A review of the benefits and risks of avacopan (Avacopan Vifor) begun by the Medicines and Healthcare products Regulatory Agency (MHRA) in June has concluded that the available evidence no longer supports a positive benefit-risk balance for the drug, previously known by its US name Tavneos. 

The review was initiated following concerns about the “integrity and reliability” of data from the pivotal clinical study underpinning avacopan's licence authorisation. However, while expert commentary acknowledged irregularities in the pivotal clinical trial underpinning the original licence, it recognised the drug's real-world effectiveness for the rare diseases it is intended to treat.

The MHRA review concluded that the study could no longer be relied upon to demonstrate the efficacy of Avacopan Vifor and has therefore suspended its use, supply, and sale to new patients from 1 September 2026. 

The drug is a complement inhibitor authorised in the UK in 2022 to be used in combination with a rituximab or cyclophosphamide regimen to treat severe, active granulomatosis with polyangiitis (GPA, previously known as Wegener granulomatosis) or microscopic polyangiitis (MPA).

Diseases Due to Small Blood Vessel Inflammation 

GPA features small blood vessel inflammation especially in the nose, sinuses, throat, lungs, and kidneys. Symptoms include nasal discharge, sinusitis, nosebleeds, haematuria, shortness of breath, and fatigue. Granulomas may lead to organ damage and impaired function, which may be fatal without early treatment. MPA may cause fever, weight loss, fatigue, haematuria, shortness of breath, and haemoptysis. 

Both conditions feature anti-neutrophil cytoplasmic autoantibodies (ANCA), host-derived autoantibodies that react against primary granules in neutrophils and monocytes to damage the host vasculature by triggering inflammation and cytokine production. ANCA-associated vasculitis may have a genetic component and may be triggered by infection, environmental factors such as pollution, and certain drugs. 

Avacopan blocks the complement 5a receptor, thereby inhibiting neutrophil attraction and activation. The phase 3 ADVOCATE trial, published in 2021, suggested that, when used alongside rituximab or cyclophosphamide, it could reduce vascular inflammation and induce remission in GPA and MPA, thereby reducing the need for glucocorticoids. 

However, after a detailed assessment of all available evidence, and on advice from the Commission on Human Medicines, along with representations made by patients and healthcare professionals, the MHRA decided to invoke regulations to suspend use, supply, and sale of the drug.

Drug Safety Controversy 

The original ADVOCATE trial paper has since been retracted. An editorial in The Lancet Rheumatology, published last month, noted that the retraction — at the request of two academic authors of the study — was “the latest instalment in an ongoing controversy” surrounding avacopan “that could spell the end for the drug.” The drug remains under intense regulatory scrutiny in the US.

In March 2026, the US Food and Drug Administration (FDA) issued a drug safety communication after postmarketing analysis flagged 76 cases of serious liver injury linked to avacopan, including deaths from vanishing bile duct syndrome. The following month, the FDA's Center for Drug Evaluation and Research proposed withdrawing avacopan from the market, asserting that its new drug application “contained untrue statements of material fact.” The Lancet Rheumatology reported that an ongoing FDA investigation has alleged the trial's 52-week primary endpoint data were manipulated by unmasked company personnel, who re-adjudicated outcomes for a subset of patients after learning the original analysis had not reached statistical significance.

The Lancet Rheumatology editorial called the data-integrity questions “deeply concerning” but noted that, despite mounting regulatory pressure, real-world studies support avacopan's effectiveness. “With the retraction of the ADVOCATE trial, the end for avacopan seems inevitable—and patients with ANCA-associated vasculitis seem set to lose access to an effective drug because of the nefarious actions of a few unscrupulous individuals,” it said. 

Do Not Start Treatment With New Patients 

The MHRA said healthcare professionals “should not initiate treatment with Avacopan Vifor in new patients” and should review those already taking it “at the earliest opportunity,” considering alternative treatment options where necessary. Julian Beach, MHRA executive director of healthcare quality and access, said the review had concluded that the data supporting avacopan's efficacy were no longer reliable enough to support a positive benefit-risk balance, and that regulatory action had been taken accordingly.

The MHRA said that the marketing authorisation holder had guaranteed sufficient supplies of avacopan to cover existing patients for a further 6 months, during which continued use will be permitted, to allow managed withdrawal. Patients continuing on the drug for this period should be subject to existing risk minimisation procedures, including monitoring of liver function and white blood cell count, and vigilance for signs of serious infections.

After the 6 months, the MHRA intends to revoke avacopan's UK marketing authorisation. This is planned for 1 March 2027. Meanwhile, any suspected adverse reactions should be reported via the MHRA Yellow Card scheme.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.