Pharming Group has released positive topline results of data from its Phase III clinical trial (NCT05438407) evaluating the investigational drug leniolisib, an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, in children aged 4 to 11 years with activated phosphoinositide 3-kinase delta syndrome (APDS).

Leniolisib, marketed under the brand name Joenja in the US, received approval from the US Food and Drug Administration (FDA) for the treatment of APDS in adult and pediatric patients 12 years of age and older in March 2023.

Pharming plans to include data from this 4-11-year-old trial in regulatory filings worldwide for the approval of leniolisib for pediatric patients with APDS, beginning in 2025.

Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented, “This is the first data from a clinical trial for younger pediatric patients with APDS, who have a significant unmet need for a disease modifying treatment. Two hallmarks of APDS, lymphoproliferation and abnormal immunophenotype, showed improvement from baseline to 12 weeks in this single arm study. More than a quarter of known APDS patients are below the age of 12, so having a potential treatment option for these patients who suffer from a progressive, serious condition could be very important. We look forward to initiating regulatory filings for these younger pediatric patients in 2025.”

The study enrolled 21 children with APDS ages 4 to 11 years at sites in the United States, Europe, and Japan. The single-arm, open-label clinical trial is evaluating the safety, tolerability, and efficacy of leniolisib. The study’s primary efficacy endpoints are a reduction in index lymph node size and an increased proportion of naïve B cells out of total B cells from baseline at 12 weeks.

Secondary endpoints include an assessment of the ability of leniolisib to modify health-related quality of life based on measures of physical, social, emotional, and school functioning using a validated patient questionnaire. These endpoints mirror those used to evaluate the clinical outcomes in previous leniolisib APDS trials for patients aged 12 and older.

All 21 patients enrolled completed the 12-week treatment period. Lymphoproliferation improved as measured by a mean reduction in index lesion size and immunophenotype correction was demonstrated by an increase in the percent of naïve B cells. The improvement in lymphoproliferation and immunophenotype correction were seen across the four dose levels being investigated and were consistent with the improvements previously reported in adolescent and adult patients.

All treatment emergent adverse events were reported to be mild to moderate in nature. There were no drug related serious adverse events, and all patients completed the 12-week treatment period.

Manish Butte, MD, PhD, E. Richard Stiehm Endowed Chair and Professor and Division Chief, Department of Pediatrics, Division of Immunology, Allergy and Rheumatology, and Department of Microbiology, Immunology and Molecular Genetics UCLA, commented, “The 12-week data from the first clinical study evaluating leniolisib in pediatric APDS patients is encouraging. These results highlight the potential for leniolisib to help pediatric patients living with APDS and their families. The pediatric APDS community needs more treatment options, and we look forward to leniolisib being one of those options.”