Dianthus launches Phase 2 trial to test DNTH103 in generalized MG
Start of MaGic trial follows positive topline data from Phase 1 study
Dianthus Therapeutics is launching a Phase 2 clinical trial to test its experimental therapy, DNTH103, in people with generalized myasthenia gravis (gMG).
Called MaGic, the trial is expected to enroll up to 60 people with gMG who are positive for antibodies that target the acetylcholine receptor (AChR), the most common type of MG-driving antibody.
Participants will be randomly assigned to receive a placebo or DNTH103 for 12 weeks, or about three months. All the participants will then be treated with DNTH103 for about a year in an open-label extension phase. DNTH103 is injected under the skin, or subcutaneously, every other week after an initial loading dose.
The study’s main goal is to assess DNTH103’s safety and tolerability. Its impact on measures of disease severity and quality of life will also be assessed. Topline results are expected in the second half of 2025.
In MG, the immune system produces antibodies that erroneously target proteins involved in nerve-muscle communication. When the disease-driving antibodies interact with the proteins, a group of immune proteins called the complement cascade is activated, which further contributes to the damaging autoimmune response in MG.
The complement cascade normally helps defend the body against infections. There are three general pathways that can be used to activate the complement system — the classical, alternative, and leptin pathways. In MG, disease-driving complement activation occurs mainly through the classical pathway.
What does DNTH103 do in gMG?
DNTH103 is designed to block the classical complement pathway’s activation by inhibiting the active form of a complement protein called C1s. Because DNTH103 doesn’t block the alternative or leptin pathways, it offers disease control with less risk of infection over medicines that block all complement pathways, according to Dianthus.
“DNTH103 provides a unique approach to complement inhibition in gMG, which could result in a more convenient and safer alternative for patients versus current options,” Simrat Randhawa, MD, Dianthus’ chief medical officer, said in a company press release.
“For patients with AchR-positive gMG, inappropriate activation of the complement classical pathway is a major driver of disease pathology and therefore patient symptoms,” said Mazen M. Dimachkie, MD, a professor at the University of Kansas Medical Center. “I am excited to collaborate with Dianthus to evaluate this investigational, highly specific classical pathway inhibitor that could fill the need for a more convenient and safe complement inhibitor for my gMG patients.”
The launch of the Phase 2 MaGic study follows the announcement of positive topline data from a Phase 1 study in healthy volunteers, which indicated DNTH103 could specifically block the classical complement pathway as intended.
DNTH103 has a relatively long half-life, making it a promising candidate for use as a long-term therapy, pharmacological data showed. Half-life refers to the time it takes for the levels of a compound or medicine to drop to half that originally administered. The longer the half-life, the longer a compound remains in circulation in the body.
“Following our encouraging Phase 1 data demonstrating a 60-day half-life and potent, specific classical pathway inhibition, we are excited to rapidly advance DNTH103, our investigational active C1s inhibitor, into a Phase 2 study in generalized myasthenia gravis,” Randhawa said.
About the Author
