India's Central Drugs Standard Control Organisation (CDSCO) has granted approval for Phase III clinical trials of two innovative cardiovascular fixed-dose combinations, marking significant regulatory milestones for companies developing simplified treatment regimens for complex cardiovascular conditions.
Ravenbhel's Triple Combination Receives Dual Approval
The CDSCO expert panel has approved Ravenbhel's proposal to conduct both bioequivalence studies and Phase III clinical trials for a novel triple fixed-dose combination containing dapagliflozin, sacubitril, and valsartan. The combination is formulated as film-coated tablets in multiple strength configurations: Dapagliflozin 5 mg combined with Sacubitril and Valsartan sodium salt complex in 24 mg and 26 mg/49 mg and 51 mg/97 mg and 103 mg formulations.
This triple combination leverages complementary mechanisms of action for comprehensive cardiovascular management. Dapagliflozin inhibits the sodium-glucose cotransporter 2 (SGLT2), which is primarily located in the proximal tubule of the nephron and facilitates 90% of glucose reabsorption in the kidneys, allowing glucose excretion in urine when inhibited. Sacubitril functions as a prodrug neprilysin inhibitor designed to reduce cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction when combined with valsartan. Valsartan serves as an angiotensin-receptor blocker for managing hypertension and heart failure in patients intolerant to ACE inhibitors.
The committee has stipulated that bioequivalence study results must be submitted to CDSCO for review before initiating the Phase III clinical trial, ensuring regulatory oversight throughout the development process.
Zydus Healthcare Advances Empagliflozin-Metoprolol Combination
Following the SEC Cardiovascular meeting held on July 10th, 2025, at CDSCO headquarters in New Delhi, Zydus Healthcare received approval to proceed with Phase III trials for their empagliflozin-metoprolol fixed-dose combination. The company submitted a revised Phase III clinical trial protocol in accordance with earlier SEC recommendations dated February 13th, 2025.
The approved combination consists of two formulation strengths: Empagliflozin 10 mg combined with either Metoprolol Succinate IP 23.75 mg (equivalent to Metoprolol Tartrate ER 25 mg) or Metoprolol Succinate IP 47.50 mg (equivalent to Metoprolol Tartrate ER 50 mg).
This dual combination targets multiple cardiovascular pathways, with empagliflozin serving as a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated for type 2 diabetes mellitus and heart failure management, while metoprolol succinate functions as a beta-blocker for treating hypertension, angina, and heart failure. The fixed-dose combination aims to simplify therapeutic regimens and potentially improve patient compliance in cardiovascular care.
Regulatory Framework and Next Steps
Both approvals emerged from detailed deliberations by CDSCO's expert panels, reflecting the regulatory body's commitment to advancing combination therapies that address complex cardiovascular conditions. The companies will be required to submit their respective Phase III clinical trial reports to CDSCO for further review upon study completion.
These regulatory approvals represent important steps toward potentially bringing simplified cardiovascular treatment options to patients, addressing the clinical need for comprehensive management approaches in conditions requiring multiple therapeutic interventions.
