Approved MS therapy found in clinical trial to ease disease severity in MG

Ublituximab-xiiy, an approved medication for certain types of multiple sclerosis (MS), was shown to safely and effectively reduce disease severity in people with myasthenia gravis (MG) who have self-reactive antibodies against the acetylcholine receptor (AChR) protein.

That’s according to new data from an early-stage clinical trial that tested the MS therapy, sold under the brand name Briumvi, in 11 people with MG. The researchers noted that, while the approved formulation of ublituximab-xiiy is administered intravenously, or directly into the bloodstream, the MG trial tested a subcutaneous, or under-the-skin, formulation that’s also under investigation for use in MS.

In the small MG trial, use of the MS therapy was shown to improve scores on a disease impact scale, indicating an easing of symptoms.

“These encouraging results support continued development of Briumvi in MG and also mark an important milestone in expanding the potential utility of Briumvi beyond Multiple Sclerosis,” Michael S. Weiss, chairman and CEO of TG Therapeutics, the therapy’s developer, said in a company press release announcing the positive top-line data.

The company also announced the start of a Phase 2 clinical trial testing ublituximab-xiiy as a maintenance therapy for MG. While no details on study site locations were provided, if successful, the trial could potentially support regulatory applications to expand the therapy’s label to include MG.

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People with MG typically produce self-reactive antibodies that target proteins, most commonly AChR, that are important in the communication between nerves and muscles. This causes symptoms such as muscle weakness and fatigue.

There are a variety of approved MG treatment options, which primarily aim to reduce these autoimmune attacks. One strategy is to reduce levels of B-cells, the immune cells that produce antibodies, including those involved in MG.

Similar therapies used for treating MS and MG

Similar strategies are common in other autoimmune conditions, including MS, a neurodegenerative disease. Ublituximab-xiiy is an intravenous B-cell-depleting therapy approved for certain forms of MS. TG Therapeutics is also testing an injectable formulation of the therapy, as it could allow patients to self-administer the medication at home.

To evaluate whether ublituximab-xiiy could also help people with MG, TG Therapeutics launched a small Phase 1 clinical trial to test the subcutaneous formulation in 11 patients who tested positive for anti-AChRs antibodies.

The participants’ mean age was 74, and about three-quarters were men. Subcutaneous dosages were calibrated to match the therapy’s approved intravenous dose for MS.

Over 24 weeks, or nearly six months, the investigators measured disease severity with two validated scales: the Myasthenia Gravis Activities of Daily Living (MG-ADL) and the Quantitative Myasthenia Gravis (QMG).

The results showed score reductions across all outcome measures over time, indicating lower disease severity. Overall, the MG-ADL score dropped by a mean of 4.6 points, reflecting a lesser impact of MG symptoms on everyday activities.

Most participants (82%) had a clinically meaningful reduction, by at least two points, in the MG-ADL score, with this drop achieved after a median of 30 days.

The therapy’s safety profile was consistent with intravenous dosing in MS, according to TG Therapeutics.

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Developer now testing ublituximab-xiiy for MG in larger trial

Based on these results, the company has now launched a larger Phase 2 trial to evaluate the safety and effectiveness of ublituximab-xiiy in people with MG who have responded to Vyvgart (efgartigimod), a medication first approved in 2021 for treating generalized MG.

“We are … excited to initiate this potentially registration-directed Phase 2 study evaluating a novel sequential treatment approach in myasthenia gravis,” Weiss said. A registration-directed, or pivotal, study is designed to provide robust results that, if positive, can support applications for regulatory approval.

The study will involve an estimated 120 people with MG. During the trial’s first part, participants will receive four weekly infusions of Vyvgart, which promotes the destruction of circulating antibodies, including those driving MG, by blocking a protein called neonatal Fc receptor (FcRn).

Individuals who experience a clinically significant reduction in MG-ADL score will then be randomly assigned to receive either intravenous ublituximab-xiiy or a placebo for 24 weeks. This sequential design aims to test if ublituximab-xiiy can act as a maintenance therapy, extending the timeline for disease control among people who respond to Vyvgart.

“By combining the rapid clinical benefit associated with FcRn [blockage] with the durable disease control provided by B-cell depletion through Briumvi, we believe this strategy has the potential to establish a differentiated treatment paradigm in MG, while reducing the treatment burden associated with chronic FcRn therapy,” Weiss said.

According to TG Therapeutics, ublituximab-xiiy’s subcutaneous formulation will be introduced at a later stage, following completion of pharmacological studies underway in MS patients.

The trial’s primary goal is to measure the time until participants experience clinical worsening, defined as a MG-ADL score increase of two or more points, or a myasthenic crisis, a complication marked by severe breathing problems that typically requires hospitalization.

Participants completing the placebo-controlled portion will be eligible to enter an open-label expansion part in which all will receive the therapy for more than one year.

TG Therapeutics noted that it expects to present full results from the Phase 1 study at a future medical meeting.