Pharming Group updates on European regulatory review of leniolisib for APDS treatment

Pharming Group N.V., based in Leiden, the Netherlands, has provided an update regarding its Marketing Authorisation Application (MAA) for leniolisib, a treatment for patients aged 12 and older with activated phosphoinositide 3-kinase delta syndrome (APDS). This announcement came after a recent meeting of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

Following the CHMP meeting from May 27-30, Pharming received a List of Outstanding Issues (LoOI) which highlighted both the clinical benefits and safety of leniolisib, echoing an earlier assessment by the Ad Hoc Expert Group (AEG). However, the LoOI included a remaining request relating to the chemistry, manufacturing, and controls (CMC) for leniolisib. Specifically, the CHMP requested more detailed information about the regulatory starting materials used in the manufacturing process. While Pharming had proposed to address this post-approval, the CHMP insisted on pre-approval completion and extended the deadline to January 2026 for Pharming to submit the necessary data. Pharming has already commenced the required manufacturing activities to meet this request.

Pharming's CEO, Sijmen de Vries, expressed disappointment over the delay in obtaining the European license but remained optimistic due to the CHMP’s acknowledgment of the clinical benefits of leniolisib. De Vries emphasized the importance of leniolisib in addressing an unmet medical need, supported by over 300 patient-years of treatment data from both clinical trials and real-world experience. He assured that Pharming would continue collaborating with the EMA and CHMP to secure approval for leniolisib in Europe while maintaining their clinical development and early access programs.

The MAA for leniolisib was supported by data from a multinational, triple-blind, placebo-controlled, randomized Phase II/III clinical trial involving 31 APDS patients aged 12 and older. The trial successfully met its co-primary endpoints, demonstrating efficacy and safety. Additionally, data from a long-term, open-label extension study involving 37 patients treated with leniolisib for a median duration of three years were included in the application.

Leniolisib is already available in the United States, having been approved by the FDA in March 2023 based on its clinical and manufacturing merits. Pharming continues to maintain its 2024 revenue guidance as previously indicated.

APDS is a rare immunodeficiency first identified in 2013, caused by variants in the PIK3CD or PIK3R1 genes, essential for immune cell development and function. These genetic variants result in an overactive PI3Kδ pathway, leading to immune cell dysfunction and subsequent immunodeficiency. Symptoms often include severe sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy. Due to symptom overlap with other conditions, APDS is frequently misdiagnosed, leading to delayed diagnosis and potential complications like permanent lung damage and lymphoma. Genetic testing is required for a definitive diagnosis. The global APDS prevalence is about 1 to 2 individuals per million.

Leniolisib, an oral PI3Kδ inhibitor, is the first targeted treatment for APDS in patients 12 years and older. It works by inhibiting the production of a crucial cellular messenger, thus regulating various cell functions. Clinical trials have shown leniolisib’s efficacy in addressing immune dysregulation and normalizing immunophenotype, with long-term safety and tolerability confirmed through ongoing studies. Currently, leniolisib is under review in several regions, including the European Economic Area, the U.K., Canada, and Australia, with plans to seek approval in Japan and South Korea. Additionally, leniolisib is being evaluated in Phase III trials for pediatric APDS patients.

Pharming Group N.V. is a global biopharmaceutical company focused on developing treatments for rare and serious diseases. With a presence in over 30 markets, Pharming continues to expand its portfolio of therapies aimed at improving patient lives.