#MDA2021 – Infection Risk Found Unaffected by Long-term Soliris Use

When used over long periods of time, Soliris (eculizumab) does not increase the risk of infections in people with generalized myasthenia gravis (gMG), according to a new analysis of clinical trial data.

Findings from this post hoc analysis were presented this week at the 2021 MDA Virtual Clinical and Scientific Conference in a poster, titled “Safety of eculizumab in MG and NMOSD – analysis of the phase 3 studies REGAIN and PREVENT and their extensions.” This research was funded by Alexion Pharmaceuticals, the company that developed and markets Soliris.

Soliris is approved in the U.S. and the EU to treat people with gMG (a more severe form of the disease) who have self-reactive antibodies against acetylcholine receptors, the most common cause of MG. It is also approved for the treatment of other rare conditions, including atypical hemolytic uremic syndrome and neuromyelitis optica spectrum disorder (NMOSD).

The medication works by blocking the activity of the complement cascade, which is part of the body’s immune system. Prior research has demonstrated that treatment with Soliris can improve muscle strength and lower the need for other immune-suppressing medications in people with gMG.

However, because Soliris works by blocking part of the immune system, there is the theoretical risk that the medication could increase the risk of infections, since the immune system is needed to fend off infectious microbes.

In the new poster, researchers from Alexion and other institutions presented a post hoc analysis of infection rates that occurred during the Phase 3 REGAIN trial (NCT01997229) and its open-label extension study (NCT02301624), which were designed to evaluate the safety and efficacy of Soliris in adults with gMG. Of note, a post hoc analysis is a type of analysis normally focused on a particular subject of interest that is performed after a trial has been completed.

In these studies, 123 gMG patients were exposed to Soliris and 63 to a placebo, for 306.5 and 31.1 patient-years, respectively. Patient-years, or PY, is a measure of the number of people participating in the study and the amount of time they were followed. For example, 100 PY refers to data gathered from 100 patients who were followed for one year.

In REGAIN and its extension study, the overall rate of infections was similar among participants given Soliris (188.9 infections per 100 PY) and those given a placebo in the original trial (208.8 infections per 100 PY). The rates of serious infections were also identical in patients treated with Soliris in both studies (14 infections per 100 PY) and in those given a placebo during REGAIN (25.7 infections per 100 PY).

Comparisons between data from the original REGAIN study and its long-term extension suggested that overall and serious infection rates did not increase with long-term Soliris use.

While detailed analyses of different types of infections were not carried out, researchers noted that “most infections were mild or moderate in severity; serious infections were uncommon.”

Additional analyses found no relationship between the use of other immune-suppressing therapies (ISTs) and infection risk. In general, infection rates were lower among patients treated with Soliris than in those given a placebo, regardless of the number of ISTs used.

“[Infection] rates per 100 PY were generally lower with eculizumab than with placebo, especially for the no-IST group,” the researchers wrote.

The team noted that, compared to placebo, the rate of serious infections on Soliris appeared to increase in people who were on three or more ISTs. However, because very few (two) patients were receiving this type of treatment, definite conclusions cannot be draw.

Investigators also presented data from the Phase 3 PREVENT trial (NCT01892345) and its open-label extension (NCT02003144), which assessed the safety and efficacy of Soliris in people with NMOSD.

Data from these studies were generally similar to that of REGAIN and its extension study, showing that long-term Soliris treatment was not associated with an increased rate of infections.

“Results from REGAIN, PREVENT, and their OLEs [open-label extensions] demonstrated that no increase in infection rates was observed with long-term eculizumab therapy compared with placebo in patients with gMG or NMOSD,” the team concluded.

The researchers added that these findings “are consistent with the established safety profile for eculizumab in other (non-neurologic) indications.”