Enrollment complete in Phase 2 trial testing DNTH103 for gMG
Global MAGIC study assessing safety, early efficacy of Dianthus therapy
Enrollment is now complete for a Phase 2 clinical trial testing Dianthus Therapeutics‘ treatment candidate DNTH103 in people with generalized myasthenia gravis (gMG).
According to the developer, the initial results from the global study, dubbed MAGIC (NCT06282159), are expected by early fall.
MAGIC was launched early last year and is being conducted at 56 locations in North and South America, Europe, and Asia. It had aimed to enroll 60 people with gMG who were positive for antibodies against the acetylcholine receptor, the most common type of MG-causing antibody. Dianthus now reports the study exceeded its recruitment goals, with a total of 65 participants enrolled.
“We are pleased to have reached this important milestone in the development of DNTH103 for gMG,” Marino Garcia, CEO of Dianthus, said in a company press release. Garcia noted that “latest estimates indicate that the gMG market in the U.S. [alone] exceeds 100,000 patients.”
Top-line results of Phase 2 trial expected in September
Myasthenia gravis (MG) is driven by antibodies that disrupt the communication between nerve and muscle cells, leading to symptoms of muscle weakness and fatigue. In gMG, the disease can affect muscles throughout the body.
Antibodies are proteins made by the immune system to combat infections. But in autoimmune diseases like MG, antibodies mistakenly target the body’s own healthy tissues instead. When antibodies bind to their targets, they activate the complement system — a group of immune proteins that are normally present in the blood and other bodily fluids in an inactive state. When the complement system is activated, these proteins go on the attack to cause cellular damage, which contributes to disease activity in MG.
DNTH103 is designed to block the activation of the complement system by inhibiting the active version of a complement protein called C1s. Per Dianthus, the therapy is designed to be given mainly through a subcutaneous, or under-the-skin, injection, which is generally more convenient than intravenous infusions given directly into the vein.
By targeting C1S, DNTH103 is specifically intended to block the so-called classical pathway — one of the three pathways that can activate the complement system and is involved in MG. The company notes that, by blocking the classical pathway while leaving other complement pathways intact, DNTH103 is expected to ease MG disease activity without substantially impairing the body’s ability to fight off infections.
That could lead to added benefits for patients, Garcia noted.
“Despite currently approved treatment options, a significant unmet need exists for patients seeking continuous symptom control, lower risk for infections, and more convenient dosing and administration, which we believe DNTH103 has the potential to address as a first-line therapy,” Garcia said.
The Phase 2 MAGIC trial is currently assessing the safety, tolerability, efficacy, and pharmacological properties of DNTH103 in adults with gMG.
Despite currently approved treatment options, a significant unmet need exists for patients seeking continuous symptom control, lower risk for infections, and more convenient dosing and administration, which we believe DNTH103 has the potential to address as a first-line therapy.
Participants in MAGIC are being randomly assigned to receive either DNTH103 at a low or high dose, or a placebo. The first dose is given by an infusion into the bloodstream, with subsequent doses being given every other week by subcutaneous injection.
After completing the randomized part of the trial, which will last approximately three months, patients may be eligible to enter an open-label extension phase, in which all will receive DNTH103 for up to a year.
The study’s main goal is to evaluate the safety of DNTH103 after about three months of treatment. Changes in measures of gMG disease activity, including the MG Activities of Daily Living and the Quantitative MG scores, will also be assessed.
Top-line results are expected by September, per the developer.
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