Researchers found that a higher-dose version of the drug induced “clinically meaningful” symptom improvement for 87% of patients after one month.
But he also stressed that the findings are based on a small “Phase 1” trial — a type of study primarily designed to measure the safety of a treatment.
The safety findings were “encouraging,” and “there were some signs of clinical benefit,” said lead researcher Jodi Carnell, a senior director of research at Horizon Therapeutics, a company that develops the drug.
Now, she said, larger trials are needed to confirm that the therapy works.
The drug, now known as VIB7734, is a monoclonal antibody – a lab-produced protein that acts like a immune system Antibodies. Such antibodies can be directed against specific substances in the body that are involved in the disease process.
Lupus is caused by an autoimmune reaction, where the immune system mistakenly attacks the body’s own tissue.
Another form, called cutaneous lupus, affects only the skin, often leading to rashes and sores on the face and scalp.
There are treatments for those skin symptoms, including anti-inflammatory corticosteroids. Anti-malarial drugs, which alter the immune response; and immune-suppressing drugs such as methotrexate.
But those treatments can have significant side effects, and they don’t always work, Cornell pointed out.
“There’s a huge unfulfilled need,” she said.
In the United States alone, approximately 1.5 million people have lupus, according to the Lupus Foundation of America.
A monoclonal antibody is approved for systemic lupus, called Benysta (belimumab). It blocks an immune system protein involved in making auto-antibodies (antibodies that attack body tissues).
The new monoclonal antibody works in a different way, Cornell explained. It destroys cells of the immune system called plasmacytoid dendritic cells.
Those cells usually fight infection by releasing inflammatory chemicals, including type 1 interferons. But uncontrolled activity in cells, pumping out too much interferon, is thought to contribute to autoimmune diseases.
For the phase 1 trial, Cornell’s team recruited 31 patients with at least one of several autoimmune conditions, including systemic and cutaneous lupus. They were randomly assigned to receive injections of monoclonal antibodies, at different doses, or a placebo. Injections were given every four weeks, for a total of three.
After one month, the group on the highest antibody dose showed the greatest benefit: seven out of eight (87.5%) had a “clinically meaningful” reduction in skin symptoms, compared with about 37% of patients on the lower dose, and 28% of placebo patients.
The findings were published on May 26 in the journal science translation medicine.
Dr. Donald Thomas, a rheumatologist who was not involved in the study, cautioned: Over the years, various lupus treatments have initially shown promising promise only in late-stage trials.
These initial results are encouraging, he said.
“If they are successful in Phase 2 and 3 trials, it will be a game-changer,” said Thomas, of the Uniformed Services University of Health Sciences and Arthritis & Pain Associates of PG County in Maryland.
Cutaneous lupus can take a toll on patients’ quality of life, Thomas said, with some people losing hair and scarring on the skin.
Thomas said that unlike therapies that target broadly at the immune system, monoclonal antibodies target specific components of the immune response. This means they may have fewer side effects and be more effective.
Thomas notes that side effects with Benlysta, the approved antibody for SLE, have been “remarkably minimal” overall.
Cornell stressed that the experimental drug worked as intended — reducing dendritic cells and type 1 interferon activity in both the blood and the patients’ skin lesions. The next phase is a larger Phase 2 trial, she said.
Researchers also found that patients with higher interferon activity initially were those whose symptoms improved with antibodies. So a question for the future, Cornell said, is whether measuring patients’ interferon activity can help identify those most likely to benefit from treatment.
According to Thomas, if doctors were able to do this, it would be an advance.
Right now, he said, lupus treatment often involves trial-and-error to find out which therapy works — a frustrating fact for patients.
The Lupus Foundation of America has more Lupus Treatment Options.
Sources: Jodi Cornell, PhD, a Senior Director, Research Group, Horizon Therapeutics, Dublin, Ireland / Deerfield, Ill .; Donald Thomas Jr., MD, associate professor, medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, and rheumatologist, Arthritis & Pain Associates of PG County, Greenbelt, MD; science translation medicine, May 26, 2021, online