HEM A and B Study Soon to Open, Leading to Pivotal SerpinPC Trials
Observational feeder study part of Centessa's plans to request SerpicPC's approval
Centessa Pharmaceuticals is set to open PRESent-5, an observational feeder study of hemophilia patients who could then move in pivotal clinical trials of SerpinPC — an investigational therapy for hemophilia A and B patients, regardless of disease severity or inhibitor status — that it plans to launch next year.
Part of the company’s registrational program, observational studies are intended to obtain sufficient data to support an application for regulatory approval. Set to begin this year, PRESent-5 will collect data over time before assigning patients to the planned PRESent-2 and PRESent-3 trials.
PRESent-2 will enroll people with moderate to severe hemophilia B without inhibitors and those with severe hemophilia A with and without inhibitors. PRESent-3 will include hemophilia B patients with inhibitors.
SerpinPC to be tested in hemophilia B patients and those with severe hemophilia A
“We are advancing the pivotal program for SerpinPC with the initiation of PRESent-5 … in the coming weeks,” Saurabh Saha, MD, PhD, Centessa’s CEO, said in a company press release.
“The SerpinPC registrational development program represents an elegant and accelerated path forward with the potential to bring a convenient, subcutaneous therapy to people with hemophilia B, as quickly as possible, subject to regulatory approval,” Saha added.
Hemophilia is marked by the lack of certain clotting factors, which are proteins that play a key role in blood clot formation to prevent excessive bleeding.
Replacement therapy is a standard treatment that provides the missing clotting factors from an external source. With long-term use, however, patients can develop neutralizing antibodies against the therapeutic clotting proteins, called inhibitors, that can affect treatment efficacy.
SerpinPC — given as an under-the-skin (subcutaneous) injection — is a biological therapy designed to block activated protein C. This, in turn, leads to a rise in the levels of thrombin, an enzyme that converts the protein fibrinogen to fibrin and stimulates blood clot formation.
The therapy aims to rebalance the altered blood clotting processes in hemophilia patients, regardless of disease severity, inhibitor status, or hemophilia type.
SerpinPC is currently being evaluated in an open-label Phase 1/2a trial (NCT04073498) called AP-0101. While the Phase 1 portion assessed safety in healthy volunteers, the Phase 2a part is testing the therapy in 23 men with severe hemophilia A or B, who were not using preventive treatments.
Top-line Phase 2a findings demonstrated that SerpinPC, administered once a month for six months, safely reduced overall bleeds by up to 88%, as well as spontaneous joint bleeds by up to 94%. Notably, similar outcomes were seen in hemophilia A and B patients.
All 22 people who completed the trial entered a 48-week (one-year) open-label extension (OLE) study to continue treatment with SerpinPC.
According to Centessa, 18-month OLE findings in those treated at higher doses will be presented next month at the American Society of Hematology (ASH) Annual Meeting.
“We are presenting the data readout from an additional 18-months of continued treatment with subcutaneous doses of SerpinPC from the open-label extension (OLE) of our Phase 2a Study,” Saha said. “This key data readout will demonstrate the long-term effect of higher doses with SerpinPC in people with hemophilia.”
The therapy was granted orphan drug status for hemophilia B in the U.S., a designation awarded to treatments for rare conditions and providing financial incentives to support their clinical development.