MELBOURNE – Subcutaneous administration of the monoclonal antibody marstacimab (PF-06741086) provides significant reductions in bleeding rates for patients with hemophilia A and B, with reasonably safety and tolerability, according to research presented at the International Society on Thrombosis and Haemostasis congress.
, of the University of Witwatersrand in Johannesburg, South Africa, presented data from a multicenter, international phase 1B/2 open-label involving 26 patients with severe hemophilia, who had experienced at least six acute bleeding episodes in the 6 months prior to enrollment. Twenty-three patients had hemophilia A, the remaining three patients had hemophilia B, and all were receiving on-demand treatment.
Patients were divided into one of four cohorts. Cohort 1 received a weekly 300-mg dose subcutaneously for 30 days, cohort 2 received a 300-mg loading dose followed by 150 mg weekly for 30 days, cohort 3 received 450 mg weekly for 30 days, and cohort 4 also received a 300-mg weekly dose for 30 days but consisted of patients with inhibitors.
With the primary outcome being safety, the researchers reported no treatment-related serious adverse events. There were four grade 3/4 adverse events, including two subjects who reported injection site reactions, and some generalized pruritus and erythematous rash.
Two patients discontinued treatment after reaching prespecified dose-limiting toxicity related to decreasing fibrinogen levels, compared with baseline. However, Dr. Mahlangu pointed out that, in one of these patients, the fibrinogen levels were still within normal levels but protocol required removing the patient from the study.
The study did see a significant 85%-97% reduction in annualized bleed rates across the four cohorts, including among patients with inhibitors.
“Most patients who were exposed to marstacimab actually did not bleed at all when they were receiving marstacimab, compared to when they weren’t receiving marstacimab,” Dr. Mahlangu said.
While three patients developed antidrug antibodies, this did not appear to impact the pharmacokinetics, pharmacodynamics, or safety, he said. No patients developed neutralizing antibodies, and the pharmacodynamics showed no difference between patients with hemophilia A and B.
“I would like to believe that the results of this study are fairly promising in terms of the safety, the efficacy, the pharmoacokinetics, and the pharmacodynamics,” Dr. Mahlangu said.
There is an unmet need for therapies that can be used in patients with either hemophilia A or B, and with or without inhibitors, Dr. Mahlangu said in an interview. Another unmet need that marstacimab could potentially address is for subcutaneous treatment options, he added.
“We are particularly pleased by the fact that injection-site reactions are very low, and they seem not to carry on every time the patients have injected,” Dr. Mahlangu said.
Commenting on the presentation, session cochair Julia Phillips, MD, from PathLab in Waikato, New Zealand, said subcutaneous treatments offered a huge advantage to patients with hemophilia and their families.
“Often more than one member of the family is affected. So [for] a family with children, if they have several sons with hemophilia, then doing IV injections before school on a regular basis can be quite a big burden on the family,” she said in an interview.
The study was sponsored by Pfizer. Dr. Mahlangu reported research support from and scientific advisory board and speakers bureau roles with several pharmaceutical companies, including Pfizer.
SOURCE: Mahlangu J et al. 2019. ISTH CONGRESS,