 3-kinase delta mutations. Twenty-one patients received leniolisib 70 mg twice daily and 10 received placebo twice daily for 12 weeks. The study had coprimary efficacy end points: improvement in lymphoproliferation, assessed by lymph node reduction, and immunophenotype normalization, assessed by the proportion of naïve B cells among total B cells.

At day 85, lymph node size was reduced among patients receiving leniolisib, and naïve B-cell counts improved by 37% compared with placebo.

Study LE 3301 provided safety and pharmacokinetic evidence for the younger age group. The single-arm, open-label study included 8 patients who received weight-based leniolisib. Pharmacokinetic data showed no clinically significant difference between patients younger or older than 12 years.

Patients aged 4 to 11 years receive leniolisib orally twice daily at weight-based doses of 40, 50, or 70 mg administered approximately 12 hours apart. The most common adverse effects in this age group were abdominal pain, respiratory tract infection, diarrhea, headache, cough, nausea, rhinitis, and alopecia. Patients with moderate to severe liver impairment should not receive leniolisib.

Leniolisib received orphan drug and rare pediatric disease designations, as well as priority review.

Source: US Food and Drug Administration