The US vasculitis community has stepped into the fight over avacopan, warning that uncertainty around the drug is already changing clinical care.
The battle over the future of avacopan has widened, with the Vasculitis Foundation calling on the US FDA to hold a public hearing before deciding whether to pull the ANCA-associated vasculitis drug from the market.
In a letter to senior FDA officials, the patient organisation said the proposed withdrawal of Avacopan (Tavneos, CSL) was sufficiently consequential for patients and clinicians to warrant a transparent public examination of the drug’s benefits and risks.
The intervention is the latest development in an increasingly fraught regulatory saga surrounding the complement C5a receptor inhibitor, which is also under review by Australia’s TGA.
As previously reported by Rheumatology Republic, the TGA announced in August that it was reviewing the benefit-risk profile of avacopan after concerns emerged about the integrity and reliability of data from the pivotal ADVOCATE trial that supported its Australian approval.
There has been no subsequent change announced by the TGA to the drug’s Australian registration. Its latest published advice remains that clinicians should carefully consider its benefits and risks for individual patients while the review continues.
The Vasculitis Foundation’s move puts patients more directly into the centre of the US regulatory dispute.
In its 24 September letter, the foundation asked the FDA to hear evidence from patients, caregivers, and vasculitis specialists before reaching a final decision on the drug.
It argued a hearing should examine avacopan’s overall benefit-risk profile in the context of the toxicities and limitations of alternative treatments, while giving patients, caregivers, and vasculitis specialists an opportunity to describe their experiences, risk tolerance, and the practical consequences of losing the drug as a treatment option.
It also urged the FDA to consider the full clinical, safety, and postmarketing evidence, including emerging international regulatory assessments, and examine whether measures such as updated labelling, enhanced liver monitoring, or restricted prescribing could address safety concerns without removing access altogether.
The foundation called for the FDA’s eventual decision and its underlying benefit-risk assessment to be communicated clearly and transparently and warned that the regulatory limbo was already having consequences in clinical practice.
It said some clinicians had pre-emptively stopped avacopan, potentially leaving patients exposed to disease flares or greater use of high-dose glucocorticoids, while patients already stable on the drug were anxious about losing access.
“Patients currently managed on avacopan are deeply anxious about the prospect of losing access to a treatment that has stabilised their disease, while newly diagnosed patients are left confused and distressed about whether avacopan remains a viable treatment option for induction or maintenance,” the foundation told the FDA in its letter.
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The letter, signed by Joyce A. Kullman, executive director of the VF, requested a written response by 30 September.
“The vasculitis community has a profound interest in ensuring that decisions affecting the treatment options available to people with severe GPA and MPA are made on the basis of a complete, transparent, and fully informed record,” it said.
“The proposed withdrawal of an approved therapy raises questions that extend well beyond the safety profile of a single drug and directly implicate the treatment landscape for a serious and potentially fatal disease.”
The FDA’s Center for Drug Evaluation and Research proposed withdrawing Tavneos in April after concluding that new information about the pivotal trial meant it could no longer find a valid demonstration of effectiveness for the drug’s approved use.
According to the FDA, unblinded study personnel altered efficacy assessments after the trial was completed in a way that made the treatment appear effective, while the original analysis was not disclosed to the regulator.
Those concerns ultimately led the New England Journal of Medicine to retract the published ADVOCATE trial and prompted the European Medicines Agency’s human medicines committee to recommend revoking the drug’s EU marketing authorisation.
The FDA has separately raised safety concerns after identifying serious postmarketing cases of drug-induced liver injury associated with avacopan, including cases of vanishing bile duct syndrome and fatal outcomes.
But the US withdrawal is not yet final.
Amgen, which acquired original developer ChemoCentryx in 2022, has challenged the FDA’s conclusions and submitted additional evidence in support of retaining the drug.
That evidence includes an independent, fully blinded re-adjudication of ADVOCATE’s primary outcomes by the Duke Clinical Research Institute.
According to data released by Amgen and summarised by the Vasculitis Foundation, the re-adjudication found avacopan remained non-inferior to the prednisone control for remission at week 26 and sustained remission at week 52, although the superiority at week 52 reported in the original ADVOCATE analysis was not reproduced.
Australia remains among the jurisdictions still considering its position.
Avacopan was approved by the TGA in January 2023, in combination with a rituximab- or cyclophosphamide-based regimen, for adults with ANCA-associated vasculitis including GPA and MPA.
For now, Tavneos remains registered in Australia, and the TGA has not advised clinicians to stop prescribing it while its review is under way.
