Ultomiris Efficacy and Safety | gMG

Efficacy and safety

Adult patients were randomised to receive either ULTOMIRIS^® (n = 86) or placebo (n = 89) for 26 weeks and were subsequently allowed to enter the OLE period for up to 4 years.^2,3

* Due to its mechanism of action, the use of ULTOMIRIS^® increases the patient's susceptibility to meningococcal infection/sepsis (Neisseria meningitidis). To reduce this risk of infection, all patients must be vaccinated against meningococcal infections at least two weeks prior to initiating ULTOMIRIS^®

^† Stable–dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period. Dose changes were permitted in the open–label extension.^2,3

AChR, acetylcholine receptor; gMG, generalised myasthenia gravis; IST, immunosuppressant therapy; OLE, open–label extension; SOC, standard of care.

* Stable–dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period. Dose changes were permitted in the open–label extension.^2,3
ISTs, immunosuppressant therapies.

In the randomised, double–blind, placebo–controlled CHAMPION–MG trial, approximately 90% of patients were taking an IST at baseline.*²

* Stable-dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period. Dose changes were permitted in the open-label extension²

ISTs, immunosuppressant therapies.

AChR, acetylcholine receptor; gMG, generalised myasthenia gravis; IST, immunosuppressant therapy; IVIg, intravenous immunoglobulin; MG, myasthenia gravis;

MGFA, Myasthenia Gravis Foundation of America; PE, plasma exchange; SOC, standard of care.

Adverse Event Reporting

Please report any adverse reactions via your national reporting system. Adverse events should also be reported to Alexion pharmaceuticals by the following link: https://contactazmedical.astrazeneca.com

ULTOMIRIS^® (ravulizumab) EU Summary of Product Characteristics. Available from: https://www.ema.europa.eu/en/documents/product-information/ultomiris-epar-product-information_en.pdf. Last accessed: September 2024.

Vu T, et al. Terminal complement inhibitor Ravulizumab in generalised myasthenia gravis. N Eng J Med Evid. 2022;1(5).

Meisel A, et al. Long-term efficacy and safety of ravulizumab in adults with acetyl-choline receptor antibody-positive generalised myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension. [published online ahead of print]. J Neurol. 2023;1-14.

Among patients in the ULTOMIRIS^® treatment arm, improvements in MG–ADL total scores from baseline were observed within 1 week of treatment, and were sustained through 26 weeks of treatment (primary endpoint).^1,2

Adapted from: Vu T, et al. N Eng J Med Evid. 2022; 1(5).²

Improvements in MG-ADL were observed within 1 week of treatment, but the primary endpoint was at Week 26. Therefore, results should be interpreted with caution.²
CHAMPION-MG study limitations: Data shown are least-squares means and 95% confidence intervals (Cls), using a mixed model for repeated measures; 95% Cls were not adjusted for multiplicity.²

* Stable-dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period.²

BL, baseline; Cl, confidence interval; C5, complement component 5; IST, immunosuppressant therapy; LS, least squares; MG–ADL, Myasthenia Gravis–Activities of Daily Living; SD, standard deviation.

In the key secondary endpoint, change in QMG total score from baseline to Week 26, ULTOMIRIS^® achieved a reduction of 2.8 points vs 0.8 points for placebo (P <0.0009).^1,2

Adapted from: Vu T, et al. N Eng J Med Evid. 2022;1(5).²

* Stable-dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period.²

BL, baseline; Cl, confidence interval; IST, immunosuppressant therapy; LS, least squares; QMG, Quantitative Myasthenia Gravis; SD, standard deviation.

