Pulmocide Announces Successful Results from the OPERA-S Study: a Phase 2 Safety Study with Inhaled Opelconazole

Inhaled opelconazole observed to be generally well tolerated in this study as prophylaxis against pulmonary aspergillosis in lung transplant patients

Discontinuations due to drug-related adverse events and drug-drug interactions lower in the opelconazole group vs standard of care

Prevention and eradication of Aspergillus and Candida in the lungs observed with opelconazole monotherapy

LONDON, April 15, 2024 (GLOBE NEWSWIRE) --  Pulmocide Ltd., (“the Company”) a late-stage biopharmaceutical company developing novel inhaled therapies for patients suffering from serious acute and chronic respiratory diseases, today announced topline results from the OPERA-S study: a Phase 2 safety and tolerability study in lung transplant patients receiving inhaled opelconazole monotherapy as prophylaxis against pulmonary aspergillosis. Opelconazole is an investigational inhaled triazole antifungal being developed to prevent and treat pulmonary aspergillosis. In this study, opelconazole was generally well tolerated with a low incidence of drug-related adverse events (AEs) and a low incidence of treatment-limiting respiratory AEs. Importantly, there were no dose reductions or discontinuations of opelconazole prophylaxis or of immunosuppressant medications due to opelconazole-related drug-drug interactions (DDIs). Despite the expected small numbers, there was evidence of prevention of pulmonary aspergillosis and of eradication in the lungs of both Aspergillus and Candida colonization with opelconazole monotherapy.

In this open-label, active-controlled trial, 102 patients were randomized in the ICU after receiving a lung transplant in a 2:1 ratio to either inhaled opelconazole or standard of care (SOC) antifungal prophylaxis, and were treated for up to 12 weeks.

The safety and tolerability of opelconazole, the main focus of this study, and the ability to remain on antifungal prophylaxis and immunosuppressive therapy, were summarized descriptively as the study was not statistically powered for between group comparisons. Results from this trial indicated that opelconazole was generally safe and well tolerated. The number of related adverse events occurring in ≥ 2% of opelconazole patients was low. These were cough (6.2%), nausea (4.6%) and respiratory tract irritation (3.1%), all of which were mild or moderate in severity. Importantly, respiratory AEs related to opelconazole were rarely treatment-limiting, leading to discontinuation in two out of 65 opelconazole patients. Drug-related AEs together with DDIs leading to discontinuation of the antifungal medication, or DDIs leading to discontinuation of an immunosuppressant medication, occurred less commonly in the opelconazole group (7.7%) versus in the SOC antifungal prophylaxis group (27.3%). Numerically, more opelconazole patients (72.3%) completed the 12 weeks of prophylaxis compared to the initial SOC antifungal treatment (69.7%). Three patients in the study died: one in the opelconazole group (1.5%) and two in the SOC group (6%).

Efficacy in preventing breakthrough pulmonary Aspergillus disease and eradication of colonization were summarized descriptively as exploratory outcomes. As expected, given the relatively small sample size, the incidence of breakthrough fungal disease in the intent-to-treat population was low and similar between groups, in 4% of the opelconazole patients and in 3% of the SOC patients. In addition, opelconazole appeared to eradicate Aspergillus colonization in all six patients who entered the study already colonized. In two patients colonized prior to randomization with Fusarium and Penicillium, opelconazole also achieved eradication. Aspergillus colonization was also eradicated in the two SOC patients who were colonized at study entry. In addition, opelconazole eradicated Candida colonization of the airways in 12 of the 15 patients colonized at study entry (80%), providing additional evidence of opelconazole’s antifungal activity. In the SOC group, Candida colonization of the airways was eradicated in four of the six patients colonized at study entry (67%). One opelconazole patient (1.5%) and three SOC patients (9.1%) developed oral candidiasis during the study.

“The data support that inhaled opelconazole was generally safe and well tolerated in this study when administered as monotherapy prophylaxis in lung transplant patients, a critically ill patient population with major pulmonary morbidity,” stated Dr. Lance Berman, Chief Medical Officer of Pulmocide. “Based on discussions with clinicians who care for lung transplant patients, it appears that a potent antifungal agent delivered directly to the lungs with a low discontinuation rate and a negligible risk for DDIs would be a promising alternative. We believe that the use of opelconazole as a prophylaxis agent in patients at risk of pulmonary aspergillosis warrants further investigation.”

