Gossamer Cuts Lymphoma Drug After Two Fatalities
Gossamer announced in an SEC filing that the FDA had placed a partial clinical hold on all studies of GB5121 after documenting serious adverse events in STAR-CNS. These included an episode of fatal intracranial hemorrhage, a case of atrial fibrillation and one sudden death.
The company’s stocks dropped 11% by market close Monday.
Designed to be orally available, GB5121 is a BTK inhibitor that can penetrate the central nervous system (CNS). Gossamer was studying the candidate in primary CNS lymphoma and other rare malignancies of the CNS.
In August 2022, the company announced it had dosed its first patient in STAR-CNS, a three-part trial including a Phase Ib dose-escalation and dose-expansion phase and a Phase II study to assess the candidate’s safety, tolerability, maximum tolerated dose, dose-limiting toxicities and preliminary activity and efficacy.
In March 2023, Gossamer reviewed GB5121’s risk-benefit profile and suspended enrollment into STAR-CNS. Instead, the company diverted its resources to seralutinib, its candidate for pulmonary arterial hypertension (PAH).
High Hopes for PAH
Seralutinib is an investigational inhaled PAH treatment currently being assessed in a Phase II study. The candidate works by inhibiting the PDGFR/CSF1R/c-Kit kinase pathway, which slows down the hyperactive cell growth typically seen in PAH patients.
In December 2022, Gossamer posted topline results from this Phase II study. Initial data showed that while seralutinib met its primary endpoint by significantly reducing pulmonary vascular resistance, the candidate had no significant effect on 6-minute (6MWD) walk distance, a key secondary functional measure.
After digging into the data, Gossamer found that seralutinib improved 6MWD by a significant 37 meters in patients with functional class III pulmonary hypertension, indicating substantial limitations in physical activity.
Still, investors weren’t convinced. The company’s stock dropped 65% due to seralutinib’s Phase II data.
The skepticism toward seralutinib could be due to intense competition. Merck is also advancing a PAH therapeutic through the clinic. The company's sotatercept aced its Phase III STELLAR trial in March, leading to a significant 40.8-meter improvement in 6MWD.
In contrast with Gossamer’s seralutinib, sotatercept targets TGF-β proteins to restore the balance between pro- and anti-proliferative pathways. Merck is preparing to present these pivotal sotatercept data to the FDA.
Meanwhile, Gossamer expects to wrap up all Phase II regulatory interactions for seralutinib in the first half of 2023 and initiate a Phase III study later this year. Bryan Giraudo, chief financial officer and chief operating officer at Gossamer, told BioSpace in an e-mail that if the study begins in the second half of 2023 as planned, Gossamer expects it could have topline results by the end of 2025.
Update (April 4): This story has been uploaded to include a comment from Gossamer Bio.