The open–label extension (OLE) period began following Week 26, when all patients received ULTOMIRIS^® and results were observed through Week 60.*³

Adapted from: Meisel A, et al. [published online ahead of print]. J Neurol. 2023;1-14.³

* Patients were randomised to receive either ULTOMIRIS® (n=86) or placebo (n = 89) for 26 weeks and were subsequently allowed to enter the open–label extension (OLE) period for up to 4 years.²

^† Stable–dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period.²

^‡ Dose changes of concomitant acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the open–label extension.³

^§ This was an open–label extension study and lacked a control group.³

BL, baseline; Cl, confidence interval; IST, immunosuppressant therapy; LS, least squares; MG–ADL, Myasthenia Gravis Activities of Daily Living; OLE, open–label extension; SD, standard deviation.

In the OLE period, 28% of patients decreased their
daily dose of corticosteroids, with 6% discontinuing
corticosteroids altogether*^†3

* N = 161, 45 patients decreased their corticosteroid dose and 10 patients discontinuing their corticosteroids entirely.³

^† In patients followed for 60 weeks in the open–label extension period.³

The open–label extension period began following Week 26, when all patients received ULTOMIRIS^® and results were observed through Week 60.*³

Adapted from: Meisel A, et al. [published online ahead of print]. J Neurol. 2023;1-14.³

* Patients were randomised to receive either ULTOMIRIS® (n=86) or placebo (n = 89) for 26 weeks and were subsequently allowed to enter the open–label extension (OLE) period for up to 4 years.²

^† Stable–dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period.²

^‡ Dose changes of concomitant acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the open–label extension.³

^§ This was an open–label extension study and lacked a control group.³

BL, baseline; Cl, confidence interval; IST, immunosuppressant therapy; LS, least squares; MG–ADL, Myasthenia Gravis Activities of Daily Living; OLE, open–label extension; SD, standard deviation.

ULTOMIRIS^®: a greater proportion of patients achieved clinically meaningful improvements in QMG total score vs placebo*^1,2

30% (n = 27/76) of patients taking ULTOMIRIS^® had a ≥ 5–point improvement in QMG total score vs 11.3% (n = 10/78) taking placebo (P = 0.005).²

* A 3 point change in QMG score was considered to be clinically meaningful.²

Adapted from: Vu T, et al. N Eng J Med Evid. 2022; 1(5).²

* Stable-dose acetylcholinesterase inhibitors and ISTs (including corticosteroids) were permitted during the randomised controlled period.²

IST, immunosuppressant therapy; QMG, Quantitative Myasthenia Gravis

Change from baseline to Week 26 in revised 15–Component MG–QoL15r: –3.3 for ULTOMIRIS^® and –1.6 for placebo
Change from baseline to Week 26 in the Neurological Quality of Life Fatigue. score: –7.0 for ULTOMIRIS^® and –4.8 for placebo
Neither of these endpoints were statistically significant

MG–QoL15r, revised Myasthenia Gravis Quality of Life 15–item.

More patients taking ULTOMIRIS^® achieved a ≥ 3–point improvement in MG–ADL total score vs placebo
57% (n= 47/78) of patients taking ULTOMIRIS^® had a ≥ 3–point improvement in MG–ADL total score vs 34% (n = 30/82) of patients taking placebo, this was not statistically significant

MG–ADL, Myasthenia Gravis Activities of Daily Living.

Primary endpoint²:

Change from baseline to Week 26 in the Myasthenia Gravis Activities of Daily Living (MG–ADL) total score*

Secondary endpoints:^{†‡ 2}

Change from baseline to Week 26 in the Quantitative Myasthenia Gravis (QMG) total score^§1d
The proportion of patients with improvements of at least 5 points in their QMG total score¹
Change in the revised Myasthenia Gravis Quality of Life 15–ltem (MG–QoL15r)²
Change in Neurological Quality of Life (Neuro–QoL) Fatigue assessment²
The proportion of patients with improvements of at least 3 points in their MG–ADL total score¹

