Catalyst Biosciences recently announced updates on two of its lead compounds — Factor VIIa (FVIIa) marzeptacog alfa (activated) (MarzAA) and Factor IX (FIX) dalcinonacog alfa (DalcA) — for treatment of hemophilia A or B with inhibitors, and for hemophilia B.
DalcA is a potent recombinant (artificial) Factor IX prophylactic therapy designed to prevent acute bleeding episodes in people with hemophilia B. Unlike other Factor IX products, DalcA can be administered by an injection under the skin (subcutaneous injection), a much less invasive method compared to conventional intravenous injections.
During Catalyst’s Research & Development Day on Dec. 18 in New York (a webcast of the event is available here), the company announced the completion of the immunogenicity (immune reaction) risk assessment for DalcA on the sixth cohort of patients enrolled in the ongoing proof-of-concept, open-label, multi-center Phase 1/2 trial (NCT03186677) carried out in collaboration with ISU ABXIS. The immunogenicity risk assessment determines a patient’s risk of producing antibodies against DalcA that can interfere with its efficacy.
According to new data, the immunogenicity risk and drug quality of DalcA is identical to other Factor IX products currently on the market.
“The results of our extensive DalcA immunogenicity risk assessment revealed a similar low immunogenicity potential compared with BeneFIX and other commercial wildtype [natural form] FIXs; therefore, we will be moving forward with the clinical development of DalcA,” Nassim Usman, PhD, chief executive officer of Catalyst, said in a press release.
“We plan to initiate a Phase 2b trial that will include 28 days of daily subcutaneous dosing in the first quarter of 2019. Based on the efficacy data that we have previously shown in which subjects achieved high mild hemophilia FIX activity, we believe that DalcA has the potential to provide a conveniently dosed subcutaneous prophylactic treatment option for those suffering from hemophilia B,” Usman said.
MarzAA is a next-generation recombinant Factor VIIa designed for long-term prophylaxis of patients with hemophilia A or B who developed blood-clotting factor inhibitors. After the promising interim results of the ongoing open-label, multi-center Phase 2/3 trial (NCT03407651) for MarzAA, the company announced new data from the Phase 2 portion of the study.
According to the new data, of the nine patients enrolled in the study so far, five completed the trial with significant reductions in the annualized bleed rate (ABR) — the number of bleeding episodes per year. Up until now, no anti-drug antibodies have been found in any of the patients participating in the study and only one adverse reaction at the injection site has occurred without long-term consequences.
“Given the promising interim results from our Phase 2/3 study of MarzAA, in which all five subjects that have completed dosing experienced clinically significant reductions in their annualized bleed rates, and the results of our commercial assessment, showing a several hundred-million-dollar revenue forecast globally, we believe that MarzAA has significant clinical and commercial potential,” Usman said.
The company plans to launch a global Phase 3 trial to evaluate ABR reductions in a group of 20-40 hemophilia patients receiving daily subcutaneous injections of MarzAA for six months.