Shares of Fulcrum Therapeutics plunged 52% on Tuesday after the company said it would abandon development of its experimental sickle-cell disease drug following cancer-risk concerns raised by the U.S. FDA, and explore strategic options including a potential sale or merger.
The oral drug, pociredir, was being tested to treat sickle-cell disease, an inherited blood disorder that can trigger pain, anemia and organ damage and reduce life expectancy.
The setback adds to a string of challenges in sickle-cell drug development. In 2024, Pfizer withdrew its approved therapy Oxbryta and stopped related studies over safety concerns.
Pociredir was designed to increase levels of fetal hemoglobin by targeting a key sub-unit in the PRC2 protein complex, which normally suppresses its production.
Fulcrum's decision followed feedback from the U.S. Food and Drug Administration over safety concerns linked to drugs targeting the protein complex, after Ipsen's cancer drug, Tazverik, was withdrawn globally earlier this year because of the risk of secondary blood cancers.
The company said it had submitted data arguing that pociredir, which targets a different component of the PRC2 complex than Tazverik, had a distinct risk profile. The FDA, however, concluded that all drugs acting on the complex pose similar malignancy risks.
Truist analyst Gregory Renza said the regulator did not differentiate between sub-units of the PRC2, instead viewing the entire complex as carrying a systemic cancer risk.
We're a bit surprised by the discontinuation in light of strong efficacy data and unmet need, said Stifel analyst James Condulis.
At least three brokerages lowered their price targets and downgraded the stock following the development.
The company also said it would now consider strategic alternatives, including a potential sale or merger, and has begun cutting costs to preserve cash.
Fulcrum said no new safety concerns had emerged in clinical trials and that the drug had shown increases in fetal hemoglobin, which can help reduce disease severity in sickle-cell patients.
