Claseprubart shows good safety, signs of effectiveness in gMG trial
Developer planning to meet with FDA, launch Phase 3 study
Treatment with the experimental injection therapy claseprubart (DNTH103) was well tolerated and appeared to ease symptoms of generalized myasthenia gravis (gMG) in a Phase 2 clinical trial involving people with the autoimmune neuromuscular condition.
That’s according to top-line data announced by the therapy’s developer Dianthus Therapeutics. The new data support claseprubart’s “potential best-in-class profile” as a treatment for gMG, the company said in a press release.
Dianthus is now preparing to meet with the U.S. Food and Drug Administration (FDA) to go over these results, as well as plans for a Phase 3 trial, which the company said it hopes to launch next year.
“We are planning for an end-of-Phase 2 meeting with the FDA to align on the proposed design of a Phase 3 trial for claseprubart in myasthenia gravis,” said Marino Garcia, Dianthus’ president and CEO, who also noted “encouraging early data” from the study’s open-label extension.
Garcia added that the Phase 2 results “mark a significant milestone for Dianthus and are an important step forward for people living with gMG.”
MG is caused by antibodies that interfere with the communication between nerve and muscle cells, leading to symptoms like muscle weakness and fatigue. When MG-driving antibodies bind to their target, they can activate a part of the immune system called the complement cascade, which further contributes to the damaging autoimmune responses that drive MG.
Claseprubart is a monoclonal antibody that’s designed to block the activation of the complement cascade by targeting the active form of a protein called C1s.
No patients given claseprubart developed serious bacterial infections
The Phase 2 MAGIC clinical trial (NCT06282159) tested claseprubart in adults with gMG. The study, launched in early 2024, enrolled 65 people with gMG, ages 18-75, who were positive for the most common type of MG-driving antibody targeting the acetylcholine receptor (AChR).
Participants were randomly assigned to receive either claseprubart or a placebo for 13 weeks, or about three months. After an initial loading dose administered by an intravenous, or into-the-vein, infusion, participants were given one of two doses of claseprubart — 300 or 600 mg — or a placebo. All were given via a subcutaneous, or under-the-skin, injection every other week.
This initial period was followed by an ongoing open-label extension, in which all eligible participants are given claseprubart for up to 52 weeks, or one year. The extension study is expected to run through 2027.
The study’s main goal was to assess the treatment’s safety and tolerability, and those results were positive: No serious side effects related to claseprubart were reported, according to Dianthus.
Injection site reactions were rare and generally mild, and none of the patients given claseprubart discontinued the treatment due to side effects. The company also noted that none of the patients given claseprubart experienced serious bacterial infections, which can be a concern with therapies that suppress the immune system.
Better scores seen with therapy vs. placebo on MG severity scales
Although the Phase 2 study was not designed to evaluate efficacy, the researchers examined how claseprubart treatment affected scores on standard measures of MG severity, namely the MG Activities of Daily Living (MG-ADL) and the Quantitative MG (QMG) scales.
Analyses showed that, by the end of the initial part of the trial, scores on both these scales improved significantly more with claseprubart than with the placebo. Specifically, with the low dose, an increase of 1.8 points was seen on the MG-ADL, with a gain of 2.4 points on the QMG. With the higher, a gain of 2.6 points was seen on the MG-ADL, with an increase of 2.5 points on the QMG.
The consistent and meaningful treatment effect seen in both treatment arms across multiple standard MG efficacy metrics in this Phase 2 trial gives me and my team great confidence in our ability to execute a successful Phase 3 trial.
According to Dianthus, a statistically significant effect on both MG-ADL and QMG scores was evident within a week of starting treatment. The company also said that “statistically significant and clinically meaningful” improvements in other measures of disease severity were seen in patients given the lower dose of claseprubart.
“The consistent and meaningful treatment effect seen in both treatment arms across multiple standard MG efficacy metrics in this Phase 2 trial gives me and my team great confidence in our ability to execute a successful Phase 3 trial,” said Simrat Randhawa, MD, chief medical officer at Dianthus.
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