‘Exciting time for myositis’: Drug pipeline shifts from organ-centric to targeted therapy
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DESTIN, Fla. — Although new targets and therapies are on the horizon, current myositis treatment strategies rely on treating impacted organ groups, according to a speaker at the 2023 Congress of Clinical Rheumatology-East.
“I think it is a very exciting time for myositis,” Julie J. Paik, MDMHS, an associated professor of medicine at Johns Hopkins University School of Medicine, told attendees during the hybrid meeting. “There are multiple clinical trials on the front lines and in the pipeline.”
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The current treatment strategy for patients with myositis is largely dependent upon the involved organ systems for each individual patient.
“The first line will be glucocorticoids, and we usually do one milligram per kilogram,” Paik said. “It is really dependent upon, I think, the extent of disease activity, how high you are going to go.”
In addition to glucocorticoids, a second agent may be added, depending on the impacted organ groups. For example, patients with significant joint, skin and muscle involvement in their myositis may do well with methotrexate, while patients with lung, skin and muscle involvement may do better with azathioprine or mycophenolate mofetil, Paik said.
“There is really no head-to-head trial comparing these three standard-of-care medications,” Paik said. “We definitely need to draft some consensus guidelines.”
Specifically considering dermatomyositis, Paik mentioned ravulizumab, a monoclonal antibody that targets the complement C5 protein. “The mechanistic studies and the thought of why this drug could potentially work is that when you look at the muscle biopsies of patients with dermatomyositis, you see the C5-9 complement deposition, and this is also present in skin biopsies,” Paik said. “Hopefully we will have some more data about this.”
Regarding immune-mediated necrotizing myopathy, Paik noted FCRN inhibitors. Specifically, she called out efgartigimod (ArgenX).
“The new kind of pipeline of drugs are all these FCRN inhibitors that you have probably heard about in myasthenia gravis,” Paik said. “The proposed mechanism of action is basically blocking the FCRN portion of the immunoglobulin and, potentially, you are reducing the pathogenic autoantibodies.”
Finally, looking at inclusion body myositis, Paik called attention to ABC008 (Abcuro), a “first-in-class, humanized monoclonal antibody that binds to KLRG1” to deplete certain T cells, Paik said.
“This was presented at our global conference on myositis,” she said. “They even had evidence of improvement on targeted MRI as well, so this was very exciting for us.”
A phase 2 trial investigating the therapy is set to initiate in September, Paik said.
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Paik JJ. Current and new targets for treating myositis. Presented at The Congress of Clinical Rheumatology East; May. 4-7, 2023; Destin, Florida (hybrid meeting).
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