SOUTH SAN FRANCISCO, Calif.—Last month at the 2019 Congress of the International Society on Thrombosis and Haemostasis (ISTH), Catalyst Biosciences Inc. presented Phase 2 data regarding its subcutaneous (SQ) Factor VIIa (FVIIa) variant marzeptacog alfa (activated) (MarzAA) for prophylaxis in patients with hemophilia A or B with inhibitors. The study met its primary endpoint of significantly reducing the annualized bleed rate, as well as all secondary endpoints of safety, tolerability and lack of anti-drug antibody or inhibitor formation.
“The results from the Phase 2 trial of MarzAA showed that SQ MarzAA achieved statistical significance in the study’s primary efficacy endpoint, with an excellent reduction in annualized bleeding rates,” said Dr. Nassim Usman, CEO of Catalyst Biosciences. “Reducing the median bleeds to zero with daily SQ prophylactic MarzAA therapy clearly demonstrated improved prophylactic therapy for patients with hemophilia A or B with inhibitors and the potential for leading normal active lives.”
The study, a Phase 2 open-label trial in patients with hemophilia A or B with inhibitors, looked at MarzAA’s ability to reduce total bleeding efficacy. The primary endpoint was a reduction in annualized bleed rate at the final dose level, with each patient’s historic annualized bleed rate serving as the control.
Daily subcutaneous administration of MarzAA for 50 days at an individual’s final dose resulted in a significantly reduced mean six-month pre-study annualized bleed rate from 19.8 to 1.6. The proportion of days with bleeding (PDB) was also reduced, dropping from a six-month pre-treatment mean of 12.3 percent to 0.8 percent during treatment. Median annualized bleed rate and PDB dropped to zero during treatment, and seven of nine subjects experienced no bleeds, traumatic or spontaneous, at their final dose level. Additionally, MarzAA proved safe and well tolerated, with side effects consisting of six mild to moderate localized skin reactions observed in two patients. Subcutaneous administration extended MarzAA’s half-life to 16.6 hours, resulting in trough levels before the next dose that were sufficient to provide bleed protection.
Howard Levy, chief medical officer at Catalyst Biosciences, stated in an investor call regarding the results that it was not necessary to increase dosage to the maximum dosing amount in order to achieve these results: “We never had to go above 60 mg/kilo; in fact, all but two subjects were well controlled at 30 mg/kilo dose level.”
“We’ve not seen any anti-drug antibodies, and consequently not any neutralizing antibodies,” he added.
“We are extremely pleased to see the study meet all endpoints with statistical significance. MarzAA therapy reduced median bleeds to zero. This is a clinically meaningful outcome, especially for individuals with hemophilia A or B with inhibitors, who now have the potential to lead normal, active lives, which we believe will alter the quality of life for the individuals and their families,” Usman commented in the investor call. “MarzAA is a best-in-class factor VIIa molecule that we designed at C Bio, and the clinical data indicate that it could be very well positioned compared with other therapies like emicizumab, also known as Hemlibra.
“MarzAA will not require a rescue treatment. It is a one-drug solution for prophylaxis and treatment of bleeding. We believe that these are important clinical properties of MarzAA, and expect that they will simplify a patient’s care. We have shown that we can achieve protective factor levels when we dose the patients on a daily basis. MarzAA has been granted orphan drug designation in both Europe and the United States.”
Usman noted that the next step for the MarzAA development program is an end-of-Phase 2 meeting with the FDA, which the company expects to occur in the fourth quarter of this year. Catalyst Biosciences expects to move MarzAA into Phase 3 development in 2020, he added.