Dazodalibep’s Benefits Seen In 2nd Sjögren’s Patient Group

Horizon Therapeutics shares Phase 2 Trial Data on investigational therapy

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Investigational therapy dazodalibep significantly eased symptom burden in people with Sjögren’s syndrome who have moderate-to-severe symptoms, but minimal systemic disease activity, meeting the goal of Horizon Therapeutics‘ Phase 2 clinical trial.

Horizon previously announced the trial also met its other main goal of reducing disease activity in Sjögren’s patients with moderate-to-high systemic disease activity.

Dazodalibep now is the only therapy in development for Sjögren’s that has achieved the Phase 2 primary endpoint in both of these patient populations, according to Horizon.

The company plans to work with the U.S. Food and Drug Administration (FDA) to design a Phase 3 clinical program of dazodalibep in Sjögren’s. The program is expected to launch this year, ahead of the original schedule.

“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,” Frederick B. Vivino, MD, said in a press release.

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Vivino is the former director of the Penn Sjögren’s Syndrome Center and chief of the 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,” Vivino said.

Sjögren’s syndrome is an autoimmune disease in which the body’s immune system mistakenly launches an attack against moisture-producing glands, leading to symptoms of dry eyes and mouth, pain, and fatigue. In more severe cases, internal organs such as the kidneys and lungs also may be affected.

Along with several other autoimmune diseases, Sjögren’s is marked by the overactivation of a signaling pathway that is initiated when the CD40 protein on the surface of antibody-producing B-cells binds to its receptor on immune T-cells.

Dazodalibep is designed to block the interaction between CD40 and its receptor, thereby preventing the overactivation of associated signaling pathways. In doing so, it is thought to be able to lower autoimmune disease activity.

Two Sjögren’s populations

The purpose of this Phase 2 trial (NCT04129164) was to evaluate the efficacy, safety, and tolerability of dazodalibep in two distinct Sjögren’s populations: those with moderate-to-severe systemic disease (organ involvement); and those with mild systemic disease (no organ involvement), but with moderate-to-severe Sjögren’s symptoms including pain, fatigue, and dryness.

The newly announced results concerned findings from the 109 adults with mild systemic involvement, reflected by a score of less than 5 on the European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI).

Still, these patients also had a score of 5 or more on the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and a residual stimulated salivary flow, reflecting moderate-to-severe subjective symptoms.

Participants were assigned randomly to receive dazodalibep, via an into-the-vein infusion, or a placebo for 24 weeks (nearly six months). Then, the two groups were switched, with participants who received dazodalibep previously receiving a placebo, and vice versa, for 16 weeks (about four months).

All were followed for at least three months after receiving the last dose.

Results showed that dazodalibep-treated patients exhibited a 1.8-point drop in ESSPRI scores after 169 days (almost six months), reflecting a decline in Sjögren’s symptoms. This was a significant improvement relative to the placebo group, in which a 0.53-point reduction was observed.

Other secondary goals also were met, including significant reductions in fatigue among dazodalibep-treated patients, according to Horizon.

“It is remarkable to see how these data demonstrated a significant separation in symptom intensity in patients treated with dazodalibep compared to placebo and this reinforces the potential of dazodalibep’s mechanism of action for patients suffering with the disease,” said Elizabeth H.Z. Thompson, PhD, executive vice president of research and development at Horizon.

The treatment was well-tolerated, with the most common adverse events being COVID-19 infection, cold-like symptoms, and anemia.

Findings in this group were similar overall to previously reported findings in the group of 74 patients with moderate-to-high systemic disease activity, defined by an ESSDAI score of five or more.

In that population, dazodalibep led to a significant 6.3-point drop in ESSDAI scores after 169 days, compared with a 4.1-point drop in the placebo group, reflecting a reduction in systemic disease activity.

Symptoms of dryness and fatigue eased significantly, the number of swollen and tender joints reduced, and physical function improved with treatment.

More trial data to come

Full data from the clinical trial for Sjogren’s syndrome will be presented at medical meetings and published in scientific journals once available, according to Horizon.

“Following these positive data, we look forward to working with regulators to continue developing dazodalibep as a potential treatment to positively impact the severe symptomatology of people living with this disease and improve their quality of life,” Thompson said.