APDS treatment in Germany: decision criteria, costs and contribution of leniolisib to outcomes

Purpose Activated PI3 Kinase Delta Syndrome (APDS) is a rare inborn error of immunity. To better classify the contribution of a potential new therapeutic precision agent, leniolisib, medically relevant decision criteria were assessed upon which an outcomes model was built. Methods Two online surveys and two roundtable discussions with 6 medical and scientific experts were conducted to obtain and discuss clinical and cost components. Based on the discussion results, key decision outcomes were modelled in an outcomes model. Results Key decision therapeutic criteria of physicians were reliably found in two rounds of Maximum Difference Scaling, with efficacy being most important, followed by safety, disease severity, and quality of life impact. Relevant clinical outcomes in APDS, that were considered well quantifiable, were frequency of infections, lymphoproliferation, bronchiectasis, lymphoma, and mortality. For these outcomes, relevant improvements versus current standard of care were estimated for the new therapeutic precision agent leniolisib. Expert assessments in the online surveys, which were carried out by the 6 participants independently, showed low variance across participants. Ratings resulted in a projected reduction of mortality by use of leniolisib of ~16% at an age of 40 years (95% CI: [9%; 22%]). This age is currently reached only by 65% of APDS patients. Other changes were expected for costs, immunoglobulin replacement, treatment of lymphoma and other malignancies, bronchiectasis, and advanced lung disease, as well as allogeneic hematopoietic cell transplantation (alloHCT). Conclusions Decision criteria of physicians for treating APDS are well in line with other therapeutic areas, with efficacy considered to be most relevant. Based on currently available data on leniolisib therapy, mortality and several patient-relevant morbidity endpoints are expected to improve in future clinical practice in Germany. Leniolisib may significantly modify the course of disease in APDS patients.