LONDON – October 16, 2023 – 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 new clinical drug-drug interaction data for its inhaled antifungal agent, opelconazole, which was presented at ID Week 2023 in Boston, Massachusetts, on October 14, 2023.
Increased drug interactions have been previously reported to limit the use of preventative and therapeutic antifungal medications.1 This is particularly concerning for triazole antifungal agents which have Cytochrome P450 drug interactions with many of the anti-rejection and oncology drugs used to treat the patients’ underlying diseases.1 Based on previously performed in vitro drug-drug interaction data, opelconazole was anticipated to have a very low risk for Cytochrome P450 induction or inhibition.
The results from these in vitro studies subsequently informed the design of a Phase 1 drug-drug interaction study in 24 healthy volunteers. In this study, opelconazole, dosed to steady state concentrations, showed no inhibition of CYP3A4 using midazolam as the probe with an AUC0-24h geometric mean ratio of 1.13 (90% CI 1.05, 1.22), and no inhibition of CYP1A2 using caffeine as the probe with an AUC0-24h geometric mean ratio of 0.81 (90% CI 0.77, 0.86). Similar results were observed for geometric ratios using Cmax.2 These data fall below the threshold stipulated by the FDA Guidance on Clinical Drug Interaction Studies (geometric mean ratio of at least 1.25), suggesting opelconazole poses a negligible risk for an inhibitory effect.3 In this study, opelconazole was generally well tolerated with no serious adverse events reported and no evidence of bronchospasm by lung function testing.2
“Conversations with clinical experts treating patients with life threatening invasive pulmonary aspergillosis have indicated that the potential for drug-drug interactions with antifungal agents and those medications used to treat the underlying disease is a foremost concern,” said Dr. Lance Berman, Chief Medical Officer of Pulmocide. “Opelconazole was specifically designed to be administered via inhalation in order to achieve high lung concentrations and low systemic uptake. These low systemic levels, now observed in multiple clinical trials and in the UK Special Needs provision, have been estimated to be too low to have an inhibition or induction of a drug-drug interaction effect. We are encouraged that these clinical trial results confirm this low potential for Cytochrome P450 drug-drug interactions for opelconazole.”
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 for adding to the toxicities and drug-drug interactions seen with systemic antifungal therapies. Under the United Kingdom’s Special Needs provision, opelconazole was found to be generally well tolerated and demonstrated remarkable clinical responses. In this program, patients with a variety of different clinical profiles who had failed previous antifungal treatment options responded well when opelconazole was added to their treatment regimen. Opelconazole has the potential to be useful in a variety of conditions where Aspergillus has been implicated, including chronic pulmonary aspergillosis, cystic fibrosis, severe asthma, allergic bronchopulmonary aspergillosis, chronic pulmonary obstructive disease, severe flu, and post-COVID-19-associated lung damage. A late-stage clinical program has been initiated to support registration in patients who have failed prior therapy for invasive pulmonary aspergillosis (IPA). The safety and efficacy of opelconazole is currently under evaluation in a Phase 3 clinical trial in patients with refractory IPA. Enrollment in a Phase 2 prophylaxis safety study in lung transplant recipients was recently completed with data expected in the first quarter of 2024.
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 immuno-compromised 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 product opelconazole is being developed initially for the treatment of invasive pulmonary aspergillosis.
References
- Patterson T. et al: Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America; Clinical Infectious Disease, 2016;63(4):e1–60
- Data on file, Clinical Study PC_ASP_009
- (FDA) Guidance for Industry: Clinical Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions. CDER, January 2020
- Where Aspergillosis Comes From, Centers for Disease Control and Prevention, accessed 12 October 2023
- Kousha M. et al: Pulmonary aspergillosis: a clinical review. Eur Respir Rev, 2011; 20(212):156-174
For further information, please contact:
Pulmocide Contact:
Jennifer Cayer
Chief Business Officer
Pulmocide Ltd
jennifer@pulmocide.com
Media Contact:
Michael Tattory
LifeSci Communications
mtattory@lifescicomms.com