Leading the Charge: ULTOMIRIS’s Impact on NMOSD Relapse Prevention Strategies

• ULTOMIRIS (ravulizumab-cwvz) is the first and only long-acting C5 complement inhibitor that offers patients with aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD) the potential to live relapse-free.
• The remarkable reduction in relapse risk observed in the CHAMPION-NMOSD trial serves as a beacon, illuminating ULTOMIRIS’s transformative potential in charting a new course for patients navigating the complexities of NMOSD.

Recently on 25^th March 2024, ULTOMIRIS (ravulizumab-cwvz) was approved in the United States for the treatment of adult patients with anti- AQP4 Ab+ NMOSD. ULTOMIRIS is also approved for certain adults with NMOSD in Japan and the European Union (EU). In the intricate landscape of neuroinflammatory disorders, AQP4+ NMOSD looms as a formidable adversary. However, amidst this labyrinth of challenges, ravulizumab emerges as a beacon of hope in the ongoing CHAMPION-NMOSD (NCT04201262) endeavor.

At the American Academy of Neurology conference 2024, Alexion, AstraZeneca Rare Disease presented interim analysis from the ongoing Phase III CHAMPION-NMOSD trial (NCT04201262). In an intricate treatment narrative, adults underwent intravenous infusions of ravulizumab on day 1, followed by maintenance doses on day 15 and every 8 weeks thereafter. The primary treatment period (PTP) spanned up to 2.5 years, succeeded by a long-term extension (LTE). Key primary endpoints, measuring the time to first adjudicated on-trial relapse and relapse risk reduction, guided the quest, alongside secondary endpoints encompassing adjudicated on-trial relapse rate, Hauser Ambulation Index (HAI) and Expanded Disability Status Scale (EDSS) score changes, and rigorous safety assessments.

Amongst the valiant cohort of 58 participants braving the PTP, with 56 venturing forth into the LTE realm, the narrative unfolds with resounding triumph. As of June 16, 2023, ravulizumab’s saga spans a median follow-up of 138.4 weeks, encompassing 153.9 patient-years. Astonishingly, the quest for relapse eludes ravulizumab’s grip, with not a single adjudicated on-trial relapse observed during the PTP or LTE phases. The hallowed halls echo with tales of 91.4% of participants witnessing stability or improvement in the Hauser Ambulation Index, while an equal cohort showcases resilience against worsening Expanded Disability Status Scale scores. Adverse events, though not without their toll, bear witness to the bravery of the participants, with 94.8% facing treatment-emergent adversities and 25.9% enduring the rigors of serious adverse events. Yet, in the face of adversity, ravulizumab’s shield remains unscathed, with the majority of events mild to moderate in severity and unrelated to its therapeutic embrace. Alas, amidst the triumph, shadows loom as two cases of meningococcal infection mar the PTP journey, albeit with no further incidents in the LTE. Regrettably, a single soul embarks on their final journey, succumbing to a cardiovascular fate unrelated to ravulizumab’s intervention.

Conclusion: The interim analysis unveils ravulizumab’s triumphant saga, wherein the specter of relapse retreats before its mighty gaze. Disability measures stand as a testament to its prowess, while safety outcomes, though marked by adversity, bear witness to the resilience of those who dare to tread this path. Ravulizumab emerges not merely as a treatment option but as a source of optimism, guiding AQP4+ NMOSD patients toward a brighter tomorrow. As the expedition marches forward, ravulizumab’s quest promises to rewrite the narrative of AQP4+ NMOSD, ushering in an era of renewed optimism and therapeutic advancement.