Experimental therapy rapidly lowers disease activity in Sjögren’s trial
Phase 3 trial met its main goal, with improvements sustained through 48 weeks
Written by |
Amgen’s experimental therapy dazodalibep led to rapid, sustained reductions in disease activity among adults with moderate-to-severe Sjögren’s disease in a global clinical trial, according to top-line data announced by the company.
“The results mark an important step forward for people living with Sjögren’s disease, a condition with significant unmet need and no approved systemic [body-wide] treatment options,” Jay Bradner, MD, Amgen’s executive vice president of research and development, artificial intelligence and data, said in a company press release.
Phase 3 trial tests dazodalibep in systemic Sjögren’s
The Phase 3 OASIZ 301 trial (NCT06104124) enrolled more than 650 people with systemic Sjögren’s who had moderate-to-severe disease activity, defined as a score of 5 or higher on the European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index (ESSDAI), a tool used to measure disease activity across organ systems.
Participants were randomly assigned to receive one of two doses of dazodalibep or a placebo. The trial’s main goal was to evaluate changes in ESSDAI scores after 48 weeks (nearly one year).
According to Amgen, top-line results showed a “statistically significant and clinically meaningful improvement at Week 48” in ESSDAI scores with dazodalibep. Improvements were seen as early as week 4 and sustained through week 48.
“The rapid and sustained improvement observed in systemic disease activity reinforces our confidence in dazodalibep and the broader Phase 3 program as we work to deliver a new, highly differentiated option for people living with this debilitating autoimmune disease,” Bradner said.
Ghaith Noaiseh, MD, the trial’s lead investigator at the University of Kansas Medical Center, said the results “provide further support for dazodalibep as an emerging treatment for improving systemic disease activity and represent an important advance for the field.”
The most common adverse events reported more often with dazodalibep than placebo were the common cold, urinary tract infection, high blood pressure, and infusion-related reactions. These events were generally mild to moderate in severity. Discontinuations due to adverse events were uncommon and occurred at similar rates across treatment groups.
Amgen did not report further details from the OASIZ 301 trial results, noting that detailed findings will be presented at an upcoming scientific meeting.
A second, global Phase 3 study, called OASIZ 303 (NCT06245408), is testing dazodalibep against a placebo in more than 400 Sjögren’s patients who have low systemic disease activity — an ESSDAI score below 5 — but still experience substantial symptoms. That study is expected to wrap up before year’s end.
Sjögren’s can affect multiple systems throughout the body
Sjögren’s is an autoimmune disorder typically marked by inflammation in the tear and salivary glands. But it can also affect other parts of the body, leading to a wide range of symptoms.
“Sjögren’s disease is a complex and [variable] autoimmune disease, and no two people experience it in exactly the same way,” said Janet E. Church, president and CEO of the Sjögren’s Foundation. “It can be relentless, creating a real burden for people living with the disease and affecting their quality of life.”
There are currently no treatments specifically approved for Sjögren’s in the U.S.
Dazodalibep is designed to reduce immune activity involved in Sjögren’s by blocking a protein called CD40 ligand (CD40L), which is found on the surface of immune cells called T-cells.
Normally, CD40L on T-cells binds to a receptor called CD40 on other immune cells, including B-cells. This interaction helps stimulate B-cells, and the CD40L-CD40 pathway is overactive in Sjögren’s. By blocking the interaction between CD40L and CD40, dazodalibep is expected to reduce autoimmune activity and ease disease activity and symptoms.
Dazodalibep was originally developed by Horizon Therapeutics, which was acquired by Amgen in 2023.
“The Sjögren’s Foundation welcomes continued progress in research that expands the possibilities for people living with Sjögren’s disease and moves us toward a future with more treatment options and better care,” Church said.
Leave a comment
Fill in the required fields to post. Your email address will not be published.