argenx's Forte acquisition delivers coeliac trial win

argenx's CD122 inhibitor FB102, added to its pipeline through the $2.2 billion acquisition of Forte Biosciences, will move into phase 3 development for coeliac disease after showing efficacy in a mid-stage trial.

There are no FDA-approved drug therapies for coeliac disease, a chronic autoimmune condition where eating gluten triggers an immune system attack on the small intestine, with those living with the disorder having to adhere to a strict, lifelong gluten-free diet to heal the intestine and prevent long-term complications.

The new study is the first readout for a drug added by the Forte takeover, which closed in August, and will relieve some of the pain felt by argenx after it reported disappointing phase 3 results with its subcutaneous FcRn inhibitor Vyvgart Hytrulo (efgartigimod) in Sjögren's disease earlier this week.

FB102 is potentially a first-in-class drug that targets pathogenic T-cell and natural killer (NK) cell activity in autoimmune disorders, and is being billed by both argenx and Forte as a "pipeline-in-a-product," with potential in other disorders, including vitiligo and alopecia areata.

In the phase 2 trial, coeliac patients treated with FB102 saw a statistically significant improvement in the primary endpoint, change from baseline in the ratio of villus height-to-crypt depth (Vh:Cd), a standard histological metric used to evaluate intestinal health , after 78 days.

Other efficacy measures – including intraepithelial lymphocyte (IEL) density, villus height-to-crypt depth intraepithelial lymphocyte (VCIEL) composite score, and symptoms – were "consistent with the primary endpoint, providing additional evidence of effect across histologic, inflammatory, and clinical measures," said the Netherlands-based company in a statement.

This is the first phase 2 clinical evidence that blocking CD122 can prevent gluten-induced intestinal damage in people living with coeliac disease, with no worrying safety signals, and argenx is now pressing ahead with plans for a pivotal trials programme.

The readout will be a relief for argenx, which has been beset by a series of disappointments in its efforts to expand the indications for its Vyvgart franchise, with the Sjögren's disappointment following failed trials in thyroid eye disease, pemphigus, and primary immune thrombocytopenia (ITP).

The intravenous formulation of Vyvgart is approved in most major markets for generalised myasthenia gravis (gMG) – and for immune thrombocytopenia (ITP) in Japan only – while Vyvgart Hytrulo is indicated gMG and for chronic inflammatory demyelinating polyneuropathy (CIDP). The franchise made sales of around $2.8 billion in the first half of this year.

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