Pociredir

Fulcrum ends development of sole clinical candidate, pociredirPraxis' vormatrigine falls short in pivotal seizure studyShionogi gets FDA nod for oral COVID-19 preventativeCEPI promises Moderna up to $50M for Ebola vaccine development Agios nabs Oscotec's SYK inhibitor Fulcrum ends development of sole clinical candidate, pociredirFulcrum Therapeutics' shares crashed close to 50% during after-hours trading on Monday after disclosing it has discontinued its sickle cell disease asset — and only clinical programme — pociredir. The company is planning to launch a comprehensive review to identify any "strategic alternatives" such as a merger, acquisition or business combination.The decision to bin pociredir, an oral small molecule EED inhibitor, was driven by feedback from the FDA. According to Fulcrum, the US regulator had "heightened" concerns about the candidate's risk-benefit profile due to a high rate of secondary haematologic malignancies observed with a mechanistically similar drug, Tazverik (tazemetostat), which Ipsen withdrew from markets in March. Though the two drugs are directed against different targets — pociredir targets EED and Tazverik targets EZH2 — they are both within the PRC2 complex. carries equivalent malignancy risk regardless of the specific subunit engaged.Feedback from the FDA "left no viable regulatory path forward for further clinical development of pociredir," Fulcrum said. The company is now significantly reducing its operating expenses to preserve capital; as of March 31, it had $333.3 million in cash on-hand. Praxis' vormatrigine falls short in pivotal seizure study Praxis Precision Medicines' focal onset seizure (FOS) hopeful vormatrigine has failed the Phase II/III POWER1 study, the company said Monday. The sodium channel inhibitor and functional state modulator did not lead to a statistically significant reduction from baseline in monthly seizure frequency as compared with placebo.  Still, the company — whose shares slipped about 10% during after-hours trade Monday — isn't giving up on vormatrigine yet. CEO Marcio Souza said Praxis was "encouraged by the signal we saw on the higher dose arm, the low discontinuation rate and solid safety profile," adding that the drugmaker is taking "some time to review these results to ensure we have the best path forward for developing vormatrigine and the ongoing POWER2 study." The Phase III POWER2 trial is the second registrational study evaluating vormatrigine in adults with FOS; it's expected complete in the second half, with topline results due in 2027.Shionogi gets FDA nod for oral COVID-19 preventativeThe FDA on Monday approved Shionogi's oral antiviral Xocova (ensitrelvir) for post-exposure prophylaxis (PEP) of COVID‑19 in adults and children aged 12 and up to prevent infection after coming into contact with someone who has the disease. The approval, which came ahead of Xocova's June 16 PDUFA date, covers a five-day treatment regimen for the SARS-CoV-2 main protease inhibitor. Three tablets are taken on the first day, following exposure, and one tablet is taken on days two through five. Xocova's green light is based on the results of the Phase III SCORPIO-PEP trial, which involved 2387 participants. The PEP treatment significantly reduced the risk of symptomatic COVID-19 by 67% in uninfected individuals following exposure to an infected individual after 10 days, compared with placebo. According to Shionogi, SCORPIO-PEP is the first and only Phase III study of an oral antiviral to meet the primary endpoint of preventing COVID-19 following exposure.CEPI promises Moderna up to $50M for Ebola vaccine development  The Coalition for Epidemic Preparedness Innovations (CEPI) is "urgently" backing the development of three Ebola vaccine candidates to combat the viral disease outbreak in the Democratic Republic of the Congo, committing about $60 million in total to the venture. Moderna said Monday that CEPI has pledged up to $50 million to support preclinical development and Phase I testing of its mRNA vaccine candidate. The funds will also go towards manufacturing so the asset can quickly move into large-scale Phase II/III trials if the early safety and immunogenicity data come back positive.  The International AIDS Vaccine Initiative will also receive financial support from CEPI to work on a Bundibugyo vaccine candidate, as will the University of Oxford. Agios nabs Oscotec's SYK inhibitor  Agios Pharmaceuticals licensed exclusive, global rights to cevidoplenib, a next-generation, oral spleen tyrosine kinase (SYK) inhibitor, from South Korea-based drugmaker Oscotec. It plans to launch a Phase III trial evaluating the drug in patients with immune thrombocytopenia (ITP) in the first half of 2028."Cevidoplenib is a next-generation SYK inhibitor uniquely designed to potentially offer improved tolerability and durability compared to first-generation SYK inhibitors," Agios CEO Brian Goff said in a company release Monday. "Backed by clinically meaningful Phase II data, we believe cevidoplenib has the opportunity to become a best-in-class treatment option for ITP."Under the deal, Oscotec will receive $25 million upfront and is eligible for up to $140 million in development and regulatory milestones across up to three indications in the US and Europe, as well as commercial milestone payments and royalties ranging from high single-digit to mid-teen. The firm also has an option to license exclusive development and commercialisation rights to cevidoplenib in South Korea after the Phase III trial reads out.

Fulcrum has been left with no option but to abandon its ambitions for pociredir in SCD and “explore strategic alternatives.”\n Fulcrum Therapeutics has scrapped its sole clinical-stage program after the FDA took a hard line on the modality following the recent withdrawal of Ipsen’s Tazverik from the U.S. market.Ipsen withdrew Tazverik in March across all indications and in all markets after a data monitoring committee observed “adverse events of secondary hematologic malignancies” in a phase 1b/3 trial.France’s Ipsen had acquired the rights to Tazverik, an inhibitor of polycomb repressive complex 2 (PRC2), when it bought Epizyme in 2022. By that point, Tazverik had already been on the U.S. market for two years as both an epithelioid sarcoma and a follicular lymphoma treatment.Fulcrum’s lead asset, pociredir, is also a PRC2 inhibitor, which the company had been evaluating in a phase 1b study for sickle cell disease (SCD). The biotech said it had been in discussions with the FDA to reassure the agency that there are “mechanistic differences” between pociredir’s target of the regulatory protein EED and Tazverik’s target of the EZH2 enzyme.These targets “perform different biological roles,” which is “relevant to the benefit-risk assessment,” Fulcrum argued in a June 1 post-market release. Unfortunately for Fulcrum, the FDA wasn’t convinced.“[The] FDA considered this position but concluded that any pharmacological intervention targeting the PRC2 complex carries equivalent malignancy risk regardless of the specific subunit engaged,” Fulcrum explained. The agency’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,” the biotech added.It’s a significant setback for Fulcrum, which, as recently as late April, reaffirmed its “conviction in pociredir’s potential to address the underlying biology” of SCD, while highlighting a “strong balance sheet” of $333 million to fund the drug’s development through 2029.Instead, Fulcrum has been left with no option but to abandon its ambitions for pociredir in SCD and “explore strategic alternatives.”Those alternatives could range from a merger or sale of the company or its assets. Fulcrum’s preclinical pipeline consists of HbF inducers being developed for SCD and prostate cancer.In the meantime, the biotech has already “initiated efforts to significantly reduce its operating expenses and preserve capital.” Fierce has asked the company whether these efforts are likely to include laying off employees.“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,” CEO Alex Sapir said in the release. “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,” Sapir added. “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.”Unsurprisingly, investors took fright at the abrupt turn in events, sending Fulcrum’s stock down 51% to $3.10 in pre-market trading Tuesday from a Monday closing price of $6.42.