Batoclimab eases disease severity; Immunovant backs IMVT-1402
Company says it will use trial findings to advance lead candidate
Investigational therapy batoclimab eased disease severity for adults with generalized myasthenia gravis (gMG) in a Phase 3 trial, but the treatment’s developer said it’s not planning to seek regulatory approval of the treatment for gMG in the U.S.
Immunovant, a Roivant subsidiary, is instead focused on using the findings to further advance its lead therapeutic candidate, IMVT-1402, which has a similar mechanism of action to batoclimab — both belong to a class of therapies called FcRn inhibitors — but is expected to have a more favorable safety profile.
“We are excited to share positive results from our … studies,” Pete Salzmann, MD, Immunovant’s CEO, said in a company press release. “While neurologists and patients are very enthusiastic about currently approved FcRn inhibitors, they tell us that they also see a lot of potential for a next-generation FcRn inhibitor that can offer deeper and more durable responses for patients whose disease is still affecting their daily function.”
Plans for a clinical trial to test IMVT-1402 in people with myasthenia gravis (MG) are underway. Meanwhile, batoclimab is under regulatory review to treat gMG in China, where it’s being developed by Harbour BioMed.
Targeting self-reactive antibodies
MG is an autoimmune disease in which self-reactive antibodies attack proteins needed for proper nerve-muscle communication, most often acetylcholine receptors (AChRs). MG-driving antibodies belong to a class of antibodies called immunoglobulin G (IgG).
Batoclimab and IMVT-1402, as well as the approved MG treatments Vyvgart (efgartigimod) and Rystiggo (rozanolixizumab), work by blocking the neonatal Fc receptor (FcRn), which normally helps stabilize IgGs in the bloodstream. In doing so, they’re expected to speed IgG breakdown, thereby lowering the levels of MG-associated antibodies and easing MG symptoms.
Immunovant has been developing batoclimab and IMVT-1402 for various diseases driven by self-reactive antibodies. While earlier clinical studies demonstrated that batoclimab could ease disease severity in people with gMG, it also led to reductions in a protein called albumin, which can cause blood cholesterol levels to rise.
IMVT-1402, on the other hand, was able to lower IgG levels with little impact on albumin or cholesterol in a Phase 1 study involving healthy adults. The company had announced plans to prioritize IMVT-1402’s development, but was refraining from making final decisions until Phase 3 trial results for batoclimab became available.
In the first part of the Phase 3 Flex study (NCT05403541), adults with gMG were randomly assigned to receive weekly, under-the-skin injections of batoclimab at a low dose (340 mg) or high dose (680 mg), or a placebo, for 12 weeks (about three months).
The study’s main goal was to evaluate changes in disease severity in the 164 participants with anti-AChR antibodies, as assessed by the MG Activities of Daily Living (MG-ADL) scale.
Reductions in disease severity
Results showed that participants given either dose of batoclimab experienced significant reductions in disease severity compared with those given a placebo. MG-ADL scores dropped (improved) by a mean of 5.6 points in the high-dose batoclimab group, by 4.7 points in the low-dose group, and by 3.6 points in the placebo group.
Moreover, 81% of participants given the low dose of batoclimab and 93% of those given the high dose were considered MG-ADL responders, meaning they had a minimum 2-point improvement in their MG-ADL scores.
By week 2, 40% of those in the high dose group and 25% of those in the low dose group were considered “super-responders,” having achieved at least a 5-point improvement in MG-ADL scores. This was seen in 11% of those in the placebo group.
Minimal symptom expression (MSE), defined as an MG-ADL score of 0 or 1, was achieved by 42% of those given the high dose and 31% of those given the low dose of batoclimab at week 12, compared with 7% of patients in the placebo group.
Three-quarters of participants in the high-dose group who achieved MSE by week 6 showed a durable response that was maintained for at least six weeks.
Immunovant said a number of therapeutic benefits of batoclimab at the higher dose appeared to outperform what had been previously observed with other FcRn inhibitors, although the findings are from different studies and can’t be directly compared.
Patients who responded to batoclimab were randomly reassigned to receive batoclimab (340 mg once every week or every other week) or a placebo once every week for another 12 weeks in the study’s second part.
Immunovant said findings in this part of the study were “as expected,” with patients assigned to the 340 mg weekly dose of batoclimab seeing stronger clinical responses than patients whose dose was reduced.
The treatment’s safety and tolerability profile was consistent with previous studies.
Per Immunovant, deeper IgG reductions were correlated with better clinical outcomes. At its high dose, batoclimab was associated with a mean 74% IgG reduction, while the lower dose led to a mean 64% reduction.
“Today’s results show that deeper IgG reduction leads to deeper responses in MG,” Salzmann said. “We believe that our core thesis — that deeper IgG reduction, at the levels achieved by high dose batoclimab and high dose IMVT-1402, leads to improved clinical outcomes — will apply to a wide range of auto-antibody mediated conditions.”
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