FDA Rejects Cempra Antibiotic, Asks for Another Clinical Trial

Xconomy Raleigh-Durham — 

[Updated 12/29/16, 2:50 pm. See below.] The FDA has rejected a Cempra antibiotic drug for community-acquired bacterial pneumonia citing the same safety issues that came to light when an independent advisory panel to the regulator evaluated the drug in November.

Chapel Hill, NC-based Cempra (NASDAQ: CEMP) said Thursday that the FDA’s rejection letter stated the company needs to provide more data about solithromycin’s safety with yet another clinical trial, and also address deficiencies in the antibiotic’s manufacturing. Cempra said that the FDA did not require any additional information about the drug’s efficacy treating community-acquired bacterial pneumonia.

Cempra’s stock price plunged more than 46 percent to $3.25 on the news.

Solithromycin is Cempra’s lead drug, an antibiotic the company has been developing since its founding in 2006. The drug is a macrolide, a class of antibiotics that has yielded drugs to treat bacterial infections from pneumonia and Legionnaire’s disease. Cempra aimed to develop a safer alternative to a different class of antibiotics called fluoroquinolones, which have been associated with increased risk of tendonitis or tendon rupture.

Capsule and intravenous forms of the drug showed efficacy in treating community-acquired bacterial pneumonia in clinical trials. Though those studies showed none of the injury risks associated with fluoroquinolones, they did suggest the potential for liver injury, a risk flagged in November by the FDA’s drug review staff and an independent advisory committee to the agency.

That committee unanimously agreed that the Cempra antibiotic showed that it was effective in treating pneumonia. But its members were also in near-unanimous agreement that the company did not adequately show the risks of liver injury in the drug’s clinical trials. The committee narrowly voted 7-6 to recommend approval of the drug.

Those same safety concerns factored into the FDA’s decision. The regulator’s letter to Cempra said that the 920 patients in the company’s safety database is “too small to adequately characterize the nature and frequency of serious hepatic adverse effects.” The FDA now recommends that Cempra conduct another study enrolling approximately 9,000 patients exposed to solithromycin. This larger study would be better-powered to evaluate whether the drug is causing liver injuries.

But that study will also likely call for more than 9,000 patients. In a conference call with analysts, interim CEO David Zaccardelli said he expects the FDA will require comparisons with a second of group of patients who aren’t treated with Cempra’s drug. Zaccardelli said he could not offer details about the design, cost, and duration of such a trial until after the company meets with the FDA. Though he said a safety study would be “considerably faster” than a trial that would require the company to demonstrate the drug’s efficacy, he said the FDA’s response sets Cempra back by more than a year. “Based on information requested in the [FDA letter], we do not expect a product approval prior to 2018,” Zaccardelli said. [Paragraph added with company comments from conference call].

Even if another study does not show that solithromycin causes serious liver injury, the FDA letter said that approval of the drug would require strict warnings and safety precautions. The FDA said solithromycin’s labeling must include a warning about the potential for liver injury and the drug’s use should be restricted to patients who have limited drug options. Cempra would also need to maintain a comprehensive post-marketing safety plan.

Besides the safety concerns, the FDA noted unspecified problems at the third-party manufacturing sites where the antibiotic is produced. The FDA said that those manufacturing issues must be resolved before the agency can approve the drug. Cempra said it has arrangements with another drug manufacturer.

Cempra has the financial resources for another clinical trial, with about $225 million in cash on hand. But the company is moving forward under new executive leadership. On Dec. 12, about a month after the advisory committee’s vote, Cempra announced that founder and CEO Prabhavathi Fernandes would retire from the company and from the board of directors effective immediately. Zaccardelli, a Cempra board member whose experience includes positions at United Therapeutics (NASDAQ: UTHR), Burroughs Wellcome, Glaxo Wellcome, and Bausch & Lomb Pharmaceuticals, was named interim CEO. In a prepared statement, Zaccardelli said that Cempra is committed to working with the FDA to secure approval of solithromycin.

Pneumonia image by the Centers for Disease Control and Prevention.