Data Integrity and the Zolgensma FDA Approval Counter-Intelligence Conspiracy Coverup at AveXis, Inc.

AveXis executives fabricated crucial data in critical regulatory filings following a covert conspiracy to subvert and disinform the FDA until post-approval.

LONDON, UNITED KINGDOM, December 8, 2023 /EINPresswire.com/ -- Zolgensma was approved by the US Food and Drug Administration (FDA) in May 2019. But it was all for nought. 2.125 million USD per patient – the most expensive of any purported cure in world history – approved by the US Food and Drug Administration (FDA) [1]. But it was all for nought. Thousands of infantile spinal muscular atrophy (SMA) patients and their families have since faced and will face disappointing clinical result over their first several years of life on Zolgensma.

Data fabrication among other counter-intelligence activity at AveXis, Inc. (AveXis) swept the FDA to a now disillusioned approval of the Zolgensma BLA. Concerted conspiracy perpetrated by AveXis executives included several instances whereby primary data were intentionally fabricated and fraudulently misappropriated in federal regulatory filings. Most brazenly, there were covert organized efforts by AveXis conspirators to disinform and subvert its discovery by FDA until post-approval [2, 3]. Novartis AG acquired AveXis during the approval process, yet were likely just as subverted as the FDA at that time.

An FDA inspection from July 24, 2019 to August 2, 2019 discovered that key efficacy data at minimum were likely fabricated at the direction of later ousted AveXis executives, including admissions that went beyond that what was initially relayed by CQO Mark Roache to FDA CBER Andrew Byrnes (CMC).

In an Incident Review Memo dated July 26, 2019, it was noted that AveXis submitted “manipulated data” in its original Zolgensma BLA which were used to evaluate product comparability and animal pharmacology, among other concerns, resulting in the finding that “some sections of several of the original BLA reviews may not be reliable and accurate” [4]. At the end of the memo, Director Wilson W. Bryan speculated the disinformation conspiracy that AveXis chose not to inform the FDA of the data manipulation issue because if it had disclosed the issue the BLA would be delayed beyond the PDFUA goal date of May 31, 2019: “the delay would have been necessary in order for the FDA to investigate the data manipulation, determine the impact of the data manipulation on the CMC, pharmacology/toxicology, and clinical trial results, and revise the relevant BLA reviews” [4].

The FDA CBER CMC review team were also intentionally misled to believe that the manufacturing of Zolgensma by AveXis had consistent quality characteristics when it did not. In fact, animal materia proctored by AveXis comprised many incongruent methods, inconsistent processes, and poor manufacturing practices aback sweeping confidentiality redactions. Even the Phase I clinical trial was plagued by what the CMC review team called an “inaccurate and imprecise” assay used to determine the concentration of the initial drug product lot. Further, differing lots were used in the Phase I-oriented animal experiments and clinical trial versus the Phase III-oriented animal experiments and clinical trial.

Discovery of the data fabrication conspiracy became peak evident August 2, 2019 to August 6, 2019. Cumulative on-premise investigations by FDA investigators and intelligence then and thereafter show that data manipulation at minimum were in fact ordered fabricated by several AveXis employees including senior executives [5]. Further, there were organized covert efforts by several AveXis employees to subvert and disinform the FDA until post-approval.

The FDA issued its 483 report on August 2, 2019. The 483 report first indicated discovery by the FDA of an internal report to the CQO alleging “that data derived from the AVXS-101 In-Vivo Relative Potency Assay Studies 1-10 may have been mismanaged or even potentially manipulated” [6]. A non-conformance report was filed as NCR-1922 by May 15, 2019, yet left unattended and unreported to the FDA until after the regulatory approval. The FDA Investigators further recommended “an audit of all other potentially impacted data, studies, and reports [where] there was evidence of data mismanagement or manipulation […]”.

Now informed that FDA approval counter-intelligence activities were occurring at its new acquisition entity, parent entity Novartis temporarily assigned its master veterinarian to Research Triangle Park, North Carolina, for the trusted precision analysis: Page Bouchard was appointed SVP of Research and CSO effective August 5, 2019, just three days after the conclusion of the inspection on August 2, 2019. His results are not inconclusive but have not yet been shared with the administration.

August 6, 2019, FDA CBER issued a press release simultaneously with AveXis acknowledging the identified “data manipulation” and the forthcoming full FDA probe. In context to AveXis counter-intelligence efforts to keep the FDA uninformed until post-approval, the FDA noted that the ongoing investigation “may include civil or criminal penalties” [7].

As the fallout and its aftermath have now settled, the critical consensus is that AveXis employees intentionally fabricated primary and secondary data across the crucial animal models and other materia which enabled the FDA in its overall approval decision. Ultimately, the FDA were gullied to no enforcement penalties levied whatsoever to date, and the European Medicines Agency have yet to even comment on the data fabrication concerns and admissions.

Data manipulation and fabrication sully the accuracy and independence of the scientific method. Data integrity is a crux assumption behind drug development programs which hinge on effectivity. Observance to data sanctity is especially critical when human lives are on the line.

REFERENCES CITED
[1] M. A. Malarkey and W. W. Bryan, "BLA Approval Letter - ZOLGENSMA," 24 May 2019. <https://www.fda.gov/media/126130/download>.
[2] R. J. Durbin, T. Baldwin, B. Sanders, E. Warren and R. Blumenthal, "Senate Letter to FDA: Zolgensma Data Issue", 9 August 2019. <https://www.durbin.senate.gov/imo/media/doc/Senate%20Ltr%20to%20FDA_Zolgensma%20Data%20Issue.pdf>.
[3] C. Grassley, "CEG to Novartis (Misconduct)," 9 August 2019. <https://www.grassley.senate.gov/sites/default/files/constituents/2019-08-09%20CEG%20to%20Novartis%20(Misconduct).pdf>.
[4] W. W. Bryan, "Incident Review Memo," 26 July 2019. <https://www.fda.gov/media/128116/download>.
[5] M. P. Roache and D. Lennon, "AveXis, lnc.'s Initial Response to the Form FDA 483," 23 August 2019. <https://cacmap.fda.gov/media/131007/download>.
[6] S. T. Ballard and M. S. Ligmond, "483," FDA, 2 August 2019. <https://cacmap.fda.gov/media/129734/download>.
[7] P. Marks, "Statement on data accuracy issues with recently approved gene therapy," 6 August 2019. <https://www.fda.gov/news-events/press-announcements/statement-data-accuracy-issues-recently-approved-gene-therapy>.

Aron Workman
Arowor Corp.
[email protected]