お知らせ • Mar 24
Pharming Group N.V. Announces Approval of Joenja for Treatment of APDS in Japan
Pharming Group N.V. announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Joenja (leniolisib), an oral, selective phosphoinositide 3-kinase (PI3K) delta inhibitor, for the treatment of activated PI3K delta syndrome (APDS) in adult and pediatric patients aged 4 years and older. With this approval, Joenja becomes the first treatment approved in Japan specifically for APDS and the first approved treatment anywhere globally, for children aged 4 to 11 with the disease. Under an agreement with Pharming, OrphanPacific Inc. serves as the Marketing Authorization Holder for Joenja in Japan and in collaboration with Pharming, is responsible for supply and distribution of the product. The launch of Joenja is expected following agreement with the MHLW on its National Health Insurance drug price. The MHLW based the approval on data from Pharming’s Phase III clinical program for leniolisib in APDS, including the global, randomized, placebo-controlled study in patients aged 12 years and older, in which leniolisib met its co-primary endpoints by significantly reducing lymphadenopathy and significantly increasing the percentage of naïve B cells out of total B cells. This reflects a clinically relevant impact on immune dysregulation and deficiency which are hallmarks of APDS. Leniolisib was generally well tolerated with the most common adverse reactions (>10%) being headache, sinusitis, and atopic dermatitis. Supporting Phase III evidence also included the open-label Japanese study in patients aged 12 years and older, as well as positive data from the open-label, multinational Phase III study in children aged 4 to 11 years, including sites in Japan, which showed improvements over 12 weeks in reduced lymphadenopathy and increased percentage of naïve B cells from total B cells. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) evaluated the application under the Priority Review pathway following the Orphan Drug Designation granted by the MHLW in May 2023. Joenja is approved and marketed in the United States and the United Kingdom for patients 12 years of age and older with APDS. APDS is a rare primary immunodeficiency that was first characterized in 2013. APDS is caused by variants in either one of two identified genes known as PIK3CD or PIK3R1, which are vital to the development and function of immune cells in the body. Variants of these genes lead to hyperactivity of the PI3Kd (phosphoinositide 3-kinase delta) pathway, which causes immune cells to fail to mature and function properly, leading to immunodeficiency and dysregulation APDS is characterized by a variety of symptoms, including severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy. Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, it has been reported that people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay. As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma. A definitive diagnosis can be made through genetic testing. APDS affects approximately 1 to 2 people per million worldwide. Leniolisib is an oral small molecule phosphoinositide 3-kinase delta (PI3K?) inhibitor approved as the first and only targeted treatment of activated phosphoinositide 3-kinase delta (PI3Kd) syndrome (APDS) in the U.S., U.K., Australia and Israel in adult and pediatric patients 12 years of age and older and in Japan for patients 4 years of age and older. Leniolisib inhibits the production of phosphatidylinositol-3-4-5-trisphosphate, which serves as an important cellular messenger and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Results from a randomized, placebo-controlled Phase III clinical trial demonstrated statistically significant improvement in the coprimary endpoints, reflecting a favorable impact on the immune dysregulation and deficiency seen in these patients, and open label extension data has supported the safety and tolerability of long-term leniolisib administration. Leniolisib is currently under regulatory review for the treatment of APDS in the European Economic Area, Canada and several other countries. Leniolisib is also being evaluated in two Phase II clinical trials in primary immunodeficiencies (PIDs) with immune dysregulation. The safety and efficacy of leniolisib has not been established for PIDs with immune dysregulation beyond APDS.