After receiving guidance from both the U.S. Food and Drug Administration and the European Medicines Agency, Catalyst Biosciences is preparing to launch a pivotal Phase 3 clinical trial assessing marzeptacog alfa activated (MarzAA) for the treatment of bleeding episodes in people hemophilia A or B with inhibitors.
The Crimson-1 study is anticipated to start enrolling participants this year, but the exact timing depends upon the resolution of the COVID-19 pandemic and on preparations by trial sites.
“Now that we have received regulatory feedback, we have initiated preparations for a Phase 3 trial of MarzAA in individuals with hemophilia A or B with inhibitors,” Nassim Usman, PhD, president and CEO of Catalyst, said in a press release.
The upcoming Phase 3 trial is aiming to recruit 75 patients worldwide to study the safety and efficacy of subcutaneous (under-the-skin) injections of MarzAA as an on-demand treatment in about 230 acute bleeds. Patients may receive up to three injections for each bleeding episode.
Crimson-1’s main goal is to assess how efficiently MarzAA controls bleeds compared with prior standard therapies in a similar number of bleeding episodes. A standard four-point assessment scale will be used for this purpose.
“We plan to enroll the first patient before year end, however that date is dependent on the readiness of our trial sites and improvements in the current effects of COVID-19 on clinical trial execution,” Usman said. “At present, manufacturing and drug supply are unaffected for our clinical trials.”
MarzAA is a man-made version of the clotting factor VIIa (FVIIa), designed to prevent acute bleeds in people with hemophilia with inhibitors. These patients produce antibodies that wrongly target their treatments, making it more difficult to stop bleeding episodes.
The trial included 12 patients who received daily MarzAA via subcutaneous injections for 50 days. Before entering the trial, patients were experiencing about 20 bleeding episodes per year, and about 12% of their days were troubled by bleeding events.
But during the treatment period, yearly bleeds dropped to 1.6, and the proportion of days with bleeding was only 0.8%.
The treatment was safe and well tolerated, with only two patients experiencing reactions at the injection site — corresponding to six of a total of 517 injections. One patient died due to untreated high blood pressure, but this was deemed unrelated to MarzAA. Notably, no inhibitors were detected.
Recent studies have suggested that MarzAA can not only prevent bleeds in hemophilia patients, but also treat acute bleeding episodes when they happen.
In mouse models of hemophilia A, subcutaneous injections of MarzAA significantly reduced traumatic bleeds with a comparable efficacy of NovoSeven (recombinant FVIIa, by Novo Nordisk), another engineered form of FVIIa approved for treatment and short-term prevention of bleedings.
An additional study also suggested that MarzAA may safely be used to treat breakthrough bleeds in people on preventive treatment with Genentech‘s Hemlibra (emicizumab). It also provides a more convenient method for treating bleeds, since current treatments used in combination with Hemlibra require intravenous (into-the-vein) injections.
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