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Horizon Therapeutics plc Announces Phase 2 Study Evaluating Dazodalibep for Treatment of Sjogren’s Syndrome Meeting Primary Endpoint

The company plans to work with the FDA Draft phase 3 program for patients with moderate to high systemic disease activity to start in 2023, earlier than expected –

Horizon Therapeutics plc (Nasdaq: HZNP) announced today that its Phase 2 study evaluating dazodalibep for the treatment of Sjogren’s syndrome met its primary endpoint in patients with moderate to high systemic disease activity, as determined by the European Alliance of Associations for Rheumatology (EULAR ) Sjogren Syndrome Disease Activity Index (ESSDAI) score of ≥ 5. At week 24, patients treated with dazodalibep achieved a 6.3 point reduction in their ESSDAI score and patients treated with placebo achieved a 4 .1-point reduction, resulting in a statistically significant minimum. Squares mean a difference of 2.2 points (p=0.017).

“These data are compelling in that dazodalibep met the primary endpoint of statistical significance in patients with moderate to high systemic disease activity as defined by ESSDAI, representing a significant step toward developing a treatment for Sjogren’s Syndrome, a non-FDA disease – Approved treatments available,” said Elizabeth HZ Thompson, Ph.D., executive vice president, research and development, Horizon. “We continue to see evidence that dazodalibep’s mechanism of action is potentially effective in many autoimmune diseases, and we look forward to working with regulators to advance our Sjogren’s clinical development program.”

In addition to the primary endpoint, numerical improvements were observed in key secondary, exploratory, and post-hoc analyses. This included measurements of dryness, which is an important symptom for patients with Sjogren’s syndrome because it affects chewing, swallowing and dentition. Fatigue, as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and physical functioning, as measured by the 36-item Short Form Health Survey (SF-36), showed numerical improvements, as did tender and swollen joint counts. In addition, a post-hoc responder analysis of patients who improved significantly on ESSDAI favored dazodalibep versus placebo. The study was operated only for the primary endpoint.

Dazodalibep was well tolerated in the study. The most common adverse events were COVID-19 infection, diarrhea, dizziness, ligament strain, and upper respiratory tract infection.

“Sjogren’s is a devastating autoimmune disease with many unmet treatment needs,” said Frederick B. Vivino, MD, MS, former director of Penn Sjogren’s Center and chief of the Division of Rheumatology at Penn Presbyterian Medical Center, University of Pennsylvania Perelman School of Medicine. “It significantly affects the quality of life of patients and leads to numerous serious complications. In addition to arthritis and debilitating fatigue, internal organs are also often affected. Dry eyes and dry mouth are not trivial symptoms and, if ignored, can lead to life-changing complications including blurred vision, corneal ulcers, accelerated tooth decay and eventual dentition.”

“These positive results from the Phase 2 trial of dazodalibep are good news for patients with Sjogren’s syndrome,” said Dr. William St. Clair, chief of the Department of Rheumatology and Immunology at Duke University Medical Center.

The top-line data announced today is specific to patients with moderate to high systemic disease activity (as defined by ESSDAI). The Phase 2 study is also evaluating a second, separate patient population with moderate to severe subjective symptoms, defined by an EULAR-Sjögren Syndrome Patient Reporting Index (ESSPRI) of ≥ 5, who is fully enrolled and continues to make progress.

The results of the Sjogren study follow positive results from the randomized, double-blind, placebo-controlled Phase 2 study in patients with rheumatoid arthritis announced earlier this year. The study met its primary endpoint of change from baseline in DAS28-CRP at Day 113 in all four dazodalibep dosing arms.

Details of the phase 2 study in Sjogren’s syndrome

Two Sjogren syndrome populations were enrolled in the Phase 2 study: the first included a total of 74 participants with moderate to high systemic disease activity, defined by an ESSDAI score ≥ 5, and the second included participants with moderate to severe subjective symptoms , defined by having an ESSPRI score ≥ 5 and stimulated salivation, but with mild systemic disease activity, defined by an ESSDAI score < 5. This study has three phases: screening (4 weeks), treatment phase (40 weeks), and Follow-up period (12 weeks). During the treatment period, participants from each population were randomized 1:1 to receive either intravenous (IV) doses of dazodalibep or placebo (Tier 1) for 24 weeks. After completion of Stage 1, subjects randomized to the dazodalibep arm in Stage 1 received placebo and subjects randomized to placebo in Stage 1 received dazodalibep for the remaining 16 weeks of the treatment period (Step 2). Participants who stopped dazodalibep were not eligible for phase 2 treatment. All study participants were followed for at least 12 weeks after their last dose of study drug. Full study data will be presented at medical meetings and published in scientific journals as they become available.

About Dazodalibep

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

About Sjogren’s Syndrome

Sjogren’s syndrome is a chronic, systemic autoimmune disease that affects the exocrine glands, primarily the salivary and lacrimal glands, with multiple organs being affected in severe cases. Like other autoimmune diseases, Sjögren’s syndrome primarily affects women. The disease also carries an increased risk of non-Hodgkin B-cell lymphoma and there is an unmet medical need for patients with extraglandular manifestations of the disease as there is currently no therapy that can improve or slow disease progression. Disease manifestations include dry mouth, dry eyes, arthritis, and kidney or lung dysfunction. There are between 250,000 and 350,000 people with Sjogren syndrome in the United States, of whom approximately 50,000 would be eligible for advanced therapies, including biologics.1

Over Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address the critical needs of people affected by rare autoimmune and serious inflammatory diseases. Our pipeline is purposeful: we use scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we are making incredible efforts to impact lives, visit www.horizontherapeutics.com and follow us TwitterLinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding the potential benefits of dazodalibep in the treatment of Sjogren’s syndrome and other autoimmune diseases, scheduled regulatory meetings, clinical trial timing, and Horizon’s future development plans. These forward-looking statements are based on management’s expectations and assumptions as of the date of this press release, and actual results could differ materially from those projected in these forward-looking statements due to a variety of factors. These factors include, but are not limited to, risks related to future data analysis or clinical trial results being consistent with previous clinical trials or Horizon’s expectations, potential delays in the initiation or completion of clinical trials, and those risks identified from time to time under the heading “Risk Factors” and elsewhere in Horizon’s filings and reports with the SEC. Forward-looking statements speak only as of the date of this press release, and Horizon undertakes no obligation to update or revise these statements, except as required by law.

references

  1. Maciel G., et al. Prevalence of primary Sjogren’s syndrome in a US population-based cohort. Arthritis care and research 2017;69(10):1612-1616

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