LONGBIO-B (01779) has announced that topline data from its Phase II clinical trial in China of LP-005, a dual-function antibody fusion protein independently developed by the company that targets C5 and C3b complement for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), have been read out.
The topline data show that LP-005 demonstrates significant efficacy along with a favorable safety and tolerability profile.
LP-005 is the first product from the company's dual-function antibody development platform and is a dual-function antibody fusion protein targeting both C5 and C3b complement. As a multi-target complement inhibitor, LP-005 simultaneously acts on multiple key nodes of the complement cascade and comprehensively inhibits all three complement signaling pathways, namely the classical pathway, the alternative pathway, and the lectin pathway. Compared with single-target inhibitors, it is expected to more comprehensively block complex disease pathological mechanisms.
The potential indications for LP-005 include complement-mediated autoimmune diseases such as PNH, complement-mediated kidney diseases, and periodontitis.
PNH is a rare acquired clonal hematopoietic stem cell disease primarily characterized by chronic intravascular hemolysis, thrombosis, and bone marrow failure. Patients typically present with symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, and anemia, and may experience major adverse vascular events. Existing complement inhibitor therapies have improved patient clinical outcomes to some extent.
LP-005 is a novel dual-function fusion protein that can simultaneously inhibit both the proximal and terminal complement pathways and has a relatively long half-life.
The Phase II clinical trial is a multicenter, randomized, open-label Phase II clinical study conducted in China (registration number: CTR20242478), designed to evaluate the efficacy, safety, and pharmacokinetic characteristics of LP-005 injection in treating PNH patients. The trial includes three dose cohorts of 900 mg, 1,200 mg, and 1,500 mg, with subjects receiving intravenous infusion once every four weeks (Q4W), for a total treatment period of 48 weeks.
The primary endpoints of the Phase II clinical trial include: (i) the change in serum lactate dehydrogenase (LDH) levels from baseline at week 12 after dosing; and (ii) the proportion of patients who are transfusion-free and achieve a hemoglobin (Hb) increase of at least 2 g/dL from baseline at week 24 after dosing.
The Phase II clinical trial enrolled a total of 30 PNH patients, of whom 27 completed 24 weeks of treatment. At week 12, LDH levels decreased significantly from baseline. The hemolysis control rate (LDH below 1.5 times the upper limit of normal (ULN)) reached 100% in both the 1,200 mg and 1,500 mg dose groups. All three dose groups achieved a 100% transfusion avoidance rate, and no breakthrough hemolysis (BTH) was observed.
At week 24, 85.7% (6/7) of patients in the 1,500 mg group achieved a hemoglobin increase of at least 2 g/dL without transfusion, and 71.4% (5/7) of patients achieved hemoglobin of at least 120 g/L. The transfusion avoidance rate was 100% (7/7), and no BTH was observed. LP-005 demonstrated potent hemolysis control and Hb improvement effects.
In terms of safety, no treatment-related serious adverse events (SAEs) were reported. LP-005 overall demonstrated a favorable safety and tolerability profile.
The board of directors believes that the topline data from the Phase II clinical trial confirm that LP-005, as a dual-target complement inhibitor, possesses competitive advantages in terms of efficacy, along with favorable safety and tolerability characteristics, while the Q4W dosing interval reflects the long-acting advantage of LP-005. These results support further advancement of the clinical development of LP-005.
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