Week 1, July 2024: Blood Disorders

Blood disorders, including anemias, coagulopathies, leukemias, lymphomas, and thrombocytopenias, disrupt the normal functioning of blood components. Antibody therapeutics, such as monoclonal antibodies (mAbs), have transformed treatment approaches by offering targeted, high-specificity interventions. These therapies work by binding to specific antigens on diseased cells, leading to targeted immune responses or inhibition of harmful pathways. Applications include Rituximab for B-cell lymphomas, Blinatumomab for acute lymphoblastic leukemia, and Emicizumab for hemophilia A.

This week, the US FDA approved Genentech's PiaSky (crovalimab-akkz) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Crovalimab was previously approved in China on February 8 earlier this year. As a monoclonal antibody that binds to complement protein C5 and inhibits its cleavage into C5a and C5b, the drug prevents the formation of the membrane attack complex. PNH is a rare, acquired, life-threatening blood disorder characterized by the destruction of red blood cells prematurely by the complement system. The prevalence is estimated to be between 0.5-1.5 per million people in the general population.

In the clinical trial space, Novo Nordisk's Factor VIIIa mimetic bispecific antibody Mim8 significantly reduced bleeds in hemophilia A patients from an ongoing Phase 3 trial. Mim8 bridges Factor IXa/X (FIXa/FX), thereby replacing missing FVIII. This restores the body’s thrombin generation capacity, helping blood to clot. Also this month, Takeda's anti-CD38 antibody mezagitamab appears to be on track for Phase 3 after boosting platelet count in patients with persistent or chronic primary immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder. Mezagitamab is a fully human IgG1 mAb with high affinity for CD38 expressing cells.

Meanwhile, researchers at the University Hospital Schleswig-Holstein (UKSH) are also developing a monoclonal antibody, lusvertikimab, which shows potential for treating blood cancer. As a humanized IgG4 mAb, the drug binds to site-1 and site-2b of CD127, preventing the heterodimerization and subsequent activation of the IL-7R, without affecting TSLP receptor signaling. It thus reduces the leukemic burden in xenograft acute lymphoblastic leukemia via antibody-dependent cellular phagocytosis.