Horizon Phase 2 Trial Meets Primary Endpoint in Second Sjögren’s Population

Horizon Therapeutics, three months after announcing positive results in a phase 2 study of its experimental therapy dazodalibep for the treatment of the rare autoimmune condition Sjögren’s syndrome, said the therapy met its primary endpoint in a second patient population as well.

Sjögren’s syndrome affects exocrine glands, primarily the salivary and tear glands, with severe cases affecting multiple organs. Like other autoimmune diseases, Sjögren’s syndrome primarily affects women. The disease also has an increased risk of non-Hodgkin’s B-cell lymphoma and there is an unmet medical need for patients with extraglandular disease manifestations, as currently there is no therapy that can improve or slow the course of the disease. Disease manifestations include dry mouth, dry eyes, arthritis, and kidney or lung dysfunction.

Dazodalibep is a CD40 ligand antagonist that blocks T cell interaction with CD40-expressing B cells, disrupting the overactivation of the CD40 ligand co-stimulatory pathway. Several autoimmune diseases are associated with the overactivation of this pathway. Horizon also plans to explore dazodalibep in focal segmental glomerulosclerosis, a rare kidney disorder characterized by scarring of glomeruli.

Horizon said the new results are in a patient population that includes those with moderate-to-severe symptomatology including dryness, pain, and fatigue despite lacking additional organ involvement, and is defined as patients with a European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI) score of ≥ 5, indicative of significant symptomatic burden, and a score of <5 on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), which measures organ involvement.

At Day 169, dazodalibep-treated patients achieved a 1.8-point reduction in their ESSPRI scores compared to placebo-treated patients who achieved a 0.53-point reduction, resulting in a least squares mean difference of 1.27. The ESSPRI is a composite endpoint that measures dryness, pain, and fatigue severity. The previously announced positive results were in patients with moderate-to-severe systemic disease: systemic clinical manifestations in one or more organ systems in addition to the traditional Sjogren’s manifestations, and an ESSDAI of ≥ 5.

“There are currently no disease-modifying FDA approved treatments for Sjögren’s and the population in this trial represents a large subset of patients who have a clear unmet clinical need,” said Frederick Vivino, former director of the Penn Sjögren’s Center and chief, division of rheumatology at Penn Presbyterian Medical Center, University of Pennsylvania Perelman School of Medicine. “Participants in this study had been excluded from other recent trials, despite their substantial disease burden. The positive results from the phase 2 trial are very promising in addressing many debilitating symptoms of people living with Sjogren’s.”

In addition to the primary endpoint, statistical significance was achieved in certain secondary quality of life measures, including fatigue as measured by Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F).

Dazodalibep was well tolerated with the most common adverse events through Day 169 being COVID-19 infection, nasopharyngitis, and anemia.

Photo: Frederick Vivino, former director of the Penn Sjögren’s Center and chief, division of rheumatology at Penn Presbyterian Medical Center, University of Pennsylvania Perelman School of Medicine

Author: Rare Daily Staff