A narrow panel vote in favour of Cempra’s lead antibiotic solithromycin might pave the way for eventual approval, but lingering safety concerns mean that even if it does reach the market it could end up as a last-resort treatment.
On Cempra’s side is the growing antibiotic resistance crisis, and the fact that the panellists did not doubt solithromycin’s efficacy, giving it a unanimous thumbs up here. But concerns over liver toxicity led to a 12-1 vote against on safety; at best the issue looks set to hamper the drug’s market potential, while a less appealing scenario for Cempra would be a delay in approval as it gathers more data on the hepatotoxicity risk.
At present, it looks like the FDA’s decision, due on December 27 and 28 for the oral and intravenous versions of solithromycin respectively, could go either way. Overall, the panel voted 7-6 that the efficacy of solithromycin outweighed its risks, “although no one sounded thrilled about their vote on either side”, according to Baird analysts.
They believe that there is a 50% chance that the agency will require more data, and concluded that even if solithromycin is approved “we believe the restrictions will be so severe that it will essentially make it commercially unviable”.
Cempra is seeking approval for community acquired bacterial pneumonia caused by S pneumoniae, H influenzae, M catarrhalis, methicillin-susceptible S aureus, L pneumophila and M pneumoniae. Solithromycin is also in phase III in gonorrhoea, and phase II in non-alcoholic steatohepatitis (NASH) and chronic obstructive pulmonary disease (COPD).
Sellside forecasts compiled by EvaluatePharma put solithromycin’s 2022 sales at $479m, a figure that seems likely to fall. The Baird analysts estimate that the peak market opportunity is now below $250m.
Cempra’s stock, which plunged 61% last Wednesday on release of the FDA’s damning briefing documents, rebounded to open up 22% today.
But investors might be wise to heed the case of another ketolide antibiotic, Sanofi’s Ketek, which was approved in the US in 2004 but was later linked with liver damage that restricted its use. Sanofi eventually discontinued it.
The FDA will surely be wary of similar problems with an agent from the same class, and at the very least seems likely to request a post-marketing study from Cempra.
Notably, the initial safety database with Ketek included around 3,400 patients but failed to uncover the liver issues – meanwhile, in the nearly 1,500 patients receiving solithromycin so far, there has been a “significant safety signal for hepatotoxicity”, the FDA noted.
Solithromycin now looks unlikely to become an unqualified success, but Cempra will no doubt hope that the positive panel vote – however close – will allow it to salvage something from the wreckage.