Kira’s KP104 Phase 2 Demonstrates Long-term Safety and Efficacy in PNH

Rare Daily Staff

Kira Pharmaceuticals reported positive long-term results from its phase 2 study of KP104 in complement inhibitor-naïve patients with the rare blood disease paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease that is characterized by the destruction of red blood cells, formation of blood clots, and impairment of bone marrow function. PNH is almost always caused by a genetic mutation that results in production of aberrant hematopoietic stem cells. These stem cells produce irregular red blood cells that are highly susceptible to destruction via complement activation. Current therapies include C5 inhibitors, which do not address extravascular hemolysis (EVH) related to the alternative pathway or a C3 inhibitor, which may address EVH but may not adequately block C5 downstream, leading to life-threatening breakthrough hemolysis.

KP104 is a first-in-class bifunctional biologic designed to simultaneously block both the alternative (Factor H) and terminal (C5) complement pathways, providing a powerful and synergistic method of targeting the validated drivers of complement-mediated disease. This dual-target mechanism of action positions KP104 to address complement-mediated diseases and potentially provides greater benefits than single-target complement agents. Engineered to have an extended half-life and enhanced potency, KP104 has a formulation suitable for both intravenous and subcutaneous administrations. KP104 is entering phase 2 POC trials across multiple renal disease and hematologic indications.

Key highlights from the study include results from 18 patients treated with KP104 subcutaneously for up to 65 weeks, with 24- 26 weeks of the treatment time being on Optimal Biological Dose (OBD) for all patients, switched from 3 cohorts in dose escalation phase.

Patients continued to show sustained improvements in hemoglobin levels after switching to OBD. The remaining two patients with co-existing conditions, one with aplastic anemia  and the other with myeloproliferative neoplasms, also demonstrated hemoglobin improvement approaching near-normal levels.

Patients showed sustained control of LDH levels to near-normal level throughout the entire treatment period, demonstrating strong IVH control. At the end of 24/26 weeks post-OBD switch, 94 percent patients achieved LDH <1.5x ULN.

All patients remained free from RBC transfusions between day 1 and week 65 of KP104 treatment.

Significant clinical improvements were also observed in all other secondary endpoints: normalization of absolute reticulocyte counts, bilirubin levels, and FACIT-fatigue scores after switching to OBD.

KP104 was safe and well-tolerated, and produced no treatment-emergent adverse events at or above grade 3.

The affirming long-term results from the phase 2 study further demonstrate KP104’s potential as an optimal first-line monotherapy to safely and effectively control both intravascular and extravascular hemolysis of PNH. Global phase 3 studies are being planned to potentially establish KP104 as the new standard of care for PNH.

“We are very encouraged by the robust efficacy and favorable safety profile demonstrated by KP104 in our phase 2 study,” said Wenru Song, head of R&D at Kira Pharmaceuticals.  “These long-term results support the advancement KP104 into phase 3 trials.”

Photo: Wenru Song, head of R&D at Kira Pharmaceuticals