#MDA2021 – Soliris Did Not Increase Infection Risk in NMOSD, Trials Show

Treatment with Soliris (eculizumab) does not increase the risk of infections or serious infections among people with neuromyelitis optica spectrum disorder (NMOSD) and antibodies against the protein aquaporin-4 (AQP4), even in those receiving accompanying immunosuppressive therapies.

Those were the findings from a post hoc analysis of the PREVENT Phase 3 clinical trial (NCT01892345) and its ongoing open-label extension study (NCT02003144), which supported the 2019 approval of Soliris for anti-AQP4-positive NMOSD patients.

The results were presented recently in a poster titled “Safety of eculizumab in MG and NMOSD – analysis of the phase 3 studies REGAIN and PREVENT and their extensions,” at the 2021 MDA Virtual Clinical and Scientific Conference.

NMOSD is an autoimmune disease in which the immune system wrongly produces antibodies that attack supportive cells of the nervous system, leading to inflammation in the optic nerve — the nerve that sends and receives signals from the eye — and spinal cord.

A majority of patients have elevated levels of antibodies targeting AQP4, which directs an immune attack against astrocytes, the star-shaped cells that contribute to the maintenance of the blood-brain barrier, provide nutrients to neurons, and repair nervous tissue following injury.

When anti-AQP4 antibodies bind to the surface of astrocytes, they activate the complement system, a group of proteins from the immune system, causing inflammation.

Soliris, developed by Alexion Pharmaceuticals, is an engineered antibody that blocks the action of a complement pathway protein known as C5, thereby suppressing complement activation, inflammation, and astrocyte damage.

The safety and efficacy of Soliris among people with anti-AQ4-positive NMOSD have been investigated in the PREVENT trial and its open-label extension.

In PREVENT, a total of 143 patients were included and assigned randomly to receive Soliris (96 patients) or a placebo (47 patients), given via an into-the-vein infusion once a week in the first five weeks, and every two weeks thereafter. Participants were in the trial for 48 weeks, and could continue to receive their immunosuppressive therapies.

A total of 137 patients who completed the trial then chose to enter an open-label extension trial and continue to receive Soliris for up to four years.

Results showed that Soliris significantly reduced the risk of relapse by 94%, lowered the need for hospitalizations, and reduced the need for treatment of acute attacks. Soliris also led to improvements in neurological and functional disability parameters even after four years of treatment.

In the recent analysis, researchers investigated whether the use of Soliris increased the rate of infections, particularly in patients who also were receiving immunosuppressive medications.

Overall, a similar number of patients in each group developed infections — 68.1% of patients on placebo, 76% of patients who received Soliris in PREVENT, and 82.5% of patients who received the active medication in both the Phase 3 trial and the extension study.

Also, no apparent differences were observed in the rate of serious infections. When infections occurred they were mostly mild or moderate in severity.

Researchers then measured the infection rates taking into account the number of immunosuppressive therapies — none, one or two — patients were taking during the trials.

Results showed that placebo-treated patients who also were receiving two immunosuppressive medications experienced an increase in infections (266.7 per 100 patient-years), compared with patients on one or no immunosuppressive therapy (192.2 and 154.1 per 100 patient-years).

Of note, patient-years is a measurement that takes into account both the number of people in the study and the amount of time each person spends in the study.

In contrast, patients on Soliris who also were receiving two immunosuppressive medications showed no increases in infections compared to others receiving fewer immunosuppressive therapies.

The same was seen for the rate of serious infections, with patients given two immunosuppressive therapies and a placebo showing a higher rate of serious infections (47.6 per 100 person-years) than those given the same number of immunosuppressive treatment plus Soliris (14.8 per 100 person-years).

Moreover, across all groups, the proportion of patients with infections did not increase with prologued exposure to Soliris.

Overall, “infection rates were similar in eculizumab and placebo groups, regardless of concomitant [immunosuppressive therapies], and were consistent with eculizumab’s established safety profile,” the researchers concluded.