Fulcrum Therapeutics recently announced the interim results from their Phase 1 trial of FTX-6058 in a press release. This selective small-molecule inhibitor of EED is in development for the treatment of hemoglobinopathies, such as sickle cell disease (SCD) and beta thalassemia. Currently, it is performing well in the ongoing single- and multiple-ascending dose (SAD and MAD) studies. If it continues to do so, it has the potential to fill an unmet need for SCD patients.

About the Study Results

This trial investigated single- and multiple-ascending doses in healthy adult participants and is still ongoing. All participants took FTX-6058 orally, once a day, or a placebo in an effort to investigate the pharmacokinetics, safety, and tolerability of this investigational drug. Interim results include:

• In the MAD arm of the trial:
  • Dose-dependent decreases in HBG mRNA combined with increases in HbF-containing reticulocytes, indicating HbF protein production
  • All doses achieved maximal target engagement, demonstrated by lowered trimethylation at lysine 27 of histone H3
  • 70% – 80% decrease in baseline H3K27me3 levels
• In both portions of the trial:
  • No severe adverse events (AEs)
  • No discontinuations
  • Generally well-tolerated

The remaining results are expected in the fourth quarter of this year, as is the enrollment of SCD patients for a Phase 1b trial. For up to three months, participants will receive 6 mg of FTX-6058 every day, changing dosages as the study continues. If all goes according to plan, Fulcrum Therapeutics plans to submit an Investigational New Drug (IND) application by the end of the year.

About Sickle Cell Disease (SCD)

SCD is an umbrella term for a group of blood disorders characterized by abnormal, sickle-shaped red blood cells. These malformed cells then get caught in the vessels and cause blockages, leading to the characteristic symptoms of the disease. These include jaundice, fatigue, pain crisis, delayed growth, and swelling of the hands and feet. Adults typically feel these symptoms constantly, whereas children experience them in episodes.

A mutated gene that is inherited in an autosomal recessive pattern is responsible for SCD. This gene is necessary to produce hemoglobin, and when it is altered, hemoglobin cannot function or perform properly. There is no cure for this disease; treatment is typically symptomatic, although a bone marrow transplant may be an option for some.