IMVT-1401 Seen to Safely Treat Generalized MG in Phase 2a Trial

Treatment with IMVT-1401 significantly eased symptoms and lowered antibody levels in adults with moderate-to-severe generalized myasthenia gravis (MG), top-line results of a small Phase 2a trial show.

Use of this investigative antibody at two doses was also seen to be safe and well tolerated. Results are expected to support a pivotal Phase 3 study planned for early 2021.

“We are absolutely thrilled with the results of this trial,” Pete Salzmann, MD, CEO of Immunovant, which is developing IMVT-1401, said in a press release.

MG is usually caused by autoantibodies that target proteins found at the site where nerve cells communicate with muscles. IMVT-1401 is designed to block the activity of a protein called neonatal Fc receptor (FcRn), which acts to prevent antibodies — specifically IgG antibodies — from being destroyed. By blocking FcRn, IMVT-1401 is designed to promote the destruction of antibodies, including those that cause MG.

ASCEND MG (NCT03863080), an Immunovant-sponsored Phase 2a trial, is investigating the safety, tolerability, pharmacological properties, and early efficacy of IMVT-1401 in people with generalized MG.

It is expected to enroll 21 patients. However, due to COVID-19 complications and validation of the therapy’s mechanism of action in MG, Immunovant elected to unblind the study and release top-line data on the first 15 participants.

The trial is still enrolling eligible adults at sites across the U.S. and Canada; information is available here.

Of these 15 patients, five were given IMVT-1401 at a dose of 340 mg weekly, five others at a 680 mg weekly dose, and the remaining five were assigned to a placebo. Treatment lasted six weeks, with an option of moving into a six-week extension phase in which all would be treated with IMVT-1401.

“Importantly, IMVT-1401 was delivered by subcutaneous [under-the-skin] injection, opening the future possibility of at-home, self-administered treatment rather than infusion center-based treatment,” Salzmann said.

Results at six weeks showed that IMVT-1401 was generally safe and well tolerated. No serious adverse events were reported and no one withdrew due to side effects.

Mean blood IgG levels decreased by 59% in patients given the lower dose, and by 76% in those on the higher dose of IMVT-1401 over the course of the study.

Efficacy was evaluated using two questionnaires: the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) and the Myasthenia Gravis Composite scale (MGC). In both questionnaires, lower scores indicate eased symptoms.

The 10 patients treated with IMVT-1401 experienced a mean MG-ADL score decrease (improvement) of 3.8 points, compared with a 0.6 points increase, or worsening, in the placebo group. Likewise, MGC scale analysis also showed an 8-point improvement with IMVT-1401’s use, which contrasted with the 1.4 point worsening among placebo patients. Differences between treatment and placebo were statistically significant on both scales.

The two patient groups given different doses of IMVT-1401 were pooled together for these analyses.

In the MG-ADL scale, a two point or greater decrease is considered clinically meaningful. Six (60%) patients on IMVT-1401 reached this goal, compared with one (20%) given placebo.

Four (40%) treated participants had an MG-ADL score decrease of at least six points, and four had a lower MGC score by at least 10 points. No placebo group patients experienced similar benefits.

“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,” Salzmann said.

“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, MD, PhD, chief of the nuromuscular 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” next year, he added.

“We look forward to engaging with the FDA later this year on the design of our Phase 3 registrational program in MG,” Salzmann said.

A webcast discussing ASCEND MG’s results is available here. This Phase 2 trial is expected to conclude in December.