Argenx’s subcutaneous Fc receptor blocker efgartigimod was unable to induce a significantly higher rate of complete remission than placebo in the skin autoimmune disease. The company’s stock plummeted in response to the news.
Pictured: Illustration showing a downward graph trend/iStock, lerbank
Argenx on Wednesday announced that its subcutaneous Fc receptor blocker efgartigimod missed its primary endpoint in the Phase III ADDRESS study, failing to significantly boost complete remission in adult patients with pemphigus vulgaris and pemphigus foliaceus.
Efgartigimod also failed to significantly outperform placebo in terms of the secondary endpoints, including cumulative corticosteroid dose and time to remission or disease control.
With this late-stage failure, argenx will no longer pursue the development of efgartigimod in pemphigus. Instead, the biotech will prioritize the assessment of the drug candidate in severe autoimmune indications.
Shares of argenx nosedived Wednesday morning on the news of the Phase III failure.
Argenx CMO Luc Truyen in a statement said the company is “disappointed” by the ADDRESS results, adding that while it will “not move forward into pemphigus” the team will “continue to be execution-focused and data-driven” as they work on the other efgartigimod clinical development programs.
ADDRESS was a randomized, double-blinded and placebo-controlled study that enrolled 222 adult patients with newly diagnosed or relapsing moderate-to-severe pemphigus vulgaris or pemphigus foliaceus. Participants were treated for a total of 30 weeks and received concomitant corticosteroids at a starting dose of 0.5 mg/kg per day.
The study’s primary endpoint was complete remission on a minimal dose of steroids (CRmin), which was achieved by 35.5% of patients treated with efgartigimod and 30.3% for those who received placebo. The difference failed to reach statistical significance, with a p-value of 0.5956, according to argenx’s announcement.
Wednesday’s readout represents efgartigimod’s second late-stage failure in recent weeks. Late last month, argenx announced that the subcutaneous drug failed the Phase III ADVANCE-SE study in primary immune thrombocytopenia. Following treatment with efgartigimod, 13% of patients achieved a sustained platelet count response, compared with 16.2% in the placebo arm—an effect that was not statistically significant.
Efgartigimod is a human IgG1 antibody fragment that works by blocking the neonatal Fc receptor, preventing its interaction with IgG. This mechanism of action leads to an overall drop in the circulating levels of IgG and promotes the degradation of the immunoglobulin.
The FDA first approved efgartigimod in 2021, under the brand name Vyvgart, for the intravenous treatment for generalized myasthenia gravis in adult patients positive for the anti-acetylcholine receptor. In June 2023, the regulator greenlit a subcutaneous formulation of Vyvgart, now being sold as Vyvgart Hytrulo, for the same indication.
According to argenx’s website, the company is also developing efgartigimod in chronic inflammatory demyelinating polyneuropathy, lupus nephritis and idiopathic inflammatory myopathies, among other indications.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
