Global trial of telitacicept for Sjögren’s doses first patient ‘within weeks’
UPSTREAM SjD to test safety, effectiveness of injection therapy in adults
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The first patient has been dosed in a newly launched global clinical trial evaluating the safety and effectiveness of telitacicept, given as subcutaneous, or under-the-skin, injections, in adults with primary Sjögren’s disease.
The Phase 3 study, dubbed UPSTREAM SjD (NCT07404865), will test the therapy, in an estimated 250 people, ages 18 to 75, with active Sjögren’s. Recruitment is so far ongoing at multiple sites in the U.S. The trial is intended to be registrational, meaning that if the results are positive, they could support the filing of an application seeking the therapy’s approval.
Telitacicept, originally developed by Remegen, is already under review by Chinese regulators for the treatment of Sjögren’s. To date in the Asian nation, it’s been approved for other autoimmune diseases, such as myasthenia gravis, lupus, and rheumatoid arthritis.
Remegen also has entered into an exclusive licensing agreement with Vor Bio, granting that company the rights to develop and commercialize the therapy outside of China, Hong Kong, Macau, and Taiwan.
“Over the past six months, Vor Bio repositioned the company around telitacicept and moved quickly to build momentum,” Jean-Paul Kress, MD, CEO and chairman of Vor Bio, said in a company press release announcing its latest financial results and business updates. Kress said such momentum was “critical” as the company moves forward with global development of its lead candidate.
“In the first [three months of the year], we initiated our global Phase 3 trial in primary Sjogren’s disease and subsequently dosed our first patient within weeks,” Kress noted.
The trial expects to ultimately test the therapy at sites across North America, Latin America, Europe, and the Asia-Pacific region, according to a program webpage.
Sjögren’s occurs when the immune system mistakenly produces self-reactive antibodies that attack healthy tissues, most often the body’s moisture-producing glands, such as the tear and salivary glands.
Symptoms often include persistent dry mouth and dry eyes, as well as fatigue and pain. In more severe cases, the disease can also affect internal organs such as the kidneys and lungs.
Sjögren’s is classified as primary when it is not associated with another underlying condition. There are no approved disease-modifying therapies for Sjögren’s, and available treatments focus on symptom management.
Telitacicept targets signaling molecules key in Sjögren’s
Telitacicept, also known as RC18, is designed to block two signaling molecules — B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) — that are critical for the maturation and survival of B-cells.
These are the type of immune cell that produces not only antibodies to help fight infections, but also self-reactive antibodies that contribute to autoimmune disorders such as Sjögren’s. By suppressing these proteins, telitacicept is expected to reduce the number of mature B-cells and help ease the autoimmune attacks that drive the disease.
In Sjögren’s, telitacicept has been evaluated in a Remegen-sponsored Phase 2 clinical trial (NCT04078386) in China involving 42 adults with active disease who received either one of two doses of the investigational therapy or a placebo. That trial tested doses of 160 mg and 240 mg against the placebo, with dosing weekly for 24 weeks, or nearly six months.
The results showed that telitacicept’s lower dose was significantly superior to the placebo at reducing disease severity, as measured by the standard European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity (ESSDAI). ESSDAI evaluates the impact of Sjögren’s across multiple organ systems, with higher scores indicating greater disease activity.
Both doses also led to significant reductions in fatigue as well as in blood antibody levels, in line with the therapy’s suppressive effects on B-cells.
These findings were reinforced in a larger, China-based Phase 3 study (NCT05673993) involving 381 adults with active primary Sjögren’s who were positive for anti-SSA antibodies, a type of self-reactive antibody commonly associated with the disease.
After 24 weeks of weekly treatment, telitacicept at doses of 80 mg or 160 mg significantly reduced disease activity compared with a placebo, meeting the trial’s primary goal. The higher dose was associated with a greater ESSDAI score drop. Participants treated with the higher dose also showed statistically significant and clinically meaningful reductions in fatigue, data showed.
Observed benefits were sustained through 48 weeks, or nearly a year, of treatment. Overall, telitacicept was safe and well tolerated, according to the developer.
Developer now seeking therapy’s approval in China
Based on these positive results, Remegen filed an application with regulators in China seeking approval of telitacicept for Sjögren’s.
In UPSTREAM SjD, adults with active primary Sjögren’s who are positive for anti-SSA antibodies will be randomly assigned to receive either telitacicept (160 mg) or a placebo. The study’s primary goal is to assess changes in ESSDAI scores after 48 weeks of treatment.
Secondary goals include changes in other measures of disease activity, including the EULAR Sjögren’s syndrome patient reported index (ESSPRI), a patient-reported measure of symptom severity. Changes in glandular function and fatigue are other secondary goals.
“We are seeing strong engagement from key opinion leaders and principal investigators, which is critical as we advance the global development of telitacicept,” Kress said.
Per the release, current funding “supports telitacicept global clinical development.”
