Formatting failings set to delay FDA ruling on cancer drug

The FDA is unlikely to review Advanced Accelerator Applications’ (AAA) gastroenteropancreatic neuroendocrine tumor (GEP-NET) drug Lutathera in time for the Dec. 28 PDUFA date. The anticipated delay stems from faults with the format, traceability, uniformity and completeness of data sets submitted in the NDA.

Saint-Genis-Pouilly, France-based AAA learnt last week that the formatting problems are preventing FDA reviewers from analyzing the clinical trial data it filed to support approval of Lu-177-labeled somatostatin analogue peptide Lutathera. AAA has gone back to its CROs to fix the failings, but it is unlikely to get its NDA in order in time for the FDA to meet the PDUFA date.

“We are disappointed by the delay that we expect this development to cause in the FDA’s consideration of Lutathera’s NDA and are focused on addressing these issues as soon as possible. We are engaging additional resources to facilitate the delivery of datasets meeting the requirements outlined by the FDA,” AAA CEO Stefano Buono said in a statement.

Depending on whether the FDA categorizes the resubmission as Class 1 or 2, the agency will review the follow-up filing within two or six months. Given that efficacy data reformatting is absent from the list of resubmissions eligible for the two-month Class 1 review, the longer delay is a possibility. Investors responded by wiping up to 10% off AAA’s market cap, which is north of $1 billion (€945 million).

To mitigate the effect of the delay on patients, AAA is extending the expanded-access program that has given Lutathera to more than 30 patients over the past four months. AAA plans to add to the seven centers offering the drug by the end of the year.

The setback is the second time in recent months that AAA has stumbled with the regulatory finish line for Lutathera in sight. In September, AAA revealed that the EMA had reversed an earlier decision to put Lutathera through its accelerated assessment pathway. The move to standard review timelines was made to give AAA time to respond to requests for clarification from the EMA and to allow the regulator to inspect one of AAA’s CROs. The FDA has already inspected both of AAA’s CROs.

For AAA, the dual delay sets back its aspiration to start carving out a slice of the market to treat NETs, a slow-growing cancer managed today by drugs including Novartis’ Sandostatin LAR Depot and Ipsen's Somatuline. A phase 3 trial pitting Lutathera against a double dose of Sandostatin LAR met its primary endpoint of improved progression-free survival last year.