SerpinPC Found to Ease Bleeding in All Hemophilia Types for 1.5 Years

New trial data show therapy can almost 'zero out' bleeds in Hem A, B

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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SerpinPC, a potential treatment for all types of hemophilia, from the drug development pipeline at Centessa Therapeutics, was found to be safe and to reduce patients’ bleeding episodes for up to 1.5 years.

In fact, the therapy candidate has the potential to nearly “zero out” the number of bleeds in people with severe hemophilia A or B.

That’s according to new data from an open-label extension of AP-0101 (NCT04073498), an ongoing Phase 1/2 clinical study involving men ages 18–55. The trial is testing how safe SerpinPC is when given as a subcutaneous (under-the-skin) injection and how its levels change in the blood over time.

The open-label extension, during which all patients received SerpinPC, also watched for changes in the number of bleeds over time. Researchers found that SerpinPC reduced overall bleeds and spontaneous joint bleeds by up to 93% at the highest dose tested.

These data “are very encouraging and have the potential to meaningfully differentiate SerpinPC from other treatment options and product candidates in development,” Saurabh Saha, MD, PhD, Centessa’s CEO, said in a company press release.

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The study’s findings were shared in an oral presentation at this year’s American Society of Hematology (ASH) annual meeting, which took place in New Orleans, Louisiana, and virtually, earlier in December. The presentation was titled “SerpinPC in Persons with Severe Hemophilia (PwH): Updated Results from a Multi-Center, Multi-Part, First-in-Human Study.”

In the coming weeks, the company plans to move forward with PRESent-5 (NCT05605678), an observational study that will feed patients into another clinical trial that’s planned for 2023. The new trial will include people with hemophilia A or B, with or without inhibitors.

“We’re now advancing the PRESent pivotal program for SerpinPC which includes elegantly designed studies focused on bringing this potential therapy to individuals with hemophilia B (with and without inhibitors) as quickly as possible, subject to regulatory approval,” Saha said.

Hemophilia occurs when the body does not make enough clotting factors that help the blood to clot and stop bleeding. While some patients undergo replacement therapy with the clotting factors they are missing, they then develop inhibitors to those clotting factors. This usually prevents such treatment from working as well.

SerpinPC is designed to allow more of the protein thrombin to be produced by reducing the activity of circulating activated protein C. Thrombin causes the blood to clot, and having more of it may mean fewer bleeding episodes for people with hemophilia.

In the Phase 1 (Part 1) of AP-0101, researchers tested how safe SerpinPC was in healthy volunteers and in men with severe hemophilia A or B (with or without inhibitors). Meanwhile, Phase 2a (Part 2) tested SerpinPC in 23 men with severe hemophilia A or B who were not on preventive replacement therapy.

According to top-line data from Part 2, SerpinPC safely reduced overall bleeding episodes by up to 88% and spontaneous joint bleeds by up to 94% when given once a month for up to six months to these hemophilia patients.

After Part 2, patients were invited to continue into an open-label extension (Part 3 and Part 4). In Part 3, 22 men who completed Part 2 received a flat dose of 60 mg of SerpinPC, given once per month for 48 weeks, or nearly one year. In Part 4, 21 men who completed Part 3 received 1.2 mg/kg of SerpinPC once every two weeks for 24 weeks, or about six months.

Over the 18 months of the open-label extension, there were no thromboembolic events related to SerpinPC. Thromboembolism occurs when a blood vessel gets blocked with a blood clot that’s carried away from another part of the body.

Moreover, there were “no observations of treatment-related, non-transient elevations in D-dimer,” the researchers wrote in their presentation. D-dimer is a measure of excess production of thrombin.

In Part 3, the median annualized bleeding rate — the number of bleeds divided by the number of months — dropped by 83% from the initial (baseline) value of 34.1 to 6.2. That of spontaneous joint bleeds dropped by 86% — from the initial value of 27.5 to 4.3.

In Part 4, there was a drop of 93% in overall bleeds, which fell from 35.5 to 2.2, and spontaneous joint bleeds, which dropped 28.3 to 2.2, at an effective monthly dose of 2.4 mg/kg (two times 1.2 mg/kg in one month). This was double the highest monthly dose used in Part 2 (1.2 mg/kg).

“SerpinPC’s continued favorable efficacy, safety and tolerability profile with subcutaneous dosing throughout the [open-label extension] period, including a dose 2x higher than that previously administered during the initial six-month Phase 2a study, are very encouraging,” Saha said.

Antoine Yver, MD, Centessa’s chairman of development, said the new data “add further weight to the durability of effect and sustained safety and tolerability observed to date in severe hemophilia.”

“We are excited that these data support the potential of SerpinPC’s new mechanism of action to provide a clinically meaningful subcutaneous therapy to people with hemophilia B who have high unmet need and limited options,” Yver said.