* The MG–ADL is a categorical scale assessing the impact on daily function of 8 signs or symptoms typically affected in gMG. Each item is assessed on a 4–point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. The total score ranges from 0 to 24, with the higher scores indicating more impairment.²
^† Hierarchical testing proceeded from the first to the fifth endpoint, and if statistical significance was not achieved (P–value > 0.05), then subsequent endpoints were not considered statistically significant.²
^‡ All secondary endpoints are at Week 26.¹
^§ The QMG is a 13–item categorical scale assessing muscle weakness. Each item is assessed on a 4–point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. The total score ranges from 0 to 39, where higher scores indicate more severe impairment.²
gMG, generalised myasthenia gravis; IST, immunosuppressant therapy; MG–ADL, Myasthenia Gravis–Activities of Daily Living; MGFA, Myasthenia Gravis Foundation of America; MG–QoL15r, the revised Myasthenia Gravis Quality of Life 15–ltem; Neuro–QoL, Neurological Quality of Life; QMG, Quantitative Myasthenia Gravis.

Patients reaching minimal manifestation status may
be better able to perform everyday activities.⁴

BL, baseline; Cl, confidence interval; C5, complement component 5; IST, immunosuppressant therapy; LS, least squares; MG–ADL, Myasthenia Gravis Activities of Daily Living; MG–QoL15r, revised Myasthenia Gravis Quality of Life 15–item; OLE, open–label extension; SD, standard deviation; QMG, Quantitative Myasthenia Gravis.

Adverse Event Reporting

Vu T, et al. Terminal complement inhibitor ravulizumab in generalised myasthenia gravis. N Eng J Med Evid. 2022;1(5).

Jaretzki A Ill, et al. Myasthenia gravis- recommendations for clinical research standards. Neurology. 2000;55(1):16–23.

The most serious adverse reactions are meningococcal infection (0.7%), including meningococcal sepsis, encephalitis meningococcal, meningococcal infection and disseminated gonococcal infection (0.1%).¹
The most common adverse reactions with ravulizumab are headache (28.2%), upper respiratory tract infection (19.9%), nasopharyngitis (19.5%), diarrhoea (16.9%), pyrexia (16.4%), nausea (13.7%), arthralgia (13.2%), fatigue (13.1%), back pain (12.6%), abdominal pain (11.8%), and dizziness (10.1%).¹

Please refer to the ULTOMIRIS^® Summary of Product Characteristics for further safety information.

* In generalised myasthenia gravis (gMG), paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS) and aquaporin–4 antibody–positive neuromyelitis optica spectrum disorder (AQP4 Ab+ NMOSD).¹

Serious adverse events were reported in 20 (23%) patients with gMG receiving ULTOMIRIS^® and in 14 (16%) patients receiving placebo²
The most frequent serious adverse events were related to worsening of gMG (1 patient receiving ULTOMIRIS^® and 3 patients receiving placebo) and COVID–19 (2 receiving ULTOMIRIS^® and 1 receiving placebo)²

The most serious adverse reactions are meningococcal infection (0.7%), including meningococcal sepsis, encephalitis meningococcal, meningococcal infection and disseminated gonococcal infection (0.1%).¹

Across all indications, the most common adverse reactions with ravulizumab are headache (28.2%), upper respiratory tract infection (19.9%), nasopharyngitis (19.5%), diarrhoea (16.9%), pyrexia (16.4%), nausea (13.7%), arthralgia (13.2%), fatigue (13.1%), back pain (12.6%), abdominal pain (11.8%), and dizziness (10.1%).¹

AChR, acetylcholine receptor; aHUS, atypical haemolytic uraemic syndrome; AQP4 Ab+ NMOSD, aquaporin–4 antibody–positive neuromyelitis optica spectrum disorder; C5, complement component 5; gMG, generalised myasthenia gravis; PNH, paroxysmal nocturnal haemoglobinuria.

Adverse Event Reporting

Vu T, et al. Terminal complement inhibitor ravulizumab in generalised myasthenia gravis. N Eng J Med Evid. 2022;1(5).

Data on file. Alexion Pharmaceuticals, Inc.

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