Pharming Group begins Phase II trial of leniolisib for PIDs with immune dysregulation

Pharming Group N.V. has announced the commencement of a Phase II clinical trial to investigate the efficacy of leniolisib in primary immunodeficiencies (PIDs) characterized by immune dysregulation due to altered PI3Kẟ signaling in lymphocytes. This trial will focus on patients with specific conditions including ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency, and PTEN deficiency, which collectively have a prevalence rate approximately five times higher than that of activated phosphoinositide 3-kinase delta syndrome (APDS).

The clinical trial is currently open for enrollment and aims to include about 12 participants. As an open-label, single-arm, dose-ranging study, the trial's main objectives are to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and potential clinical efficacy of leniolisib. This Phase II study is designed to inform the structure of a subsequent Phase III trial. The study is being carried out at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), under the guidance of lead investigator Dr. Gulbu Uzel and co-investigator Dr. V. Koneti Rao.

Dr. Anurag Relan, Chief Medical Officer of Pharming, emphasized the importance of this study as a significant milestone for the company. He noted that leniolisib, which has shown promise in treating APDS, may offer therapeutic benefits for other PIDs with underlying immune dysregulation and deficiencies, such as ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency, and PTEN deficiency. The initiation of this clinical trial marks Pharming's expansion of leniolisib's application beyond APDS.

The trial's first patient enrollment is expected to occur in the upcoming weeks. This initiative is Pharming's first effort to explore leniolisib in a broader range of PIDs with immune dysregulation. The genetic variations in ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency, and PTEN deficiency patients lead to increased PI3Kẟ signaling, resulting in immune dysregulation similar to that seen in APDS. Specifically, PTEN deficiency is often described as 'APDS-like,' with ALPS-FAS patients experiencing lymphoproliferative symptoms and frequent cytopenic episodes. Patients with CTLA4 and NFKB1 haploinsufficiency often face lymphoproliferative, cytopenic, and autoimmune/inflammatory complications.

Leniolisib, an oral small molecule PI3Kẟ inhibitor, is already marketed in the U.S. and approved in several other countries for APDS treatment in patients aged 12 and older. This drug functions by inhibiting phosphatidylinositol-3-4-5-trisphosphate production, which is crucial for various cellular functions, including proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Previous clinical trials have shown significant improvements in patients with APDS, highlighting leniolisib’s potential in addressing immune dysregulation and deficiency. The drug is currently under regulatory review in several regions, including the European Economic Area, Canada, and Australia, and further approvals are being pursued in Japan and South Korea. Leniolisib is also being evaluated in two Phase III trials for children with APDS and in a Phase II trial for PIDs with immune dysregulation linked to altered PI3Kẟ signaling.

Pharming Group N.V. is committed to transforming the lives of patients with rare and severe diseases. The company is developing a diverse portfolio of therapies, including protein replacement and precision medicines, and has a global presence, serving patients in over 30 markets worldwide.