Kira Pharmaceuticals announced positive long-term results from its Phase 2 study of KP104 in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) at the 2024 American Society of Hematology (ASH) Annual Meeting. KP104, a first-in-class dual-targeting complement inhibitor (C5 & Factor H), is designed to act on both the alternative and terminal pathways.
The updated data demonstrated long-term safety and efficacy of KP104 as a monotherapy for PNH, addressing unmet medical needs in this rare condition. Over a two-year treatment period, KP104 showed sustained clinical benefits by significantly improving hemoglobin levels and overall hematological outcomes in PNH patients.
Key Phase 2 Results
The data presented at ASH 2024 are from 18 patients treated with KP104 subcutaneously, with 56/58 weeks of the treatment time being on Optimal Biological Dose (OBD) for all patients. Key highlights include:
- Hemoglobin Improvement: 100% (18/18) of patients achieved a ≥2 g/dL increase from baseline, and 89% (16/18) attained hemoglobin normalization (≥12 g/dL) with an average (SD) of 13.6 (1.5) g/dL in the absence of RBC transfusions. The remaining two patients with co-existing conditions, one with aplastic anemia (AA) and the other with myeloproliferative neoplasms (MPN), also demonstrated hemoglobin improvement approaching near-normal levels.
- LDH Control: 94% (17/18) of patients achieved LDH <1.5x ULN at 56/58 weeks post-OBD switch, demonstrating strong intravascular hemolysis (IVH) suppression.
- Transfusion Independence: All patients remained free from RBC transfusions between day 1 and week 84/85 of KP104 treatment.
- Secondary Endpoints: Significant clinical improvements were observed in normalization of absolute reticulocyte counts, bilirubin levels, and FACIT-fatigue scores after switching to OBD.
- Safety: KP104 was safe, well-tolerated and produced no treatment-emergent adverse events (TEAEs) at or above grade 3.
Clinical Implications
"We are excited to share these promising long-term results with the hematology community," said Dr. Wenru Song, Head of R&D at Kira Pharmaceuticals. "PNH patients urgently need innovative therapies that offer lasting efficacy and safety. KP104's unique dual-targeting mechanism and this long-term safety and efficacy data position it as the best monotherapy for both naïve and treated PNH patients who are non-responsive or sub-responsive to current complement therapies".
The positive long-term results from the Phase 2 study further demonstrate KP104's potential as an optimal first-line monotherapy, providing safe and effective control of both intravascular and extravascular hemolysis in PNH patients. Building on these findings, global Phase 3 studies are being planned to establish KP104 as a potential new standard of care for PNH.
About KP104
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 of action uniquely positions KP104 to address complement-mediated diseases and potentially provide greater benefits than single-target complement agents. KP104 has been granted Orphan Drug Designation by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria.
