Author Topic: (CMSC) Ublituximab, going into Phase 3 trials, may be as good as Ocrevus or better  (Read 85 times)

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Offline agate

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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.
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.


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