FDA concerns with manufacturing by India’s Wockhardt and Pfizer’s Hospira are one of the factors to derail the approval of a new antibiotic being developed by a U.S. biotech.
North Carolina-based Cempra on Thursday reported that it had received the CRL from the FDA that focused primarily on the need for a much larger clinical study to determine the safety of its experimental oral and intravenous antibiotic solithromycin for the treatment of community-acquired bacterial pneumonia (CABP) in adults. The FDA also told the Chapel Hill company that manufacturing deficiencies noted at its API makers will have to be resolved before the drug can be considered again for approval.
“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 may be approved,” Cempra said in its announcement.
As far as the safety is concerned, the FDA said Cempra's clinical study of 920 patients is too small to adequately characterize the” nature and frequency of serious hepatic adverse effects.” Instead, the FDA wants a study with about 10 times that many patients. It told Cempra that regardless of the outcome of the larger study, “labeling will need to include adequate information about the potential for hepatotoxicity, limiting use to patients who have limited therapeutic options and limitations regarding duration of therapy.”
But the CRL also noted that investigators had noted deficiencies Wockhardt’s and Hospira’s manufacturing facilities during recent inspections and that those needed to be taken care of prior to approval of the antibiotics.
Cempra said it intends to request a meeting with the FDA to discuss all of the issues in the CRL, including what needs to be done 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 GMP manufacturing facility for solithromycin active pharmaceutical ingredient (API).”
Cempra in November had acknowledged that the main source of its API was a Wockhardt plant in Ankleshwar, India, which the FDA put on its import alert list several months after the agency accepted the applications for its drugs. Cempra said at the time it was working to get another API supplier lined up ASAP.
Cempra joins a record number of companies to have their NDA’s delayed in 2016 by CRL’s with concerns over manufacturing, although the other 5 focused primarily on manufacturing, and did not involve the safety concerns the FDA raised with Cempra’s treatments.
In addition, Roche announced last month that it had the PDUFA date for a new treatment for multiple sclerosis pushed off by three months to give the FDA time to review additional data provided about Roche’s commercial manufacturing process.