Drugs

Inspection Looked at AveXis Manipulated Assay Data

A recently posted Establishment Inspection Report (EIR) on AveXis’ Zlogensma, a gene therapy product associated with data manipulation allegations, shows an extensive review of a controversial in vivo potency assay (SOP-285) and FDA’s acceptance that problems raised with the assay have been resolved with its discontinuance and the introduction of a new assay. The earlier assay and the company’s role in relying on its data is now the center of an FDA investigation to determine what, if any, penalties and fines should be assessed for not timely informing the agency about its problems (see story).

FDA has said that the data manipulation seems likely to impact the interpretation of Phase 1 clinical trial results, as well as the interpretation of some nonclinical studies in the original BLA. At this time, it said, the data manipulation does not appear to impact animal toxicology studies or the Phase 3 clinical trial.

In the EIR, FDA investigators note that their February inspection examined a company report that “describes errors discovered in AveXis reports when reviewing mouse survival data from the old in vivo potency assay (SOP-285), and these errors triggered an extensive investigation, including reviewing all of the original records of experimental mice for SOP-285 and SOP-346.” FDA notes that SOP-346 replaced SOP-285. “We were already aware (through BLA amendment 4) of the problems and their resolution, and we have already performed an independent analysis of the corrected survival data that were submitted to the BLA in REC-1606.”

FDA’s EIR also noted that the root cause for the errors with the assay were related to use of a non-validated spreadsheet to calculate the data. Additional contributory factors were difficulty in obtaining accurate data from a redacted source and the firm’s quality assurance unit not properly verifying calculations, the report said. “Appropriate action has been taken to restate results, to validate the spreadsheet, and to improve QA review,” the reviewers said.

FDA has said its investigation of the data manipulation is ongoing and it will also rely on another inspection of the AveXis testing site, the results of SOP-346 (which replaced the SOP associated with the data manipulation) and SOP-347, which is another potency assay. The agency also has said that it will likely require that AveXis submit and FDA review one or more BLA supplements that may take at least several months.

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