- Cempra received a Complete Response Letter from the Food and Drug Administration for its oral and intravenous versions of Solithera (solithromycin), a next-generation macrolide antibiotic, to treat community-acquired bacterial pneumonia in adults, the biotech said Dec. 29.
- According to the agency's CRL, the FDA is requiring more clinical safety information and correction of manufacturing facility inspection deficiencies at Wockhardt Ltd. in India and Pfizer's Hospira before Cempra's NDAs may be approved. The letter did not provide details of the deficiencies.
- After reviewing Cempra's NDAs, the FDA said in its letter that Cempra's clinical safety database of 920 patients is too small to determine the risk of hepatotoxicity from solithromycin, its lead product.The FDA suggested that Cempra set up a much larger safety study of closer to 9,000 patients.
In November, Cempra's solithromycin narrowly won support from an independent FDA advisory panel, although agency scientists worried about an increase in liver enzymes associated with its use. This prompted analysts' skepticism that the FDA would actually approve the drug despite the panel's recommendation. While the FDA usually follows the recommendations of its panels, it is not required to.
In response to the latest news, Cempra's stock plummeted by 56% Dec. 29. Jefferies analysts said in a note to investors that while a CRL for Solithera was widely expected, the FDA's recommendation for a comparative study of 9,000-odd patients to exclude the possibility of serious drug-induced liver injury "is impractical for a company of Cempra's size."
Even if Cempra decides to run the study, it would need additional capital – at least $300 million versus the $30 million to $50 million cost of its Phase 3 trials for Solithera oral/IV – with no guarantee of the drug's approval upon study completion, the analysts said. They also expressed their skepticism about the ability of the company to bring the drug further.
In an effort to reassure investors, David Zaccardelli, Cempra's acting CEO, said the company has sufficient cash to work its way through the FDA's concerns.
"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," Zaccardelli said.
Community-acquired bacterial pneumonia is the most frequently treated infectious disease in the U.S., with 5 million to 10 million cases occurring annually that result in more than one million hospitalizations per year, according to the company.
Zaccardelli said that 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." The FDA didn't request more information on the drug's efficacy.
Specifically, Cempra said it will request a meeting with the FDA as soon as possible to discuss issues in the CRL, including design of the recommended safety study and the steps necessary to resolve manufacturing deficiencies.
Cempra said it also will update the FDA on manufacturing progress at Uquifia, a Mexican supplier that the company describes as an alternate GMP manufacturing facility for solithromycin active pharmaceutical ingredient.
Zaccardelli's appointment as Cempra's acting chief was announced Dec. 12, as the company geared up for an anticipated U.S. launch of solithromycin in 2017. In a Dec. 29 management conference call, he said Cempra now doesn't expect federal approval for the drug prior to 2018.
Even in the absence of serious drug-induced liver injuries in future studies, the FDA said in the CRL that solithromycin's label will have to include adequate information about the potential for liver toxicity and its use will be confined to patients with limited therapeutic options.
According to Reuters, Morgan Stanley analyst Andrew Berens told investors that, given the size and cost of the proposed new study and restrictive labeling, Cempra likely won't continue to develop solithromycin.
A few months ago, the United Nations' member countries signed a declaration to fight the escalating global threat of antimicrobial resistance. Only one new class of antibiotics has been introduced since 1980, and a 2014 British study estimated that annual deaths due to antimicrobial resistance could climb to 10 million by 2050.