Global clinical trial launches to test self-given, long-acting gMG drug
Developer says positive findings could support regulatory approval filings
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- A new global trial involving nearly 200 people with generalized myasthenia gravis will test the self-administered injection therapy claseprubart.
- The experimental treatment, designed to require less frequent dosing, aims to reduce muscle weakness and fatigue in gMG.
- Positive results from this Phase 3 trial could lead to regulatory submissions seeking the treatment's approval.
Dianthus Therapeutics has launched a global, late-stage clinical trial to evaluate the safety and effectiveness of its self-administered injection therapy claseprubart versus a placebo in people with generalized myasthenia gravis (gMG).
The Phase 3 study, dubbed EMERGE (NCT07647510), is expected to enroll an estimated 195 adults with gMG and self-reactive antibodies targeting the acetylcholine receptor (AChR) protein — the most common type of MG-causing antibodies.
In MAGIC (NCT06282159), an earlier Phase 2 trial that was also placebo-controlled, claseprubart was found to be safe and effective in easing symptoms in people with gMG. EMERGE is designed to confirm those benefits and provide robust results that, if positive, may support an application for the treatment’s approval. Top-line results are anticipated in the second half of 2028, according to the company.
“Given the impressive Phase 2 MG results, the medical team has been eagerly anticipating the initiation of this important study and the opportunity to implement important Phase 2 learnings,” Simrat Randhawa, MD, Dianthus’ executive vice president and head of research and development, said in a company press release. “Our internal enthusiasm has been matched by site and principal investigator interest globally so far.”
Dianthus called claseprubart a “highly potent” therapy with “best-in-disease, pipeline-in-a-product potential” for treating gMG.
An autoimmune neuromuscular disorder, gMG is driven by self-reactive antibodies that mistakenly target proteins, most commonly AChRs, needed for nerve-muscle communication. This leads to muscle weakness across several parts of the body, as well as fatigue and other symptoms.
The binding of anti-AChR antibodies to their target promotes activation of the classical pathway of the complement cascade, a part of the immune system, contributing to MG-related damage.
Claseprubart designed to require less frequent dosing
Claseprubart, formerly known as DNTH103, is an antibody-based therapy that specifically blocks the active form of the complement protein C1s, thereby reducing activation of the classical complement pathway. This is expected to ease complement-mediated damage and disease symptoms.
The therapy received orphan drug designation in the U.S. for the treatment of myasthenia gravis (MG), which is expected to speed its clinical development.
Self-administered via a subcutaneous, or under-the-skin, injection, claseprubart was designed to stay in the body for longer periods, thus allowing less frequent dosing. In clinical trials, it is being tested as subcutaneous injections every two or four weeks, following an initial intravenous, or into-the-vein, loading dose.
The previous MAGIC trial tested two claseprubart doses — 300 mg or 600 mg — against a placebo in 65 adults with gMG and anti-AChR antibodies. Three-month data demonstrated that both claseprubart doses were generally well tolerated, and significantly reduced disease severity relative to the placebo.
Still, the low dose, but not the high dose, was significantly superior to the placebo in all five key efficacy measures. These included the MG Activities of Daily Living (MG-ADL) scale, which assesses the disease’s impact on daily life activities, and the Quantitative MG (QMG) scale, used to evaluate muscle weakness.
Participants who completed the three-month placebo-controlled portion could enter the trial’s open-label extension part, in which all are receiving the treatment for up to one year. Early pharmacological data from this part also supported the selection of the lower 300 mg dose for the Phase 3 trial.
EMERGE trial will test gMG treatment vs. a placebo
In the newly launched EMERGE study, participants are being randomly assigned to receive either claseprubart or a placebo for about four months. The treatment regimen involves an initial loading dose of claseprubart, followed by 300 mg doses administered every two or four weeks.
Dianthus has stated that the trial will be “multicenter” and “global,” but has not yet announced the study locations or provided enrollment information.
The study’s main goal is to assess whether the therapy is superior to the placebo at reducing scores on the MG-ADL scale, indicating less severe disease. Secondary goals include changes in muscle weakness, as assessed with the QMG scale, and in disease severity, evaluated with the MG Composite Scale.
The trial will also look at any changes in participants’ life quality using the MG Quality of Life 15-item Revised questionnaire.
Researchers will also assess the proportion of participants reaching minimal symptom expression, defined as an MG-ADL score of zero or one, indicating no symptoms to minimal ones, without the need for rescue therapy.
After completing the study’s placebo-controlled portion, participants may enter its extension period, during which all will receive claseprubart for up to two years, or 104 weeks.
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