Opelconazole is an antifungal agent that is potent against Aspergillus.12 It is designed to be administered via inhalation directly to the site of infection in the lungs with high lung retention and low systemic exposure. It may offer a new way of treating patients with pulmonary aspergillosis with the potential for improved patient outcomes, while minimizing the risk of antifungal-related side effects and drug-drug interactions. Pulmonary aspergillosis has a historical growth rate of 3% per year, and is expected to increase as a result of new immunosuppressive therapies and increased prevalence of pulmonary disease after COVID-19 infection.13
Opelconazole is a new chemical entity designed to be delivered as an inhaled antifungal agent specifically intended for activity in the lungs, where most Aspergillus disease occurs. Opelconazole has been shown to inhibit the growth of Aspergillus fumigatus clinical isolates and other pathogenic Aspergillus species, such as Aspergillus terreus, Aspergillus flavus, and Aspergillus carbonarius in vitro.14 The anti-Aspergillus fumigatus effect has also been demonstrated in vitro and in non-clinical in vivo studies, with encouraging results having also been observed in patients participating in a limited “Specials” program (similar to a compassionate use program) ongoing in the United Kingdom.15-18
The safety and efficacy of inhaled opelconazole is currently being investigated in clinical trials as a treatment for patients with invasive pulmonary aspergillosis who are not responding to systemic standard-of-care antifungal treatment. Opelconazole has not yet been approved by any health authority for commercial use.
Inhaled route of administration
Low systemic exposure
The targeted delivery of opelconazole in the lungs and the resulting minimal systemic distribution may potentially:
Improve efficacy in treating the lung disease
Result in fewer systemic side effects
Extended duration of activity at the site of infection
Results to Date
Robust data from in vitro, in vivo, and clinical outcomes in patients with refractory invasive pulmonary aspergillus supported studying opelconazole in a Phase 3, randomized, controlled superiority study. Opelconazole has already shown significant efficacy against Aspergillus fumigatus in an immunocompromised mouse model, exhibiting more than a 47-fold increased potency over the current first-line standard-of-care.20
Multiple Phase 1 and Phase 2 clinical trials have been undertaken with opelconazole to date. Available data from clinical trials and the “Specials” program (described below) has shown no major safety or tolerability concerns after single and repeat dosing of opelconazole.
Clinical experience with opelconazole under the Specials Program (UK)
Opelconazole is being supplied within the UK for patients with serious or life-threatening pulmonary Aspergillus infections according to Medicines & Healthcare Products Regulatory Agency (MHRA) of the UK Guidance Note 14: “The supply of unlicensed medicinal products (‘specials’)”.21 The supply of opelconazole via this process has been limited to adults with laboratory-confirmed Aspergillus infections who are not eligible to enter any known, available clinical trials and for whom there is currently no equivalent licensed medicinal product that can meet the special needs of the patient. Patients treated with opelconazole in this program included patients with confirmed invasive pulmonary aspergillosis (fungal pneumonia), tracheobronchitis, and Aspergillus infection of the anastomosis site in lung transplant recipients. The program also included patients with severe asthma and allergic bronchopulmonary aspergillosis (ABPA) who had been chronically treated with high dose steroids. All the patients included in the program had either failed or could not tolerate multiple standard-of-care antifungal therapies before initiating treatment with opelconazole.
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 inhaled opelconazole was generally well tolerated and effective in treating these patients.12,18,22 The clinical observations in this program were exciting in that patients had failed, or were intolerant of, prior antifungal therapy. These encouraging treatment responses led to advancing the clinical development of this investigational product which is currently in a Phase 3 clinical trial. These observations do not constitute substantial evidence of efficacy or safety and opelconazole cannot be used outside of this program or the currently approved clinical trials. Opelconazole has not been approved for the treatment of Aspergillus related diseases by any regulatory agency.
Global Clinical Development Program
Based on the encouraging antifungal effects observed in vitro and in the in vivo animal studies, as well as in the clinical results observed in patients included in the “Specials” program (UK), Pulmocide has now advanced the clinical development of opelconazole into a registration program described below:
- PC_ASP_007 (NCT05037851) is a Phase 2 clinical trial evaluating the safety and tolerability of opelconazole for the prevention of pulmonary aspergillosis in patients who have received a lung transplant
- PC_ASP_006 (NCT05238116) is a randomized, placebo-controlled Phase 3 superiority study assessing the efficacy of opelconazole in combination with standard-of-care systemic antifungal therapy for the treatment of refractory invasive pulmonary aspergillosis vs. standard-of-care alone
- Enrolled patients must have previously failed to adequately respond to the current standard-of-care antifungal therapy
Opelconazole has received several FDA designations that may facilitate its expedited development and/or review, including orphan drug designation, Fast Track designation, and qualified infectious disease product (QIDP) designation. It has also been granted orphan drug designation in the European Union.
Access to Opelconazole
The goal of our current clinical study program for opelconazole is to enroll patients and obtain clinical data that is required by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other regulatory authorities for review and approval of marketing applications for this investigational agent. We believe that focusing on clinical studies is the most appropriate way to achieve this goal; therefore, we do not currently offer access to opelconazole outside of clinical studies and, at this time have no Expanded Access program outside of the UK (sometimes referred to as “compassionate use” or “pre-approval access”).