The U.S. Food and Drug Administration (FDA) on Friday delivered a Complete Response Letter (CRL) to Pharming Group concerning its supplemental New Drug Application (sNDA) for Joenja (leniolisib). The application sought approval to expand the use of Joenja to children between the ages of 4 and 11 diagnosed with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency disorder.
APDS manifests through recurrent respiratory infections, chronic viral infections, and immune system dysfunction. Key clinical features include lymphoproliferation—involving enlargement of the spleen and lymph nodes—as well as autoimmunity and an elevated risk of lymphoma.
In its letter, the FDA highlighted concerns about potential underexposure to Joenja among pediatric patients at the lower weight range. This raised questions regarding whether the proposed dosing adequately ensures comparable drug levels to those observed in adolescents and adults, who already have FDA approval for this treatment.
Consequently, the agency requested additional pediatric pharmacokinetic data to better evaluate and potentially adjust the dosing regimens for these younger, lighter weight children. The goal is to confirm that children in these lower weight categories will achieve Joenja exposure levels similar to those approved for older populations.
The CRL additionally pointed out an issue related to one of the analytical methods employed during production batch testing. The FDA’s request included demands for more comprehensive data and clarifications to address this quality control concern.
Despite these obstacles, Pharming announced plans to arrange a Type A meeting with the FDA, aiming to resolve these regulatory hurdles expediently. Importantly, the FDA’s action does not affect the existing approval of Joenja for patients aged 12 years and older, which was granted in March 2023.
Pharming’s submission for expanded use in younger pediatric patients was supported by data from a Phase 3 clinical study. This multinational, open-label, single-arm trial involved children aged 4 to 11 and assessed treatment effects over 12 weeks.
The study demonstrated improvements in two critical aspects of APDS: a reduction in lymphadenopathy (enlarged lymph nodes) and an increase in naïve B cells. These outcomes suggest partial correction of the underlying immune deficiency associated with APDS. The clinical data also included safety observations from eight months of treatment duration.
Notably, these positive effects on lymphoproliferation and immunophenotype were observed consistently across four dosing levels tested in the trial. This efficacy profile aligns closely with results previously reported in adolescent and adult patient populations receiving Joenja.
Following the FDA's announcement, Pharming’s shares experienced a marked decline. During premarket trading on Monday, the company’s stock fell approximately 16.76% to $17.03, reflecting market reaction to the regulatory setback.
Despite the current challenges, Pharming remains engaged with the FDA to address the agency’s concerns. The supplemental approval for younger children represents an important potential expansion of Joenja’s indication, given the severity of APDS and the limited treatment options available to this patient group.