San Diego, CA - The American Society of Hematology (ASH) 2024 meeting featured promising updates on novel therapies for rare blood disorders. Key highlights included Sanofi's rilzabrutinib for immune thrombocytopenia (ITP), Novo Nordisk's etavopivat for sickle cell disease, and Beam Therapeutics' CRISPR-based therapy, BEAM-101, also for sickle cell disease.
Sanofi's Rilzabrutinib Shows Promise in ITP
Rilzabrutinib, an oral Bruton's tyrosine kinase (BTK) inhibitor developed by Sanofi, has shown positive results in a Phase 3 study for patients with persistent or chronic immune thrombocytopenia (ITP). The study demonstrated that 65% of participants treated with rilzabrutinib achieved an improved platelet response compared to 33% on placebo. Furthermore, 23% of the rilzabrutinib group experienced a durable platelet response, while none was observed in the placebo group. The drug also reduced bleeding episodes and improved fatigue. David Kuter, a physician and director of hematology at Massachusetts General Hospital, noted that rilzabrutinib appears safer and better tolerated than existing BTK inhibitors. Sanofi has submitted rilzabrutinib for regulatory approval in the U.S. and Europe, with a decision expected in the U.S. by next August.
Novo Nordisk's Etavopivat Reduces Pain Crises in Sickle Cell Disease
Novo Nordisk presented Phase 2 study results for etavopivat, an oral drug that improves the oxygen-carrying capacity of red blood cells, in patients with sickle cell disease. The study showed a 46% reduction in the occurrence of pain crises compared to placebo, although this did not reach statistical significance. Specifically, the annualized rate of pain crises fell from an average of 3.3 per year to just over one in the etavopivat group, compared to just under two in the placebo group. Etavopivat also increased hemoglobin levels and improved fatigue. Common side effects included headaches, stomach discomfort, and elevated liver enzymes. Julie Kanter, a physician and director of the adult sickle cell program at the University of Alabama at Birmingham, sees etavopivat as a potential standard treatment alongside existing therapies like hydroxyurea. Novo Nordisk is conducting a larger Phase 3 study, with results expected in 2026. Etavopivat activates pyruvate kinase, improving red blood cell health and slowing their destruction.
Beam Therapeutics' CRISPR Therapy Shows Consistent Results
Beam Therapeutics shared updated results from its clinical trial of BEAM-101, a CRISPR-based therapy for sickle cell disease. The data showed that seven patients treated with BEAM-101 produced more than 60% fetal hemoglobin, with sickled hemoglobin levels falling below 40%. No patients have reported severe pain crises since treatment. These results align with previous findings from an analysis of four patients reported in November. BEAM-101 utilizes base editing, a gentler form of CRISPR that only nicks DNA and changes a single letter. A participant in the Beam study died due to respiratory failure caused by the toxic chemotherapy regimen required to prepare the bone marrow before BEAM-101 can be administered.
Fertility Preservation for Sickle Cell Patients
New research presented at ASH highlighted the importance of fertility preservation for sickle cell patients undergoing potentially curative therapies. A review of medical records from five treatment centers showed that oocyte cryopreservation is a viable option for patients, provided they have access to the procedure. While patients with sickle cell disease may require higher levels of gonadotropin to stimulate their ovaries, the number of oocytes retrieved and preserved was comparable to those without the disease. Marti Goldenberg, a pediatric hematologist at Johns Hopkins, emphasized the need for counseling and careful management to minimize complications, such as pain crises, following oocyte retrieval.
