video: Jodi Karnell, Sr. director, research, Horizon Therapeutics, discusses how HZN-7734 depletes plasmacytoid dendritic cells and demonstrates clinical benefit in cutaneous lupus. This material relates to a paper that appeared in the May 26, 2021, issue of Science Translational Medicine, published by AAAS. The paper, by J.L. Karnell at Viela Bio in Gaithersburg, MD; and colleagues was titled, "Depleting plasmacytoid dendritic cells reduces local type I interferon responses and disease activity in patients with cutaneous lupus."
Jodi Karnell and colleagues have developed a monoclonal antibody, VIB7734, that reduces symptom severity in people with cutaneous lupus by targeting and depleting plasmacytoid dendritic cells (pDC) in blood and skin. In two phase I clinical trials involving a total of 67 people with autoimmune diseases such as lupus, treatment with VIB7734 was as safe as a placebo and significantly reduced pDC frequencies, the researchers found. The antibody also reduced the activity of a group of key immune proteins called type 1 interferons in skin. Both pDCs and type 1 interferons are suspected to play a role in autoimmune conditions including lupus, so the new antibody may be an effective treatment option against autoimmunity if these initial results are supported in further clinical trials. VIB7734 targets a molecule on the surface of pDCs to deplete them, often halving the number of these cells after just one dose in non-human primates and patients with autoimmune diseases. In patients with cutaneous lupus treated with a high dose (150 milligrams) of VIB7734, 87.5% had clinically meaningful reductions in their symptoms one month after treatment, compared with 37.5% for those treated with a 50-milligram dose and 28.6% for those treated with a placebo. Karnell et al. also note that VIB7734 seems to work best in people with high concentrations of type 1 interferons circulating in the blood, suggesting that baseline type 1 interferon concentrations could predict patient responses.