Global trial testing oral Sjögren’s treatment seeking over 300 patients

A global clinical trial testing the safety and early effectiveness of MRT-6160, an oral treatment for Sjögren’s disease, is now recruiting an estimated 344 adults with the autoimmune condition.

The experimental therapy is designed to reduce the activity of two major types of immune cells that help drive Sjögren’s, ultimately aiming to ease disease symptoms.

The Phase 2a/b trial (NCT07737743), running across nine study locations, will assess the safety, tolerability, and efficacy of different doses of MRT-6160. Enrollment is underway at sites in the U.S., Canada, Australia, and Israel.

The study, sponsored by Novartis, is expected to run through March 2029, and its results will be used in selecting the most appropriate dose for a subsequent Phase 3 trial.

The launch of this mid-stage trial was announced by Monte Rosa Therapeutics, the therapy’s original developer. Last year, Novartis gained exclusive worldwide rights to develop, manufacture, and commercialize MRT-6160, and took responsibility for its clinical development, starting with Phase 2 trials. As per the agreement, Monte Rosa is eligible to receive as much as $2.1 billion in development, regulatory, and sales milestones.

“We are very pleased that Novartis is advancing MRT-6160 into clinical development for Sjögren’s disease by launching a global Phase 2 study,” Markus Warmuth, MD, CEO of Monte Rosa, said in a company press release that noted that a “milestone payment” will be made at the time of the trial’s first patient visit.

“Sjögren’s disease is not only an area of high unmet medical need, but also an indication driven by both [disease-causing] autoimmune T cells and B cells,” Warmuth said.

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Sjögren’s occurs when the immune system mistakenly launches inflammatory attacks against the body’s own tissues, particularly the glands that produce tears and saliva. This leads to its hallmark symptoms of dry eyes and dry mouth — though the disease often also affects other parts of the body.

B-cells, which produce antibodies, and T-cells, which help coordinate the immune response, are thought to contribute to the autoimmune responses that drive Sjögren’s.

MRT-6160 already tested in healthy volunteers

MRT-6160 (DDY391), a type of therapy called a molecular glue degrader, is designed to specifically tag for destruction VAV1, a key signaling protein involved in T- and B-cell activation.

By eliminating VAV1, the experimental oral therapy is expected to reduce the activity of both T- and B-cells, which, in turn, can potentially ease disease activity and symptoms in people with Sjögren’s.

Before handing clinical development over to Novartis, Monte Rosa sponsored a Phase 1 clinical trial (NCT06597799) that tested single and multiple ascending doses of MRT-6160 in more than 70 healthy volunteers.

That trial’s main goal was to assess the therapy’s overall safety and tolerability. The researchers also examined whether MRT-6160 could successfully eliminate VAV1 and affect immune cell activity.

The results showed that MRT-6160 led to sustained, dose-dependent VAV1 breakdown, of more than 90%, in T-cells circulating in the blood after single and multiple doses, with similar effects seen in B-cells. Treatment also reduced the activation of both immune cell types. The treatment was generally well tolerated, with no serious adverse events reported.

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New trial will look for treatment benefits in Sjögren’s patients

The newly launched Phase 2a/b trial will test whether these biological effects can translate into benefits for people with Sjögren’s.

Eligible participants will be randomly assigned to receive either one of three doses of MRT-6160 or a placebo for up to 52 weeks, or about one year. After 24 weeks, or about six months, participants originally assigned the placebo will switch to MRT-6160 for the remainder of the study.

In the study’s parts A and B, the main goal is to determine whether MRT-6160 can reduce overall Sjögren’s activity after 24 weeks, as measured by the EULAR Sjögren’s Syndrome Disease Activity Index. Part C will focus primarily on assessing changes in Sjögren’s symptoms reported by participants, using the EULAR Sjögren’s Syndrome Patient Reported Index.

All three parts will also evaluate the therapy’s safety and tolerability through week 52.

Together, the three parts are designed to show how different doses affect treatment response and help researchers select an appropriate dose for a subsequent Phase 3 study.

“We look forward to the continued development of MRT-6160, and to building on the momentum across our partnered and wholly owned pipeline as we work to bring meaningful new therapeutic options to patients,” Warmuth said.