JanssenAt the heart of Johnson & Johnson’s (NYSE:JNJ) $6.5 billion acquisition of Momenta Pharmaceuticals in 2020 is a portfolio of drug candidates for immune-mediated diseases.

One of the promising compounds in the acquisition is nipocalimab, which Janssen sees as a potential “pipeline in a pathway.” Nipocalimab holds promise for an array of diseases, ranging from rheumatoid arthritis and lupus and rare diseases such as myasthenia gravis. In all, Janssen is testing the drug in ten rare diseases as well as in rheumatoid arthritis and systemic lupus erythematosus.

When taken as a whole, rare diseases are not altogether rare, said Dr. Neely Mozaffarian, vice president and autoantibody pathway area leader at Janssen Immunology.

According to an analysis in the European Journal of Human Genetics, anywhere from 3.5% to 5.9% of the world’s population suffers from a rare disease, affecting 263–446 million people globally.

Rare autoantibody-mediated diseases alone likely affect more than 2% of the population worldwide, Mozaffarian estimated, referring to immune-system-produced antibodies that can cause pathological damage to the body’s tissues or organs. “We’ve known for decades about autoantibodies,” Mozaffarian said. “Normally, your immune system makes antibodies to protect you against pathogens like bacteria and viruses. But sometimes the immune system makes antibodies — autoantibodies — that bind to your own tissues and can cause disease.”

One of the reasons Janssen is upbeat about nipocalimab is its potential to treat various conditions, including autoantibody-mediated rare diseases, including myasthenia gravis, Hemolytic disease of the fetus and newborn and hemolytic disease of the fetus and newborn.

“Nipocalimab is a very elegant molecule,” Mozaffarian said. “The body has a very natural mechanism for recycling and removing antibodies from your bloodstream. Nipocalimab takes advantage of this natural recycling system.”

The compound binds to a recycling protein known as FcRn. “FcRn normally takes IgG antibodies in your bloodstream, protects them and puts them back into the bloodstream to last longer,” Mozaffarian said. “But nipocalimab binds to FcRn and prevents it from recycling these antibodies, and so the IgG in the bloodstream gets taken up and degraded.”

“Nipocalimab is really fit for purpose,” said Dr. Hong Sun, senior director, global compound development team leader, neuroscience at Janssen. The drug candidate is precise in its mechanism of action — whether the condition in question is immunological or an autoimmune disease. Nipocalimab could offer promise across a spectrum of conditions where a pathogenic autoantibody is involved.

Sun is involved in testing the potential of nipocalimab in myasthenia gravis, which is challenging to diagnose and causes weakness and fatigue of muscles. The condition can make breathing and swallowing difficult. Unfortunately, few treatments are available to treat the disease.

“We know that the disease is caused by the pathogenic autoantibody immunoglobulin G (IgG),” Sun said. “So nipocalimab can remove that IgG without interfering with cellular immunity or other antibodies such as IgM or IgA, which are important immune protectors,” she added.

Compared to traditional treatments, which tend to be more broadly immunosuppressant, nipocalimab potentially offers a much more selective approach. “It is still an investigational therapy, but we have seen in clinical trials that it does very nicely reduce the amount of IgG in the patients’ bloodstream, including those autoantibodies that cause disease are also reduced in the presence of nipocalimab,” Mozaffarian said.