(CMSC) Ublituximab, going into Phase 3 trials, may be as good as Ocrevus or better

Presented at the annual CMSC conference (New Orleans, May 2017), this paper is discussed in MedPage Today, May 28, 2017. The shorter infusion time (than Ocrevus) looks promising:

CMSC: Anti-CD20 Tx Offers Rapid B-Cell Depletion in MS Patients

Agent can be delivered with shorter infusions

 
by Ed Susman, Contributing Writer, MedPage Today

NEW ORLEANS -- Treatment with ublituximab, an investigational glycoengineered anti-CD20 antibody, was well tolerated and demonstrated rapid and robust B-cell depletion in patients with relapsing or primary progressive multiple sclerosis (MS), researchers reported here.

"Ublituximab efficiently depletes 99% of B cells, meeting the endpoint of the greater than 95% depletion within 2 weeks of the second dose, comparable to ocrelizumab (Orcevus)," said Amy Lovett-Racke, PhD, of the Ohio State University in Columbus, at the Consortium of Multiple Sclerosis Centers (CMSC).

However, Lovett-Racke reported that T-cell populations dipped a bit after patients took ublituximab, but then remained stable through 24 weeks of therapy.

Ublituximab is a novel chimeric monoclonal antibody targeting a unique epitope on the CD20 antigen. It is glycoengineered to enhance affinity for all variants of receptors, thereby demonstrating greater antibody-dependent cellular cytotoxicity activity than rituximab (Rituxan) and ofatumumab (Arzerra), Lovett-Racke said.

Ublituximab is currently in multiple phase III trials for treatment of hematologic malignancies, Lovett-Racke and co-authors pointed out. For this MS study, the dose was reduced, she explained.

The 52-week, phase II, placebo-controlled, multi­center study was designed to assess the infusion time and optimal dose as well as safety/tolerability of the agent in relapsing MS patients The patients were about age 40, and 67% were women. The mean duration of MS was 8.8 years.

During the placebo run-in phase of the trial, about 5% to 10% of B cells are in the peripheral blood, and "that is pretty normal levels of B cells," Lovett-Racke said. She illustrated how one patient with a normal level of B cells at the start of the treatment phase of the study showed a "complete loss of B cells within just 24 hours of treatment. And this loss is maintained through the initial 4 week period" of analysis.

The researchers studied 60-minute, 90-minute, and 3-hour infusions schedules. The initial infusion schedule for patients was 4 hours, and then shortened for the second dose at day 15, and again at week 24 to 1-1.5 hours. During the first 2 weeks, each person in the study-drug arm received 450 mg of ublituximab.

The primary endpoint was the responders rate, defined as the percentage of patients who achieved a 95% or greater reduction in peripheral CD19-positive B-cells within 2 weeks of the second infusion of ublituximab on day 15.

Patients who began the study on placebo showed fluctuating B cells counts until they were switched over to ublituximab therapy, and then their B cell levels dropped dramatically.

"After 2 days of treatment with ublituximab, the B cell counts have effectively dropped to 0 and remains at that level through week 4 for all the cohorts no matter what their initial therapy was or how long the infusions took to deliver the drugs," Lovet-Racke said.

There were no severe adverse events reported, even in patients who received rapid infusions with the study drug.

Lovett-Racke also noted that T-cell counts remain stable across the different subgroups. "There is some fluctuation, but all the values remain in the normal range," she said.
The authors concluded that "unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients."

CMSC session moderator Aliza Ben-Zacharia, DNP, of Mt. Sinai School of Medicine in New York City, praised the authors for presenting B-cell and T-cell data.
"One of my concerns is that when you engineer certain molecules, there can always be some safety concerns," she noted. "When you manipulate a molecule, what are we creating? I liked that Dr. Lovett-Racke presented both B-cell and T-cell data. Most of the time, people just present the B-cell information."

But she cautioned that this was a phase II study, "so we have a long way to go yet with this molecule before it will be used in practice."

The study was sponsored by TG Therapeutics. Some co-authors were company employees.
______________________
Lovett-Racke and Ben-Zacharia disclosed no relevant relationships with industry.

From Multiple Sclerosis Journal (April 30, 2020)--"A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of MS":


https://journals.sagepub.com/doi/full/10.1177/1352458520918375