NMOSD treatment approved in China blocks relapses, study finds
MIL62 injection therapy keeps most patients relapse-free for 2 years
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MIL62, an injection therapy approved exclusively in China for neuromyelitis optica spectrum disorder (NMOSD), was found to keep most NMOSD patients free of relapses for up to two years, while being generally safe and well tolerated.
That’s according to data from the Phase 1b portion of a single-center Phase 1b/3 clinical trial (NCT05314010) that tested two MIL62 doses in 11 adults with NMOSD and self-reactive antibodies against the AQP4 protein, the most common type of NMOSD-driving antibody.
The trial’s Phase 3 portion is ongoing, but top-line data showed that the therapy reduced the risk of relapse by 93.1% compared with a placebo in the same patient population. This led to MIL62’s approval in China earlier this year under the brand name Bejescin to treat adults with AQP4-related NMOSD.
The Phase 1b trial findings were described in the study, “Safety and Efficacy of Obinutuzumab β (MIL62), a Novel Glycoengineered Type II Anti-CD20 Monoclonal Antibody, in Patients with Neuromyelitis Optica Spectrum Disorder: A Multicenter, Single-Arm, Phase Ib Clinical Trial,” published in Neurology and Therapy. Five of the authors work at Beijing Mabworks Biotech, the therapy’s developer, which also funded the study.
NMOSD occurs when self-reactive antibodies attack cells in the nervous system. Most often, this leads to damage of the spinal cord and the optic nerve, which carries messages from the eye to the brain. The most common antibodies causing NMOSD target AQP4, a protein found at the surface of neuron-supporting cells.
Relapses and remission
The disease is marked by relapses, periods when NMOSD symptoms suddenly worsen or return, interspersed with periods of remission, when symptoms are reduced or absent. Repeated relapses can cause irreversible disability.
MIL62 (obinutuzumab beta) is a new, third-generation antibody-based therapy designed to target the CD20 protein, which is found at the surface of B-cells (the immune cells responsible for producing antibodies, including self-reactive ones).
By targeting B-cells for destruction, the treatment aims to reduce the number of self-reactive antibodies and their erroneous attacks. Its design also suggests greater potency and efficacy relative to previous anti-CD20 antibody-based therapies.
The trial’s Phase 1b portion, sponsored by Beijing Mabworks Biotech, involved 11 NMOSD patients at a single site in China. They had a median age of 42, and all tested positive for anti-AQP4 antibodies.
Participants, who had lived with an NMOSD diagnosis for a mean of 3.94 years, received into-the-vein (intravenous) infusions of MIL62 at doses of 500 mg (three patients) or 1,000 mg (eight patients). The interval between the last relapse and the first MIL62 dose ranged from about two months to one year.
They received infusions in weeks 1 and 3, then in weeks 25 and 27, and once every 26 weeks (about six months) thereafter. Participants who tolerated the lower dose were increased to 1,000 mg after 24 weeks.
The patients were followed for a median of 94.9 weeks (nearly two years). Researchers monitored MIL62’s safety, pharmacokinetics (movement into, through, and out of the body), pharmacodynamics (effects in the body), and immunogenicity (ability to induce immune reactions).
Two participants experienced relapses less than one month after receiving the first dose. One of them left the study immediately, while the other continued treatment for about a year before experiencing another relapse that prompted study withdrawal.
The majority of participants remained stable. After two years of treatment, most (81.8%) had not experienced a relapse. The annualized relapse rate, which estimates the average number of relapses a patient experiences each year, decreased significantly, by 87.7% from 1.3 relapses in the two years before treatment to 0.2 in the two years after starting MIL62.
Scores on the Expanded Disability Status Scale (EDSS), a standard measure of disability, remained stable or improved throughout the study. The cumulative number of new or active lesions on MRI was low, “suggesting effective radiological disease control,” the team wrote.
Each patient experienced at least one adverse event within 24 weeks of receiving the first MIL62 dose. During the study, most (90.9%) experienced a treatment-related adverse event, and severe events were reported in 27.3%. However, no patient stopped treatment because of adverse events, and there were no deaths.
MIL62 quickly and strongly reduced the number of B-cells, with most patients reaching very low counts within one day. These low counts were maintained between doses. The treatment also reduced blood levels of anti-AQP4 antibodies. MIL62 levels in the body increased with higher doses and showed similar behavior across dose groups.
“The results support the eventual use of obinutuzumab [beta] for the treatment of NMOSD and support the selection of a 1000-mg dosing regimen for future studies,” the researchers wrote. “The phase III clinical trial of obinutuzumab [beta] versus placebo is … ongoing in patients with [AQP4-related] NMOSD to confirm its efficacy and safety.”
