Fulcrum Discontinues Pociredir Program and Reviews Strategic Alternatives
Fulcrum Therapeutics announced the discontinuation of its pociredir program for the treatment of sickle cell disease, or SCD, and the initiation of a review of strategic alternatives. On May 28, Fulcrum received meeting minutes from recent end-of-phase interactions with the FDA. The minutes reflected heightened FDA concerns regarding pociredir's benefit-risk profile in SCD, stemming from an unexpectedly high rate of secondary hematologic malignancies observed with Tazverik, another PRC2 inhibitor, which was withdrawn from the global market in March. Fulcrum submitted information to FDA supporting the position that mechanistic differences between EED and EZH2, which perform different biological roles, were relevant to the benefit-risk assessment. FDA considered this position but concluded that any pharmacological intervention targeting the PRC2 complex carries equivalent malignancy risk regardless of the specific subunit engaged. FDA's position is informed by pociredir's previously disclosed preclinical malignancy observations and left no viable regulatory path forward for further clinical development of pociredir. Fulcrum will explore potential strategic alternatives, including, but not limited to, a merger, acquisition, business combination, or other strategic transactions involving the company or its assets. In connection with this review, Fulcrum has initiated efforts to significantly reduce its operating expenses and preserve capital. Fulcrum has not set a timeline for the completion of this review and does not intend to provide further updates unless and until the board has approved a course of action, the review process is concluded, or other disclosure is otherwise determined to be appropriate. "Following a thorough review of regulatory feedback, the totality of available data, and the implications for a viable regulatory path, we have made the very difficult decision to discontinue development of pociredir," said Alex Sapir, Fulcrum's president and CEO. "While no new safety signals have been observed to date with pociredir, the FDA raised concerns regarding the potential malignancy risk associated with pociredir's inhibition of the PRC2 complex given the experience with Tazverik that was recently withdrawn from the market. We arrived at this decision after discussion with the FDA, and despite robust elevations in fetal hemoglobin seen with pociredir and the potential for clinical benefit, we do not see a path forward with pociredir. We know the SCD community has faced many disappointments and setbacks related to innovation for this devastating disease, and we are not only humbled but forever grateful to the SCD warriors, investigators, and broader SCD community who have worked tirelessly alongside Fulcrum to evaluate new treatment options for this devastating disease."
