#AANAM – Soliris Has Long-term Relapse Prevention

Soliris (eculizumab) significantly reduced the risk of disease relapses in people with neuromyelitis optica spectrum disorder (NMOSD) over nearly three years, according to new data from the clinical trial PREVENT and its extension study.

Additional findings project that long-term Soliris treatment may reduce relapse risk over the course of decades and consequently lead to improvements in quality of life.

The results were presented recently by researchers at Alexion Pharmaceuticals, which developed Soliris, at the 2021 Virtual American Academy of Neurology Annual Meeting (AANAM), held April 17–22.

Soliris is an approved treatment for NMOSD patients with antibodies against the protein aquaporin-4 (AQP4-IgG). It works by blocking the activity of part of the immune system called the complement cascade, which contributes to the disease-causing inflammation in NMOSD.

The safety and efficacy of Soliris in NMOSD were demonstrated in the Phase 3 clinical trial PREVENT (NCT01892345) and its ongoing open-label extension study (NCT02003144). Results demonstrated that treatment with Soliris significantly reduced the rate of relapses, improved neurological function, and reduced hospitalization rates.

Participants in the PREVENT trial were allowed to take concurrent treatment with immune-suppressing medicines other than Soliris, mainly corticosteroids. However, taking Soliris without any other medications (referred to as monotherapy) may be beneficial for some patients.

“Use of [Soliris] as a monotherapy could minimize the burdensome immunosuppressive therapy adverse event profile, and the deleterious long-term effects of corticosteroids use,” Sean Pittock, MD of the Mayo Clinic, said in a presentation at AANAM.

Pittock’s talk was titled, “Long-term efficacy and safety of eculizumab monotherapy in AQP4+ neuromyelitis optica spectrum disorder.”

“The objective of this post-hoc analysis was to examine the long-term efficacy and safety of [Soliris] monotherapy in AQP4-IgG-positive NMOSD during PREVENT and/or its ongoing open-label extension,” Pittock said. A post-hoc analysis is one done after a study is already finished.

Pittock’s presentation focused on the 34 participants in PREVENT who did not receive corticosteroids or other immunosuppressive therapies. Of these participants, 21 were on Soliris monotherapy in the original trial, while 13 were given placebo.

The therapy was administered at a dosage of 900 mg weekly for four doses, and then 1,200 mg every two weeks, given via infusion into the bloodstream.

Pittock noted that the number of PREVENT participants who were relapse-free after 192 weeks (more than three-and-a-half years) of treatment was similar among participants given Soliris monotherapy (96.2%) or Soliris in addition to other immunosuppressive therapies (93.8%).

Of the 21 participants given Soliris alone from the start, no relapses were reported during the trial itself, and none have been reported so far for those who continued to the open-label extension.

Among the 13 participants originally given only placebo, seven (54%) experienced relapses over a median time of six months. All but one of these participants chose to enroll in the open-label extension, during which they were given Soliris monotherapy. So far, only one of these patients has had one relapse while on Soliris.

Rates of adverse events were similar among participants given Soliris or placebo alone. Serious adverse events and serious infections were substantially more common among individuals on placebo, as were hospitalizations. No patients on Soliris required hospitalization for a relapse or started other immunosuppressive therapy.

Also, there have been no deaths in the monotherapy group, and participants who discontinued the open-label extension so far have done so mostly due to patient choice.

“Long-term [Soliris] monotherapy was well-tolerated, and these data support the long-term effectiveness of [Soliris] monotherapy in reducing relapse risk in AQP4-IgG-positive NMOSD,” Pittock concluded. “[Soliris] as monotherapy may be valuable for patients at increased risk of adverse events with immunosuppressant therapies, and for those unable to tolerate immunosuppressant therapies.”

A second presentation

At a separate presentation at AANAM, researchers used data from PREVENT in order to predict how Soliris treatment would affect the risk of NMOSD relapses over the course of decades. This poster was titled, “The potential impact of long-term relapse reduction: a disease model of eculizumab in neuromyelitis optica spectrum disorder.”

“The question was: in a disease that is chronic, that goes far beyond the duration of the PREVENT study, what is the long-term potential benefit if patients stay on [Soliris]?” said Adrian Kielhorn, senior director of global health economics and oucomes research at Alexion, who presented the poster.

Kielhorn and colleagues created various statistical models to assess relapse rate. Then, by comparing these models to data from PREVENT so far, they found the model that best fit the data, and reported what that model predicted 20 years after starting treatment.

Notably, these models used collective data from PREVENT, and did not differentiate between Soliris alone, or Soliris with other immunosuppressive therapies.

The model predicted that, after 20 years, no PREVENT participants given a placebo would have been completely free of relapses. By contrast, nearly two-thirds (66.2) of those given Soliris were predicted to remain relapse-free over two decades.

The reduction in relapse rate, “translated into impressive results when it comes to life years and quality-adjusted life years, so years of perfect health,” said Kielhorn. Both life years and quality-adjusted life years improved by nearly eight years with Soliris, compared with a placebo.

Additionally, the model predicted that, relative to patients on a placebo, those on Soliris would have more relapse-free years (16.5 vs. 2.4 years) and fewer years spent in a state of long-term disability (0.8 vs. 5.2 years).

Kielhorn said that the main limitation of this study is that the findings are dependent on their statistical model, which is inherently imperfect.

“This is not real, actual data; this is a simulation,” Kielhorn said. However, he stressed that, since the model fits the clinical trial data so far, the results “are not overstating the likelihood of an effect.”

“Together, these data suggest that [Soliris] can prevent the long-term accumulation of relapse-associated disability and improve quality of life in patients with NMOSD,” Kielhorn concluded.