SerpinPC, for Hemophilia A and B, Safely Prevents Bleeds in Phase 2a Trial
SerpinPC, an experimental hemophilia therapy, at high dose safely reduced overall bleed rates by up to 88% and spontaneous joint bleeds by up to 94% in adults with severe hemophilia A and B, who were not using preventive treatment, according to top-line results from a Phase 2a proof-of-concept study.
The therapy — administered subcutaneously, or as an under-the-skin injection — has the potential to treat all types of hemophilia regardless of disease severity or inhibitor status.
“The compelling reduction in bleeds and continued tolerability that we observed in both hemophilia A and hemophilia B patients in this proof-of-concept study are very encouraging, and we are eager to move SerpinPC into a global development plan,” Antoine Yver, MD, chief medical officer of Centessa Pharmaceuticals, the therapy’s developer, said in a press release.
People with hemophilia A and B lack specific clotting factors, which are proteins that help forming blood clots to prevent excessive bleeding. SerpinPC is a biological therapy designed to increase the levels of thrombin, an enzyme that converts the protein fibrinogen to fibrin, triggering blood clot formation.
The safety, tolerability, and pharmacological properties of SerpinPC are being investigated in an ongoing, open-label Phase 1/2a trial called AP-0101 (NCT04073498).
Its Phase 1 portion assessed the therapy’s safety in healthy volunteers when given at different doses and through two different routes of administration: either subcutaneously or intravenously (into-the-vein).
The Phase 2a part is evaluating SerpinPC in 23 men with severe hemophilia A or B who were not receiving prophylactic treatment to prevent bleeds. While eligible, none of the participants had inhibitors, or neutralizing antibodies targeting clotting factors provided in replacement therapies, which typically lower their effectiveness.
In this phase, participants were assigned to one of three doses of SerpinPC (0.3, 0.6, and 1.2 mg/kg) administered as a subcutaneous injection every four weeks for 24 weeks (about six months).
In addition to treatment safety and tolerability, investigators assessed SerpinPC’s ability to lower annualized bleeding rates (ABRs) as exploratory outcomes. Final ABRs were compared to all bleed ABRs measured before SerpinPC exposure.
Top-line AP-0101 data showed the therapy was well-tolerated, with one patient with a history of a skin disorder discontinuing treatment after an injection site reaction. No other adverse events related to SerpinPC were reported. Although there were no reports of elevated D-dimer, a measure of excess thrombin, two patients developed anti-therapy antibodies, which did not impact ABRs.
In the 0.3 mg/kg dose group, the self-reported median ABR for all bleeds decreased by 80%, and by 76% for spontaneous joint bleeds during the last 12 weeks of treatment, a pre-specified primary assessment period, the company reported.
For those treated with SerpinPC at the 0.6 mg/kg dose, the median ABR for all bleeds dropped by 70%, and for spontaneous joint bleeds by 69%.
At its highest 1.2 mg/kg dose, SerpinPC reduced all bleeds by 88% and spontaneous joint bleeds by 94%. Five of the eight patients in the high dose group also had one or fewer (zero) bleeds over the 12-week assessment period.
Notably, results were similar between patients with hemophilia A or B.
The median number of target joints — those having more than three bleeds over any six-month period — dropped from 2.5 before treatment to zero by the end of the study.
All 22 hemophilia patients who completed the Phase 2a trial enrolled in a 48-week open-label extension study, Centessa stated. Here, a 60 mg subcutaneous dose of SerpinPC will be given every four weeks for 13 treatments in total. The trial is due to conclude in April 2022, and Centessa plans to announce data from the open-label extension later that year.
“The results of this Phase 2a study of SerpinPC continue to show an excellent tolerability profile for this molecule, and the exploratory efficacy results seen in this study of severe hemophilia A and B patients are also very promising,” said David Lillicrap, MD, professor at Queen’s University in Canada and former member of the World Federation of Hemophilia’s advisory board.
“A safe, subcutaneous, prophylaxis option for both hemophilia A and B patients would be an important addition to our treatment choices,” Lillicrap added.