UPDATED: Sanofi and Regeneron's expected blockbuster hit with FDA CRL for manufacturing concerns

Sanofi and R&D partner Regeneron were all lined up for a possible FDA approval today for their experimental IL-6 inhibitor sarilumab, an expected blockbuster that will compete with AbbVie’s Humira. Instead, the companies announced that the FDA issued them a complete response letter related to “manufacturing deficiencies” at a Sanofi fill-finish facility, delaying its potential approval.

The day had started out with an omen. In Sanofi's earnings call today, CEO Olivier Brandicourt said that "manufacturing deficiencies, not specifically related to sarilumab," were cited during a routine FDA inspection of a fill-finish facility where sarilumab syringes are filled. He said the company was working with the FDA on the issues and at that point didn't know if it would keep the drug from being approved today.

Hours later, Sanofi and Regeneron said the plant had been issued a Form 483 and the companies had received a CRL that said "satisfactory resolution of these deficiencies is required before the BLA can be approved. Sanofi submitted a comprehensive corrective action plan to the FDA and is implementing the corrective actions specified in that plan. Sanofi is working closely with the FDA towards a timely resolution that addresses these concerns. The CRL does not identify any concerns relating to the safety or efficacy of sarilumab."  

Earlier in the day, there were signs of hope. Partner Regeneron informed investors in an SEC filing that the drug continued to be under review, saying at that point that there was no Form 483 issued during the inspection of the fill-finish facility. A Form 483 is issued by the FDA if it sees cGMP problems in a plant. Regeneron also pointed out that the API for sarilumab is manufactured at a Regeneron plant in Rensselaer, NY. But, the company said, “it is unclear whether or how this situation may impact the timing of the potential approval.”

It is now clear what it means for sarilumab in the U.S., but not for the approval process in Europe, where the partners expected an action by early 2017.

The two companies are looking for great things from sarilumab. The drug candidate has outperformed AbbVie's ($ABBV) Humira in a Phase III head-to-head study in rheumatoid arthritis and is projected by EvaluatePharma to reach 2020 sales of $1.8 billion.

But the partners now join a handful other drugmakers that have had drug approvals delayed this year because of manufacturing concerns. 

Portola had consideration of AndexXa, its breakthrough anticoagulant reversal agent, delayed in August when it received a CRL focused primarily on manufacturing questions. Valeant Pharmaceuticals and Ocular Therapeutix both got CRLs for their eye drugs tied to manufacturing, as did AstraZeneca for its investigational treatment for hyperkalemia, a drug candidate that was the target of AstraZeneca’s $2.7 billion buyout of ZS Pharma.

Starting it all off this year was the CRL that Miami-based OPKO received because of issues the FDA had with the manufacturing plant in Florida where its drugs are being manufactured by Catalent. But in that case, the company won approval weeks later for its chronic kidney disease drug Rayaldee after Catalent worked with the FDA to quickly get the issues resolved.

- here's the press release

- here’s the SEC filing

Related Articles:
Sanofi/Regeneron eye 2017 EU approval for Humira-beater sarilumab
Regeneron's arthritis drug aces Phase III with the FDA in sight
Sanofi and Regeneron line up for FDA approval with an arthritis treatment
OPKO wins FDA approval for Rayaldee after Catalent quickly resolves plant concerns

Editor's Note: The story had been updated with information that Sanofi and Regeneron have received a complete response letter from the FDA for sarilumab since this morning when they noted to investors there were FDA concerns over manufacturing.