India's drug regulatory panel has granted Zydus Healthcare approval to conduct Phase III clinical trials for two combination therapies targeting chronic obstructive pulmonary disease (COPD), marking significant progress in the company's respiratory treatment portfolio.
The Subject Expert Committee (SEC), operating under the Central Drug Standard Control Organization (CDSCO), approved Zydus Healthcare's proposal to conduct Phase III trials for Glycopyrrolate IP (equivalent to Glycopyrronium 25 mcg) plus Indacaterol Maleate (equivalent to Indacaterol 55 mcg) metered dose inhalation.
In a separate decision, the committee also approved the company's Phase III clinical trial for Vilanterol 25 mcg plus Umeclidinium 62.5 mcg powder for inhalation, with specific exclusion criteria for severe COPD patients.
Glycopyrrolate-Indacaterol Combination
The Glycopyrrolate-Indacaterol combination represents a dual-action approach to COPD management. This fixed-dose combination (FDC) pairs two established bronchodilators with complementary mechanisms of action.
Glycopyrronium, a long-acting muscarinic antagonist (LAMA), works by binding to muscarinic receptors in bronchial smooth muscle, particularly the M3 receptors that are primarily responsible for bronchoconstriction in COPD. By preventing acetylcholine from binding to these receptors, Glycopyrronium helps prevent airway constriction.
"Glycopyrronium can improve lung function, reduce the risk of exacerbations, and relieve breathlessness in COPD patients," noted the regulatory documentation.
Indacaterol, a long-acting beta-2 adrenergic agonist (LABA), stimulates beta-2 receptors in airway smooth muscle, causing relaxation and increasing airway diameter. The drug is characterized by both rapid onset (within 5 minutes) and long duration of action due to its high affinity to lipid raft domains in airway membranes.
The SEC reviewed Zydus Healthcare's Phase III clinical trial protocol and recommended approval after detailed deliberation, requesting that a revised protocol be submitted to CDSCO for final review.
Vilanterol-Umeclidinium Combination
The second approved combination therapy follows a similar LAMA/LABA approach but utilizes different active ingredients in a dry powder formulation for inhalation.
Umeclidinium bromide, the LAMA component, blocks muscarinic M3 receptors in the lungs to prevent bronchoconstriction. Vilanterol, the LABA component, stimulates beta-2 receptors to promote bronchodilation.
This combination is indicated for long-term, once-daily maintenance treatment of airflow obstruction in COPD patients, including those with chronic bronchitis and/or emphysema.
The SEC's approval came with a specific condition: "Severe COPD patients with an inspiratory flow rate of less than 30 liters per minute must be excluded from the study." This requirement addresses concerns about delivery efficacy in patients with severely compromised lung function, as dry powder inhalers require adequate inspiratory flow for proper drug deposition.
The committee has requested that Zydus Healthcare submit a revised Phase III clinical trial protocol incorporating this exclusion criterion for CDSCO review. Following approval, the company will need to submit the completed Phase III clinical trial report for further evaluation.
COPD Treatment Landscape
COPD represents a significant health burden globally, characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities. The condition encompasses chronic bronchitis and emphysema, affecting millions worldwide.
Current treatment approaches focus on bronchodilation to improve airflow, reduce symptoms, and decrease exacerbation frequency. LAMA/LABA combinations have become cornerstone therapies for moderate to severe COPD, offering dual bronchodilation through complementary mechanisms.
These approvals position Zydus Healthcare to potentially expand treatment options for COPD patients in India, where respiratory diseases represent a significant public health challenge due to factors including air pollution, smoking, and occupational exposures.
The development of these combination therapies aligns with current treatment guidelines that recommend dual bronchodilation for patients whose symptoms are not adequately controlled on single-agent therapy.
