The show is over for Pulmocide’s phase 3 trial after patients who received its investigational inhaled antifungal had lower response rates and a higher number of deaths than those in the control arm.
The decision was based on an interim analysis of the phase 3 Opera-T study, conducted after around half of the patients had been randomized and had reached day 84 of treatment, Pulmocide said in a Jan. 7 release. This analysis was done to recalculate the trial’s sample size.
The London-based biotech was trialing opelconazole, a nebulized azole compound, in treatment-resistant invasive pulmonary aspergillosis. Aspergillosis is an infection of the lungs caused by mold in the genus Aspergillus, and is most common in patients with compromised immune systems, like those who have received lung transplants.
In the most severe invasive form of the infection, the fungus has spread from the lungs to other parts of the body, such as the skin, brain, heart or kidneys.
Opera-T was set to enroll around 123 patients and compare twice-daily opelconazole and placebo in patients also being treated with other antifungals. Enrolled patients were “severely immunocompromised,” Pulmocide said in the release, “most of whom had a life-threatening underlying hematological malignancy or were recipients of a stem cell or solid organ transplant.”
Based on the analysis, most of the patients’ disease had not responded to at least two earlier antifungal treatments before joining the study, the British biotech added.
“The analysis showed a numerically lower favorable response rate and a numerically higher mortality rate in the opelconazole arm compared to the control arm,” the company explained.
None of the undisclosed number of patient deaths were attributed to opelconazole itself.
The early termination has put the entire opelconazole program on the rocks. Pulmocide is now performing “a thorough review of the unblinded data” from Opera-T to determine the program’s future, according to the release.
Pulmocide previously reported in April 2024 that opelconazole, its sole drug candidate, had appeared to eradicate Aspergillus from six patients infected with the fungus in the phase 2 Opera-S trial, with substantially lower levels of treatment discontinuation compared to control. However, the primary goal of Opera-S was the prevention of aspergillosis in lung transplant patients, not invasive fungal infections like in Opera-T.
The fungal-minded biotech pulled in a $147.5 million series C spread across 2021 and 2022 to fund development of opelconazole. At the time, the company was riding the high of “very remarkable responses” seen in case studies of patients given the antifungal candidate through the U.K.’s compassionate use program, CEO Daniel Burgess told Fierce back in May 2021.