“As a physician who regularly treats these patients, I find the results to be very promising,” commented Dr. Shahid Husain, Professor of Medicine, Infectious Diseases, at the University of Toronto and who served on the study steering committee in addition to being an investigator in the trial. “If we can provide and maintain potent antifungal protection without having to compromise vital immunosuppressive therapy, then we may be able to further improve outcomes for our patients.”

More detailed results from this study are expected to be provided at medical meetings and through peer-reviewed publication in the months ahead.

About Opelconazole
Pulmocide’s investigational product, opelconazole, is a potent novel azole therapy specifically designed for inhaled use to maximize the amount of drug in the lung while providing minimal systemic exposure. This profile is anticipated to enhance efficacy with a low risk of adding to the toxicities and drug-drug interactions seen with systemic antifungal therapies. Opelconazole has the potential to be useful in a variety of conditions where Aspergillus has been implicated, including chronic pulmonary aspergillosis, patients with severe asthma complicated by allergic bronchopulmonary aspergillosis, and severe flu or COVID-19 complicated by invasive aspergillosis. Opelconazole also has the potential to be used as prophylaxis in immunocompromised patients at risk of developing pulmonary aspergillosis, most commonly patients with an underlying hematological malignancy or recipients of a stem cell or solid organ transplant. Opelconazole is being supplied within the UK for patients with serious or life-threatening pulmonary aspergillosis according to the MHRA’s Guidance Note 14 (the Specials program). ¹ Although drawing definitive conclusions regarding efficacy and safety from this program is limited by the open-label, non-randomized, uncontrolled nature of the program, observations suggest that in this program, inhaled opelconazole was generally well tolerated and effective in treating these patients.^{2, 3, 4} These clinical observations were noted in patients who had failed, or were intolerant of, prior antifungal therapy. These treatment responses led to advancing the clinical development of this investigational product which is currently in a Phase 3 clinical trial in patients with Invasive Pulmonary Aspergillosis (IPA) who are not responding to antifungal therapy (the OPERA-T study).⁵

About Pulmonary Aspergillosis
The incidence of pulmonary fungal disease has increased substantially over the past two decades with Aspergillus species being the most common pathogen.⁴ Invasive pulmonary aspergillosis is associated with high morbidity and mortality rates in immunocompromised patients including those undergoing hematological stem cell or solid organ transplantation (particularly lung transplants) and some patients in critical care, including those with COVID-19 or influenza-associated pulmonary aspergillosis.⁵ Aspergillus infection also plays an important role in severe asthma and cystic fibrosis and has been correlated with poorer clinical outcomes in patients with chronic obstructive pulmonary disease.⁵ Chronic lung infections with Aspergillus can leave patients with extensive and permanent lung damage, requiring a lifetime of antifungal treatment.⁵

About Pulmocide
Pulmocide Ltd (www.pulmocide.com) is a late-stage biopharmaceutical company focused on the development of a novel inhaled azole therapy for patients at risk of developing serious complications associated with aspergillosis, such as immunocompromised patients and those with severe pulmonary diseases. The company is currently focused on acute and chronic treatments for pulmonary aspergillosis and its lead Phase 3 product opelconazole is being developed initially for the treatment of invasive pulmonary aspergillosis.

References:

1. MHRA. (2014). The supply of unlicensed medicinal products (“specials”). Retrieved from https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/373505/The_supply_of_unlicensed_medicinal_products__specials_.pdf
   
2. Murray, A., Cass, L., Ito, K., et al. (2020). PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections. J Fungi (Basel), 6(4). https://doi.org/10.3390/jof6040373
   
3. Pagani, N., Armstrong-James, D., & Reed, A. (2020). Successful salvage therapy for fungal bronchial anastomotic infection after -lung transplantation with an inhaled triazole anti-fungal PC945. J Heart Lung Transplant, 39(12), 1505-1506. https://doi.org/10.1016/j.healun.2020.09.015
   
4. Singh, S., Moore, L. S. P., Mughal, N., et al. (2023). Novel inhaled antifungal for pseudomembranous Aspergillus tracheobronchitis complicating connective tissue disease. Thorax, 78(1), 110-111. https://doi.org/10.1136/thorax-2021-218375
   
5. https://www.clinicaltrials.gov/study/NCT05238116?term=opelconazole&rank=2
   

For further information, please contact:

Pulmocide Contact:

Jennifer Giottonini Cayer
Chief Business Officer and Head of Corporate Development
Pulmocide Ltd
[email protected]

Media Contact:
Michael Tattory
LifeSci Communications
[email protected]