Cempra, Inc., has received a complete response letter (CRL) from the FDA regarding the company’s new drug applications (NDAs) for oral and intravenous solithromycin for the treatment of community-acquired bacterial pneumonia (CABP) in adults.
The CRL states that the FDA cannot approve the NDAs in their present form and notes that additional clinical safety information and the satisfactory resolution of manufacturing facility inspection deficiencies are required before the NDAs can be approved. The FDA did not request any further information on solithromycin efficacy in CABP.
Based on its review of the NDAs, the FDA determined that the risk of hepatotoxicity had not been adequately characterized. The agency noted that the safety database was limited to 920 patients who received solithromycin at the proposed dose and duration and was too small to adequately characterize the nature and frequency of serious hepatic adverse effects.
To address this deficiency, the FDA has recommended that a comparative study be conducted to evaluate the safety of solithromycin in patients with CABP. Specifically, the CRL recommends that Cempra consider a study involving approximately 9,000 patients exposed to solithromycin to allow the exclusion of serious drug-induced liver injury (DILI) events occurring at a rate of approximately 1:3,000 with a 95% probability.
The CRL noted that while the FDA reserves comment on the proposed labeling until the NDAs are otherwise adequate, even in the absence of a case of Hy’s law or another form of serious DILI in future studies, the labeling of solithromycin will have to include adequate information about the potential for hepatotoxicity, limiting the use of the product to patients who have limited therapeutic options and limitations regarding the duration of therapy. A comprehensive plan for a post-marketing safety assessment of solithromycin, including an enhanced pharmacovigilance program, would also be required.
Moreover, the CRL stated that during recent inspections of the Wockhardt Limited and Hospira, Inc., manufacturing facilities, the FDA field investigator conveyed deficiencies to representatives of the facilities. Satisfactory resolution of these deficiencies is required before approval. Details on these deficiencies were not provided in the CRL.
Cempra plans to request a meeting with the FDA to discuss the issues identified in the CRL, including the design of the recommended clinical safety study and the steps necessary to resolve the deficiencies noted at Wockhardt and Hospira. The company also plans to provide the FDA with an update on manufacturing progress at Uquifia, an alternate manufacturing facility for the solithromycin active pharmaceutical ingredient.
Source: Cempra; December 29, 2016.