Clinical Trials

Date: 2022-04-01

Type of information: Presentation of results at a congress

phase: 2-3

Announcement: presentation of results at the Clinical Immunology Society (CIS) 2022 Annual Meeting

Company: Pharming (The Netherlands)

Product: leniolisib

Action mechanism: phosphoinositide 3-kinase (PI3K) inhibitor. Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA PI3K with immunomodulating and potentially anti-neoplastic activities. Leniolisib inhibits the production of phosphatidylinositol-3-4-5-trisphosphate (PIP3). PIP3 serves as an important cellular messenger specifically activating AKT (via PDK1) and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Unlike PI3K? and PI3K?, which are ubiquitously expressed, PI3K? and PI3K? are expressed primarily in cells of hematopoietic origin. The central role of PI3K? in regulating numerous cellular functions of the adaptive immune system (B-cells and, to a lesser extent, T cells) as well as the innate immune system (neutrophils, mast cells, and macrophages) strongly indicates that PI3K? is a valid and potentially effective therapeutic target for several immune diseases.

Disease: activated phosphoinositide 3-kinase delta (PI3K?) syndrome (APDS)

Therapeutic area: Immunological diseases


Trial details:

Latest news:

  • On April 1, 2022, Pharming announced new data from the pivotal Phase II/III trial of leniolisib for the treatment of activated phosphoinositide 3-kinase delta (PI3K?) syndrome (APDS), a primary immunodeficiency. Principal Investigator V. Koneti Rao, M.D., a staff physician in the Primary Immune Deficiency Clinic at the National Institutes of Health in Bethesda, Maryland, shared the findings in a presentation at the Clinical Immunology Society (CIS) 2022 Annual Meeting.
  • As announced on February 2, 2022, the multinational, triple-blind, placebo-controlled, randomized, Phase III portion of the clinical trial, conducted by Novartis, met its co-primary endpoints, which evaluated reduction in lymph node size and correction of immunodeficiency. The shrinking of lymphadenopathy lesions and increased proportion of naïve B cells are important in this population, as they indicate a reduction in APDS disease markers. Presented for the first time at CIS, the co-primary endpoints at day 85 after baseline demonstrated: - In the index lymphadenopathy lesions, a statistically significant adjusted mean change in the log10 transformed sum of product of diameters (SPD) of -0.30 among patients who received leniolisib compared with -0.06 among patients who received placebo (95% CI: -0.37, -0.11; p=0.0012). - From a baseline level of ?48%, an increase of 34.76% in the proportion of naïve B cells in patients who received leniolisib versus a -5.37% decrease in patients who received placebo (95% CI: 28.51, 51.75; p?0.0001). - The study drug was well-tolerated. There were no adverse events that led to discontinuation of study treatment, there were no deaths, and the incidence of serious adverse events (SAEs) was lower in the leniolisib group than in the placebo group. None of the SAEs were suspected to be related to study treatment.
  • Pharming plans to begin submitting global regulatory filings for leniolisib in the second quarter of 2022 and, subject to approval, launching the treatment in the U.S. in the first quarter of 2023 and starting a series of European launches in the second half of 2023.

Is general: Yes