FDA has issued a second Complete Response Letter for Unicycive’s oxylanthanum carbonate NDA, citing unresolved manufacturing inspection issues but raising no new clinical or safety concerns.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has issued a second Complete Response Letter (CRL) to Unicycive Therapeutics for the resubmitted New Drug Application (NDA) of oxylanthanum carbonate (OLC), an investigational oral phosphate binder for hyperphosphatemia in patients with chronic kidney disease (CKD) receiving dialysis.
The latest CRL, following an initial letter in June 2025, does not identify new clinical or safety concerns. Instead, the FDA again cited deficiencies at a third-party manufacturing facility, which has not yet undergone inspection during the current review cycle. No additional clinical data were requested, and the agency did not question the efficacy or safety package supporting the application.
Manufacturing Inspection Remains the Key Regulatory Hurdle
Unicycive resubmitted the NDA after concluding that its manufacturing partner had made sufficient remediation progress. The company discussed the plan with the FDA during a Type A meeting in September 2025, where regulators acknowledged progress and raised no new concerns.
Despite this, the FDA did not conduct a pre-approval inspection before issuing the latest CRL, leaving manufacturing compliance as the sole outstanding issue. Labeling discussions, including carton and container feedback received June 29, continue in parallel.
Clinical Data Continue to Support OLC
The NDA is supported by three clinical studies – a Phase 1 trial, a bioequivalence study, and a tolerability study in dialysis patients along with preclinical and CMC data. The FDA did not identify deficiencies in efficacy, safety, or the overall data package.
Lower Pill Burden Could Improve Treatment Adherence
OLC uses proprietary nanoparticle technology to increase phosphate-binding potency while reducing pill size and number. Hyperphosphatemia affects nearly all dialysis patients, and high pill burden often limits adherence. By lowering pill count, OLC could improve long-term treatment outcomes if approved.
The NDA was filed under the 505(b)(2) pathway and is supported by patent protection through 2031, with potential extension until 2035.
Company Plans Rapid NDA Resubmission After Inspection
Chief Executive Officer Shalabh Gupta, MD, reaffirmed confidence in OLC’s clinical profile and said the company continues to work with the FDA on labeling and packaging. Unicycive expects the outstanding manufacturing inspection to be the final major step before resubmission. If the facility successfully completes inspection, the company plans to promptly refile the NDA and continue pursuing approval for OLC in CKD patients on dialysis.
Reference
About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.