Pharming announces First Patient Enrolled in Pediatric Clinical Trial of leniolisib

Pharming Group announces that the first patient has been enrolled in its Phase III clinical trial (NCT05438407) evaluating the investigational drug leniolisib, an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, in children with activated phosphoinositide 3-kinase delta syndrome (APDS). There is currently no approved treatment for this complex and progressive disease caused by genetic variants.

At sites in the United States, Europe, and Japan, the single-arm, open-label, multinational clinical trial will evaluate the safety, tolerability, and efficacy of leniolisib in approximately 15 children aged 4 to 11 years who have a confirmed APDS diagnosis. 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.

Pharming plans to initiate a similar clinical trial in the third quarter of 2023 that will include children aged 1 to 6 years, with APDS, to evaluate a new pediatric formulation of leniolisib. Eligible patients enrolled in either of the pediatric trials will continue to receive leniolisib for a year after the initial 12-week treatment period through an open-label extension trial.

Manish Butte, MD, PhD, E. Richard Stiehm Endowed Chair, Professor with tenure in the Department of Pediatrics, and Division Chief of Immunology, Allergy, and Rheumatology at UCLA, commented, “In treating APDS, the current standard of care is to use an array of supportive therapies. While these therapies can treat some of the manifestations of APDS, they do not target the underlying cause of the disease. Pharming’s studies of leniolisib in children with APDS are important for evaluating the possibility of minimizing symptoms earlier in the disease progression.”

Pharming’s program for the clinical development of leniolisib in pediatric APDS is supported by positive data from a Phase II/III clinical trial that investigated the drug as a treatment for patients with the disease aged 12 years and older. As announced on February 2, 2022, and recently detailed in Blood1, the international medical journal of the American Society of Hematology, the trial met both its co-primary endpoints, with patients who took leniolisib versus placebo achieving significant reductions in lymphoproliferation as measured by index lymph node size and increases in immunophenotype corrections as measured by the percentage of naïve B cells in peripheral blood. During the first half of 2022, positive opinions were received from the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) on the Pediatric Investigation Plan (PIP) for leniolisib as a treatment for APDS in children. The PIP(s) included the plans for both pediatric clinical trials.

Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented, “I am pleased we have initiated the first trial in our Phase III pediatric clinical program evaluating leniolisib in children with APDS, and I look forward to our second pediatric trial getting underway. Building on the encouraging findings from our successful Phase II/III study in patients aged 12 years and older with APDS, we are committed to bringing leniolisib to even younger patients with the goal of intervening before they develop immune-related symptoms likely to progress throughout their lives. While continuing to focus on patients of all ages with APDS, we are dedicated to collaborating with regulatory authorities with the goal of generating regulatory filings to gain approval that could support the treatment of children under 12 years of age who are living with this disease.”