Kira Pharma's KP104 Phase 2 PNH Study Shows Long-term Safety and Efficacy at EHA 2024

Kira Pharmaceuticals, a global biotechnology firm, has announced promising long-term results from its Phase 2 study of KP104 in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH), who had not previously received complement inhibitors. The findings were unveiled at the 2024 European Hematology Association Hybrid Congress held in Madrid, Spain. KP104 is a pioneering dual-targeting complement inhibitor that acts on both the alternative and terminal pathways (C5 & Factor H). This innovative approach showcases KP104's potential to address significant unmet medical needs in PNH treatment.

The study included 18 patients who were administered KP104 subcutaneously over a period of up to 65 weeks. For all patients, this included 24-26 weeks on the Optimal Biological Dose (OBD), following dose escalation from three cohorts of six patients each. The results were highly encouraging, with 100% of patients showing a hemoglobin increase of at least 2 g/dL from baseline, and 89% achieving hemoglobin normalization of at least 12 g/dL without the need for red blood cell (RBC) transfusions. Even the two patients with co-existing conditions—one with aplastic anemia and the other with myeloproliferative neoplasms—showed significant improvement in hemoglobin levels.

The study also demonstrated sustained control of lactate dehydrogenase (LDH) levels, a key indicator of hemolysis, to near-normal levels throughout the treatment period. By the end of the 24-26 week post-OBD phase, 94% of patients achieved an LDH level of less than 1.5 times the upper limit of normal. Importantly, all patients remained free from RBC transfusions from the beginning of the study to week 65.

Secondary endpoints also showed notable improvements. These included normalization of absolute reticulocyte counts, bilirubin levels, and FACIT-fatigue scores after switching to OBD. Moreover, KP104 was found to be safe and well-tolerated, with no treatment-emergent adverse events reaching grade 3 or higher.

These promising long-term results underscore KP104's potential as a first-line monotherapy for controlling both intravascular and extravascular hemolysis in PNH. Plans are underway for global Phase 3 trials to further validate KP104 as a new standard of care for PNH.

Dr. Wenru Song, Head of R&D at Kira Pharmaceuticals, expressed optimism about the findings, stating, "We are very encouraged by the robust efficacy and favorable safety profile of KP104 in our Phase 2 study. These long-term results support the advancement of KP104 into Phase 3 trials. We are committed to bringing this promising therapy to patients suffering from PNH as quickly as possible."

KP104 is a first-in-class bifunctional biologic designed to simultaneously block both the alternative (Factor H) and terminal (C5) complement pathways. This dual-target mechanism aims to provide a more comprehensive treatment for complement-mediated diseases, offering potentially greater benefits than single-target therapies. KP104 is formulated for both intravenous and subcutaneous administration and has an extended half-life and enhanced potency. It is currently in Phase 2 proof-of-concept trials across various renal and hematologic conditions and has been granted Orphan Drug Designation by the FDA for PNH treatment.

Paroxysmal Nocturnal Hemoglobinuria is a rare and life-threatening blood disorder characterized by the destruction of red blood cells, blood clot formation, and impaired bone marrow function. It affects between 1 and 5 people per million and is usually caused by a genetic mutation leading to the production of abnormal hematopoietic stem cells. Current therapies often fall short in addressing all aspects of the disease, highlighting the need for more effective treatment options like KP104.

Kira Pharmaceuticals is dedicated to developing transformative therapies for immune-mediated diseases. The company has a global presence with headquarters in Cambridge, Massachusetts, and facilities in China and Australia.