Japan’s MHLW has approved Pharming’s Joenja (leniolisib) for activated PI3K delta syndrome (APDS) in adults and children aged 4+, marking the first targeted therapy for the rare immunodeficiency in the country.
Written By: Karthik Teja Macharla PharmD
Reviewed By: Pharmacally Editorial Team
Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Joenja® (leniolisib) for the treatment of activated phosphoinositide 3-kinase delta syndrome (APDS) in adults and pediatric patients aged 4 years and older, marking the first approved therapy for this rare primary immunodeficiency in Japan.
The approval also represents a global milestone, as leniolisib becomes the first therapy approved anywhere for children aged 4 to 11 years with APDS, expanding treatment access to younger patients affected by the condition. In Japan, OrphanPacific, Inc. will serve as the marketing authorization holder and will manage supply and distribution in collaboration with Pharming. Commercial launch is expected after pricing negotiations under Japan’s National Health Insurance system.
Targeted Therapy for a Rare Immune Disorder
APDS is a rare, progressive primary immunodeficiency caused by mutations in the PIK3CD or PIK3R1 genes, which regulate immune cell development and signaling. These mutations lead to hyperactivation of the PI3Kδ pathway, resulting in immune dysregulation, recurrent infections, lymphoproliferation, and autoimmune complications. The disease affects approximately 1–2 people per million worldwide, and patients often face a median diagnostic delay of about seven years due to overlapping symptoms with other immune disorders.
Leniolisib is an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor designed to target the underlying signaling pathway driving the disease. By inhibiting PI3Kδ activity, the therapy helps restore immune cell balance and function, addressing both immune deficiency and dysregulation associated with APDS.
Phase III Clinical Data Supporting Approval
The Japanese approval was supported by data from Pharming’s Phase III clinical development program (NCT02435173) for leniolisib. In a global randomized, placebo-controlled study involving patients aged 12 years and older, the therapy met its co-primary endpoints, significantly reducing lymph node enlargement (lymphadenopathy) and increasing the proportion of naïve B cells among total B cells key indicators of improved immune regulation.
Additional evidence included an open-label Japanese study (NCT06249997) in patients aged 12 years and older and a multinational Phase III study (NCT05438407) in children aged 4 to 11 years, which demonstrated improvements over 12 weeks in lymphadenopathy and naïve B-cell levels. The treatment was generally well tolerated, with the most common adverse reactions including headache, sinusitis, and atopic dermatitis.
Professor Hirokazu Kanegane said the approval represents an important advance for patients with APDS in Japan, who have largely relied on supportive care until now. He noted that the availability of a targeted therapy could significantly reduce disease burden for patients and their families.
Leverne Marsh, Chief Commercial Officer of Pharming, described the approval as a major milestone, highlighting that Joenja is the first therapy approved in Japan specifically for APDS and the first globally authorized treatment for children aged 4–11 with the condition. He added that the company will work with OrphanPacific to make the therapy available to patients in Japan as soon as possible.
Regulatory Pathway and Global Status
Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) evaluated the application under the Priority Review pathway, following the drug’s Orphan Drug Designation granted by MHLW in May 2023.
Joenja is already approved in the United States and the United Kingdom for patients aged 12 years and older with APDS, and regulatory submissions are currently under review in the European Economic Area, Canada, and other regions. Pharming is also exploring the potential of leniolisib in additional primary immunodeficiencies associated with immune dysregulation through ongoing Phase II clinical trials.
Reference
Pharming Group announces approval of Joenja® (leniolisib) in Japan for the treatment of APDS in patients aged 4 years and older, 24 March 2026, https://www.pharming.com/sites/default/files/imce/Press%20releases/News%20items/FINAL_Pharming%20Group%20announces%20approval%20of%20Joenja%C2%AE%20in%20Japan_EN_24Mar2026.pdf
Study of Efficacy of CDZ173 in Patients With APDS/PASLI, ClinicalTrials.gov ID NCT02435173, https://clinicaltrials.gov/study/NCT02435173
An Open-Label Study to Assess the Safety & Efficacy of Leniolisib in Japanese Patients With APDS, ClinicalTrials.gov ID NCT06249997, https://clinicaltrials.gov/study/NCT06249997
Pediatric Patients Aged 4 to 11 Years With APDS, ClinicalTrials.gov ID NCT05438407, https://clinicaltrials.gov/study/NCT05438407
About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.