Marstacimab

• Maintaining high Factor VIII (FVIII) levels in people with hemophilia A provides significant clinical benefits, including reduced bleeding risk and better joint health preservation. • Despite advances in prophylactic treatment, standard-of-care prophylaxis does not completely prevent joint damage or chronic pain, with approximately 47% of hemophilia patients experiencing ongoing pain. • Recent innovations in hemophilia treatment, including extended half-life therapies, non-factor replacement options, and gene therapy, offer new approaches to sustaining higher FVIII levels and improving patient outcomes.

Pfizer has announced the cessation of development and commercialization of Beqvez, its FDA-approved gene therapy for hemophilia B, citing limited interest from patients and healthcare providers.

• The FDA approved 50 novel drugs in 2024, slightly down from 55 in 2023, while the EMA increased its approvals to 46 from 39 in the previous year. • Over half of FDA's novel drug approvals targeted rare diseases affecting fewer than 200,000 people, with 68% of approvals occurring first in the US before other countries. • Both agencies approved significant breakthrough treatments, including Hympavzi for hemophilia, needle-free anaphylaxis spray Neffy/Eurneffy, and new therapies for primary biliary cholangitis.

Pfizer's fidanacogene elaparvovec (SPK-9001) gene therapy met its primary endpoint in the Phase 3 BENEGENE-2 study for haemophilia B, demonstrating non-inferiority and superiority in annualized bleeding rate.

• ASH 2024 highlighted significant progress in hemophilia care since Hemlibra's approval, including gene therapies for hemophilia A and B, offering curative potential. • Despite advances, unmet needs persist, including spontaneous bleeds in prophylaxis patients, limited gene therapy access, and concerns about long-term risks like liver toxicity. • Emerging therapies like Pfizer's giroctocogene fitelparvovec and Sanofi's fitusiran show promise, with ongoing trials and regulatory reviews potentially expanding treatment options. • Novel on-demand treatments like Staidson's bemiltenase alfa offer alternatives, particularly in price-sensitive markets, demonstrating a 12-hour bleed clearance rate of 83%.