CHICAGO — Positive phase 3 trials for two drugs, telitacicept and ianalumab, showed promise for offering systemic treatment for Sjögren disease, rather than only symptom control.

Findings of both abstracts were presented at American College of Rheumatology (ACR) 2025 Annual Meeting.

Telitacicept is a novel fusion protein that targets and neutralizes BlyS (a B-lymphocyte stimulator) and APRIL (a proliferation-inducing ligand), whereas ianalumab is a fully human immunoglobulin G1 monoclonal antibody that depletes B cells through enhanced antibody-dependent cellular cytotoxicity and inhibits their activation and survival by blocking the B cell-activating factor receptor.

“They both show significant improvement” and “appear safe and effective,” Shailendra Singh, MD, a rheumatologist with Unity Health in Searcy, Arkansas, told Medscape Medical News. Singh, who was not part of either study, pointed out that telitacicept achieved its primary endpoint of change in European Alliance of Associations for Rheumatology (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) from baseline to 24 weeks while ianalumab achieved its primary endpoint of change in ESSDAI from baseline to 48 weeks.

These two drugs are among many in development, Singh said. “I’m happy that there has been an increased interest in treatment options. With new treatments we will be able to improve the symptoms and slow down the progression of the disease. Plus, if we are keeping inflammation under control, we are reducing the risk of lymphoma. Hopefully that’s the direction we are moving in.”

Telitacicept

In the telitacicept study, a total of 381 patients in China with active, anti-Sjögren syndrome-related antigen A-positive primary Sjögren disease were randomly assigned to get weekly injections of the biologic at 80 or 160 mg or placebo. Compared with placebo, both telitacicept 160 mg and 80 mg demonstrated consistent clinical symptom improvement through 48 weeks and mild side effects.

Greater improvements on the ESSDAI were seen with the telitacicept 160 mg dose. Researchers found that 71.8% of patients receiving the 160 mg dose had a ESSDAI reduction of least 3 points at 24 weeks compared with 19.3% of patients receiving placebo.

At week 24, the ESSDAI improved with a reduction of -4.4 with the 160-mg dose, -3.0 with 80 mg, and -0.6 with placebo. Improvement in ESSDAI at week 48 was -4.6 with 160 mg, -3.2 with 80 mg, and -0.4 with placebo.

The study author who presented the results, Lin Qiao, MD, of the Department of Rheumatology and Clinical Immunology at Peking Union Medical College Hospital, Beijing, China, told Medscape Medical News this was the first trial for a systemic treatment to reach phase 3 in China.

The trial also met all key secondary endpoints, including changes in ESSDAI and EULAR Sjögren Syndrome Patient Reported Index at 12, 24, 36, and 48 weeks. The telitacicept 160-mg dose reached highly significant P values (P < .0001) for every endpoint at week 24 and 48 compared with placebo.

Adverse reactions were “very mild,” Lin said, “such as respiratory infections and some injection site reactions. We did not find any new adverse events” since the phase 2 trial, she said.

Ianalumab

Two complementary phase 3 trials, called NEPTUNUS-1and NEPTUNUS-2, showed the safety and efficacy of ianalumab. They were 52-week, global, multicenter, randomized, double-blind, placebo-controlled studies.

“NEPTUNUS-1 and NEPTUNUS-2 are the first global, replicate phase 3 studies in Sjögren’s to meet their primary objective, showing a statistically significant improvement in ESSDAI,” said Thomas Grader-Beck, MD, associate professor of clinical medicine at Johns Hopkins University School of Medicine, Baltimore, who presented the results of the two trials in a late-breaking abstracts session. “The safety of ianalumab was favorable overall. Incidence of adverse effects and serious adverse effects were comparable to placebo in both studies.”

The primary endpoint was ESSDAI change from baseline at week 48 for ianalumab compared with placebo and it was met in both trials.

In the NEPTUNUS-1 trial of 275 patients who were randomly assigned to a subcutaneous injection of 300 mg ianalumab once monthly or placebo, the ianalumab group saw an ESSDAI score drop of -6.4 from baseline compared with a drop of -5.1 for the placebo group (P = .0496).

In NEPTUNUS-2 trial of 504 patients who were randomly assigned to a subcutaneous injection of 300 mg ianalumab once monthly or once every 3 months or placebo, the once-monthly ianalumab group averaged an ESSDAI score drop of -6.5 compared with -5.5 in the placebo group (P = .041). The ESSDAI score dropped -6.0 in the group that received ianalumab every 3 months, which was not statistically different from placebo.

The phase 3 trial of telitacicept was sponsored by RemeGen. Lin reported no relevant financial relationships, but several coauthors are employees of RemeGen.

NEPTUNUS-1 and NEPTUNUS-2 were sponsored by Novartis.

Grader-Beck reported being a consultant and steering board member with Novartis. Some coauthors are employees of Novartis, and others reported financial relationships with Novartis and other pharmaceutical companies.

Singh reported no relevant financial relationships.

Marcia Frellick is a Chicago-based, independent healthcare reporter and a regular contributor to Medscape.