Dazodalibep therapy now in Phase 3 testing for Sjögren’s disease
Two studies underway, with one still recruiting participants
Two global Phase 3 clinical trials are now testing dazodalibep, Amgen’s experimental therapy for Sjögren’s disease, in two groups of adults. One of the studies is still recruiting participants.
One of the trials, called HZNP-DAZ-301 (NCT06104124), has completed enrollment of 651 people with moderate-to-severe systemic (body-wide) Sjögren’s disease. The second, HZNP-DAZ-303 (NCT06245408), is currently enrolling up to 435 participants with moderate-to-severe symptomatic burden and low systemic disease activity at more than 200 sites worldwide.
Both studies are comparing dazodalibep against a placebo to assess its safety and effectiveness. They are expected to be completed in 2026.
The announcement regarding the studies was made by Amgen in a company press release that also outlined its latest financial results and pipeline updates.
“With disciplined investment and a pipeline of first-in-class medicines, we’re focused on expanding access, advancing innovation, and sustaining long-term growth,” said Robert A. Bradway, Amgen’s chairman and CEO.
How the therapy works to calm autoimmune activity
Sjögren’s is caused by the abnormal production of self-reactive antibodies that primarily target the glands that produce tears and saliva. Symptoms include dry eyes and mouth, along with pain and fatigue. In more severe cases, it can also damage internal organs such as the kidneys and lungs.
Dazodalibep is a first-in-class experimental therapy originally developed by Horizon Therapeutics, which was acquired by Amgen. It is the first non-antibody fusion protein that blocks the CD40 ligand (CD40L) — a protein present at the surface of immune T-cells and key for their interaction with, and stimulation of, antibody-producing immune B-cells.
By blocking CD40L, dazodalibep prevents it from interacting with CD40. Considering Sjögren’s, like other autoimmune diseases, is marked by overactivation of the CD40L-CD40 pathway, dazodalibep is expected to reduce autoimmune responses and ease disease activity and symptoms.
In an earlier placebo-controlled Phase 2 clinical trial (NCT04129164), dazodalibep safely and effectively eased systemic disease activity and symptoms in people with Sjögren’s.
Benefits were observed in two groups — people with moderate-to-severe systemic disease (organ involvement) and those with mild systemic disease (no organ involvement) but experiencing moderate-to-severe symptoms.
Global studies will assess safety and symptom relief
In both ongoing Phase 3 trials, participants are randomly assigned to receive intravenous (into-the-vein) infusions of one of two dazodalibep doses or a placebo for about a year.
In the HZNP-DAZ-301 study, participants have moderate-to-severe systemic disease activity, defined as a score of five or higher on the European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI).
The main goal of this trial is to assess whether dazodalibep works better than a placebo at reducing disease activity, as measured by changes in the ESSDAI score.
The second trial, HZNP-DAZ-303, is recruiting people with mild systemic disease activity (ESSDAI score less than five), but moderate-to-severe symptoms, defined as a score of five or higher on the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). Eligible adults must also have residual salivary gland function.
The study’s main goal is to assess whether dazodalibep works better than a placebo at easing symptoms, as measured by the ESSPRI and the Diary for Assessing Sjögren’s Patient Reported Index.
Both trials will also evaluate dazodalibep’s safety and tolerability over a period of more than a year.
Participants who complete either Phase 3 trial can choose to enroll in the Phase 3 long-term extension study (NCT06747949), where all will receive dazodalibep for 132 weeks (about 2.5 years). The goal is to assess the treatment’s long-term safety and tolerability.
About the Author
