Pulmocide exits OPERA with phase 2 evidence of antifungal safety and efficacy

Pulmocide has added new nuances to the chorus of evidence for its antifungal, reporting data from the phase 2 OPERA-S study to show the candidate can prevent and eradicate infections without causing the problems associated with existing therapies. 

London-based Pulmocide raised almost $150 million in series C funds from a storied set of investors to fund development of its novel azole therapy opelconazole. The British biotech has identified the inhaled drug candidate as a treatment that can maximize the impact on fungi in the lungs while minimizing systemic exposure. Such a profile could enhance efficacy while limiting the toxicities and drug-drug interactions that force some patients to stop taking systemic antifungals.

The phase 2 study is part of Pulmocide’s push to validate that hypothesis. Investigators randomized 102 people to receive opelconazole or standard-of-care antifungal treatment after receiving a lung transplant. 

Opelconazole had a slight numerical advantage on the primary endpoint, with 72.3% of participants on the investigational drug completing 12 weeks of therapy versus 69.7% of people in the control cohort. Pulmocide didn’t power the study for statistical comparisons between the two groups.

Pulmocide saw a lower rate of drug-drug interactions that lead to discontinuation of the antifungal or an immunosuppressant in the opelconazole arm than the control group. Opelconazole won that battle with a discontinuation rate of 7.7% compared to 27.3% on the standard of care.

The result provides early support for Pulmocide’s pitch for opelconazole but the molecule will also need to trigger antifungal responses to become part of the treatment arsenal. The incidence of breakthrough fungal disease in the intent-to-treat population was 4% in the opelconazole arm and 3% in the control group. 

Opelconazole appeared to eradicate Aspergillus in the six patients who were infected at the start of the study. Opelconazole also eradicated Candida from the airways in 12 of the 15 people who were colonized by that fungus at study entry. The standard of care respectively eradicated 100% and 67% of Aspergillus and Candida colonies but the small numbers of cases make it hard to draw any conclusions. 

A phase 3 study, OPERA-T, is scheduled to wrap up next year. Pulmocide is running the trial to compare the response rates of opelconazole and placebo in patients with refractory invasive pulmonary aspergillosis.