FDA lifts its clinical hold on oral therapy FTX-6058 for SCD
Enrollment in Phase 1b trial expected to resume soon - with some changes
The U.S. Food and Drug Administration (FDA) has lifted its clinical hold on FTX-6058, an investigational oral treatment for sickle cell disease (SCD) that’s being developed by Fulcrum Therapeutics.
With the hold lifted, Fulcrum is planning to resume enrolling patients in a Phase 1b clinical trial (NCT05169580) that’s testing FTX-6058 in people with SCD. In line with discussions with the FDA, the trial’s design has been modified to include stricter criteria about who is allowed to participate.
“We are pleased with the FDA’s decision to lift the clinical hold and are eager to advance FTX-6058 through clinical development to address the significant unmet need in the sickle cell disease community,” Alex C. Sapir, president and CEO of Fulcrum, said in a company press release.
Sapir noted that early data from the trial had been promising, with FTX-6058 showing the potential to offer SCD patients a new treatment option for the inherited disorder.
New stricter criteria limit enrollment to patients with more severe SCD
FTX-6058, taken by mouth, is designed to boost the production of fetal hemoglobin, known as HbF, in patients. SCD is caused by genetic mutations that affect the adult version of hemoglobin, the protein that carries oxygen through the bloodstream.
HbF is usually made during fetal development, but then stops being produced in the first months of life, as the body switches on the production of the adult version of the protein.
Importantly, fetal hemoglobin is more effective at transporting oxygen than its adult counterpart. Thus, increasing HbF levels may help to improve oxygen transport and ease SCD symptoms.
The therapy candidate specifically aims to block polycomb repressive complex 2, or PRC2, a group of proteins that normally work to turn off the production of HbF in infancy. By blocking PRC2, the therapy aims to turn back on HbF production.
Early data from the Phase 1b trial had indicated that FTX-6058 can increase HbF levels as designed, with greater gains seen in patients given higher doses of the experimental therapy.
Based on the initial data from the Phase 1b trial, which showed increasing levels of HbF with each dose escalation, we believe in the potential of FTX-6058 to not only shift the current standard of care but importantly, offer these patients a differentiated oral option.
Dosing in that trial was stopped in February when the FDA issued the clinical hold.
Now, according to Sapir, “we look forward to building on these results with plans to resume enrollment for patients with SCD.”
“Based on the initial data from the Phase 1b trial, which showed increasing levels of HbF with each dose escalation, we believe in the potential of FTX-6058 to not only shift the current standard of care but importantly, offer these patients a differentiated oral option,” Sapir said.
When the FDA issued the clinical hold, the agency cited as its reason certain preclinical data on FTX-6058, as well as non-clinical and clinical data from other therapies targeting PRC2. That data suggested these medications might increase the risk of blood cancers.
While the Phase 1b trial now will be reopening, the study’s participation criteria have been updated to address the FDA’s concerns, according to plans announced by Fulcrum. Essentially, the new criteria limit participation in the trial to people with relatively more severe SCD.
Among other criteria, eligible participants must have experienced at least four SCD pain crises in the year before entering the trial, or at least two crises in the six months preceding trial screening. Patients who have experienced multiple episodes of other SCD-related complications, such as acute chest syndrome, or who have other ongoing SCD-related problems like chronic kidney disease, also may be eligible.
The trial also is limited to patients who have tried and failed to respond, were intolerant, or ineligible to receive treatment with hydroxyurea and at least one other approved SCD therapy. Among these therapies are Oxbryta (voxelotor), Adakveo (crizanlizumab), and Endari (L-glutamine). Participants cannot have been on these treatments within 60 days of receiving FTX-6058. Patients who do not have access to these treatments may be considered eligible.
Fulcrum estimates that there are 7,500 to 10,000 people with SCD in the U.S. who meet the updated eligibility criteria for the trial. The company did not specify when recruitment is expected to reopen.
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