New Data From PREVENT Show Benefits of Eculizumab in NMOSD

Eculizumab (Soliris), a particularly high-cost biologic that treats several rare diseases, has been the subject of increased interest in recent months as challengers advance their biosimilar candidates, and as the brand-name product has gained its most recent indication for the treatment of neuromyelitis optica spectrum disorder (NMOSD).

During this week’s meeting of the European Committee for Treatment and Research in Multiple Sclerosis, held September 11-13 in Stockholm, Sweden, researchers are presenting new data for eculizumab in the treatment of this rare autoimmune disorder that typically affects the optic nerves and spinal cord and that can cause significant, irreversible disability.

Eculizumab Proves Safe and Effective in the Long Term

First, Dean Wingerchuck, MD, of the department of neurology at the Mayo Clinic, presented combined long-term safety and effectiveness data from the PREVENT study and an ongoing open-label extension study.¹

PREVENT was a phase 3, randomized, time-to-event study in which 143 patients were randomized to receive either 900 mg of intravenous eculizumab once per week for 4 weeks (followed by a fifth dose of 1200 mg, and 1200 mg every 2 weeks from the sixth dose onward) or placebo.

Patients treated in PREVENT entered the extension based on their relapse status or at the end of PREVENT, and received eculizumab at the maintenance dose of 1200 mg ever 2 weeks. Data from PREVENT and the extension, with a data cutoff of October 31, 2018, were combined.

In total, 137 patients received eculizumab and were followed for a median of 107.8 weeks (range, 5.1-237.9). The rates of adverse events (AEs) and serious AEs per 100 patient-years (PY) were 758.5 and 32.9, respectively. The most commonly reported AEs were headache (27.0%), upper respiratory tract infection (25.5%), and nasopharyngitis (22.6%). The most commonly reported serious AEs were pneumonia (2.9%), urinary tract infection (2.9%), and optic neuritis (2.2%). One patient died during PREVENT from pulmonary empyema. No cases of meningococcal infection were reported.

Of the 137 patients treated, 8 experienced an on-trial relapse of NMOSD, and the estimated percentage of patients who were relapse-free at 192 weeks was 93.9% (95% CI, 87.5%-97.1%).

Relapse-Related Hospitalizations Decline With Therapy

Additionally, eculizumab was shown, again in the PREVENT study, to be associated with a lower relapse-related hospitalization rate.² In the study, results of which were presented in a poster session, hospitalizations were recorded as part of AE tracking.

The overall annualized hospitalization rate for patients treated with eculizumab was 0.26 versus 0.78 in the placebo group (P <.0001); the annualized relapse-related hospitalization rate was 0.04 in the eculizumab group and 0.31 in the placebo group (P <.0001).

Given the fact that relapse-relate hospitalization is a driver of costs, treating NMOSD with eculizumab could, say the poster’s authors, have a favorable impact on healthcare resource utilization.

The Biologic Also Provides Benefits in Terms of Disability

Finally, in a poster presentation, a research group presented data, also derived from PREVENT, on disability assessments that were performed during the study at baseline and at weeks 4, 8, and 12, then every 12 weeks thereafter until the study ended.³

The investigators used the Expanded Disability Status Scale (EDSS), the modified Rankin Scale (mRS), and the Hauser Ambulation Index (HAI) to assess disability. The EDSS scale ranges from 0 to 10; mRS measures disability in daily actives and has a scale ranging from 0 to 6; HAI assesses walking mobility and has scores ranging from 0 to 9. On all scales, higher scores correspond with greater disability. At baseline, most patients had moderate to severe disability.

The mean change in EDSS score from baseline to the study’s end was —0.18 (standard deviation [SD], 0.814) in the eculizumab group versus 0.12 (SD, 0.945) in the placebo group (P = .0597); for mRS, —0.2 (0.72) for the eculizumab group versus 0.1 (SD, 0.75) for the placebo group (P = .0154); and for HAI, —0.4 (SD, 1.08) versus 0.5 (SD, 1.61) in the placebo group (P = .0002).

According to the researchers, disability endpoints consistently favored eculizumab over placebo, and while patients in the eculizumab group tended to have no change or more improvement in their disability scores, patients in the placebo group tended to see their scores worsen.

References

1. Wingerchuk DM, Pittock SJ, Berthele A, et al. Long-term safety and effectiveness of eculizumab in neuromyelitis optica spectrum disorder. Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Abstract 142.

2. Palace J, Pittock SJ, Berthele A, et al. Impact of eculizumab on disability measures in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: phase 3 PREVENT study. Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Abstract P1343.

3. Kim HJ, Pittock SJ, Berthele A, et al. Impact of eculizumab on hospitalization rates and relapse treatment in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: findings from the phase 3 PREVENT study. Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Abstract P604.