Phase 2 trials of SerpinPC to begin dosing this year
Goal of the studies is to monitor bleed rates over the course of treatment
SerpinPC, an investigational treatment that Centessa Pharmaceuticals is developing for hemophilia, will advance to interventional Phase 2 clinical testing later this year.
The studies will support Centessa’s registrational program for hemophilia B. Such a program involves clinical trials that ultimately will lead to the company seeking regulatory approval for that indication.
It also will include the ongoing observational PRESent-5 study (NCT05605678), which is seeking to enroll up to 200 males, ages 12–65, with hemophilia A or B (with or without inhibitors). The study is actively recruiting participants at sites in South Africa, Taiwan, and the U.K.
PRESent-5’s goal is to obtain patients’ baseline bleeding rates under standard therapies, and then to feed participants into future interventional studies, including the PRESent-2 and PRESent-3 trials that will begin dosing this year.
PRESent-2 (NCT05789524) aims to enroll 120 patients with severe hemophilia A (with or without inhibitors) or moderate-to-severe hemophilia B (without inhibitors), and PRESent-3 (NCT05789537) aims to enroll 12 hemophilia B patients with inhibitors.
All of these trials come on the heels of positive data from a Phase 1/2a trial, which found under-the-skin (subcutaneous) SerpinPC to be safe and effective at controlling bleeds in hemophilia patients.
“We believe these data support the potential for SerpinPC to be a first-in-class subcutaneously administered therapy with a differentiated safety profile for individuals with hemophilia, subject to regulatory review and approval,” Saurabh Saha, MD, PhD, CEO of Centessa, said in a press release.
“We are excited to be enrolling subjects in PRESent-5, an observational feeder study, and are preparing to begin dosing in the PRESent-2 and PRESent-3 interventional studies this year,” Saha said.
Hemophilia is caused by genetic mutations that render the body unable to produce enough of certain blood-clotting factors.
How SerpinPC works
SerpinPC works by inhibiting a protein called activated protein C, which allows for a greater production of thrombin, a blood-clotting protein. As such, SerpinPC is expected to help prevent bleeding episodes in people with hemophilia, regardless of inhibitor status, and potentially in other bleeding disorders.
The open-label Phase 1/2a AP-0101 study (NCT04073498), which involves healthy men and men with severe hemophilia A or B (with or without inhibitors), is being conducted in several parts.
After a first part to test the treatment’s safety in healthy volunteers and hemophilia patients, Part 2 evaluated SerpinPC’s efficacy in 23 men with severe hemophilia.
Top-line data from Part 2 found that SerpinPC, given as a subcutaneous injection once per month for up to six months, safely reduced the number of bleeding episodes by up to 88% and spontaneous joint bleeds by up to 94%.
Those patients then were invited to continue into an open-label extension phase (Parts 3 and 4). In Part 3, 22 men received a 60 mg dose of SerpinPC once per month for nearly a year. In Part 4, 21 of those 22 men received 1.2 mg/kg SerpinPC once every two weeks for about six months.
Over the 18 months spanning Parts 3 and 4, SerpinPC was found to be safe, without causing potentially dangerous blood clots, and significantly reduced bleeding rates relative to those seen at the study’s start.
In its fifth part, participants who completed Part 4 will receive SerpinPC at the same 1.2 mg/kg dose every two weeks for a full year. Centessa expects to share these data at a scientific meeting this year.
PRESent-2 also will be conducted in multiple parts. In its first part, participants will receive 1.2 mg/kg SerpinPC every week, two weeks, or four weeks, for about six months. In Part 2, all participants will receive the most beneficial dose for an additional period of six months.
Patients who complete Parts 1 and 2 can enter Part 3, an extension period during which all will receive the therapy for an additional six months.
In PRESent-3, participants will receive 1.2 mg/kg SerpinPC every two weeks for about a year.
The main goal of both studies is to monitor bleed rates over the course of treatment.