AMGEN ANNOUNCES POSITIVE PHASE 3 RESULTS FOR DAZODALIBEP IN SJÖGREN'S DISEASE
Both dosing regimens reduced systemic disease activity versus placebo, while every-four-weeks dosing also improved patient-reported dryness.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Amgen (NASDAQ: AMGN) reported that both dazodalibep dosing regimens met the primary endpoint in its Phase 3 OASIZ-301 Sjögren's disease trial.
The 648-patient study measured systemic disease activity using ESSDAI, a disease activity score. At Week 48, scores fell 5.6 points with 1,500 mg every four weeks and 5.2 points with 3,000 mg every 12 weeks, versus 3.8 points with placebo; both differences were statistically significant. Effects appeared by Week 4 and persisted through Week 48. The every-four-weeks regimen also significantly improved patient-reported dryness. Additional analyses favored dazodalibep on symptom scores, response measures and salivary flow.
Common adverse events occurring more frequently than with placebo included infections, hypertension and infusion-related reactions, generally mild to moderate. Serious adverse events and discontinuations due to adverse events were balanced across treatment groups.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Positive
- Major point1,500 mg every four weeks reduced Week 48 ESSDAI scores 5.6 points versus 3.8 with placebo; adjusted p<0.001.
- Major point3,000 mg every 12 weeks reduced Week 48 ESSDAI scores 5.2 points versus 3.8 with placebo; adjusted p=0.010.
- Moderate pointEvery-four-weeks dosing improved Week 48 dryness versus placebo: ESSPRI difference −1.17 points; DASPRI difference −0.93; adjusted p<0.001 for both.
- Moderate pointWeek 48 ESSDAI responses of at least 3, 5 or 7 points occurred more frequently than with placebo.
- Moderate pointTotal ESSPRI and DASPRI symptom scores favored dazodalibep over placebo over 48 weeks.
- Moderate pointWeek 48 STAR composite responses, combining symptoms and objective disease measures, occurred more frequently than with placebo.
- Moderate pointStimulated salivary flow increased more with dazodalibep than with placebo.
7 minor points
- Minor pointDisease activity treatment effects appeared as early as Week 4 and persisted through Week 48.
- Minor pointTotal ESSPRI mean improvement exceeded 1.5 points with both dosing regimens.
- Minor pointESSDAI domain-level responses showed consistent improvement at Week 48 across reported systemic manifestations.
- Minor pointSafety comparisons showed balanced serious adverse events and adverse-event discontinuations across all three groups.
- Minor pointThromboembolic events and opportunistic infections showed no incidence imbalance; malignancy rates were low and comparable.
- Minor pointOASIZ-303 is evaluating dazodalibep in Phase 3 patients with high symptom burden and low systemic disease activity.
- Minor pointOASIZ-304 is evaluating long-term safety and tolerability in eligible OASIZ-301 and OASIZ-303 participants.
Negative
- Minor pointAdverse events at ≥5% incidence and higher rates than placebo included nasopharyngitis, urinary tract infection, hypertension and infusion-related reactions.
News Explained
Beyond OASIZ-301, Amgen says it is conducting OASIZ-303, a Phase 3 study in patients with high symptom burden and low systemic disease activity, and OASIZ-304, an open-label long-term safety and tolerability extension for eligible participants from both studies.
Key Figures
- ESSDAI reduction
- 5.6 points vs 3.8 for placebo; difference 1.8 points; adjusted p<0.001
- Week 48; 1,500 mg every four weeks
- ESSDAI reduction
- 5.2 points vs 3.8 for placebo; difference 1.4 points; adjusted p=0.010
- Week 48; 3,000 mg every 12 weeks
- ESSPRI dryness-domain difference
- −1.17 points; adjusted p<0.001
- Week 48; placebo-adjusted change from baseline, 1,500 mg every four weeks
- DASPRI dryness-domain difference
- −0.93 points; adjusted p<0.001
- Week 48; placebo-adjusted change from baseline, 1,500 mg every four weeks
- Study enrollment
- 648 patients
- OASIZ-301 Phase 3 study
Previous Clinical trial Reports
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OASIZ-301 topline met its primary endpoint with sustained Week 48 systemic disease improvement.
