Ultomiris has the potential to eliminate relapses and redefine the treatment landscape for AQP4 Ab+ NMOSD.

Ultomiris (ravulizumab) has been approved in Japan as the first and only long-acting C5 complement inhibitor for the prevention of relapses in patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD), including neuromyelitis optica.¹

The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was based on positive results from the CHAMPION-NMOSD Phase III trial, which were recently published in the Annals of Neurology and selected as an abstract of distinction at the 2023 American Academy of Neurology Annual Meeting.² In the trial, Ultomiris was compared to an external placebo arm from the pivotal Soliris PREVENT clinical trial. 

Ultomiris met the primary endpoint of time to first on-trial relapse as confirmed by an independent adjudication committee. Zero relapses were observed among Ultomiris patients with a median treatment duration of 73 weeks (relapse risk reduction: 98.6%, hazard ratio (95% CI): 0.014 (0.000, 0.103), p<0.0001) and continuing through a median duration of 90 weeks.²

NMOSD is a rare and debilitating autoimmune disease that affects the central nervous system (CNS), including the spine and optic nerves.^3-5 Most people living with NMOSD experience unpredictable relapses, characterised by a new onset of neurologic symptoms or worsening of existing neurologic symptoms, which tend to be severe and recurrent and may result in permanent disability.^6-8 The diagnosed prevalence of adults with NMOSD in Japan is estimated at approximately 4,000.⁹

Ichiro Nakashima, MD, Professor at the Division of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan said: “As a single NMOSD relapse can result in long-term and life-altering disability, relapse prevention is the primary treatment goal in this disease and essential to help patients maintain quality of life. With no relapses observed in the pivotal CHAMPION-NMOSD trial, the approval of this long-acting C5 complement inhibitor in Japan is a significant advance for patients with AQP4 Ab+ NMOSD, offering dosing every eight weeks and the potential to live relapse-free.”

Marc Dunoyer, Chief Executive Officer, Alexion, said: “Alexion transformed the NMOSD landscape by uncovering the exceptional efficacy of C5 complement inhibition in reducing the risk of relapses for patients. With today’s approval, we continue to deliver on our commitment to the NMOSD community, offering patients an innovative long-acting treatment option that has the potential to eliminate relapses with convenient dosing every eight weeks. We are proud to expand the reach of Ultomiris as we work to improve patients’ lives around the world.”

Overall, the safety and tolerability of Ultomiris in the CHAMPION-NMOSD trial were consistent with previous clinical studies and real-world use, and no new safety signals were observed. The most common adverse events (AEs) were COVID-19, headache, back pain, arthralgia and urinary tract infection. All cases of COVID-19 were non-serious and considered to be unrelated to Ultomiris.²

Ultomiris was recently approved in the European Union (EU) for the treatment of adult patients with NMOSD who are AQP4 Ab+, and regulatory reviews are ongoing in additional countries, including in the United States (US).

Notes

NMOSD
NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the CNS.^3,4 Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4 (AQP4).¹⁰ This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body’s defence against infection, to destroy cells in the optic nerve, spinal cord and brain.^3,9,11

NMOSD most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even more rare.^12,13 People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations (e.g., tingling, prickling or sensitivity to heat/cold) and impact on coordination and/or movement.^5-7,14,15 Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis and sometimes premature death.^6-8 NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.^16-18

CHAMPION-NMOSD
CHAMPION-NMOSD is a global Phase III, open-label, multicentre trial evaluating the safety and efficacy of Ultomiris in adults with NMOSD. The trial enrolled 58 patients across North America, Europe, Asia-Pacific and Japan. Participants were required to have a confirmed NMOSD diagnosis with a positive anti-AQP4 antibody test, at least one attack or relapse in the twelve months prior to the screening visit, an Expanded Disability Status Scale Score of 7 or less and body weight of at least 40 kilograms at trial entry. Participants could stay on stable supportive immunosuppressive therapy for the duration of the trial. ¹⁹

Due to the potential long-term functional impact of NMOSD relapses and available effective treatment options, a direct placebo comparator arm was precluded for ethical reasons. The active treatment was compared to an external placebo arm from the pivotal Soliris PREVENT clinical trial. 

Over a median treatment duration of 73 weeks, all enrolled patients received a single weight-based loading dose of Ultomiris on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks. The primary endpoint was time to first on-trial relapse, as confirmed by an independent adjudication committee. The end of the primary treatment period could have occurred either when all patients completed or discontinued prior to the Week 26 visit and two or more adjudicated relapses were observed, or when all patients completed or discontinued prior to the Week 50 visit if fewer than two adjudicated relapses were observed. In the trial, there were zero adjudicated relapses, so the end of the primary treatment period occurred when the last enrolled participant completed the 50-week visit. 

Patients who completed the primary treatment period were eligible to continue into a long-term extension period, which is ongoing. 

Ultomiris
Ultomiris (ravulizumab), the first and only long-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks in adult patients, following a loading dose.

Ultomiris is approved in the US, EU and Japan for the treatment of certain adults with generalised myasthenia gravis.

Ultomiris is also approved in the US, EU and Japan for the treatment of certain adults with paroxysmal nocturnal haemoglobinuria (PNH) and for certain children with PNH in the US and EU.

Additionally, Ultomiris is approved in the US, EU and Japan for certain adults and children with atypical haemolytic uraemic syndrome to inhibit complement-mediated thrombotic microangiopathy.

Further, Ultomiris is approved in the EU and Japan for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

As part of a broad development programme, Ultomiris is being assessed for the treatment of additional haematology and neurology indications.

Alexion

Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

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