New treatment for multiple sclerosis shows promise in trial

By Amy Norton HealthDay Reporter

An experimental antibody therapy for multiple sclerosis can cut symptom flare-ups by half compared with standard treatment, a new clinical trial has found.

The drug, called ublituximab, outperformed a standard oral MS medication in reducing patients’ relapses – periods of new or worsening symptoms. It has also been shown to be better at preventing areas of inflammatory damage in the brain.

Ublituximab has not yet been approved for the treatment of MS; The U.S. Food and Drug Administration is reviewing the trial data and is expected to make a decision by the end of the year, according to drugmaker TG Therapeutics.

If approved, ublituximab would be the latest in a new group of MS therapies called anti-CD20 monoclonal antibodies: laboratory-developed antibodies that target specific cells in the immune system that drive the MS process.

The new findings offer further evidence that the approach benefits patients, according to an expert who was not involved in the study.

“Is this revolutionary? No. But it is further confirmation of a clinical benefit in targeting this population of cells in the blood,” said Dr. Lauren Krupp, who directs the Center for Comprehensive Care for Multiple Sclerosis at NYU Langone in New York City. New York.

MS is a neurological disorder that usually appears between the ages of 20 and 40. It is caused by a mistaken attack by the immune system on the body’s own myelin – the protective sheath that surrounds nerve fibers in the spine and brain. Depending on where the damage occurs, symptoms include vision problems, muscle weakness, numbness, and difficulty with balance and coordination.

Most people with MS have the relapsing-remitting form, in which symptoms worsen for a period and then subside. Over time, the disease becomes progressively more constant.

Immune system cells called B cells appear to play an especially important role in driving MS. In recent years, we have seen the development of monoclonal antibodies that deplete B cells in the blood. One, called ocrelizumab (Ocrevus), was approved in the United States in 2017. A second – ofatumumab (Kesimpta) – was approved in 2020.

Both antibodies deplete B cells by targeting a protein on the cells called CD20. Ublituximab has the same target, but is designed to be more potent in killing B cells, said Dr. Lawrence Steinman, principal investigator of the new trial.

The trial did not compare ublituximab to any existing anti-CD20 antibodies, emphasized Steinman, a professor of neurology at Stanford University. Therefore, it is not known whether it is more or less effective.

But one potential advantage of the new antibody, Steinman said, is that it can be administered quickly.

Both Ocrevus and ublituximab require patients to attend a medical center for infusions every six months. But an infusion of Ocrevus takes about three hours, while ublituximab can be administered in an hour.

Kesimpta, in turn, avoids infusions completely. It is taken at home once a month, using an autoinjector.

“There are different solutions for different people,” Steinman said. “I think it’s always good to have options.”

The findings, published Aug. 25 in New England Journal of Medicine, are based on more than 1,000 patients with MS, mainly the relapsing-remitting form. A small percentage had secondary progressive MS, a second phase of the disease that follows the relapsing-remitting years.

About half were randomly assigned to receive ublituximab infusions, while the other half took the oral medication Aubagio (teriflunomide).

Over 96 weeks, ublituximab patients were half as likely to relapse—with an average annual rate of just under 0.1, versus nearly 0.2 among Aubagio patients. And on MRIs, they showed fewer areas of inflammation in the brain.

B cells are responsible for producing antibodies that fight infections. Therefore, the main safety concern with B cell depletion is that it may leave people more vulnerable to infection. That was the case in this trial: 5% of patients on ublituximab developed a serious infection, including pneumonia, versus 3% of patients on Aubagio.

There are many medications approved to treat MS. But Krupp said some recent studies show that patients do better in the long term when they receive “highly effective” drugs — which include anti-CD20 antibodies — compared with older drugs with more moderate effects.

For Steinman, earlier is better when it comes to starting highly effective treatment.

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“My philosophy is, if insurance covers it, end the disease hard and fast,” he said.

This brings up the issue of real-world cost: CD20 monoclonal antibodies are expensive; the current list price of Ocrevus is about US$68,000 per year, according to pharmaceutical company Genentech.

Often, Krupp and Steinman said, decisions about medications depend on which medications are covered by a patient’s insurance plan.

More information

The National Multiple Sclerosis Society has more information about treating MS.

SOURCES: Lawrence Steinman, MD, director and professor of neurology and neurological sciences and pediatrics, Beckman Center for Molecular Medicine, Stanford University, Stanford, California; Lauren Krupp, MD, director of the NYU Langone Multiple Sclerosis Comprehensive Care Center and professor of pediatric neuropsychiatry, NYU Grossman School of Medicine, New York City; New England Journal of MedicineAugust 25, 2022

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