FDA approves Wockhardt’s ZAYNICH (cefepime and zidebactam) for adults with complicated urinary tract infections, including pyelonephritis, based on the Phase 3 ENHANCE-1 trial.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Wockhardt’s ZAYNICH (cefepime/zidebactam) for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis, caused by susceptible Gram-negative pathogens. This marks the first approval of ZAYNICH in the United States and introduces a novel dual-targeting antibiotic combination to the market at a time of escalating antimicrobial resistance.
Clinical Evidence: ENHANCE-1 Demonstrates Superiority
The approval was supported by results from the pivotal Phase 3 ENHANCE-1 trial (NCT04979806), a multinational, randomized, double-blind study comparing ZAYNICH with meropenem in 530 adults with cUTI. In the microbiological modified intent-to-treat population, ZAYNICH achieved composite clinical and microbiological cure in 89.0% of patients versus 68.4% with meropenem, representing a treatment difference of 20.6 percentage points.
Superiority was consistent across baseline pathogens including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Pseudomonas aeruginosa. Among patients with bacteremia at baseline, ZAYNICH achieved an 89% composite response compared with 44% in the meropenem arm, underscoring its potential in severe systemic infections.
Mechanism of Action: Dual PBP Targeting
ZAYNICH combines cefepime’s activity against penicillin-binding protein 3 (PBP3) with zidebactam’s selective inhibition of penicillin-binding protein 2 (PBP2), creating a complementary dual-targeting approach that enhances bacterial killing. The combination has demonstrated activity against Ambler Class A, B, C, and D beta-lactamases, including metallo-beta-lactamase producers, among the most challenging resistance mechanisms globally.
Dosing and Administration
The FDA-approved regimen is 3 g (2 g cefepime plus 1 g zidebactam) administered intravenously every eight hours over a one-hour infusion in adults with normal renal function. Treatment duration ranges from seven to ten days. Dose adjustments are required in patients with renal impairment, including those receiving intermittent hemodialysis.
Safety Profile
In the safety population, which included 352 patients treated with ZAYNICH and 177 patients treated with meropenem, the most common adverse reactions occurring in at least 2% of patients were diarrhea (4%), hypertension (3%), headache (3%), and hypokalemia (3%).
The prescribing information includes warnings regarding serious hypersensitivity reactions, neurotoxicity associated with cefepime-containing therapies, and Clostridioides difficile infection. Adverse events were generally manageable and consistent with the established safety profile of cephalosporin-based therapies, although careful monitoring is recommended in patients with renal impairment.
Parallel Approval in India
On May 28, 2026, India’s Central Drugs Standard Control Organisation (CDSCO) granted marketing authorization for ZAYNICH for the treatment of adult patients with complicated urinary tract infections, including pyelonephritis and concurrent Gram-negative bacteremia.
The CDSCO approval was supported by the same Phase 3 ENHANCE-1 study that formed the basis of the U.S. approval. According to Wockhardt, ZAYNICH demonstrated statistical superiority over meropenem, achieving the primary composite endpoint in 89% of treated patients compared with 68.4% in the comparator arm.
Wockhardt highlighted the therapy’s potential role in addressing carbapenem-resistant and metallo-beta-lactamase-mediated infections, two of the most significant antimicrobial resistance challenges facing India and other regions with a high burden of multidrug-resistant Gram-negative pathogens.
Broader Regulatory Momentum
ZAYNICH has previously received Priority Review, Fast Track, and Qualified Infectious Disease Product (QIDP) designations from the FDA for multiple serious infections. Wockhardt has also submitted a Marketing Authorisation Application (MAA) for cefepime/zidebactam in the European Union, which remains under regulatory review.
With approvals now secured in both the United States and India, Wockhardt strengthens its anti-infectives portfolio while positioning ZAYNICH as a potential new treatment option for serious multidrug-resistant Gram-negative infections.
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About the Writer
Samiksha Vikram Jadhav (LinkedIn) is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.