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Living With Sjögren’s

Research Reports

Efficacy and Safety of Dazodalibep in Subjects with Sjögren's: Phase 2 Results

Currently there are no medications available for the treatment of Sjögren’s as a systemic inflammatory autoimmune disease that have been specifically approved for Sjogren’s. The medications which are commonly prescribed such as hydroxychloroquine and rituximab were developed for arthritis and other autoimmune diseases. As the medical community becomes better at recognizing symptoms and diagnosing patients, more drug options become available. In recent years, several pharmaceutical companies have attempted to develop medications for the management and treatment of Sjögren’s. This research report aims to expand on an new drug option that may come to market in the future. These are the results of a completed Phase 2 trial (NCT04129164) that were presented at the 2023 European Alliance of Associations for Rheumatology (EULAR) conference.

One of the front runners for the treatment Sjögren’s disease is Dazodalibep, Horizon Therapeutics’ experimental therapy that was found to ease disease activity and symptoms of Sjögren’s safely and effectively. Dazodalibep works by preventing the binding between a receptor protein present at the surface of antibody-producing immune B-cells, and its ligand present at the surface of immune T-cells. This mechanism blunts the immune response by reducing the autoimmune reaction that drives it.

A global Phase 2 trial tested Dazodalibep against a placebo in two populations of adults, aged 18-75, with a diagnosis of Sjögren’s. The first population included 74 patients with moderate-to-severe organ involvement, or systemic disease activity, as defined by a ESSDAI (EULAR Sjögren’s Syndrome Disease Activity Index) score >5 points. The second patient population comprised 109 individuals with no organ involvement, but moderate-to-severe symptoms as defined by a ESSPRI (EULAR Sjögren’s Syndrome Patient Reported Index) score >5 points.

All participants were randomly assigned to receive either Dazodalibep (1.5 mg) or a placebo for 24 weeks. After that, patients were switched to the other regimen (placebo or drug) for 16 weeks. Treatment in the first six months was given every other week for the first three doses and then once a month for four doses. In the remaining 16 weeks, patients received five doses once a month.

In the first population, six months of treatment was associated with a significantly greater drop, by 2.2 points, in the ESSDAI score — indicating lower disease activity — relative to the placebo group. Reported adverse events were generally mild-to-moderate (e.g., COVID-19, diarrhea, dizziness, ligament sprain, and upper respiratory tract infection) and similar in frequency between the treatment group and the placebo group.

In the second population, six months of treatment showed a greater drop, by 1.27 points, in the ESSPRI scores — reflecting a reduction in the severity of symptoms for those given Dazodalibep when compared to the placebo group. More specifically, a reduction in dryness (1.9 vs. 0.8 points), fatigue (1.7 vs. 0.3 points), and pain (1.8 vs. 0.4 points).

To date, Dazodalibep is the only therapy in development to have met the end points of a Phase 2 trial in both Sjögren’s patient populations. That said, it is important to acknowledge that like any systemic disease, Sjögren’s manifests differently in every patient. While dry eye and dry mouth are the most common symptoms, a proportion experience digestive symptoms or other extra-articular manifestations. Currently the best measures of Sjögren’s disease status, the ESSDAI and ESSPRI, do not account for other symptoms, nor are there potential treatment options. Thus, advocacy is needed to ensure that a variety of medications are rigorously developed and brought to market to treat an array of symptoms. As they often say in research, more work is needed!

Compiled by Ellen Wang