Longer-acting experimental MG treatment shows promise in early trial
VRDN-008 sustainably reduced levels of key class of antibodies
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VRDN-008, Viridian Therapeutics' investigational treatment for myasthenia gravis, sustainably reduces levels of a class of antibodies that includes those driving MG, according to trial results. (Photo from iStock)
- The experimental MG treatment VRDN-008 successfully reduces disease-relevant antibodies with an extended half-life.
- These findings in healthy volunteers support potential dosing every eight weeks.
- Next steps include launching a registrational clinical trial in mid-2027 to further evaluate VRDN-008.
VRDN-008, Viridian Therapeutics’ investigational under-the-skin treatment for myasthenia gravis (MG), sustainably reduces levels of a class of antibodies that includes those driving MG and has the potential for once-every-other-month dosing.
That’s according to data from a Phase 1 clinical trial testing the therapy in healthy volunteers. Results also showed that VRDN-008’s half-life, the time it takes for drug levels in the body to fall by half, was up to six times longer than other currently approved therapies for MG that, like VRDN-008, belong to a treatment class called FcRn inhibitors.
“Today’s VRDN-008 data exceeded expectations and demonstrates a potentially transformative FcRn-inhibitor profile,” Steve Mahoney, Viridian’s president and CEO, said in a company press release. “Based on these data, we believe VRDN-008 dosed … every 8 weeks can deliver deep and sustained [antibody] reductions and could provide patients a potential best-in-class option for extended disease control and convenience.”
Meanwhile, Viridian plans to launch a registrational trial next year to evaluate VRDN-008 in people with MG. A registrational trial is meant to generate robust data that, if positive, can support an application for the therapy’s approval.
“We plan to advance VRDN-008 rapidly into registrational development starting with MG in mid-2027, pending feedback from regulatory authorities,” Mahoney said.
VRDN-008 designed to block specific protein
MG is an autoimmune disease in which self-reactive antibodies, also called autoantibodies, interfere with communication between nerves and muscles, which causes muscle weakness. These MG-driving antibodies belong to an antibody family called immunoglobulin G, or IgG.
VRDN-008, administered via under-the-skin injection, is designed to block FcRn, a protein that helps stabilize IgG antibodies in the bloodstream. By suppressing FcRn, the therapy is expected to lower IgG levels, including MG-driving ones, thereby reducing autoimmune attacks and easing MG symptoms.
While other FcRn inhibitors are currently approved for MG, VRDN-008 has an extended half-life, meaning it remains active in the bloodstream longer, which can reduce the number of treatments given over time while maintaining efficacy.
In the Phase 1 study, healthy volunteers received two doses of VRDN-008, one at the start of the study and one at week four.
Data showed that VRDN-008 had a half-life of 15 to 18 days, up to six times longer than first-generation FcRn inhibitors, according to Viridian. IgG reduction was deep and sustained through eight weeks after dosing, with a maximum reduction of 74%. These data support the potential for dosing every eight weeks, the company said.
Beyond MG, there are multiple autoantibody-mediated autoimmune diseases where we believe that we can develop VRDN-008, including several that are clinically validated for FcRn inhibition.
Regarding safety, VRDN-008 was not associated with substantial changes in blood levels of albumin, a major blood protein, and low-density lipoprotein (LDL), a fatty molecule commonly known as “bad cholesterol.” FcRn also typically preserves albumin in circulation, and a reduction in albumin levels can result in an increase in LDL levels.
The treatment was generally well tolerated, with no serious adverse events or dose-limiting toxicities, which are side effects severe enough to prevent a dose from being increased or continued.
The planned MG trial will test two dosing schedules for VRDN-008, one every four weeks and one every eight weeks, against a placebo in people with MG. The company said that this design supports a direct-to-registration path toward an approval application.
Viridian plans to deliver VRDN-008 using Enable enFuse, a hands-free, on-body injector developed by Enable Injections. The device operates with a single push of a button and is intended for at-home self-administration. Viridian licensed exclusive global rights to enFuse for FcRn-targeted therapies in January 2023.
Viridian will also develop VRDN-008 as a potential treatment for other autoimmune diseases.
“Beyond MG, there are multiple autoantibody-mediated autoimmune diseases where we believe that we can develop VRDN-008, including several that are clinically validated for FcRn inhibition,” Mahoney said.
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