The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for leniolisib for the treatment of activated phosphoinositide 3-kinase delta syndrome (APDS) in patients 12 years of age and older.
APDS is a rare primary immunodeficiency caused by variants in either the PIK3CD or PIK3R1 genes, which are important to the development and function of white blood cells. Variants of these genes lead to hyperactivity of the phosphoinositide 3-kinase delta (PI3Kδ) pathway resulting in immunodeficiency and dysregulation. Leniolisib is an oral, selective PI3Kδ inhibitor.
The NDA is supported by data from a phase 2/3 trial (ClinicalTrials.gov Identifier: NCT02435173) evaluating the efficacy and safety of leniolisib in patients 12 years of age and older with APDS. Findings showed that leniolisib met the coprimary endpoints demonstrating a statistically significant reduction in index lymph node size (P =.006) and normalization of immunodeficiency (as evidenced by an increased proportion of naïve B cells from baseline; P =.002), compared with placebo. Positive results presented at the Clinical Immunology Society 2022 Annual Meeting further demonstrated the efficacy of leniolisib in reducing disease markers associated with APDS.
As for safety, leniolisib was well tolerated with a lower incidence of serious adverse events reported compared with the placebo arm. The application also includes safety data from a long-term, open-label extension trial (ClinicalTrials.gov Identifier: NCT02859727) that included 38 patients with APDS who received leniolisib for a median of 102 weeks.
“With FDA’s review, leniolisib moves further along the regulatory pathway as a potential disease-modifying targeted treatment for APDS in adults and adolescents 12 years of age and older in the US, who currently rely on supportive therapies such as antibiotics and immunoglobulin replacement therapy,” said Anurag Relan, MD, MPH, Chief Medical Officer of Pharming. “We look forward to continuing to work closely with the FDA, as well as with regulatory authorities across the globe, to make leniolisib available to immunologists, hematologists, and their APDS patients.”
A Prescription Drug User Fee Act goal date of March 29, 2023 has been set for the application.
- Pharming announces US FDA acceptance for Priority Review of its New Drug Application for leniolisib. News release. Pharming Group N.V. Accessed September 28, 2022. https://www.prnewswire.com/news-releases/pharming-announces-us-fda-acceptance-for-priority-review-of-its-new-drug-application-for-leniolisib-301634871.html
- Pharming announces positive data from phase II/III leniolisib trial presented at Clinical Immunology Society 2022 Annual Meeting. News release. Pharming Group N.V. April 1, 2022. Accessed September 28, 2022. https://www.pharming.com/sites/default/files/imce/Press%20releases/Leniolisib%20Trial%20Presented%20at%20Clinical%20Immunology%20Society%202022%2031MAR22%20SEM.pdf