Express delivery effect lasted for 52 weeks, and long-acting complement inhibitor reached the primary phase 3 clinical endpoint

▎ WuXi AppTec content team editor July 15, 2021, Alexion Pharmaceuticals announced that in adults with systemic myasthenia gravis (gMG), its long-acting C5 complement inhibitor Ultomiris (ravulizumab) phase 3 clinical trial has achieved positive results
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The trial reached the primary endpoint, that is, at the 26th week, the patient's ability of daily living has achieved a statistically significant improvement
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Ultomiris showed a significant effect in the first week of treatment, and this positive effect can last for 52 weeks
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Based on these positive results, Alexion plans to submit regulatory applications to relevant regulatory agencies in the United States, European Union (EU) and Japan in late 2021 or early 2022
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The complement system is a part of the innate immune system.
In a variety of complement-mediated immune diseases, the complement-mediated immune response attacks the patient's own healthy tissues and cells, causing damage to different tissues and organs
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The complement protein C5 is at the end of the complement cascade, so targeting this protein can regulate the complement signals activated by all three different pathways
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Alexion official website pointed out that Ultomiris is the first approved long-acting C5 complement inhibitor.
By inhibiting the effector protein C5 of the complement cascade pathway, it can inhibit the activation of the complement signaling pathway
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Previously, the drug has been approved by the US FDA for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), and has been approved in the European Union and Japan respectively
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In the treatment of PNH patients, it only needs to be administered intravenously once every 8 weeks to effectively control the occurrence of hemolysis
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This global randomized double-blind, placebo-controlled, multi-center phase 3 clinical trial enrolled 175 patients
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The results of the trial showed that Ultomiris reached the primary endpoint.
At week 26, compared with the placebo group, the Ultomiris group’s MG-ADL score (a score for assessing the ability of daily living of patients with myasthenia gravis) was statistically statistically significant compared to baseline Improvement of academic significance (Ultomiris group: -3.
1; placebo group: -1.
4; p<0.
001)
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In addition, the Ultomiris group also showed clinically significant and statistically significant improvements on the secondary endpoints assessed using the Quantitative Myasthenia Gravis Score (QMG), which means that the clinical severity of MG assessed by doctors is reduced
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The patient observed improvement in MG-ADL and QMG scores within the first week of administration, and the effect lasted for 52 weeks
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In addition, in the assessment of other secondary end points of quality of life, the data obtained by the experimental group is not statistically significant
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In terms of safety, the Ultomiris group and the placebo group had similar adverse events
.

The most frequently observed adverse events were headache (Ultomiris group: 18.
6%; placebo group: 25.
8%), diarrhea (Ultomiris group: 15.
1%; placebo group: 12.
4%) and nausea (Ultomiris group: 10.
5%; placebo Group: 10.
1%)
.

No cases of meningococcal infection were observed within 52 weeks
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gMG is a rare autoimmune disease.
Approximately 85% of gMG patients produce specific antibodies that bind to the cell surface of the neuromuscular junction, thereby activating the complement cascade and causing the immune system to attack the neuromuscular junction
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This damage leads to interruption of communication between the patient’s brain and muscles, causing loss of muscle function and severe weakness
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The initial symptoms of patients include slurred speech, drooping eyelids, double vision, lack of balance, etc.
, which can often lead to more serious symptoms such as suffocation, dysphagia, extreme fatigue and even respiratory failure
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GMG weakness can occur at any age, but it is most common in women before the age of 40 and men after the age of 60
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"The positive results obtained in this trial prove that Ultomiris has the potential to provide clinically meaningful effects for a wider range of patients
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" said Dr.
John Orloff, executive vice president and head of research and development at Alexion.
"These data indicate that Ultomiris is expected to become a new standard for gMG.
Treatment, and may reduce the burden on patients through its less frequent dosing schedule, so as to obtain better treatment compliance and patient satisfaction
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"Reference: [1] Alexion Announces Positive Topline Results from Phase 3 Study of ULTOMIRIS® ( ravulizumab-cwvz) in Adults with Generalized Myasthenia Gravis (gMG).
Retrieved July 15, 2021, from https://ir.
alexion.
com/news-releases/news-release-details/alexion-announces-positive-topline-results -phase-3-study Note: This article aims to introduce the progress of medical and health research, not a treatment plan recommendation
.

If you need guidance on treatment plans, please go to a regular hospital for treatment
.