Clinical hold put on experimental sickle cell treatment FTX-6058
A formal notice is expected from the FDA within 30 days
The U.S. Food and Drug Administration (FDA) has placed a clinical hold on FTX-6058, an experimental therapy that Fulcrum Therapeutics is developing to treat sickle cell disease (SCD).
Fulcrum announced it would be stopping dosing in an ongoing Phase 1b clinical trial (NCT05169580) that’s testing different doses of FTX-6058 in adults with SCD.
“Patient safety remains paramount to me. I am encouraged by the Agency’s willingness to work with us to clarify the therapeutic potential of FTX-6058,” said Robert Gould, PhD, interim president and CEO of Fulcrum, in a press release.
According to Fulcrum, the FDA verbally informed the company of the hold in late February and is expected to issue a formal clinical hold letter within 30 days. The hold was issued due to “previously reported preclinical data.” No further details were provided by the company.
Sickle cell disease is caused by mutations in a gene that provides instructions for making a subunit of hemoglobin — the protein in red blood cells that transport oxygen through the bloodstream. Sickle cell specifically affects the adult form of hemoglobin. Another form of the protein, known as fetal hemoglobin, or HbF, is produced during fetal development, but stops being made in the first months of life as the adult form is produced. HbF is more efficient at transporting oxygen than its adult counterpart.
FTX-6058 is designed to increase HbF levels, thus improving oxygen transport and helping to ease SCD symptoms. It’s specifically designed to block the activity of a group of proteins known as polycomb repressive complex 2 (PRC2). The PRC2 complex normally keeps the genes that provide instructions for making HbF turned off. By blocking its activity, FTX-6058 would activate these genes, leading ultimately to HbF being produced.
Early data from a Phase 1 study (NCT04586985) of healthy volunteers indicated FTX-6058 could boost HbF production as intended. The ongoing Phase 1b trial was launched to explore its safety and pharmacological properties in adults with sickle cell. Early data from the trial suggested treatment led to an increase in HbF levels, according to Fulcrum.
The company said FTX-6058 has generally been well tolerated during the study, with no serious side effects reported at up to three months of treatment.
“Fulcrum intends to address questions related to modulation of the PRC2 complex and the preclinical data. We continue to have confidence in the benefit-risk profile of FTX-6058 and remain committed to our goal of providing a differentiated therapeutic option for people living with sickle cell disease,” Gould said.