FDA CRL - Chelsea Therapeutics Inc

On March 28, 2012, the FDA issued a Complete Response Letter to Chelsea Therapeutics, Inc. regarding its application for NORTHERA (droxidopa) for the treatment of neurogenic orthostatic hypotension. Under the Federal Food, Drug, and Cosmetic Act, the agency determined that the application could not be approved in its current form due to several critical deficiencies. The primary issue involved inconsistent clinical evidence; out of three submitted trials, only one yielded positive results, and its statistical significance was disproportionately reliant on a single testing site. Furthermore, the FDA noted a lack of evidence regarding the durability of the drug's effect beyond one week. Regulatory inspections by the Office of Scientific Investigations also found that data from a key bioequivalence study were unreliable. Other concerns included insufficient stability data for commercial-scale batches and a lack of information regarding the risk of high blood pressure when patients are lying down. To address these issues, Chelsea Therapeutics is required to conduct a new clinical trial demonstrating effectiveness over a two-to-three-month period and perform a new bioequivalence study for the 300 mg dose. The company must also provide updated stability data, assess supine blood pressure risks, and submit a comprehensive safety update covering all recent clinical findings.