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Key Terms
double-blind technical
placebo-controlled technical
primary endpoint technical
least-squares mean technical
fusion protein technical
AI-generated analysis. How Rhea-AI works. Not financial advice.
Only Global Phase 3 Trial to Show Clinically Meaningful Improvements in Systemic Disease Activity and Patient-Reported Symptoms of Sjögren's Disease
"These Phase 3 results support dazodalibep's potential as a first-in-class treatment for Sjögren's disease and strengthen the clinical rationale for targeting CD40L-mediated immune signaling in these patients," said Jay Bradner, M.D., executive vice president, Research and Development, Artificial Intelligence and Data at Amgen. "In OASIZ-301, improvements in systemic disease activity were observed as early as Week 4 and sustained through Week 48. We look forward to building on these findings as we advance a broader Phase 3 program."
In the randomized, double-blind, placebo-controlled OASIZ-301 study, patients had a mean baseline score of 10.2 on the European Alliance of Associations for Rheumatology Sjögren's Syndrome Disease Activity Index (ESSDAI), which measures systemic disease activity. Both dazodalibep dosing regimens (1,500 mg every four weeks and 3,000 mg every 12 weeks) met the primary endpoint at Week 48, demonstrating statistically significant reductions in systemic disease activity compared with placebo, as measured by the ESSDAI score. The 1,500 mg every four weeks regimen (n=217) showed a least-squares mean reduction of 5.6 points from baseline in ESSDAI score, compared with 3.8 points for placebo (difference of 1.8 points; adjusted p<0.001). The 3,000 mg every 12 weeks regimen (n=217) showed a reduction of 5.2 points, compared with 3.8 points for placebo (difference of 1.4 points; adjusted p=0.010). A treatment effect with dazodalibep was observed as early as Week 4 and sustained through Week 48.
At Week 48, dazodalibep 1,500 mg every four weeks also significantly improved patient-reported dryness, a debilitating symptom of Sjögren's disease, compared with placebo. The placebo-adjusted least-squares mean differences in change from baseline were −1.17 points on the dryness domain of the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and −0.93 points on the dryness domain of the Diary for Assessing Sjögren's Patient Reported Index (DASPRI) (adjusted p<0.001 for both).
"Sjögren's disease is complex and heterogeneous. People may experience dry eyes and mouth, fatigue and joint pain, as well as systemic manifestations affecting organs such as the lungs, kidneys or nervous system, underscoring the complexity of recognizing and managing the disease," said Ghaith Noaiseh, M.D., associate professor of Medicine at the University of Kansas Medical Center and lead investigator of the study. "In OASIZ-301, both dosing regimens reduced systemic disease activity compared with placebo, and the every four weeks regimen also improved patient-reported dryness. These results are encouraging and represent important progress in our effort to better address patients' unmet needs."
The ACR presentation will also include additional OASIZ-301 analyses of systemic disease activity, patient-reported outcomes and oral dryness, including:
- At Week 48, greater proportions of patients receiving dazodalibep achieved clinically meaningful reductions of at least 3, 5 or 7 points on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) compared with placebo. These responder analyses show how many patients reached different levels of improvement in systemic disease activity and complement the average ESSDAI change.
- Over 48 weeks, total ESSPRI and DASPRI scores favored dazodalibep over placebo. Mean improvement in total ESSPRI exceeded 1.5 points with both dosing regimens, consistent with clinically meaningful improvement.
- Dazodalibep showed consistent improvement in ESSDAI domain-level responses at Week 48. These domains reflect some of the most common systemic manifestations, including constitutional, glandular, articular, lymphadenopathy, cutaneous, and biological.
- A greater proportion of patients receiving dazodalibep than placebo met the STAR response criteria at Week 48, a composite assessment that considers both patient-reported symptoms and objective measures of disease activity.
