US-based biopharmaceutical company Apellis Pharmaceuticals has reported positive results of two Phase I clinical trials of its complement C3 inhibitor, APL-2, to treat paroxysmal nocturnal hemoglobinuria (PNH).
The randomised, double-blind, placebo-controlled, single and multiple ascending dose trials were designed to determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of APL-2 administered through a subcutaneous injection in healthy adult volunteers.
The trials involved 40 subjects who were administered with APL-2 subcutaneously (SC) either as a single dose or repeated doses over a period of 28 days.
The results of both trials demonstrated the safety and tolerability of the pharmacological doses of APL-2 and its PK / PD profile supportive of daily SC administration.
Apellis CEO Cedric Francois said: "We are pleased to have accomplished this major milestone in the clinical development of APL-2.
"Targeting C3 is very challenging as it is the most abundant complement protein in the body.
"It is the first time a study demonstrates that inhibiting complement at the C3 level can be safely achieved in a clinical study."
Additionally, daily dosage of APL-2 has also proved effective against mediated hemolysis (destruction of the red blood cells) with a consistency maintained throughout the dosing period.
APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that bonds specifically with C3 and C3b and inhibits the activation of C3a and C3b.
It inhibits all three potential pathways of complement activation (classical, lectin, and alternative) with a high potency against the alternative pathway.