Approval based on interim results from Phase III trial demonstrating complete terminal complement inhibition with reduced dosing frequency compared to Soliris 

LONDON, UK I September 03, 2021 I Ultomiris (ravulizumab) has been approved in the European Union for expanded use to include children (with a body weight of 10 kg or above) and adolescents with paroxysmal nocturnal haemoglobinuria (PNH), an ultra-rare and severe blood disorder characterised by the destruction of red blood cells that can cause thrombosis (blood clots) and result in organ damage and potentially premature death.1-4

The approval by the European Commission was based on interim results from the Phase III clinical trial in children and adolescents with PNH that demonstrated the safety and efficacy of Ultomiris in these patients.

Ultomiris has an established safety and efficacy profile, offering reduced dosing frequency compared to Soliris (eculizumab), which is the current standard of care in the EU for the treatment of children and adolescents with PNH. Ultomiris is administered every four or eight weeks (depending on body weight), following a loading dose. The approval follows the recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2021. 

Austin Kulasekararaj, MD, King’s College Hospital, London, UK, said: “PNH is a devastating disease, and Ultomiris provides an advancement for paediatric patients in the EU with an established safety and efficacy profile. By requiring fewer infusions each year than Soliris, Ultomiris may reduce the need for these young patients to miss school to receive treatment.”

Marc Dunoyer, Chief Executive Officer, Alexion, said: “This approval of Ultomiris reflects our ongoing commitment to delivering new treatments that can make a meaningful difference in patients’ lives. Ultomiris has become the standard of care for the treatment of adults with PNH and we will make it available to this younger patient population as soon as possible.”

Interim results from the Phase III trial demonstrated Ultomiris was effective in achieving complete C5 complement inhibition through 26 weeks for the treatment of patients up to 18 years of age with PNH. Additionally, Ultomiris had no reported treatment-related severe adverse events, and no patients discontinued treatment during the primary evaluation period or experienced breakthrough haemolysis, which can lead to disabling or potentially fatal blood clots.1 The efficacy and safety profile of Ultomiris in children and adolescents is consistent with the profile of Ultomiris in clinical trials involving adults with PNH and is representative of the broad PNH patient population seen in the real-world clinical setting.5,6

Ultomiris was first approved in the EU in 2019 for the treatment of adults with PNH and is also approved in the EU for the treatment of adults and children with atypical haemolytic uraemic syndrome (aHUS). In June 2021, the US Food and Drug Administration approved the expanded use of Ultomiris to include children (one month of age and older) and adolescents with PNH, the first and only treatment for this age group in the US.

PNH is a serious ultra-rare blood disorder with devastating consequences. It is characterised by the destruction of red blood cells, which is also referred to as haemolysis. PNH occurs when the complement system – a part of the body’s immune system – over-responds, leading the body to attack its own red blood cells. PNH often goes unrecognised, with delays in diagnosis from one to more than five years. Patients with PNH may experience a range of symptoms, such as fatigue, difficulty swallowing, shortness of breath, abdominal pain, erectile dysfunction, dark-coloured urine and anaemia. The most devastating consequence of chronic haemolysis is the formation of blood clots, which can occur in blood vessels throughout the body, damage vital organs, and potentially lead to premature death. The prognosis of PNH can be poor in many cases, so a timely and accurate diagnosis – in addition to appropriate treatment – is critical to improving patient outcomes.

Ultomiris (ravulizumab), 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 or, for paediatric patients less than 20 kg, every four weeks, following a loading dose. Ultomiris is approved in the US for the treatment of adults and children (one month of age and older) with PNH; in the EU for adults, as well as for children (with a body weight of 10 kg or above) and adolescents with PNH who experience haemolysis with clinical symptom(s) indicative of high disease activity, as well as for individuals who are clinically stable after having been treated with Soliris for at least the past six months; and in Japan as a treatment for adults with PNH. It is also approved in the US for aHUS to inhibit complement-mediated thrombotic microangiopathy in adult and paediatric (one month of age and older) patients, in the EU for the treatment of adults and children with a body weight of at least 10 kg with aHUS, as well as in Japan for adults and children with aHUS.

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 (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 and follow the Company on Twitter @AstraZeneca


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3. Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ. Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. The Journal of clinical investigation. 1989;84(1):7-17.

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SOURCE: AstraZeneca