First Patient Dosed in Open-label Trial of MarzAA

The first participant has been dosed in a Phase 1/2 clinical trial evaluating marzeptacog alfa activated (MarzAA) to treat bleeding episodes in patients with factor VII (FVII) deficiency, Glanzmann thrombasthenia, and hemophilia A with inhibitors receiving treatment with Hemlibra (emicizumab).

The open-label study, called MAA-202 (NCT04548791), is being sponsored by the investigational therapy’s developer, Catalyst Biosciences, and is currently enrolling up to 24 patients, ages 12 and older, at the Children’s Hospital of Michigan and in Bengaluru and Pune, India. Other study sites in the U.S., India, Italy, Russia, and Ukraine are expected to open soon. More information about locations and study contacts is available here. 

Hemophilia comprises a group of blood disorders characterized by the lack of specific blood-clotting proteins that impair the body’s ability to make blood clots needed to prevent excessive bleeding. People with hemophilia A, for example, lack the blood-clotting protein called factor VIII (FVIII).

Patients with Glanzmann thrombasthenia (GT) also have blood-clotting issues that can lead to excessive bleeding. However, in these patients blood-clotting problems are not driven by the lack of blood-clotting factors. Rather, they are caused by impairments on platelets, which are specialized cells that help blood clot. 

MarzAA is a lab-made, under-the-skin injectable version of the blood-clotting factor VIIa (FVIIa), which can replace the missing FVII in patients with FVII deficiency and also has been beneficial for those with GT. 

MarzAA also can be used as a bypassing agent in those with hemophilia A receiving replacement therapies, such as Hemlibra, who have developed inhibitors or neutralizing antibodies against FVIII, reducing the therapy’s effectiveness. Unlike replacement therapies, bypassing agents promote blood clotting through alternative mechanisms that do not involve the administration of conventional blood-clotting factors. 

“MarzAA is the only bypassing agent under development for the episodic treatment of bleeding events that can be rapidly administered subcutaneously and, if successful, will address a significant unmet medical need,” Nassim Usman, PhD, president and CEO of Catalyst, said in a press release. 

“We look forward to providing updates on the MarzAA clinical development program, including reporting interim data from MAA-202 later this year,” Usman added. 

In the Phase 1 portion of the MAA-202 trial, participants will receive 18 micrograms per kilogram of body weight (mcg/kg) of MarzAA, followed by increasing doses for five to 11 days. In addition to safety, this initial portion of the study will evaluate the therapy’s pharmacokinetic and pharmacodynamic properties. Pharmacokinetics evaluates how a medication moves into, through, and out of the body, while pharmacodynamics assesses its effects on the body.

These results will confirm dosing for the Phase 2 portion, in which MarzAA will be administered on demand during bleeding episodes for a maximum of three doses. Treatment success will be determined based on the proportion of bleeding episodes successfully controlled within 24 hours following treatment administration. 

In addition to MAA-202, a Phase 3 trial, Crimson-1 (NCT04489537), also is evaluating the safety and efficacy of MarzAA at treating bleeding episodes in patients with hemophilia A and B with inhibitors. Dosing started earlier this month, and the trial is expected to conclude by March 2022.

Crimson-1 is recruiting up to 60 patients, ages 12 and older, at sites in Spain, Turkey, Ukraine, Russia, Poland, Georgia, and India. Additional sites in the U.S., U.K., and other countries are expected to open. More information on study contacts and sites, is available here.