Galecto’s bumpy clinical ride developing an inhaled treatment for idiopathic pulmonary fibrosis came to a screeching halt after midstage data showed that the drug was ineffective.
The company is now discontinuing work on the candidate, a small-molecule inhibitor of galectin-3 dubbed GB0139, and funneling resources toward a treatment for liver cirrhosis with a new trial on the horizon, according to an announcement Tuesday.
GB0139 failed to hit the phase 2 trial’s primary endpoint, a change from baseline in the rate of decline in forced vital capacity (FVC)—a measure of air exhaled from the lungs—compared to placebo. In fact, the average reduction in FVC was 316.6 ml among patients treated with a 3-mg daily dose of Galecto’s candidate for a year, compared to a less pronounced drop of 127.5 ml for those given placebo, meaning treated patients fared much worse.
Galecto also said that levels of the galectin-3 protein rose in both arms, indicating a lack of target engagement for the treatment. The trial enrolled 173 patients who had not previously received standard-of-care IPF treatments—Genentech’s Esbriet or Boehringer Ingelheim’s Ofev.
The results and subsequent decision to call it quits mark an abrupt end to a tough clinical journey. In March 2021, the data safety and monitoring board recommended that the company ax the 10-mg treatment arm after an “imbalance” in serious side effects was cropping up.
That left the 3-mg arm as the only option moving forward, with recruitment restarting a few months later. Still, the safety profile now disclosed failed to differentiate, with 7.8% of treated patients reporting serious side effects compared to 1.4% for the placebo arm, with one severe case in the treatment arm attributable to the drug.
“We clearly saw more side effects in the sort of IPF infection exacerbation with the drug and that's where we're searching for the explanation for what's happening,” CEO Hans Schambye, M.D., Ph.D., told Fierce Biotech in an interview.
Adverse events leading to death were similar in both the treatment and placebo arms, Galecto reported, with Schambye explaining that mortality was slightly lower among treated patients. None of the deaths in the treatment arm were attributable to the study drug.
Galecto’s attention now turns to another galectin-3 inhibitor called GB1211 and its development as a treatment for liver cirrhosis. The company just wrapped a type C meeting with the FDA and is gearing up for a placebo-controlled phase 2 trial in patients with decompensated nonalcoholic steatohepatitis (NASH) cirrhosis, set to start in early 2024.
Schambye told Fierce that he believes that, given the bleak prognosis for patients who develop cirrhosis, the market potential is high even as other biotechs show promise at treating NASH earlier in the disease progression.
“It's very different from the NASH compounds that are focused mainly on reducing the inflammation and reducing the fat storage in the liver cells and trying to sort of prevent the disease from happening,” the CEO said. “We’re in those places where this has already happened.”
What’s been made clear is that Galecto will need to raise additional funds to see GB1211 through the upcoming study and beyond. Schambye said investors were wary while the focus was the IPF med, given the difficulty treating the lung condition. But with liver disease as the focus, the CEO thinks he can corral fresh interest and fresh capital.
GB1211 is also being developed as a cancer treatment, alongside a LOXL2 inhibitor called GB2064, opening the door for partnership opportunities.
“I firmly believe that biotech companies should go where the data tells them to go and then pursue the opportunities that present themselves,” Schambye added.