Horizon Therapeutics plc announced the first patient has enrolled in a Phase 2 trial to evaluate its development-stage medicine HZN-7734 (formerly VIB7734), a first-in-class, fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7), to treat people with moderate to severely active systemic lupus erythematosus (SLE). SLE, which accounts for 70 percent of lupus cases1, is an autoimmune disease in which the immune system mistakenly attacks healthy cells and tissues. The Lupus Foundation of America estimates at least 5 million people worldwide are living with a form of lupus, 90 percent of whom are women.

“Systemic lupus erythematosus has many manifestations, its severity can negatively impact a patient’s quality of life and there are limited treatment options,” said Victoria Werth, MD, professor of medicine at the Perelman School of Medicine at the University of Pennsylvania and chief of dermatology at the Corporal Michael J. Crescenz Veteran’s Administration Medical Center. “This trial will help determine the safety and efficacy of Horizon’s ILT7 antagonist in reducing overall disease activity for patients who live with moderate to severely active SLE.”

The initiation of the Phase 2 trial follows encouraging efficacy and safety data from a Phase 1b trial in patients with cutaneous lupus erythematosus, a form of lupus affecting the skin. The Phase 1b study showed HZN-7734 decreased plasmacytoid dendritic cells (pDCs) and reduced Type 1 Interferon both in circulation, as well as the skin of people with cutaneous lupus, demonstrating that this molecule has activity in specific tissues where the disease occurs. HZN-7734 also improved Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) scores, a clinical measure of cutaneous lupus, versus placebo.

The composite primary endpoint of the Phase 2 trial is change in the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) and reduction in oral glucocorticoid dose after 48 weeks. BICLA is a composite measure of overall SLE disease activity. Additional trial endpoints include other measures of both lupus disease activity and oral glucocorticoid reduction.

“Research suggests pDCs, a type of immune cell that produces Type 1 Interferon and causes inflammation, play a critical role in the pathogenesis of lupus and possibly other autoimmune diseases related to the interferon pathway,” said Elizabeth H.Z. Thompson, Ph.D, executive vice president, research and development, Horizon. “Early studies indicate that HZN-7734 can deplete pDCs in blood and tissue thereby reducing Type 1 Interferon and the resulting inflammation, potentially addressing an unmet treatment need for patients with lupus. The enrollment of the first patient in this study represents an important milestone for these patients.”

About HZN-7734

HZN-7734 is a fully human monoclonal antibody that targets ILT7 and, in early studies, has been shown to promote the destruction of plasmacytoid dendritic cells (pDCs). pDCs are thought to play a critical role in the pathogenesis of lupus and other autoimmune diseases through their capacity to produce rapid and robust quantities of Type 1 IFN as well as through IFN-independent mechanisms.