Despite positive trial, Roche says Enspryng fell short of expectations in myasthenia gravis

Drug developers often try to spot tidbits of positive information from a failed clinical trial. But Roche is doing the opposite for its Enspryng study in the competitive autoimmune disorder of generalized myasthenia gravis (gMG).

Enspryng delivered a statistically significant benefit in improving symptoms and daily life metrics when used on top of standard-of-care therapy in gMG patients who are anti-AChR-seropositive, which represents about 80% of the disease population. The phase 3 LUMINESCE trial has met its primary endpoint as measured by the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at 24 weeks.

However, in announcing the positive readout, Roche’s Chugai said the degree of clinical benefit observed “did not reach our expectations.”

Just a few days ago, Roche touted Enspryng’s “best-in-disease potential in MG” during a neurology investor event, a company presentation shows. At that time, Roche highlighted the remaining unmet need in gMG, including about 10% to 30% of patients who fail on standard-of-care therapies, and at least 60% of patients on novel biologics who couldn’t achieve stable remission.

Roche’s labeling of the Enspryng’s data as weak was a relief for other developers of biologics for gMG, such as Johnson & Johnson, UCB and argenx. As Enspryng was tested under the skin once every four weeks in LUMINESCE, it could have held a convenience edge over other once-weekly regimens given either subcutaneously or through intravenous infusions.

While Enspryng inhibits IL-6 signaling, UCB’s Rystiggo and argenx’s Vyvgart are anti-FcRn antibodies. And J&J just reported a positive outcome for the anti-FcRn candidate nipocalimabin a phase 3 gMG trial, although the magnitude of improvement remains under wraps. AstraZeneca’s Soliris and long-acting Ultomiris are C5 inhibitors.

Originally approved by the FDA in late 2021 as the first FcRn inhibitor, Vyvgart last year generated $1.2 billion in sales from gMG. Enspryng, with a 2020 FDA nod in certain patients with the neurological autoimmune disease of neuromyelitis optica spectrum disorder, only generated 256 Swiss francs ($285 million) in 2023 sales.

Despite the disappointing gMG results, Roche remains committed to developing Enspryng in other neurological autoimmune and inflammatory diseases. Phase 3 trials are ongoing for Enspryng in myelin oligodendrocyte glycoprotein-associated disorder and autoimmune encephalitis, as well as thyroid eye disease.