Cempra hit with FDA delay as manufacturing, safety issues blight antibiotic

The FDA said it had concerns over the drug's potential impact on the liver, as well as manufacturing issues.

Its PDUFA dates came and went this week, and both the FDA and Cempra were ominously silent. Then Thursday morning, the Chapel Hill, North Carolina-based biotech announced what looked inevitable: a complete response letter for solithromycin.

The letter, which is for both the oral and intravenous forms of the drug, will likely mean a lengthy delay for the company, which was seeking a license for solithromycin in community-acquired bacterial pneumonia (CABP) in adults.

The first issue was safety: The FDA said it was concerned over potential liver injury from the drug, saying “hepatotoxicity had not been adequately characterized.”

The FDA said the size of the safety database on this issue was limited to 920 patients who received solithromycin, but said this was “too small to adequately characterize the nature and frequency of serious hepatic adverse effects.”

So, Cempra will need to undertake a study of around 9,000 patients who have been exposed to solithromycin in order to see whether the drug is hitting patients’ livers.

On top of this, a “comprehensive plan for post-marketing safety assessment including an enhanced pharmacovigilance program would also be required,” the FDA said in relation to hepatotoxicity.

And what's more, even if no liver problems show up in the new study, its label will still include the potential for liver toxicity, and will be given only to those with limited treatment options.

And then there was the blight of 2016 for many biopharmas, manufacturing worries. For Cempra, this came out of recent inspections of the Wockhardt and Pfizer's Hospira's facilities it uses to make its med, although Cempra said in a statement the FDA had not enlightened it to exactly what these issues are.

They will however need to be resolved, along with the safety issue, before any approval can be made.

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

“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.”

This comes nearly two months after an FDA panel narrowly voted 7-6 that solithromycin should be recommended for U.S. regulatory approval.

But this came several days after its shares plummeted on safety fears from the agency’s briefing docs—docs that showed a risk of the med raising liver enzymes compared to the generic antibiotic moxifloxacin, which can indicate damage to the organ. 

In a phase 3 study published last year, involving 863 patients, Cempra's intravenous solithromycin demonstrated noninferiority to injected moxifloxacin, sold as Avelox, in treating CABP within 72 hours.

If it does gain approval, solithromycin would become the first new macrolide antibiotic with an oral and IV formulation in over 20 years. The drug is a next-gen macrolide that has activity against most macrolide-resistant CABP pathogens.

But that now seems much further down the road, and the biotech was hit hard today on the news that, premarket, its shares were down nearly 40%.