Positive high-level results from the open-label Phase III CHAMPION-NMOSD trial showed that Ultomiris (ravulizumab-cwvz) achieved a statistically significant and clinically meaningful reduction in the risk of relapse in adults with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD) compared to the external placebo arm from the pivotal Soliris PREVENT clinical trial.

Ultomiris, the first and only long-acting C5 complement inhibitor, met the primary endpoint of time to first on-trial relapse, as confirmed by an independent adjudication committee. Notably, no relapse was observed in 58 patients over a median treatment duration of 73 weeks.

NMOSD is a rare and devastating autoimmune disease that affects the central nervous system (CNS), including the spine and optic nerves.[1-3] Most people living with NMOSD often experience unpredictable relapses, a new onset of neurologic symptoms or worsening of existing neurologic symptoms, also referred to as attacks, which tend to be severe and recurrent and may result in permanent disability.[4-6][ ]

Sean J. Pittock, MD, Director of Mayo Clinic's Center for Multiple Sclerosis and Autoimmune Neurology and of Mayo's Neuroimmunology Laboratory and lead primary investigator in the CHAMPION-NMOSD trial, said: "Every NMOSD relapse can have debilitating and irreversible consequences, so reducing relapses is critical. Patients on Ultomiris remained relapse free over a median treatment duration of 73 weeks in the trial."

Marc Dunoyer, Chief Executive Officer, Alexion, said: "Soliris established the role of complement inhibition in preventing relapses in NMOSD, and with Ultomiris, we continue to innovate for patients with a more convenient every eight-week dosing schedule. These trial results show that Ultomiris may help patients move towards eliminating relapses, which is an important advancement in the treatment of NMOSD."

The safety and tolerability of Ultomiris in the Champion-NMOSD trial were consistent with previous clinical studies and other approved indications. Fifty-six patients are continuing to receive treatment in a long-term extension period, which is ongoing.

The data will be presented at a forthcoming medical meeting and submitted to global health authorities as rapidly as possible to bring forward Ultomiris to the NMOSD community.

Notes

NMOSD

NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the CNS.[1,2] Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4 (AQP4).[7] 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.[1,8,9]

It most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even more rare.[10,11] People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations (eg, tingling, prickling or sensitivity to heat/cold) and impact on coordination and/or movement.[3-5,12,13] 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.[4-6] NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.[14-16]

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.[17]

Due to the potential long-term functional impact of NMOSD relapses, 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-cwvz), the first and only long-acting C5 complement inhibitor, offers 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 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 and children with paroxysmal nocturnal haemoglobinuria. 

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.

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 nearly 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 (http://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca).

Contacts

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Dr. Pittock has provided consulting services to Alexion.