Developed and marketed by Alexion Pharmaceuticals, Ultomiris is the first and only long-acting inhibitor of the complement C5 protein approved to help patients with aHUS manage their symptoms. It is meant to be administered every eight weeks in people weighing at least 20 kg (44.1 lbs), and every four weeks in patients weighing less.
“Today’s approval marks another important step in our efforts to continue innovating for patients and improving their treatment experience,” John Orloff, MD, executive vice president and head of research and development at Alexion, said in a press release.
“Ultomiris’ extended dosing interval offers patients more flexibility and time to focus on living their lives beyond their disease while also reducing the burden on healthcare systems, hospitals and providers, which are all under a tremendous amount of stress in the current environment,” he said.
The treatment is an antibody that binds and inhibits the activity of the C5 protein, one of the proteins that makes up part of the body’s immune system, known as the complement system. Through this mechanism, Ultomiris is thought to lower the overactivation of the complement system that leads to the formation of blood clots in people with aHUS.
Ultomiris’ approvals were based on data from two ongoing Phase 3 trials: aHUS-311 (NCT02949128), which enrolled aHUS patients, 12 years or older, and aHUS-312 (NCT03131219), which enrolled patients up to 17 years of age. None of the patients participating in these trials had been treated with a complement inhibitor.
The main goal of both studies was to assess the percentage of patients who attained a complete thrombotic microangiopathy (TMA) response within a period of 26 weeks. Of note, TMA is defined by the destruction of red blood cells, low platelets, and organ damage due to the presence of tiny blood clots in capillaries and small arteries. Since the kidneys are more commonly involved, it can potentially lead to kidney failure.
To achieve a complete TMA response, patients must have normal platelet counts, as well as normal levels of the enzyme lactate dehydrogenase (LDH; a marker of red blood cell destruction), and a reduction of at least 25% in the levels of creatinine (a marker of kidney malfunction) in their blood.
Interim data from these trials, which included data from 56 enrolled adults and 18 children and adolescents, showed that after 26 weeks of treatment, 54% of adults and 77.8% of children attained a TMA complete response.
The proportion of patients in both trials who achieved a TMA complete response continued to rise thereafter, with 61% of adults and 94% of children achieving this goal after being treated with Ultomiris for approximately one year.
During this period of time, most saw their platelet counts (86% adults; 94% children) and LDH levels (84% adults; 94% children) normalize.
More than half (63%) of the adults included in the analyses also saw their creatinine levels drop by at least 25% since entering the study. The percentage of children and adolescents achieving this goal was even higher (94%).
Data from an additional group of 10 children previously treated with Soliris (eculizumab), another complement inhibitor developed by Alexion, who were included in aHUS-312 showed that switching to Ultomiris kept their disease under control without causing any new safety concerns.
The most common side effects observed in both studies included upper respiratory tract infections, diarrhea, nausea, fatigue, headache, common cold, and fever. None of the 89 patients included in these analyses had serious meningococcal infections, which had been reported in patients treated with Ultomiris in other studies.
In addition to aHUS, Ultomiris is currently approved in the U.S., Europe, and Japan for the treatment of paroxysmal nocturnal hemoglobinuria, a serious blood disorder also caused by the abnormal function of the complement system.
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