In a news release from May 18, 2021, biopharmaceutical company Catalyst Biosciences, Inc. (“Catalyst”) shared that the first patient was dosed in the Phase 1/2 MAA-202 clinical trial. During the trial, researchers will evaluate marzeptacog alfa (activated), or MarzAA, for patients with bleeding disorders. In particular, researchers want to understand the therapy’s safety, efficacy, tolerability, pharmacodynamics, and pharmacokinetics.

MarzAA

According to Catalyst, MarzAA is being developed for patients with bleeding disorders, including Glanzmann thrombasthenia, hemophilia A and hemophilia B, and FVII deficiency. The treatment is administered subcutaneously. Altogether, MarzAA is an engineered coagulation Factor VIIa (FVIIa). In this particular Phase 1/2 clinical trial, researchers are evaluating MarzAA as a treatment for episodic bleeding in patients who are using Hemlibra as a prophylactic therapy.

In December 2020, MarzAA received Fast Track designation from the FDA. Beyond this clinical trial, researchers are also evaluating MarzAA in the Phase 3 MAA-304 clinical trial. While the Phase 1/2 clinical trial is evaluating MarzAA in regards to a variety of bleeding disorders, MAA-304 is specifically centered around patients with hemophilia.

Bleeding Disorders Potentially Treated with MarzAA

Factor VII Deficiency

F7 gene mutations cause Factor VII deficiency, a rare bleeding disorder causing excessive bleeding. Normally, F7 helps to create coagulation factor VII. But gene mutations prevent enough of this protein, causing clotting difficulties. Because FVII deficiency is inherited in an autosomal recessive pattern, patients must receive one defective gene from each parent. An estimated 1 in every 300,000-500,000 individuals has FVII deficiency. Typically, those diagnosed earlier in life experience the most severe symptoms. These symptoms include:

• Easy bruising and bleeding
• Frequent nosebleeds
• Prolonged menstrual bleeding
• Black, tarry stool
  • Note: This symptom is particularly associated with gastrointestinal bleeding.
• Excessive bleeding following surgery, injury, or dental work
• Joint bleeding
  • Note: When bleeding into joint spaces occurs, patients may also experience joint damage, joint pain, and a limited range of motion.
• Bloody urine (rare)
• Intracranial bleeding (rare/severe)

Glanzmann Thrombasthenia

Glanzmann thrombasthenia is a rare inherited bleeding disorder characterized by improper blood clotting. Because the condition is inherited in an autosomal recessive pattern, someone must inherit one defective gene from each parent to develop this condition. These mutations cause abnormal platelet GPIIb/IIIa integrin family receptors. Ultimately, this prevents platelets from clotting when bleeding occurs. Glanzmann thrombasthenia affects both males and females equally. Oftentimes, the serious and prolonged bleeding begins at birth. Both the severity and frequency of bleeds varies between patients.

Symptoms associated with Glanzmann thrombasthenia include:

• Easy bruising and bleeding
• Heavy menstruation or bleeding after childbirth (females)
• Petechiae — red or purple spots on the skin caused by broken capillaries
• Hematoma — swelling caused by bleeding within tissue
• Gastrointestinal bleeding
• Excessive bleeding after surgery, injury, or dental work
• Bleeding from the nose and gums
• Bloody urine
  • Note: This symptom is not as common in patients as those listed above.

Hemophilia

Overall, F8 gene mutations cause hemophilia A and F9 gene mutations cause hemophilia B. Hemophilia is an inherited bleeding disorder which prevents the blood from clotting normally. In hemophilia A (‘classic’ hemophilia), this is caused by clotting factor VIII deficiencies. Alternately, in hemophilia B, clotting issues result from clotting factor IX deficiencies. Altogether, hemophilia A affects an estimated 1 in 5,000 males globally, while hemophilia B affects an estimated 1 in 20,000 males globally. Because hemophilia is inherited in an X-linked recessive pattern, it is much more likely for males to have hemophilia and for females to be carriers.

Symptoms vary in severity. These may include:

• Joint pain and swelling
• Bloody urine and/or stool
• Irritability
• Prolonged and excessive bleeding following vaccinations, dental work, surgery, or injury
• Large, deep bruising
• Excessive bruising and bleeding
• Random nosebleeds

However, if you have hemophilia and are experiencing any of the following symptoms, please seek emergency care immediately:

• Nausea and vomiting
• Severe headache
• Prolonged, heavy bleeding
• Extreme fatigue
• Sudden joint pain, swelling, or warmth
• Neck pain
• Double or blurred vision