Immunovant Reports Positive Results from Mid-Stage Trial of Experimental Treatment for Myasthenia Gravis

Rare Daily Staff

Immunovant reported positive topline results from a phase 2a study of IMVT-1401, its experimental treatment for the rare autoimmune condition myasthenia gravis.

Myasthenia gravis (MG) is a rare and chronic autoimmune disease where IgG antibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. More than 85 percent of people with MG progress to generalized MG (gMG) within 18 months, where muscles throughout the body may be affected, resulting in extreme fatigue and difficulties with facial expression, speech, swallowing and mobility. In more life-threatening cases, MG can affect the muscles responsible for breathing.

IMVT-1401 is a novel, fully human monoclonal antibody targeting the neonatal Fc receptor (FcRn). The company sbelieve that this product has the potential to address a variety of IgG-mediated autoimmune diseases as a subcutaneous injection.

The multi-center, randomized, placebo-controlled trial was designed to evaluate the safety, tolerability, pharmacodynamics, and efficacy of IMVT-1401 in patients with moderate-to-severe generalized MG. Results from the six-week treatment period of 15 patients randomized to two dosage arms and placebo demonstrated that IMVT-1401-treated patients showed a mean 3.8-point improvement on the MG-ADL scale vs. a mean decline of +0.6 for placebo, a result that was statistically significant. IMVT-1401-treated patients also showed a highly statistically significant improvement on the MGC scale, with an average improvement of 8.0 points vs. a mean decline of +1.4 for placebo.

MG-Activities of Daily Living (MG-ADL) responder rates, defined as the percentage of patients showing a greater than 2-point improvement, were 60 percent for IMVT-1401-treated patients versus 20 percent for placebo. MG-ADL deep responder rates, defined in the study as the percentage of patients showing a greater than 6-point improvement, were 40 percent for IMVT-1401-treated patients versus none for placebo. MG Composite deep responder rates, defined in the study as the percentage of patients showing a greater than 10-point improvement, were 40 percent for IMVT-1401-treated patients versus none for placebo.

Consistent with previously reported phase 1 results, IMVT-1401 was observed to be generally safe and well-tolerated with no serious adverse events, no withdrawals due to adverse events, and no imbalance in headaches. Mean reductions in total serum IgG from baseline for the 340 mg and 680 mg cohorts were 59 percent and 76 percent, respectively.

“The clinical benefits we observed in this trial provide strong support that IMVT-1401 might ultimately become a best-in-class anti-FcRn agent for MG patients. Importantly, IMVT-1401 was delivered by subcutaneous injection, opening the future possibility of at-home, self-administered treatment rather than infusion center-based treatment,” said Pete Salzmann, CEO of Immunovant. “We look forward to engaging with the FDA later this year on the design of our phase 3 registrational program in MG.”

Immunovant unblinded the study after 15 of the anticipated 21 patients completed the six-week treatment course due to the impact of COVID-19 and the validation of the anti-FcRn mechanism in MG that the company reported at the end of June.

“Although this small phase 2a study was designed principally to evaluate safety and tolerability, as well as changes in IgG antibody levels, it is extremely encouraging to see such promising early results on a range of MG outcome measures,” said Michael Benatar, chief of the Neuromuscular Division at the University of Miami. “Results of this study will provide critical insights for the design and implementation of a pivotal phase 3 study.”

Photo: Pete Salzmann, CEO of Immunovant