番茄社区

STOCKHOLM -- Satralizumab monotherapy significantly reduced relapse rates in neuromyelitis optica spectrum disorder (NMOSD) -- especially among people with aquaporin-4 antibodies (AQP4-IgG) -- the pivotal phase III SAkuraStar trial showed.

Compared with placebo, monotherapy with satralizumab led to a 55% risk reduction in relapses among all NMOSD patients in the study and 74% risk reduction in relapses among those who were AQP4-IgG positive, according to Jeffrey Bennett, MD, PhD, of the University of Colorado Denver, and colleagues, who presented data from SAkuraStar at the ECTRIMS Congress.

NMOSD is a relapsing inflammatory disorder characterized by recurrent optic neuritis and myelitis. Its prevalence is 0.5 to 10 persons per 100,000 and it predominantly affects women. About 65% to 88% of NMO patients produce antibodies that target the water-channel protein aquaporin-4; binding of AQP4 antibodies to central nervous system cells is thought to trigger NMOSD attacks.

Unlike multiple sclerosis (MS), disability in NMOSD is due to attacks, not disease progression between attacks. "Neuromyelitis optica is an autoimmune condition where you have relapses that are potentially debilitating," Bennett told 番茄社区. "If you can stop attacks, you can stop disability accumulating in patients."

Until this year, no drug had been approved to treat NMOSD. That changed in June, when the FDA approved eculizumab (Soliris) -- a drug that -- for AQP4-IgG positive patients. The agency currently is reviewing the biologics license application (BLA) for another drug, , a which, like eculizumab, has demonstrated lower relapse rates compared with placebo.

Satralizumab is designed to inhibit interleukin-6 (IL-6)-driven pro-inflammatory signaling processes associated with NMOSD and limit disease activity. "What drives the onset of disease activity -- or what we determine clinically as a relapse -- appears to have as a key mediator the interleukin-6 pathway," Bennett said. "We see interleukin-6 levels elevated in patients who are active with neuromyelitis optica, and levels of interleukin-6 signaling activity appear to correlate with disease activity."

SAkuraStar is one of a pair of phase III studies testing the efficacy of satralizumab in NMOSD. The other trial, known as SAkuraSky, showed that satralizumab as add-on to baseline treatment with immunosuppressants or corticosteroids reduced relapse rates by 62% overall and by 79% among AQP4-IgG positive patients, compared with placebo.

In , Bennett and colleagues studied 95 NMOSD patients who were randomized 2:1 to satralizumab or placebo, administered (120 mg subcutaneously) at weeks 0, 2, 4, and every 4 weeks after that. A total of 64 patients in the study were AQP4-IgG positive.

Patients met , or were AQP4-IgG seropositive and had experienced one or more episodes of optic neuritis or longitudinally extensive myelitis. All had one or more documented relapse in the year prior to screening and were not allowed to take concomitant immunosuppressant medications during the study. The primary endpoint was time to first protocol-defined relapse, adjudicated by a clinical endpoint committee.

Compared with placebo, satralizumab reduced the risk of protocol-defined relapse by 55% (HR 0.45, 95% CI 0.23-0.89; P=0.018). A pre-specified sub-group analysis showed that relapse risk reduction increased to 74% among AQP4-IgG positive participants (HR 0.26, 95% CI 0.11-0.63; P=0.0014).

The proportion of relapse-free patients overall was 76.1% at week 48 and 72.1% at week 96 in the satralizumab group, compared with 61.9% and 51.2% in the placebo group.

The proportions of AQP4-IgG positive patients who were relapse-free at weeks 48 and 96 were 82.9% and 76.5% on satralizumab, compared with 55.4% and 41.1% on placebo."In the sero-negative patients, there was no evidence of reduction in relapse risk," Bennett noted, similar to what the SAkuraSky study showed.

Satralizumab was well tolerated. On a per-100 patient-years basis (calculated because satralizumab patients had longer exposure time than placebo patients), a similar proportion of patients in the satralizumab and placebo groups experienced adverse events, most commonly infections. A higher rate of severe adverse events were reported in the treatment group than in placebo, but these occurred in small numbers in different system organ classes, making the data difficult to interpret, Bennett noted. No deaths occurred in either arm.

Some findings in the study were limited by the small sample size of subgroups, Bennett said. The FDA has granted satralizumab breakthrough designation and orphan drug status. Drug maker Roche plans to submit a BLA for satralizumab in the next few months, a company spokesperson said.