- Patients treated with dazodalibep showed greater increases in stimulated salivary flow, an objective measure of oral dryness, compared with placebo.
"For people living with Sjögren's disease, the need for new treatment options is significant, particularly given the wide-ranging and often debilitating impact of this disease," said Janet Church, president and chief executive officer, Sjögren's Foundation. "For our community, continued progress in research is important. The Sjögren's Foundation is encouraged by the momentum in Sjögren's research and hopeful that ongoing clinical development will lead to new treatment options that can help address the diverse needs of people living with Sjögren's disease."
The most common adverse events (≥
About Dazodalibep
Dazodalibep is a potential first-in-class CD40L antagonist fusion protein that is designed to target immune activation by disrupting interactions between T cells, glandular epithelial cells, B cells and other antigen-presenting cells. Dazodalibep is being studied in two Sjögren's disease patient groups: those with moderate-to-severe systemic disease and those with high symptom burden and low systemic disease who suffer from dryness, fatigue, and/or pain that profoundly impact daily life.
About OASIZ-301 and the Dazodalibep Development Program
OASIZ-301 is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of dazodalibep in patients with Sjögren's disease with moderate-to-severe systemic disease activity (ESSDAI ≥ 5) (n=648). The primary endpoint of the study is change from baseline in ESSDAI score at Week 48.
Key secondary endpoints evaluated dryness, tender and swollen joints, fatigue, and ESSDAI[5] response, defined as a decrease of at least 5 points from baseline.
Additionally, Amgen is conducting OASIZ-303, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of dazodalibep in patients with high symptom burden with low systemic Sjögren's disease activity. Amgen is also conducting OASIZ-304, an open-label, long-term extension study evaluating the long-term safety and tolerability of dazodalibep in eligible participants from OASIZ-301 and OASIZ-303.
About Sjögren's Disease
Sjögren's disease (SjD) is a heterogeneous autoimmune disease, where patients can experience persistent dryness, fatigue, and pain, often alongside systemic involvement that can be progressive. Although SjD is the second most common autoimmune rheumatic disease, it remains widely underrecognized, with the full extent of its systemic severity and debilitating symptomatic impact on patients' lives often underestimated. Despite this burden, there are currently no approved therapies for SjD, and many patients continue to experience persistent systemic disease activity and debilitating symptoms.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to fight some of the world's toughest diseases. Harnessing the best of biology and technology, Amgen reaches millions of patients with its medicines.
More than 45 years ago, Amgen helped establish the biotechnology industry at its U.S. headquarters in Thousand Oaks, California, and it remains at the cutting edge of innovation, using technology and human genetic data to push beyond what is known today. Amgen is advancing a broad and deep pipeline and portfolio of medicines to treat cancer, inflammatory conditions, rare diseases, heart disease and obesity and obesity-related conditions.
Amgen has been consistently recognized for innovation and workplace culture, including honors from Fast Company and Forbes. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, YouTube, Facebook, TikTok and Threads.
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FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
Did Amgen's dazodalibep meet the primary endpoint in OASIZ-301?
Both dosing regimens met the Week 48 primary endpoint for reducing systemic disease activity. ESSDAI scores fell 5.6 points with 1,500 mg every four weeks and 5.2 points with 3,000 mg every 12 weeks, compared with 3.8 points for placebo. The adjusted p-values were p<0.001 and p=0.010, respectively.
What did Amgen's OASIZ-301 trial show about dazodalibep and dryness?
Dazodalibep 1,500 mg every four weeks significantly improved patient-reported dryness versus placebo at Week 48. Placebo-adjusted differences in change from baseline were −1.17 points on the ESSPRI dryness domain and −0.93 points on the DASPRI dryness domain, with adjusted p<0.001 for both.
Which patients were enrolled in Amgen's OASIZ-301 dazodalibep trial?
OASIZ-301 enrolled patients with Sjögren's disease and moderate-to-severe systemic disease activity, defined by an ESSDAI score of at least 5. The randomized, double-blind, placebo-controlled study included 648 patients, whose mean baseline ESSDAI score was 10.2.