THE PROBLEM: APDS (activated PI3 Kinase delta syndrome) – also known as PASLI (p110 delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency) disease – is a rare disorder that severely impairs the immune system’s ability to fight bacterial and viral infections, making patients susceptible to severe and recurrent infections, lymphoma, autoimmune diseases and other health issues. This disease is estimated to affect up to 2 people per million, and it can only be cured via bone marrow transplant. The only alternative for APDS patients was to treat their symptoms, using immunoglobulin replacement therapy, immunomodulatory drugs and treatments targeting infections.  

THE SOLUTION: Researchers at the National Institutes of Allergy and Infectious Disease (NIAID) and Novartis Pharmaceuticals Corporation developed the first Food and Drug Administration (FDA)-approved medication to treat the source – not the symptoms – of APDS. NIAID researchers discovered that APDS patients have a common gene variation in the PI3 kinase gene, and that causes that gene’s pathway to become hyperactive and produce an imbalance in white blood cells that makes it difficult for the body to fight infections. Through this technology transfer, they developed a medication that controls the overactive gene pathway to provide more effective, targeted treatment with fewer long-term side effects. 

THE TECH TRANSFER MECHANISM: In 2013, NIAID researchers published their findings about the PI3 Kinase delta gene mutation. Novartis had developed a proprietary compound, called leniolisib, as an inhibitor of this same gene. In 2015, NIAID entered into a CRADA with Novartis to assess the safety and efficacy of leniolisib as a treatment for APDS in a clinical trial. After this trial produced positive results, the team launched a Phase III clinical trial in 2018 and an extension study to test the drug’s long-term safety and efficacy in APDS patients. In 2019, the commercialization rights to the clinical development of leniolisib were transferred from Novartis to Pharming Group N.V. (Pharming). The CRADA was amended to establish Pharming as NIAID’s new collaborator for the leniolisib/APDS trial. In July of 2022, Pharming submitted a New Drug Application (NDA) for leniolisib; the following March, the FDA granted full approval of leniolisib (tradename Joenja) to treat APDS in adults and patients 12 years and older.  

THE TECH TRANSFER EXCELLENCE: NIAID’s Technology Transfer and Intellectual Property Office (TTIPO) played a key role in formalizing the collaboration with Novartis under a CRADA. Upon the successful completion of the Phase II trial, TTIPO took the lead and negotiated an amendment to the CRADA to launch the Phase III trial and an extension study for APDS patients from Phase II. TTIPO worked tirelessly with NIAID’s clinical and research teams, NIAID’s budget office and Novartis’s clinical and legal teams, ultimately amending the CRADA 10 times to achieve a range of needs, including modifying the research plan, adding extension studies and securing additional funds. TTIPO’s diligence and meticulousness were substantial in the smooth and timely execution of the CRADA and the subsequent amendments. 

THE OUTCOMES: This technology transfer has fulfilled an unmet medical need: Joenja is the first and only treatment approved in the U.S. for APDS, an ultra-rare and progressive primary immunodeficiency disorder. The FDA approval of leniolisib was an important milestone for APDS patients who will now have access to a treatment option that targets the root cause of the disease, rather than relying upon treatment of symptoms. At the time of publication, Pharming is investigating the safety and efficacy of leniolisib to treat APDS in patients under 12.