In another blow to the future market prospects of Amgen’s rare disease therapy, Tavneos (avacopan), the New England Journal of Medicine (NEJM) has retracted the drug’s pivotal study paper.
This comes after two academic authors associated with the paper requested its removal after an ongoing post-publication investigation by the US Food and Drug Administration (FDA) revealed that primary endpoint assessments in nine patients enrolled onto the trial were “readjudicated after database lock and trial unblinding”.
This factor, the editors say, was “not disclosed in the article and is inconsistent with proper research conduct”, in a retraction notice from the NEJM.
The 2021 paper’s removal from the NEJM database comes amid mounting scrutiny on the therapy’s risk-benefit profile from the FDA, as the agency’s drug review division proposed to withdraw Tavneos’ approval after uncovering “reasonable evidence of a causal association” between 76 cases of drug-induced liver injury – including eight deaths and seven cases of rare liver condition, vanishing bile duct syndrome (VBDS) – and the medicine’s use. The regulator also called the drug’s proven efficacy into question.
The European Medicines Agency (EMA) recently took a similar stance to the FDA by calling for Tavneos’ market rollback at the end of June, after its own review of the Phase III Advocate study, which formed the foundations of Tavneos’ initial approval, was in breach of good clinical practice (GCP) guidelines.
Amgen originally absorbed the US rights to Tavneos, a therapy for two rare inflammatory blood vessel conditions called microscopic polyangiitis (MPA) and severe, active granulomatosis with polyangiitis (GPA), through its $3.7bn 2022 takeover of the drug’s original developer, ChemoCentryx. Before the Committee for Medicinal Products for Human Use (CHMP) recommended revoking Tavneos' approval, CSL Vifor commercialised the drug in Europe.
Filling the European Tavneos gap
As Amgen grapples with heightening regulatory hurdles linked to Tavenos’ place on the market, some new players are looking to fill the potential void left by the drug.
This includes German biopharma company InflaRx, which is planning to engage with the EMA about the potential path to approval for two of its clinical-stage therapies, vilobelimab and izicopan, in ANCA-associated vasculitis – the umbrella term for the group of autoimmune diseases under which MPA and GPA sit.
Currently, InflaRx is preparing izicopan for Phase II, while it considers vilobelimab to be “a Phase III-ready asset”. According to the company, these drugs provide a complementary biologic and oral pipeline “well positioned” to address the unmet needs of patients with AAV.
According to GlobalData’s Pharmaceutical Intelligence Center, there are more than 30 ongoing clinical trials in Phase I-III for MPA and GPA, with a quarter of these being late-stage studies.
GlobalData is the parent company of Pharmaceutical Technology.
