Fulcrum Therapeutics’ is down more than 50% Tuesday morning as the biotech discontinues development of its lead asset. Ipsen’s Tazverik, which belongs to the same class, was pulled from the market in March due to the risk of secondary malignancies.
Fulcrum Therapeutics no longer sees a viable regulatory path for its lead asset pociredir in sickle cell disease, so the biotech has decided to discontinue the drug’s development.
In a recent meeting with the FDA, the regulator raised concerns with pociredir’s benefit-risk profile in this indication, Fulcrum said in a news release on Monday. In particular, the regulator pointed to the “unexpectedly high rate of secondary hematologic malignancies” in patients treated with Ipsen’s cancer drug Tazverik, which is a PRC2 inhibitor like pociredir.
Ipsen voluntarily pulled Tazverik from shelves worldwide in March. Fulcrum is down more than 50% before Tuesday’s opening bell, hitting $3.15 per share.
Fulcrum initially tried to defend pociredir’s position, arguing that the drug targets a different part of PRC2, but the FDA “concluded that any pharmacological intervention targeting the PRC2 complex carries equivalent malignancy risk,” the biotech wrote on Monday. This determination “left no viable regulatory path forward for clinical development of pociredir,” Fulcrum said.
Analysts at Stifel were surprised by pociredir’s discontinuation, calling the decision “disappointing.” Despite the safety overhang from Tazveriik, Stifel said that it had been “optimistic that there were nuances”—such as dosing, target patient population and the overall efficacy of the drug—"that made the calculus” for pociredir in sickle cell disease different.
“We had thought the risk/reward here was compelling if FULC were able to align on a favorable regulatory alignment,” the analysts continued. “Admittedly, we’re a bit surprised to see the full discontinuation in-light of the strong efficacy data on a validated target.”
Fulcrum was testing pociredir in the Phase 1b PIONEER study, which in February showed a 12.2% increase in fetal hemoglobin levels at 12 weeks. All 12 patients treated saw a “clinically relevant” improvement in fetal hemoglobin, the biotech said at the time. Fulcrum also noted that pociredir was “generally well-tolerated,” with no discontinuations or serious adverse events linked to the asset.
With its lead asset axed, Fulcrum on Monday said that it will look at potential strategic alternatives for its business. Its options include a merger, a business combination or other similar transactions, though the company has yet to set a timeline for this strategic review. Fulcrum is also taking measures to “significantly reduce its operating expenses and preserve capital,” according to its news release. It is unclear if this will involve layoffs.
As of March 31, Fulcrum had $333.3 million in cash, equivalents and marketable securities, enough to keep it going into 2029.
