Telitacicept shows promise for primary Sjögren’s in Phase 3 trial
Treatment safely and effectively eased disease activity, data show
Telitacicept safely and effectively eased disease activity in adults with primary Sjögren’s disease, according to data from a now-complete Phase 3 clinical trial conducted in China.
Because the trial met its primary goal, developer Remegen plans to ask China’s regulator, the Center for Drug Evaluation of the National Medical Products Administration, to approve the drug, according to a company press release.
The U.S. Food and Drug Administration recently granted Remegen permission to launch a global, multicenter Phase 3 trial to test telitacicept in people with Sjögren’s. The agency also awarded the therapy fast-track designation for the disease, a status meant to accelerate the treatment’s development and regulatory review.
Sjögren’s is caused by the abnormal production of self-reactive antibodies that attack healthy tissue, most often the tear and salivary glands. Beyond symptoms of persistent dry mouth and dry eyes, the disease can cause pain and fatigue, and in more severe cases, affect internal organs, like the kidneys and lungs. The disease can be classified as primary when found on its own and secondary when associated with an underlying condition.
Research indicates that the overactivation of self-reactive B-cells, the immune cells that produce antibodies, drives the inflammatory attacks in Sjögren’s.
Treatment suppresses proteins to ease autoimmune attacks
Telitacicept combines fragments from two proteins: TACI and an antibody type called immunoglobulin G. Together, they block two signaling molecules, B Lymphocyte Stimulator (BLyS) and A Proliferation-Inducing Ligand (APRIL), that are involved in the inflammatory activation of immune cells, particularly B-cells.
By suppressing these proteins, telitacicept is expected to reduce the growth and maturation of self-reactive B-cells, thereby easing the autoimmune attacks that drive Sjögren’s.
The therapy, administered as an under-the-skin injection, was conditionally approved in China in 2021 for people with the autoimmune disease lupus, and has been recommended in several authoritative guidelines for off-label use in Sjögren’s.
Telitacicept was evaluated in a Remegen-sponsored Phase 2 trial (NCT04078386), in which 42 people with primary Sjögren’s were randomly assigned to receive telitacicept at one of two doses (160 or 240 mg) or a placebo, given weekly for 24 weeks, or about six months.
Final data showed that telitacicept significantly reduced disease activity compared with the placebo, as assessed with the European League Against Rheumatism’s Sjögren’s syndrome disease activity (ESSDAI) scores. ESSDAI is a standardized measure of disease activity that assesses symptoms across different bodily systems.
In addition to meeting the trial’s main goal, the treatment significantly reduced fatigue as well as antibody levels in the bloodstream, which was consistent with the therapy’s mechanism of action to mitigate B-cell activity.
The now-completed Phase 3 study (NCT05673993) evaluated the safety and efficacy of two doses of telitacicept (80 mg and 160 mg) against a placebo in 381 adults, ages 18-79, with primary Sjögren’s disease. Participants received their assigned treatment given once a week for up to 48 weeks (nearly one year).
The trial’s main goal was to assess changes in ESSDAI scores after 24 weeks. Secondary goals included ESSDAI score changes after 48 weeks, percentage of participants achieving specific score drops, changes in a validated measure of fatigue, and frequency of adverse events and serious adverse events.
The newly announced results showed that after 24 weeks of treatment, telitacicept effectively and sustainably reduced disease activity versus the placebo, as demonstrated by significant changes in ESSDAI scores. The therapy was also generally safe and well tolerated, according to Remegen.
The company did not specify the magnitude of change in ESSDAI scores or the difference in score change between telitacicept and placebo groups, or provide details on the therapy’s safety profile in its announcement. The company said it will present detailed data “at major international academic conferences in due course.”
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