India's pharmaceutical giant Cipla has received regulatory approval to advance its inhaled antifungal therapy to Phase III clinical trials, potentially offering a new treatment option for patients with fungal respiratory infections.
CDSCO Panel Approves Phase III Trial for Inhaled Itraconazole
The Subject Expert Committee (SEC) under India's Central Drug Standard Control Organization (CDSCO) has accepted Cipla's Phase II clinical trial results for inhaled itraconazole dry powder formulation (PUR1900) and approved the company's proposal to proceed with Phase III trials at a 40mg dose.
PUR1900 is a specialized dry powder formulation of itraconazole designed specifically for inhalation delivery. The therapy is being developed primarily to treat Aspergillus infections in patients with cystic fibrosis (CF) and may have applications for other respiratory diseases.
"The direct-to-lung delivery approach could potentially improve efficacy while reducing systemic exposure and associated side effects," noted a clinical researcher familiar with antifungal therapies, though not directly involved in the Cipla trials.
Mechanism of Action and Clinical Significance
Itraconazole belongs to the triazole class of antifungals. Its mechanism of action involves inhibiting the fungal cytochrome P-450-dependent enzyme lanosterol 14-α-demethylase, which disrupts ergosterol production and compromises fungal cell membrane integrity.
While oral and intravenous itraconazole formulations are already available for treating various fungal infections, they can cause significant side effects including nausea, vomiting, liver damage, and neurological issues. The inhaled formulation aims to deliver the medication directly to the site of infection in the lungs while potentially minimizing systemic exposure and related adverse effects.
Fungal infections represent a significant challenge for cystic fibrosis patients, with Aspergillus species being particularly problematic. These infections can exacerbate respiratory decline and are associated with poorer clinical outcomes.
Trial Details and Regulatory Pathway
The SEC meeting, held on March 11, 2025, reviewed Cipla's Phase II clinical trial data before granting approval for the Phase III study. The committee has instructed Cipla to submit the detailed Phase III protocol to CDSCO for further regulatory action.
The approved formulation consists of 10mg capsules of itraconazole dry powder for inhalation, with the Phase III trial set to evaluate a 40mg total dose regimen.
Cipla's Expanding Respiratory Portfolio
In a parallel development, Cipla has also received SEC approval to conduct Phase III clinical trials for Revefenacin Inhalation Solution (175 mcg/3ml), further strengthening its respiratory disease portfolio.
Revefenacin is a long-acting muscarinic antagonist (LAMA) indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD). The compound features a novel biphenyl carbamate tertiary amine structure with a labile primary amide that facilitates rapid systemic clearance, potentially reducing systemic side effects.
The drug works as a competitive antagonist of muscarinic cholinergic receptors, with studies showing kinetic selectivity for the M3 receptor subtype over M2. This pharmacological profile results in bronchodilation through suppression of acetylcholine-evoked calcium mobilization and contractile responses in airway tissue.
Market Implications and Future Outlook
These regulatory approvals highlight Cipla's continued focus on respiratory therapeutics, an area where the company has established significant expertise and market presence.
If successful in Phase III trials and subsequently approved, inhaled itraconazole could represent an important addition to the limited arsenal of treatments available for fungal respiratory infections, particularly for vulnerable populations such as cystic fibrosis patients.
Similarly, the addition of Revefenacin to Cipla's portfolio could strengthen the company's position in the COPD treatment market, where once-daily maintenance therapies are increasingly valued for improving patient adherence and quality of life.
Industry analysts suggest these developments align with the growing trend toward specialized respiratory formulations that optimize drug delivery while minimizing systemic exposure and side effects.
