Argenx Discontinues Pemphigus Program After Vyvgart Hytrulo Fails in Phase 3 Study

Rare Daily Staff

Dutch biotech Argenx disclosed disappointing topline results from the ADDRESS study evaluating Vyvgart Hytrulo in adults with pemphigus vulgaris and pemphigus foliaceus and said it will not pursue development in the indication.

Shares of the company fell 30 percent in early trading on the news.

The ADDRESS results show the proportion of pemphigus vulgaris patients achieving the primary endpoint of complete remission on a minimal dose of steroids was not significantly different between Vyvgart Hytrulo (efgartigimod) and placebo.

“We are disappointed by today’s results, particularly for pemphigus patients who have seen little innovation in this treatment space,” said Luc Truyen, chief medical officer at Argenx. “While we will not move forward into pemphigus, our job today is the same as yesterday – continue to be execution-focused and data-driven, apply learnings across our ongoing development programs, and pursue optimal development of efgartigimod, empasiprubart, and our earlier stage programs.”

Pemphigus (PV) is a rare group of chronic blistering autoimmune diseases that affect the skin and mucous membranes, and are characterized by painful blisters, erosions and acantholysis, or disruption of keratinocyte adhesion. Blisters often break open, causing serious pain and increased risk of infection. Pemphigus vulgaris and pemphigus foliaceous are the most common forms of pemphigus. Bullous pemphigoid is a rare chronic blistering autoimmune disease and is the most common form of pemphigoid diseases. It is characterized by autoantibodies against structural proteins of the dermal-epidermal junction and, clinically, by tense blisters and erosions of skin or mucous membranes close to the skin surface. The disease has a strong impact on a person’s quality of life and is associated with a high mortality.

Vyvgart Hytrulo is a subcutaneous combination of efgartigimod alfa, a human IgG1 antibody fragment marketed for intravenous use as Vyvgart, and recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s Enhanze drug delivery technology to facilitate subcutaneous injection delivery of biologics. In binding to the neonatal Fc receptor (FcRn), Vyvgart Hytrulo results in the reduction of circulating IgG. The U.S. Food and Drug Administration approved Vyvgart Hytrulo in June 2023 to treat patients with generalized myasthenia gravis. It is marketed in Europe as Vygart and may be marketed under different proprietary names following approval in other regions.

The phase 3 ADDRESS study enrolled 222 adult patients with newly diagnosed or relapsing moderate-to-severe PV or PF. Patients were randomized to efgartigimod subcutaneous or placebo with both treatment groups receiving concomitant steroids at a starting dose of 0.5mg/kg, which is a lower dose than recommended by current treatment guidelines and was tapered according to protocol upon achievement of complete remission.

The study did not meet primary endpoint. Treatment with efgartigimod SC led to complete response on a minimal dose of steroids (CRmin) in 35.5 percent of patients compared to 30.3 percent with placebo. Secondary endpoints were also not met, including CRmin in the overall pemphigus population (PV and PF), cumulative dose of corticosteroids and time to disease control or complete remission. The observed safety and tolerability profile was consistent with other clinical trials and the confirmed safety profile of Vyvgart and Vyvgart Hytrulo.

In light of these results, Argenx is reviewing the BALLAD study evaluating Vyvgart Hytrulo in adult patients with bullous pemphigoid and the comparable biology between pemphigus and bullous pemphigoid and has decided not to make a GO/NO GO decision at this time but rather wait for learnings from all currently enrolled patients and consider a new trial design for the path forward.

Photo: Luc Truyen, chief medical officer at Argenx