Dosing with SerpinPC begins in Phase 2b trial of hemophilia A and B
Hem B patient findings a priority given their need for 'new treatment options'
Dosing has begun in a Phase 2b clinical trial evaluating the safety and efficacy of SerpinPC, Centessa Pharmaceuticals’ investigational therapy for hemophilia.
The open-label study, called PRESent-2 (NCT05789524), is part of the company’s registrational program for hemophilia B, which includes multiple clinical trials aiming to generate data to support the therapy’s approval for people with this disease.
“We believe SerpinPC has the potential to be a first-in-class … therapy with a differentiated safety profile for persons with hemophilia B, subject to regulatory review and approval,” Antoine Yver, MD, Centessa’s chairman of development, said in a company press release.
SerpinPC promotes production of thrombin, a blood clotting protein
Hemophilia is caused by genetic mutations that impair the production or function of proteins required for proper blood clotting. There are different types of hemophilia, depending on the specific clotting protein that’s missing: factor VIII in the case of hemophilia A and factor IX in the case of hemophilia B.
SerpinPC works by blocking a protein called activated protein C, allowing for greater production of a blood clotting protein called thrombin.
As such, SerpinPC has the potential to help prevent patient’s bleeds regardless of hemophilia type or severity, or the presence of neutralizing antibodies called inhibitors. These antibodies can lower the effectiveness of standard hemophilia replacement therapies that work to supply the clotting factors patients are missing.
“There remains a significant global need for new treatment options for persons with hemophilia B,” Yver said, and the company is prioritizing this patient group in its registrational work.
PRESent-2 is evaluating the efficacy, safety, and pharmacological properties of SerpinPC in people with moderate to severe hemophilia B without inhibitors or with severe hemophilia A with or without inhibitors. It is expected to enroll 120 male patients, ages 12 to 65, at sites worldwide.
The study consists of three parts, each lasting 24 weeks or about six months. In Part 1, participants will receive a subcutaneous (under the skin) injection of SerpinPC, at 1.2 mg/kg every one, two, or four weeks.
In Part 2, all enrolled will be treated at the dosing regimen found to have the greater benefit-risk profile. Those who complete either Part 1 or Part 2 may enter a Part 3 extension phase.
Before starting treatment with SerpinPC, patients undergo a mandatory observational period — lasting at least 12 weeks in Part 1 or 24 weeks in Part 2 — of baseline evaluations that will serve as a reference of their disease status under current standard replacement therapy.
“We expect to enroll and dose additional patients across our clinical trial sites and advance toward the interim analysis planned when 36 subjects reach 12 weeks on treatment in Part 1 of the study,” Yver said.
PRESent-3 trial to assess SerpinPC in hemophilia B patients with inhibitors
The company’s registrational program for SerpinPC in hemophilia B includes another open-label Phase 2 trial, called PRESent-3 (NCT05789537), evaluating the safety, efficacy, and pharmacological properties of preventive treatment with SerpinPC in hemophilia B patients with inhibitors. An observation period prior to treatment start also is required of those enrolled.
The main goal of both of studies is to evaluate SerpinPC’s ability to reduce bleed rates over 24 weeks of treatment. These rates will be compared with patients’ annual bleeding rate determined during the observation period.
PRESent-5 (NCT05605678), an observational feeder study, also is ongoing — and enrolling hemophilia A and B patients — at sites across the U.S., Canada, Europe, and elsewhere. It is tracking patients’ bleeding rates while on standard therapies, and those enrolled will be treated with SerpinPC if they enter the PRESent-2 and PRESent-3 studies.
These trials followed top-line findings in a Phase 1/2a trial (NCT04073498) showing that SerpinPC safely reduced overall bleeding rates by up to 88% and spontaneous joint bleeds by as much as 94%, in adults with severe hemophilia A and B.
The U.S. Food and Drug Administration recently granted fast track designation to SerpinPC as a hemophilia B treatment and gave it orphan drug status in 2022. Both designations are intended to accelerate SerpinPC’s development and regulatory approval review.
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