FDA hits Cosmo with CRL, asks for second phase 3 

The FDA has told Cosmo Pharmaceuticals to run a second phase 3 of its imaging agent before refiling for approval. Cosmo sought FDA approval of the colon lesion visualization aid on the basis of one statistically significant phase 3 trial but has encountered resistance at the agency.

Switzerland’s Cosmo first learnt that the FDA had identified deficiencies with the filing for approval of Methylene Blue MMX earlier this month but at that stage was yet to learn the details. Now, Cosmo has received a complete response letter that sets out what the FDA wants to see in the revised filing, denting hopes that the issue can be resolved quickly.

The FDA reportedly told Cosmo the findings of the phase 3 are not “robust” enough to support the approval of Methylene Blue MMX. The trial followed a special protocol assessment agreed upon with the FDA and met its primary endpoint, leaving observers to speculate about why the agency deemed the data insufficient. 

“We infer the agency perhaps views the magnitude of benefit demonstrated by MB MMX, while statistically significant may not be clinically meaningful,” Jefferies analyst Peter Welford wrote in a note to investors. 

Cosmo filed for approval on the strength of data linking Methylene Blue MMX to a better adenoma detection rate and lower false positive rate than high-definition white-light colonoscopy. The imaging agent appeared to improve the detection rate by around eight percentage points—56.3% versus 47.8%—and cut the false positive rate by 22%. Both results, and other secondary endpoints, were statistically significant.

Management at Cosmo thinks the concerns raised by the FDA are “fully addressable” and plans to meet with the agency as soon as possible in a bid to clear the logjam. For now though, Cosmo faces the prospect of putting Methylene Blue MMX through another phase 3 trial, adding to its costs and deferring sales of the product. The first phase 3 enrolled 1,249 participants and ran for three years.   

Shares in Cosmo fell 16% following the news. The drop more than wiped out the ground regained by Cosmo since news of the setback first broke, sinking the stock to its lowest point since 2014.