Rozanolixizumab

Immunovant will not seek approval for its candidate for the autoimmune disorder myasthenia gravis (MG), despite a reasonable showing in its pivotal trial. Instead, the company said Wednesday that it will use the data from the trial of batoclimab to develop its second-generation therapy, IMVT-1402. Investors were alarmed last May when the company delayed the batoclimab trial’s readout in order to prioritize development of IMVT-1402. Now the wait is over, and batoclimab — like Vyvgart an anti-FcRn antibody — has been shown to improve MG patients’ symptoms by 5.6 points on a widely-used rating scale. This measurement was taken after three months of treatment. Leerink analysts wrote in a March 17 note that in their base case, batoclimab would show a reduction on a symptom measurement scale called the Myasthenia Gravis Activities of Daily Living, or MG-ADL, of around four to five percentage points. This would be in line with competing anti-FcRn agents and complement inhibitors. MG is caused by immunoglobulin G (IgG) antibodies that disrupt the links between nerves and muscles, causing potentially life-threatening muscle weakness. The condition can worsen, with severely affected patients having difficulty swallowing and breathing. It can be treated with generic steroids, immunosuppressants and acetylcholinesterase inhibitors as well as Alexion’s Soliris, but some patients do not respond to these. Other approved therapies include complement factor C5 inhibitors like AstraZeneca’s Ultomiris and UCB’s Zilbrysq. But most excitement in this area centers on neonatal Fc receptor (FcRn) inhibitors. FcRn works to preserve levels of IgG, so blocking it can improve MG symptoms. Vyvgart was approved in 2021 on the basis of a slightly different interpretation of the MG-ADL scale to that reported by Immunovant today. After one cycle of treatment in the ADAPT trial, 68% of treated MG patients were MG-ADL responders, versus 30% of those given placebo. Response was defined as a drop of at least two points on the scale, with the improvement sustained for at least four weeks. In a prior Phase 3 trial in China, batoclimab had yielded a 58.2% response rate on MG-ADL vs. 31.3% with placebo. However, the response here had a more stringent definition than in the Vyvgart trial, requiring a three-point reduction from baseline. Leerink analysts note that if a two-point reduction in MG-ADL score had been used as the threshold for response in the China trial, the rate would have been 65.7% for batoclimab. A subcutaneous form of Vyvgart was approved for adults with MG in 2023. Another FcRn blocker, such as UCB’s Rystiggo is also approved for adults. Meanwhile, Johnson & Johnson said in July 2024 that its FcRn inhibitor nipocalimab had generated a 4.7-point drop on the MG-ADL in its Phase 3 trial, significantly more than the 3.3 points seen with placebo. Other mechanisms are also being developed. Last September , Amgen’s anti-CD19 antibody Uplizna produced a significant reduction on MG-ADL of 4.2 points after six months, versus 1.9 points with placebo. Separately, Immunovant reported data on batoclimab in a Phase 2 chronic inflammatory demyelinating polyneuropathy (CIDP) trial but said it would not seek approval for the drug in this disease either. Editor’s note: This is an evolving story and will be updated.