Akari Therapeutics announces Phase III trial design of nomacopan in HSCT-TMA
Akari Therapeutics announces the design of a pivotal Phase III pediatric trial in HSCT-TMA following a FDA End-of-Phase II meeting. Akari also announces that, in another hematological condition, all six patients from the long-term Phase II PNH study who were transfusion dependent at entry are now transfusion independent on long-term treatment with nomacopan. HSCT-TMA is an orphan hematological condition with no approved treatments and an estimated mortality rate of more than 80% in children with the severe form of the disease. It is this severe form that is being targeted with nomacopan. Following a recent End-of-Phase II meeting with the FDA, Akari plans to initiate a single arm responder-based study design, based on treatment with nomacopan for up to 24 weeks. The primary endpoints are focused on disease response defined primarily by renal improvement and reduced transfusion dependence. The study will be in two parts, with data from seven patients in Part A used to confirm dosing and endpoints for Part B, with the pharmacokinetic modelling agreed with the FDA through Akari's participation in the Model Informed Drug Discovery Program. Following an interim efficacy and safety readout from Part A and meeting with the FDA, patients would then be recruited into Part B of the responder study. While the role of complement inhibition is understood to play an important role in HSCT-TMA, LTB4 may also be an important target in reducing epithelial activation in both TMA and graft versus-host disease which often occur simultaneously. Daily dosing with nomacopan is also likely to be of a particular advantage in facilitating more complete complement suppression, especially in HSCT-TMA patients with high transfusion requirements. HSCT-TMA is Akari's second haematological clinical program and follows a successful Phase II study in PNH completed in early 2018, after which patients continued treatment with nomacopan in a long-term safety study. New data from Akari's ongoing long-term study, shows that all six patients from the Phase II study who were transfusion dependent at entry are now transfusion independent on nomacopan, having had in all cases no transfusions for a minimum of six months. In addition, during more than 20 cumulative patient-years of PNH patient treatment with nomacopan, there have been no reported drug-related serious adverse events.