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

Pharming Group N.V., a prominent biopharmaceutical company based in Leiden, the Netherlands, has initiated a Phase II clinical trial to evaluate leniolisib, a promising therapeutic candidate, in patients diagnosed with common variable immunodeficiency (CVID) exhibiting immune dysregulation. This study marks an important step in addressing the significant unmet medical needs of CVID patients, who often suffer from severe autoimmune and lymphoproliferative complications due to their immune dysfunction.

The Phase II trial is structured as a single-arm, open-label, dose-finding study. It aims to enroll around 20 patients aged 12 and above who have been diagnosed with CVID. To participate, patients must display evidence of lymphoproliferation and at least one additional immune dysregulation manifestation, such as interstitial lung disease, autoimmune cytopenias, or enteropathy. The primary objectives of this trial are to assess the safety and tolerability of leniolisib, as well as its pharmacokinetics and pharmacodynamics. Furthermore, the study aims to explore the potential clinical efficacy of leniolisib in treating this specific CVID patient population.

Dr. Jocelyn Farmer, the lead investigator of this Phase II study, serves as the Director of the Clinical Immunodeficiency Program at Beth Israel Lahey Health in Massachusetts. She emphasizes the severe burden faced by patients with CVID due to the lack of effective treatment options. Dr. Farmer believes that leniolisib, which acts as a phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor, holds significant promise in addressing the immune dysregulation experienced by these patients. This disorder often leads to early mortality, and leniolisib’s ability to modulate lymphocyte functions, such as proliferation and immune response, offers hope for a new therapeutic approach.

CVID is recognized as the largest subgroup of symptomatic primary immunodeficiency (PID) disorders. It is characterized by a spectrum of clinical manifestations that resemble those seen in activated phosphoinositide 3-kinase delta syndrome (APDS), with nearly half of CVID patients presenting autoimmune or lymphoproliferative conditions. The global prevalence of CVID with immune dysregulation is estimated at about 39 individuals per million. These patients face a significantly increased mortality risk, underscoring the urgent need for innovative therapies.

Dr. Anurag Relan, Chief Medical Officer at Pharming, highlights the expansion of the company's research efforts beyond the initial focus on APDS. The commencement of this second Phase II clinical trial illustrates Pharming’s commitment to broadening its work in the realm of primary immunodeficiency disorders. Unlike APDS, CVID patients are diagnosed based on clinical criteria rather than genetic markers, making the development of targeted treatments critical for this larger patient population. Dr. Relan expresses optimism about leniolisib’s potential to transform the care landscape for CVID patients with immune dysregulation.

Currently, leniolisib is marketed in the United States under the brand name Joenja® for treating APDS in patients aged 12 and older. As a PI3Kẟ inhibitor, leniolisib works by blocking the production of phosphatidylinositol-3-4-5-trisphosphate, a key cellular messenger involved in various immune cell functions. Previous clinical trials have demonstrated significant improvements in immune dysregulation and deficiency symptoms in patients treated with leniolisib.

Pharming Group N.V. remains committed to advancing its clinical programs and exploring new therapeutic applications for leniolisib, with ongoing regulatory reviews and planned Phase III trials targeting pediatric populations and additional primary immunodeficiencies. Through these efforts, Pharming aims to broaden the availability of leniolisib and address the diverse needs of patients with rare immune disorders.