Pharming Group N.V. announced data, including new evidence, from an interim analysis of its open-label extension study evaluating the investigational drug leniolisib, an oral, selective phosphoinositide 3-kinase delta (PI3Kd) inhibitor, to treat adult and adolescent patients with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare 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, U.S., shared the positive findings in an oral presentation at the 2022 Annual Meeting of the American Society of Hematology (ASH). The ongoing extension study includes 37 patients with APDS aged 12 years or older who, at the time of data cutoff for the interim analysis, had received 70 mg of the selective PI3Kd inhibitor leniolisib twice a day for up to six years and three months, with a median duration on study therapy of 102 weeks.

The study was primarily designed to assess the safety and tolerability of long-term leniolisib treatment in adolescent and adult patients with APDS who previously participated in a Phase II/III leniolisib study. The extension study's secondary endpoints are intended to evaluate the efficacy and pharmacokinetics of long-term leniolisib treatment in these patients. The interim analysis found that leniolisib was well tolerated to this point in the study.

It also indicated the durability of the efficacy results seen in the randomized, controlled trial, which showed significant improvement over placebo in the co-primary endpoints of reduction in lymph node size and increase in naïve B cells. The interim results indicate a favorable long-term impact on the immune dysregulation and deficiency often seen in patients with APDS, with clinical manifestations including infections, lymphoproliferation, autoimmunity, enteropathy, bronchiectasis, increased risk of lymphoma, and early mortality. The majority of adverse events (AEs) reported in the interim analysis were grades 1 and 2, and included upper respiratory tract infection, headache and pyrexia.

Grade 1 AEs are the least severe and grade 5 the most severe. Overall, 13.5% of AEs were study drug-related; these affected five patients and included weight gain, arthralgia, hyperglycemia, and decreased neutrophil count. Of all AEs assessed in the analysis, 16.2% were classified as serious, but none of these were identified as related to study treatment.

There was one death among study participants which was identified as not related to study treatment. Among study participants, some experienced reductions in APDS disease markers, with levels of response varying between individuals. Responses included: reduced lymphadenopathy, splenomegaly, and IgM levels; improved or resolved anemia, thrombocytopenia, and lymphopenia; and resolved neutropenia in all affected patients.

Importantly, 37% of participants who were on immunoglobulin replacement therapy (IRT) were able to reduce their IRT use while taking leniolisib. Six patients became IRT-independent, with four of those patients having been IRT-independent for 1 to 2.5 years at the data cutoff. As of the data cut-off for the interim analysis, among three patients who had a history of lymphoma prior to the trial, none had a recurrence or new lymphoma while participating in the study.