European agency reevaluates AAV drug Tavneos after trial data concerns
Therapy was approved in the EU in 2022 as an add-on to standard treatment
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Following questions about the integrity of clinical trial data, regulators in Europe are taking a second look at Tavneos (avacopan), an oral therapy approved for ANCA-associated vasculitis (AAV).
In a press release, the European Medicines Agency (EMA) announced that it “will now review all available data to assess whether this emerging information has an impact on the balance of benefits and risks of Tavneos.” Once the review is complete, the agency said it will decide whether Tavneos’ current approval status in the European Union (EU) “should be maintained, amended, suspended or revoked.”
Regulatory approvals based mainly on data from Phase 3 clinical trial
Tavneos is an oral therapy designed to block activation of the complement cascade, a group of immune proteins that play a key role in driving AAV’s hallmark blood vessel inflammation.
The therapy was originally developed by Chemocentryx, which was acquired by Amgen in 2022. Amgen sells the therapy in the U.S., while in Europe and most other parts of the world, rights to the therapy are held by CSL Vifor Pharma.
Tavneos was approved in the EU in 2022 as an add-on to standard treatment, including glucocorticoids, for adults with severe and active microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two most common types of AAV. This followed a similar decision in the U.S. in 2021.
Regulatory approvals were primarily based on data from a Phase 3 clinical trial, ADVOCATE (NCT02994927). The study enrolled 331 adults with MPA or GPA. Participants were randomly assigned to treatment with Tavneos or a glucocorticoid, on top of other standard immunosuppressive treatments (rituximab or cyclophosphamide).
ADVOCATE’s main goal was to show that Tavneos was at least non-inferior to glucocorticoids at reducing AAV activity after six and 12 months. Glucocorticoids are anti-inflammatory medicines commonly used for AAV, but they can cause problematic side effects, especially if taken long-term.
Chemocentryx announced in 2019 that the ADVOCATE study had met both of its goals, with patients given Tavneos achieving comparable remission rates after six months to those given glucocorticoids, and significantly higher remission rates after one year. These data ultimately led to approvals of Tavneos in the EU and elsewhere.
Concerns raised about interpretability of data
However, concerns have been raised about the data’s interpretability.
Before the approval, the U.S. Food and Drug Administration (FDA) stated that “a noninferiority comparison would not be sufficient to show that [Tavneos] can replace glucocorticoids” as it would be “very difficult to determine if a finding of similar remission rates on the [two groups] was due to the efficacy of [Tavneos] or to the fact that the remission rates on both [groups] were primarily driven by the underlying [cyclophosphamide] or [rituximab].”
Additionally, as reported in a U.S. lawsuit filed in 2022, most participants receiving Tavneos also used glucocorticoids over the study’s first six months, which may further complicate comparisons between Tavneos and standard of care.
Moreover, subgroup analyses showed Tavneos was superior to glucocorticoids only among patients receiving rituximab. Those on rituximab did not receive standard maintenance treatment, while those on cyclophosphamide did.
“The result of the subgroup analysis suggests the possibility that [Tavneos] was efficacious only in the population who did not receive standard-of-care maintenance immunosuppression therapy and may be considered undertreated, raising questions about the adequacy of the comparisons and clinical meaningfulness of the [Tavneos] effect at [one year],” the FDA stated.
In the U.S. lawsuit, plaintiffs also allege that Chemocentryx ignored and repeatedly downplayed concerns raised by the safety committee overseeing the trial about the potential for serious liver injury as a side effect of Tavneos.
The European Commission — which has final say on drug approvals in the EU — has now asked the EMA to look into the data again. The agency is now doing so. It did not provide a timeline for when a decision is expected.
