#ACTRIMS2018 – Ublituximab Led to Major Drop in MS Brain and Spine Lesions, Trial Shows

TG Therapeutics‘ ublituximab (TG-1101) led to a remarkable reduction in multiple sclerosis patients’ brain and spine lesions, a Phase 2 clinical trial showed.

In fact, none of the treated patients had new gadolinium-enhancing lesions — or damaged nerve cell areas — six months after treatment, researchers said. Their analysis covered patients with the relapsing form of MS.

Ublituximab works by honing in on a region of the CD20 protein that is present in immune B-cells, which are known to be involved in MS development.

TG Therapeutics will present the trial results at the ACTRIMS Forum Meeting in San Diego, Feb. 1-3. The poster-session presentation will be titled “6 Month Results of a Phase 2a Multicenter Study of Ublituximab, a Novel Glycoengineered Anti-CD20 Monoclonal Antibody, in Relapsing Multiple Sclerosis.”

Two of the key goals of the multi-center TG1101-RMS201 trial (NCT02738775) were to find an optimal dose and intravenous delivery time for ublituximab in relapsing MS subjects. The study is also assessing the therapy’s safety and patients’ ability to tolerate it.

Researchers randomized patients to receive intravenous infusions of either Ublituximab or a placebo on the first and 15th days of their participation in the trial. They were then followed for 28 days. At that point, those in the placebo group could receive ublituximab. All participants were then followed up to a year.

The team collected blood samples to assess the drug’s ability to deplete B-cells. They used magnetic resonance imaging to see whether it would reduce patients’ brain and spine lesions.

Their initial analysis covered 16 patients, whom researchers had followed up to six months.

Ublituximab led to a 99 percent reduction in B-cell levels. Researchers detected the depletion in the fourth week, and it held during the six-month follow-up period.

Another important finding was that ublituximab-treated patients had no relapses during the six months. In the year before they enrolled in the trial, 83 percent had relapsed at least once.

Patients’ disability also improved during the six months. Their mean score on the Expanded Disability Status Scale at the start of the study was 2.7. It fell to 1.9 after six months.

The most important finding may have been that none of the ublituximab-treated patients had lesions at six months.

Overall, the initial analysis showed that “ublituximab, a novel glycoengineered anti-CD20 antibody,  demonstrates rapid and robust B-cell depletion” and “a profound reduction” in lesions at six months, the researchers wrote.

In addition, the treatment led to no serious side effects, and patients tolerated it well. The most frequent adverse effects were infusion-related reactions. Speeding up the drug’s administration to as little as one hour did not increase the frequency of infusion-related reactions, researchers said.

“Unlike other IV-administered anti-CD20s, UTX [ublituximab] has been delivered in shorter infusions, providing a potential convenience benefit for future patients,” the researchers wrote.

“We look forward to presenting updated data from our Phase 2 study of ublituximab in relapsing multiple sclerosis at the ACTRIMS conference in February,” Michael S. Weiss, the company’s CEO, said in a press release.

“In addition to providing updated data this year from our Phase 2 program, our Phase 3 MS trial is well under way and we are targeting complete enrollment in the first quarter of 2019,” he added.

TG Therapeutics is also conducting an extension (NCT03381170) of the Phase 2 TG1101‐RMS201 trial to evaluate ublituximab’s long-term safety and effectiveness.