Fulcrum Therapeutics (Nasdaq: FULC) has announced significant progress in its Phase 1b PIONEER trial evaluating pociredir for sickle cell disease (SCD), marking a crucial advancement in the development of oral therapeutics for this genetic blood disorder.
The company has successfully enrolled 10 patients in the trial's 12mg dose cohort, maintaining its timeline for key data releases. Clinical results from this cohort are expected in mid-2025, followed by data from the 20mg dose cohort by year-end 2025.
"Having recently enrolled the 10th patient in the 12 mg dose cohort, we remain on track to share important clinical data this year," stated Alex C. Sapir, Fulcrum's president and chief executive officer. "Based on both its mechanism of action and data generated in the Phase 1b trial to date, pociredir has the potential to ameliorate SCD symptoms by increasing fetal hemoglobin."
Novel Mechanism of Action
Pociredir functions as an oral small-molecule inhibitor of Embryonic Ectoderm Development (EED). The drug's mechanism involves downregulating key fetal globin repressors, including BCL11A, which leads to increased fetal hemoglobin (HbF) production. Initial clinical data has demonstrated proof-of-concept with HbF increases that could potentially benefit patients.
The FDA has recognized the drug's potential by granting it both Fast Track designation and Orphan Drug Designation for SCD treatment. Prior to a clinical hold that was lifted in August 2023, pociredir showed favorable tolerability in SCD patients with up to three months of exposure, with no serious treatment-related adverse events reported.
Financial Position and Pipeline Development
Fulcrum enters 2025 with a robust financial foundation, reporting $241.0 million in cash, cash equivalents, and marketable securities as of December 31, 2024. This represents an increase from $236.2 million at the end of 2023, bolstered by an $80.0 million upfront payment received from Sanofi in the second quarter of 2024.
Beyond its lead SCD program, Fulcrum is advancing research in inherited aplastic anemias, including Diamond-Blackfan anemia (DBA), with plans to submit an IND during the fourth quarter of 2025.
Addressing Unmet Needs in SCD
Sickle cell disease remains a challenging genetic disorder characterized by abnormal hemoglobin that causes red blood cells to become sickle-shaped and less flexible. These affected cells can block blood vessels and rupture, leading to severe complications including anemia, pain crises, organ damage, and reduced life expectancy.
The development of pociredir as an oral therapy represents a potentially significant advance in SCD treatment. Current management options often require complex administration methods or have limited accessibility, making an effective oral medication an attractive alternative for patients and healthcare providers.
