FDA Rejects Cempra's NDAs for Solithromycin, Shares Sink

FDA Rejects Cempra's NDAs for Solithromycin, Shares Sink December 29, 2016
By Mark Terry, BioSpace.com Breaking News Staff

Cempra , headquartered in Chapel Hill, NC, announced today that it had received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) concerning its new drug applications (NDAs) for its antibiotic solithromycin. Solithromycin, both oral and intravenous, was being evaluated for the treatment of community-acquired bacterial pneumonia (CABP) in adults.

The FDA indicated it could not approve the NDAs in their current form. The agency also requested more clinical safety data and a resolution to inspection deficiencies found at the company’s manufacturing facility. It did not request more efficacy data.

Of particular concern was insufficient characterization of hepatotoxicity. The company stated, “The FDA noted the size of the safety database is limited to 920 patients who received solithromycin at the proposed dose and duration, and is too small to adequately characterize the nature and frequency of serious hepatic adverse effects.”

The FDA recommended a comparative study, as well as a study of about 9,000 patients, to exclude serious drug induced liver injury (DILI) at a rate of about 1:3000 with a 95 percent probability.

The manufacturing concerns arose during inspections of the Wockhardt Limited and Pfizer ’s Hospira, Inc. manufacturing plants.

The company plans to meet with the FDA as soon as possible to discuss the issues, as well as the design of future clinical safety studies. Cempra also will give the FDA an update on manufacturing progress at Uquifia, an alternate GMP manufacturing plant for solithromycin active pharmaceutical ingredient (API). Uquifia is in India-based Vivimed Labs Ltd’s Spanish business.

“As the rates of antibiotic resistance continue to rise, there is an unmet medical need for new antibiotics to treat patients with CABP and Cempra is committed to working with the FDA to achieve the approval of solithromycin as quickly as possible,” said David Zaccardelli, acting chief executive officer of Cempra, in a statement.

Cempra plunged at the news, dropping approximately 130 percent to a current value of $2.65.

Zaccardelli also stated, “With more than $225 million of cash on hand, patent protection for solithromycin through 2032 and a pipeline that includes fusidic acid and other potential programs for solithromycin, including an ophthalmic formulation, we have flexibility to determine the best course forward for solithromycin and Cempra.”

Fusidic acid is Cempra’s second lead product candidate. It has completed enrollment of a Phase III clinical trial in patients with acute bacterial skin infections. It is also evaluating a study of the drug for refractory infections in bones and joints.

There is some speculation that Cempra will abandon solithromycin development. At a conference call, Zaccardelli indicated that they wouldn’t know what the cost of a new trial would be until after meetings with the FDA. Andrew Berens, an analyst with Morgan Stanley, predicted in a note to clients that due to the size and cost of the study, as well as the probability of restrictive labeling were the drug to be approved, that the company will likely halt development of solithromycin.

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