The company is ending its investigational drug GB0139’s run in idiopathic pulmonary fibrosis after the small-molecule inhibitor failed to slow lung function decline in a Phase IIb study.
Pictured: Air sacs inside the lungs/iStock, Ozgu Arslan
Galecto’s investigational drug GB0139 fell short of its primary efficacy endpoint in the Phase IIb GALACTIC-1 trial, failing to slow the decline of forced vital capacity in patients with idiopathic pulmonary fibrosis, the company announced Tuesday.
Following the failure, Galecto will discontinue the clinical development of GB0139 in idiopathic pulmonary fibrosis (IPF) and instead focus its resources on advancing assets for severe liver diseases, the company said in the announcement.
Galecto CEO Hans Schambye said in a statement that results from GALACTIC-1 “do not support the continued development of GB0139 as a new treatment for IPF” and that the company is currently re-evaluating its options and resource allocation plans “with the goal of extending our cash runway into 2025.”
Previously granted the FDA’s Orphan Drug Designation, GB0139 was an inhaled small-molecule inhibitor of the galectin-3 protein, which is a key player in the fibrosis cascade. This mechanism of action allows the candidate to disrupt galectin-3 signaling, which when otherwise left unchecked could lead to the progressive interstitial thickening commonly seen in IPF, according to Galecto’s website.
GB0139 was designed to be administered through a once-daily generic dry powder inhaler and had been shown in previous studies to be safe and effective at suppressing galectin-3 levels in the lungs in a dose-dependent manner. The candidate had also led to lower levels of key plasma biomarkers known to be associated with clinical outcomes in IPF.
In GALACTIC-1, however, galectin-3 levels increased through 52 weeks in both the GB0139 and placebo arms, indicating that there was no target engagement in the study. Patients treated with Galecto’s candidate saw a 316.6-mL reduction in forced vital capacity at 52 weeks, while this lung function decline was just at 127.4 mL in placebo comparators.
“The observed decrease in lung function in the placebo group was lower than similar placebo groups reported in previous IPF trials with other drugs,” the company said in its press release.
Tuesday’s Phase III failure and discontinuation mark the end of GB0139’s troubled clinical development. In March 2021, a Data Safety Monitoring Board recommended that Galecto stop testing GB0139’s 10-mg dose, citing an “imbalance in the serious adverse experiences across the study groups.” The company pushed through with the 3-mg dose of the candidate and in July of the same year the company restarted enrollment in GALACTIC-1.
Galecto will now focus its R&D efforts on GB1211, another galectin-3 inhibitor being developed for severe liver diseases. In October 2022, the company presented topline data from the Phase Ib/IIa GULLIVER-2 study, showing that the candidate had a favorable tolerability and pharmacokinetic profile, while demonstrating promising signs of efficacy.
Galecto had recently closed a type C meeting with the FDA to determine the best regulatory path forward for GB1211 and is preparing to launch a long-term, randomized and placebo-controlled Phase IIa study—dubbed GULIVER-3—in early 2024.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
