SerpinPC safe, reduces bleeds for almost 3 years: Study
Centessa shares update of experimental therapy for severe hemophilia A and B
SerpinPC, an experimental treatment being developed by Centessa Therapeutics, continues to be safe when used for up to nearly three years and to almost zero out the number of bleeds in adults with severe hemophilia A or B.
Those findings come from a one-year extension of the Phase 1/2a clinical trial AP-0101 (NCT04073498) that tested how safe SerpinPC is when given as a subcutaneous (under-the-skin) injection at a dose of 1.2 mg/kg once every two weeks.
The open-label extension study, which included 20 men in their third year of treatment with SerpinPC, also watched for changes in the annualized bleeding rate (ABR, a measure of the number of bleeds adjusted to a one-year window), which dropped by 96%.
“We are excited to share additional data that further demonstrate the potential for SerpinPC to be a convenient subcutaneous treatment with a differentiated safety profile for people living with hemophilia,” Saurabh Saha, MD, PhD, Centessa’s CEO, said in a press release.
“Specifically, these data show that an additional 52-weeks of continuous treatment with SerpinPC further reduced the median all-bleed ABR to 1.0, representing a 96% reduction from the prospective baseline [up to six months before the trial’s start],” Saha said.
While the AP-0101 trial is ongoing, the company has moved SerpinPC into two Phase 2 registrational studies designed to obtain enough data to support filing an application for the treatment’s regulatory approval for hemophilia B.
SerpinPC has been granted fast track designation by the U.S. Food and Drug Administration, a couple of months short from the launch of PRESent-2 (NCT05789524). PRESent-3 (NCT05789537) also began dosing people with hemophilia B who have developed inhibitors.
“These data highlight the strong foundation on which we are advancing SerpinPC in registrational studies for the treatment of hemophilia B,” Saha said. “We would like to extend our sincere thanks to everyone involved in this study including the patients, investigators, and site coordinators.”
SerpinPC poster presentation
The data were presented in the poster “SerpinPC in persons with severe hemophilia (PwH): Updated results from a multi-center, multi-part, first-in-human study,” at the 65th American Society of Hematology annual meeting, which was held Dec. 9-12 in San Diego, California.
Hemophilia occurs when a clotting factor — a protein involved in blood clotting — is missing or is faulty, causing patients to bleed excessively, sometimes without an apparent reason.
Replacement therapies can make up for the missing or defective clotting factor temporarily. However, some people develop inhibitors or neutralizing antibodies against the delivered clotting factors that can prevent replacement therapies from working as well.
SerpinPC is designed to reduce the levels of circulating activated protein C, thereby allowing more thrombin to be produced. Thrombin is a protein that causes the blood to clot. This is expected to help prevent bleeds, regardless of the presence of inhibitors.
Earlier data from the AP-0101 clinical trial showed that SerpinPC was safe and tolerated well, and capable of reducing the number of bleeds when taken for up to 96 weeks (about 1.8 years) without resulting in excess levels of thrombin in the blood.
“SerpinPC was well tolerated and reduced bleeding in persons with severe hemophilia with no observations of unexplained chronic elevations in D-dimer, an indicator of excessive thrombin generation,” researchers wrote in the poster.
Significant ABR reductions
New data showed that taking SerpinPC for an additional 52 weeks continued to reduce the number of bleeds, as demonstrated by a drop of 96% in the overall ABR, which dropped from a median of 35.6 bleeds per year at the prospective baseline to 1.0 bleed per year at this part of the study.
For spontaneous joint bleeds, the ABR dropped from a median of 30.3 bleeds per year at the prospective baseline to 1.0 at part 5 of the AP-0101 study — a 95% reduction.
SerpinPC also continued to be safe and tolerated well in this part of the study, with no side effects reported. Most men (96%) had low D-dimer levels. Only one man had elevated D-dimer levels, which returned to normal after he took antibiotics to treat a gum infection.