Leniolisib: positive phase 3 data in children aged 4 to 11 years with APDS

Leniolisib: positive phase 3 data in children aged 4 to 11 years with APDS | Image Credit: © ธนากร บัวพรหม - © ธนากร บัวพรหม - stock.adobe.com.

In a phase 3 clinical trial (NCT05438407) among children aged 4 to 11 years with activated phosphoinositide 3-kinase delta syndrome (APDS), leniolisib (Joenja; Pharming Group N.V.) demonstrated topline positive results, according to an announcement from Pharming Group N.V.

The oral small molecule phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor was approved in the United States for adult and pediatric patients aged 12 years and older in March of 2023 as the first and only targeted treatment indicated for APDS.

The syndrome is a rare primary immunodeficiency that is caused by variants in either of the PIK3CD or PIK3R1 genes, which are vital to the development and function of immune cells in the body, according to Pharming Group. The progressive disease is characterized by symptoms including severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy.

"Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, it has been reported that people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay," the company stated in a press release.

The study enrolled 21 children with APDS aged 4 to 11 years from locations the United States, Europe, and Japan, evaluating the safety, tolerability, and efficacy of leniolisib in a single-arm, open-label design.

The primary efficacy endpoints were 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.

Initial results on all 21 patients who completed the 12-week treatment period demonstrated lymphoproliferation improvement, measured by a mean reduction in index lesion size, and immunophenotype correction demonstrated by an increase in the percent of naïve B cells.

These improvements were present across the 4 dose levels being investigated and were consistent with the improvements previously reported in adolescent and adult patients, according to the press release.

“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," said Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, in a statement.

"Two hallmarks of APDS, lymphoproliferation and abnormal immunophenotype, showed improvement from baseline to 12 weeks in this single arm study," added Relan. "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."

Eligible patients who enrolled in this trial will continue to receive leniolisib for an additional year through an open-label extension trial, with the aim to further evaluate safety, tolerability, and efficacy. Additionally, stated Pharming, a separate phase 3 clinical trial including children aged 1 to 6 years with APDS is ongoing.

"These results highlight the potential for leniolisib to help pediatric patients living with APDS and their families," said 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.

"The pediatric APDS community is in need of more treatment options, and we look forward to leniolisib being one of those options," added Butte.

Reference:

Pharming announces positive topline data in pediatric clinical trial of leniolisib. Pharming Group N.V. Press release. December 11, 2024. Accessed December 11, 2024. https://www.pharming.com/sites/default/files/imce/Press%20releases/Pharming%20announces%20topline%20data%20pediatric%20clinical%20trial%20leniolisib_EN_11DEC24.pdf