Cempra acknowledged today that its NDAs for oral and intravenous solithromycin for community-acquired bacterial pneumonia (CABP) in adults have been rejected by the FDA.

The company said it received a Complete Response Letter (CRL) from the agency concluding that additional clinical safety information and the satisfactory resolution of manufacturing facility inspection deficiencies are required before the NDAs can be approved.

In a statement, Cempra said it plans to request a meeting with the FDA “as soon as possible” to discuss issues identified in the CRL, including the design of the recommended clinical safety study and actions necessary to resolve the deficiencies noted at the Wockhardt and Hospira manufacturing facilities.

“The company also plans to provide the FDA with an update on manufacturing progress at Uquifia, an alternate GMP manufacturing facility for the solithromycin active pharmaceutical ingredient,” Cempra added.

According to Cempra, the FDA stated in its CRL that the risk of hepatotoxicity had not been adequately characterized, noting that the size of the safety database is limited to 920 patients who received solithromycin at the proposed dose and duration—a group too small to adequately characterize the nature and frequency of serious hepatic adverse effects, in the agency’s view.

To address the issue, the FDA has recommended that Cempra undertake a comparative study designed to evaluate the safety of solithromycin in patients with CABP. The CRL recommended that Cempra consider a study of approximately 9000 patients exposed to solithromycin, to enable exclusion of serious drug-induced liver injury (DILI) events occurring at a rate of approximately 1:3000 with a 95% probability, the company said.

The CRL also stated that 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, Cempra said.

The company added that the FDA reserved comment on the proposed labeling until the NDAs are otherwise adequate, even in the absence of a case of Hy's Law or of another form of serious DILI in future studies,

Cempra would also be required, it said, to develop a comprehensive plan for post-marketing safety assessment, including an enhanced pharmacovigilance program.

The CRL also stated that during recent inspections of the Wockhardt and Hospira manufacturing facilities, an FDA field investigator conveyed deficiencies to representatives of the facilities, without providing details, according to Cempra. The company acknowledged that it will have to show that the deficiencies have been resolved to the FDA’s satisfaction to gain approval of its NDAs.

Cempra added that the CRL did not request further information on solithromycin’s efficacy for CABP.

News of the CRL touched off an investor sell-off that sent Cempra shares tumbling 56% this morning to $2.70 as of 10:05 a.m. Shares closed yesterday at $6.10.








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