Catalyst Halts MarzAA Program for Hemophilia, Despite Positive Results
In an unexpected turn, Catalyst Biosciences is discontinuing the clinical development of marzeptacog alfa activated (MarzAA), its experimental under-the-skin therapy for hemophilia A and B patients with inhibitors, which was being evaluated in an international Phase 3 clinical trial.
“Based on several factors including a recently updated feasibility assessment, we determined that we cannot continue to develop MarzAA through completion of the ongoing trials” — notably the Phase 3 Crimson-1 trial (NCT04489537) and the Phase 1/2 MAA-202 study (NCT04548791) — Nassim Usman, PhD, Catalyst’s CEO, said in a press release.
Enrollment in these trials “has been adversely impacted by several factors, including pandemic-related logistical challenges, competition for subjects, and increasing availability of prophylaxis [preventive] therapy globally,” making it impossible to deliver top-line data in 2022, Usman added.
Catalyst plans to share Crimson-1’s results obtained to date, “showing that we have successfully treated bleeds with [under-the-skin] MarzAA and have not observed any treatment-related adverse or thrombotic [blood clotting-related] events,” he said.
“We want to thank our study [participants], clinical trial investigators and site staff, employees, and investors for their partnership and commitment to the MarzAA programs over the last several years,” Usman said, adding that the company will donate standard-of-care treatment to the clinical sites where patients are enrolled.
Discontinuing MarzAA’s clinical development is expected to allow Catalyst to reduce its costs by about 40% and to instead advance its promising therapeutic platform for diseases affecting the complement system, a set of more than 30 blood proteins that contribute to the body’s natural immune defenses.
“We have made a strategic decision to stop the clinical development of MarzAA (engineered FVIIa) and focus solely on our complement programs and protease medicines platform,” Usman said.
Meanwhile, the company will seek buyers for all its hemophilia assets: MarzAA for the treatment of both hemophilia A and B patients with inhibitors, and Dalcinonacog alfa (DalcA) and the gene therapy CB 2679d-GT for people with hemophilia B.
DalcA was found to safely and effectively prevent bleeds in people with severe hemophilia B in a previous Phase 2b trial (NCT03995784), while CB 2679d-GT showed promise in a mouse model of the disease.
Current mainstay treatment for hemophilia A and B consists of replacement therapy, which supplies patients with the blood clotting protein they are missing — factor VIII in the case of hemophilia A, or factor IX in the case of hemophilia B.
However, many patients end up developing inhibitors, or neutralizing antibodies, against the delivered factors, lowering the therapy’s effectiveness.
A bypassing agent, MarzAA is a lab-made version of factor VII, a protein that promotes blood clotting through alternative mechanisms that do not require factors VIII and IX. In contrast to most available bypassing agents, which are administered directly into the bloodstream, MarzAA is delivered through an under-the-skin injection, which is thought to reduce patient burden and healthcare costs.
As such, the experimental therapy is expected to be an effective and more convenient approach for preventing or treating bleeds in hemophilia patients with inhibitors. MarzAA received fast-track designation in the U.S. for this indication, a status meant to accelerate its clinical development and regulatory review.
Positive results from a previous Phase 2 trial (NCT03407651) had shown that daily preventive treatment with MarzAA safely lowered bleed frequency in 11 hemophilia A and B patients. Those findings prompted the launch of the pivotal, global, Phase 3 Crimson-1 trial.
Crimson-1, which dosed its first patient in May, was designed to evaluate MarzAA’s safety and effectiveness against standard of care for on-demand treatment of spontaneous or traumatic bleeds. It was enrolling up to 60 adults and children, ages 12 and older, with hemophilia A or B, with inhibitors.
The Phase 1/2 MAA-202 trial also was testing the therapy in hemophilia A patients with inhibitors who were being treated with standard Hemlibra (emicizumab), and in people with other inherited blood disorders.
Both trials were expected to conclude in March 2022.
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