Having a potential blockbuster sidelined because of manufacturing issues is bad enough, but AstraZeneca has now had that experience twice—both times receiving a complete response letter from the FDA.
AstraZeneca announced on Friday that for the second time the FDA has issued a CRL tied to the manufacturing of its ZS 9, a potential blockbuster treatment for hyperkalemia that was the target of AstraZeneca’s $2.7 billion buyout of ZS Pharma in 2015.
The U.K. company said it was “committed to working with the FDA to resolve the remaining matters under review as soon as possible,” again pointing out the FDA is not looking for any more clinical data. The FDA issued the first CRL in May after the initial preapproval inspection.
AstraZeneca said Tuesday that the drug candidate is being manufactured in the ZS Pharma plant in Coppell, Texas.
"The manufacturing process for ZS-9 is novel and complex, and since the feedback from the May 2016 CRL AstraZeneca has addressed most of the 12 observations and open items from the FDA, including operational manufacturing practices, quality processes and systems," Rob Skelding, director of global media relations, said in an email. "While we are disappointed with the news of a second CRL, AstraZeneca and ZS Pharma are committed to working with the FDA to resolve the remaining matters under review as soon as possible. We do not have sufficient information to assess the review timelines appropriately at this stage. The CRL does not require the generation of any new clinical data."
Since getting its first CRL for the drug in May 2016, AstraZeneca has been joined by a number of other drugmakers that have had drug launches sidelined by manufacturing problems. Among those are Sanofi and Regeneron, which in October were issued a CRL for sarilumab, a candidate for the treatment of rheumatoid arthritis that has also been predicted to hit blockbuster numbers. The CRL was issued because of a long list of deficiencies at a Sanofi fill-finish plant in Le Trait, France.
Sanofi CEO Olivier Brandicourt recently said that the FDA in correspondence has deemed the plant acceptable and that he expected FDA inspectors to return for a reinspection this quarter.
A test of this belief may come shortly. The Le Trait plant is also doing the fill-finish work on dupilumab, a treatment for a severe form of eczema that was also developed jointly by Sanofi and Regeneron. The PDUFA date for it is March 29.
Editor's Note: The story was updated with a comment from AstraZeneca.