ChemoCentryx, the $3.7 billion biotech bought by Amgen in 2022, allegedly ignored repeated warnings from a data monitoring committee and withheld or manipulated trial results on the firm’s since-approved drug Tavneos, according to new evidence in an investor lawsuit.
The lawsuit, filed in 2021 against ChemoCentryx and then-CEO Thomas Schall, Ph.D., alleges the company misled investors in its FDA application for Tavneos and the underlying phase 3 clinical trial.
ChemoCentryx’s stock price was flying high from late 2019 to early 2021 thanks to positive readouts from the phase 3 Advocate trial for Tavneos (avacopan) in a rare autoimmune disease called antineutrophil cytoplasmic antibody-associated vasculitis. During the period, Schall sold about $40 million worth of ChemoCentryx shares.
However, multiple efficacy and safety issues flagged by FDA reviewers for an advisory committee meeting sent the stock tumbling and forced the biotech to amend its application. The drug eventually got its FDA nod with a narrower label than ChemoCentryx had originally planned, and the company was acquired by Amgen in 2022 at a discount on its peak value.
Investors who lost money in ChemoCentryx allege that the company had known about the FDA’s concerns all along in private but told the public that its interactions with the agency were smooth, according to an amended complaint filed in 2022 in the U.S. Northern District Court of California.
According to that complaint, ChemoCentryx promoted Tavneos as a safer alternative to steroids—even though the Advocate trial included off-protocol steroid use in the Tavneos arm and raised liver toxicity concerns.
Now, in opposing the defendants’ request for summary judgment, plaintiffs in the class-action case have submitted new evidence suggesting broader misconduct ahead of the FDA’s big revelation.
Pirow Bekker, M.D., Ph.D., then clinical lead of the Tavneos program and former chief medical officer at ChemoCentryx, allegedly flipped five nonresponders in the Tavneos group to responders after learning that the study had failed to show superiority at the one-year mark, according to the plaintiffs. The changes occurred after the trial database was locked, a step that typically should prevent further changes to protect data integrity.
ChemoCentryx later provided regulators with a revised database lock date that did not match the actual lock date, plaintiffs alleged.
The changes were not scientifically justified, the plaintiffs argued, citing several experts in the field.
But Steven Weisman, Ph.D., global president of clinical and regulatory at consultancy firm Lumanity, contends the reclassification was part of a prespecified statistical analysis plan. Although Bekker was unblinded to treatment assignments during the reevaluation, the adjudicator who made the final determinations remained blinded, he said.
“[T]he re-adjudication of the patients at issue was performed by the still-blinded Adjudication Committee Chair in a manner consistent with the Adjudication Committee Charter,” Weisman wrote in an expert report filed in June.
The FDA and other regulators had access to all information related to the post-lock adjustment of data, he added.
On Nov. 26, 2019, ChemoCentryx issued a press release announcing that the Advocate trial met both of its primary endpoints, saying Tavneos showed noninferiority of disease remission at 26 weeks and superiority of sustained remission at 52 weeks versus glucocorticoid steroids. The company described the drug’s safety profile as “acceptable.”
In another key argument for their case, the plaintiffs provided evidence showing that the independent data monitoring committee for Advocate had repeatedly warned ChemoCentryx that the company’s public statements had downplayed Tavneos’ liver toxicity.
The panel went so far as to question the New England Journal of Medicine article about the Advocate trial results, co-authored by Schall, Bekker and other trial investigators. In a March 2021 letter sent to Schall, the six-member data monitoring committee asked the CEO to “[i]mmediately submit a letter to the editor of the [NEJM] clarifying the hepatotoxicity risks” and to send the committee’s previous emails and meeting minutes to the FDA, according to a copy of the email that the plaintiffs logged into the trial docket.
Plaintiffs allege Schall did neither.
Investors first learned of the liver toxicity concerns when the FDA’s briefing documents for its advisory committee revealed that a patient receiving Tavneos had experienced liver toxicity meeting Hy’s Law criteria—markers doctors use to determine whether a patient is at high risk of a fatal drug-induced liver injury.
Liver toxicity is the first of four items listed in the “warnings and precautions” section of Tavneos’ FDA label.
ChemoCentryx’s then-chief medical officer, Cass Kelleher, M.D., said she urged Schall internally to call out the liver toxicity publicly. In response, Schall allegedly told Kelleher that she was too vocal and to “stop talking” about the liver safety signal, according to a deposition of Kelleher.
In a May 2020 text, which appears to be about security, Schall told Kelleher: “No back and forth other than if you need to push back if someone incorrectly says something like H law.”
Then Kelleher, as CMO of ChemoCentryx at the time, was seemingly excluded from certain internal communications about Tavneos. Kelleher was not an author of the 2021 NEJM paper, and she testified that she didn’t even know a paper was coming.
“[O]riginally, this paper was going to be authored by me, and I thought it was dead,” Kelleher said, per a court transcript, “And I didn’t even know there was a paper until somebody called and said it’s been published.”
In his expert report, Lumanity’s Weisman argued that the FDA’s approval of Tavneos “fundamentally undermines” the plaintiffs’ assertion that the liver adverse events “have a significant negative impact” on the drug’s risk-benefit profile. The approval confirms that Tavneos’ safety profile was “acceptable” as ChemoCentryx had claimed, he said.
Amgen declined to comment on pending litigation.
After the amended complaint was filed in 2022, the defendants successfully won a motion to dismiss certain allegations but failed to disband the class certification. Last May, RA Capital joined the fight, filing similar lawsuits against ChemoCentryx and Schall in the California Superior Court in Ventura County and the Northern District Court of California.