An investigational drug has the potential to reset a faulty immune system in some individuals with Rheumatoid Arthritis. Rheumatoid arthritis, known as RA, manifests when the body mistakenly attacks its own joints and tissues, resulting in symptoms such as joint pain, stiffness, fatigue, and others.
The drug, peresolimab, represents a monoclonal antibody that activates human programmed cell death protein 1 (PD-1), responsible for regulating the immune system. Dr. Ajay Nirula, the study author and Vice President of Immunology at Lilly Research Laboratories in San Diego, which is developing peresolimab, disclosed that the drug’s funding supported the recently published research in the New England Journal of Medicine.
PD-1 is a protein present on T cells, responsible for aiding in the regulation of the body’s immune responses.
Nirula stated that certain autoimmune diseases, such as RA, might occur due to an inability to activate the normal brakes on the immune system.The new drug hits this brake by stimulating PD-1. “We are trying to turn down the immune system by replacing a missing signal,” he added.
The new study included 98 people with difficult-to-treat RA. They received 700 mg of peresolimab, 300 mg of peresolimab, or a placebo intravenously once every four weeks.
Compared to folks who got a placebo, participants who took the higher dose of peresolimab had significantly less joint pain, swelling, tenderness and inflammation at 12 weeks as measured on a standard scale assessing RA symptom severity. The safety profiles were similar across all groups in the study.
“We saw a level of efficacy that was intriguing,” Nirula said.
Steroids
“In the past, steroids were effective in alleviating symptoms of RA, but chronic steroid use has its toxicities, so we moved to different types of drugs that suppress the immune system,” he said.
Then came biologics such as tumor necrosis factor (TNF) alpha-blockers. These drugs target specific proteins, such as TNF, that play a role in stirring the inflammatory cascade, Nirula said.
The new study included people who had not done well on traditional immune-suppressing drugs or existing biologics.
“We saw good responses in both patient populations, and we are looking for medications that work in RA patients who have failed multiple therapeutics,” Nirula said.
PD-1 is also a target of some current cancer drugs, but in cancer, the goal is to shut this pathway down, not stimulate it. Longer studies are needed to see if peresolimab increases cancer risk in people with RA, Nirula noted.
The drug is still a few years away from the bedside, assuming further research pans out and no new safety signals emerge. Results of a phase 2 study are expected next year. If they are positive, it could set the stage for phase 3 clinical trials, which would take two to three years to complete.