US approval for ULTOMIRIS® for gMG

Posted on 30 April, 2022 - Uncategorised

ULTOMIRIS® (ravulizumab-cwvz) approved in the US for Adults with Generalised Myasthenia Gravis

First and only long-acting C5 complement inhibitor to demonstrate clinical improvement in patients with generalised myasthenia gravis

ULTOMIRIS showed early effect and lasting improvement in activities of daily living and has potential to reduce treatment burden with dosing every 8 weeks

April 28, 2022: ULTOMIRIS®(ravulizumab-cwvz) has been approved in the US for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of people living with the disease.1-5

The approval by the Food and Drug Administration (FDA) was based on positive results from the CHAMPION-MG Phase III trial, in which ULTOMIRIS was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients’ abilities to perform daily activities.1

This FDA action marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of gMG.

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.6 The diagnosed prevalence of gMG in the US is estimated at approximately 90,000.7

Despite recent advances, managing gMG is complex. Earlier intervention can preserve function and quality of life. This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early onset and reliable efficacy.

Professor James F. Howard, Jr, MD, Department of Neurology at The University of North Carolina School of Medicine and lead primary investigator in the CHAMPION-MG trial.

Samantha Masterson, Chief Executive Officer, Myasthenia Gravis Foundation of America (MGFA), said: “gMG takes a physical and emotional toll on those living with the disease. We are grateful for continued innovation and research into new treatment and dosing options to meet the needs of more patients and reduce the treatment burden. With the approval of ULTOMIRIS, we’re excited that MG patients now have another option to consider as part of their personalized treatment strategies that may offer more convenience and improve muscle weakness.”

Marc Dunoyer, Chief Executive Officer, Alexion, said: “Since bringing forward thefirst complement inhibitor, we’ve continued to listen to the community and focused innovation on the needs of gMG patients. We’re proud to deliver on this commitment with today’s approval. ULTOMIRIS, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms. As presented at the 2022 American Academy of Neurology Annual Meeting, ULTOMIRIS has demonstrated clinical benefit through 60 weeks, with treatment every eight weeks, compared to SOLIRIS every two weeks.”

In the trial, the safety profile of ULTOMIRISwas comparable to placebo and consistent with that observed in Phase III trials of ULTOMIRIS in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The most common adverse reactions in patients receiving ULTOMIRIS were upper respiratory tract infection and diarrhea.1

Results from the CHAMPION-MG trial were recently published online in NEJM Evidence and presented at the 2022 American Academy of Neurology Annual Meeting in April.

Regulatory submissions for ULTOMIRISfor the treatment of gMG are currently under review with multiple health authorities, including in the European Union (EU) and Japan.

References

  1. Ultomiris (ravulizumab-cwvz) US prescribing information; 2022.
  2. Anil, R., Kumar, A., Alaparthi, S., Sharma, A., Nye, JL., Roy, B., O’Connor, KC., Nowak, R., (2020). Exploring outcomes and characteristics of myasthenia gravis: Rationale, aims and design of registry – The EXPLORE-MG registry. J Neurol Sci. 2020 Jul 15;414:116830.
  3. Oh SJ., (2009). Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. Journal of Clinical Neurology. 2009b Jun 1;5(2):53-64.
  4. Tomschik, M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M., Cetin, H., Löscher, W., Zimprich, F., (2020). Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis. Neurology. 2020 Sep 8;95(10):e1426-e1436.
  5. Hendricks, TM., Bhatti, MT., Hodge, D., Chen, J., (2019). Incidence, Epidemiology, and Transformation of Ocular Myasthenia Gravis: A Population-Based Study. Am J Ophthalmol. 2019 Sep;205:99-105.
  6. Howard, J. F., (2017). Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of The New York Academy of Sciences, 1412(1), 113-128.
  7. Westerberg, E., Punga, A., (2020). Epidemiology of Myasthenia Gravis in Sweden 2006–2016. Brain and behavior. 2020 Nov;10(11):e01819.
  8. Myasthenia Gravis. National Organization for Rare Disorders (NORD). Available here. Accessed March 2022.
  9. Howard, J. F., (2015). Clinical Overview of MG. Available here. Accessed March 2022.
  10. Sanders, D. B., Raja, S. M., Guptill J. T., Hobson-Webb, L. D., Juel, V. C., & Massey, J. M., (2020). The Duke myasthenia gravis clinic registry: I. Description and demographics. Muscle & Nerve, 63(2), 209-216.
  11. Myasthenia Gravis Fact Sheet. (2020, April 27). National Institutes of Neurological Disorders and Stroke. Available here. Accessed March 2022.
  12. Ding, J., Zhao, S., Ren, K., Dang, D., Li, H., Wu, F., Zhang, M., Li, Z., & Guo, J., (2020). Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology, 20(238).
  13. ClinicalTrials.gov. Safety and Efficacy Study of Ravulizumab in Adults With Generalized Myasthenia Gravis. NCT Identifier: NCT03920293. Available here. Accessed March 2022.

Tags: