PRESS RELEASE
from UCB
UCB Media Room: U.S. FDA acceptance of new drug application and EMA MAA validation for zilucoplan for the treatment of generalized myasthenia gravis in adult patients
https://mb.cision.com/Public/18595/3666193/9cece37fb36d9bab_800x800ar.png
** UCB announces U.S. FDA acceptance of new drug application and EMA MAA va=
lidation for zilucoplan for the treatment of generalized myasthenia gravis =
in adult patients
------------------------------------------------------------
=C2=B7 New drug application (NDA) for zilucoplan seeks approval for the tre=
atment of generalized myasthenia gravis (gMG) in adult patients who are ace=
tylcholine receptor antibody positive (AChR-Ab+)=C2=A0
=C2=B7 Acceptance by U.S. Food and Drug Administration (FDA) follows the re=
cent European Medicines Agency (EMA) validation of Marketing Authorization =
Application (MAA) for treatment of adult patients with AChR-Ab+ gMG and who=
require treatment in addition to steroids or non-steroidal immunosuppressa=
nts=C2=A0
=C2=B7 Both NDA and MAA are based on pivotal Phase 3 RAISE study in gMG, wh=
ich demonstrated treatment with zilucoplan resulted in clinically meaningfu=
l and statistically significant improvements in key MG-specific outcomes co=
mpared to placebo
=C2=B7 UCB expects to receive feedback from the agencies in Q4 of 2023=C2=
=A0
Brussels (Belgium), 14 November 2022 =E2=80=93 7:00 (CEST) =E2=80=93 UCB, a=
global biopharmaceutical company, today announced that the U.S. Food and D=
rug Administration (FDA) has accepted for review the New Drug Application (=
NDA) for its investigational treatment, zilucoplan.=C2=A0
Zilucoplan is a subcutaneous (SC), self-administered peptide inhibitor of c=
omplement component 5 (C5 inhibitor) for the treatment of adult patients wi=
th acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthen=
ia gravis (gMG).=C2=A0
In 2019, the U.S. FDA granted orphan drug designation to zilucoplan for the=
treatment of MG.^1 The safety and efficacy of zilucoplan have not been est=
ablished and it is not currently approved for use in any indication by any =
regulatory authority worldwide.
This acceptance follows the recent European Medicines Agency (EMA) validati=
on of the Marketing Authorization Application (MAA) for zilucoplan for the =
treatment of adult patients with AChR-Ab+ gMG and who require treatment in =
addition to steroids or non-steroidal immunosuppressants. Validation confir=
ms that the application is complete and the formal review process by the EM=
A=E2=80=99s Committee for Medicinal Products for Human Use (CHMP) can begin=
. Orphan designation was granted in 2022 by the European Commission to zilu=
coplan for the treatment of myasthenia gravis.^2
gMG is a chronic and unpredictable auto-immune disease in which pathogenic =
autoantibodies can impair synaptic transmission at the neuromuscular juncti=
on by targeting specific proteins on the post-synaptic membrane. This disru=
pts the ability of the nerves to stimulate the muscle and results in a weak=
er contraction.^4 People living with MG can experience a variety of symptom=
s, including drooping eyelids, double vision, and difficulty in swallowing,=
chewing and talking, as well as severe muscle weakness that can result in =
life-threatening weakness of the muscles of respiration.^3 In the U.S. the =
prevalence of MG is estimated at 14 to 20 per 100,000 population; approxima=
tely 36,000 to 60,000 cases.^4 In Europe, the prevalence is estimated at 10=
per 100,000 population.^5
=E2=80=9CPeople living with gMG experience high treatment burden, on top of=
the debilitating impact of the condition, and there is a clear need for ad=
ditional targeted treatments to support the gMG community. Our goal is to p=
rovide a solution that can help meet these needs and transform lives,=E2=80=
=9D said Charl van Zyl, Executive Vice President Neurology Solutions & Head=
of EU/International Markets, UCB. =E2=80=9CThe acceptance of the NDA by th=
e FDA as well as the acceptance of the MAA by the EMA, brings us one step f=
urther on our journey towards approval for this medicine. We look forward t=
o working with the FDA and EMA to help bring this important new treatment o=
ption to patients.=E2=80=9D
The NDA and MAA are based on data from the pivotal Phase 3 RAISE study (NCT=
04115293), which demonstrated at week 12 that treatment with zilucoplan (0.=
3 mg/kg daily) resulted in clinically meaningful and statistically signific=
ant improvements in key gMG-specific outcomes compared with placebo in pati=
ents with AChR-Ab+ gMG. The study met its primary endpoint with zilucoplan =
showing a placebo-corrected mean improvement of 2.09 points in the Myasthen=
ia Gravis Activities of Daily Living (MG-ADL) score at week 12 (p<0.001).^6
Zilucoplan demonstrated a favorable safety and tolerability profile, showin=
g a similar rate of treatment-emergent adverse events (TEAEs) between ziluc=
oplan (76.7%) and placebo (70.5%). The most common TEAEs were injection sit=
e bruising, headache, and diarrhea. Rates of treatment discontinuation due =
to a TEAE were low and all patients who completed the 12-week treatment per=
iod have entered the ongoing RAISE-XT open-label extension study (NCT042258=
71).^6,7
In the RAISE study, 174 adult patients were randomised to receive daily SC,=
self-administered doses of placebo (N=3D88) or zilucoplan 0.3 mg/kg (N=3D8=
6). Patient demographics and baseline disease characteristics were generall=
y balanced between treatment arms.^6
As a complement C5 inhibitor, zilucoplan is a targeted therapy that inhibit=
s key components in the underlying pathophysiology of gMG, addressing the u=
nderlying mechanism of neuromuscular junction damage.^8,9
=E2=80=9CWe are deeply committed to improving outcomes for the gMG communit=
y. People who live with gMG suffer unpredictable, fluctuating, and debilita=
ting symptoms, which have a huge impact on their lives. We want to help red=
uce the day-to-day burden of this challenging disease,=E2=80=9D said Iris L=
oew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. =
=E2=80=9CIf approved, zilucoplan has the potential to address the unmet nee=
d for people with gMG by providing targeted improvements in signs and sympt=
oms of gMG disease activity and severity. A benefit of targeted treatment i=
s that it may help reduce the adverse events that can be associated with no=
n-specific immunosuppressive treatment of gMG.=E2=80=9D=C2=A0
UCB anticipates making regulatory filings for zilucoplan in gMG in Great Br=
itain, Japan, and rest of the world from Q3 2022 onwards.=C2=A0
Alongside zilucoplan, UCB is also investigating rozanolixizumab, a SC-admin=
istered, humanized monoclonal antibody that specifically binds, with high a=
ffinity, to human neonatal Fc receptor (FcRn), as a potential treatment for=
gMG. UCB anticipates filing regulatory submissions for rozanolixizumab lat=
er this year.=C2=A0
For further information, contact UCB:=C2=A0
Brand Communications, Rare Diseases
Jim Baxter
T+32.2.473.78.85.01=C2=A0
jim.baxter@ucb.com=C2=A0
Corporate Communications, Media Relations
Laurent Schots=C2=A0
T+32.2.559.92.64 =C2=A0
Laurent.schots@ucb.com=C2=A0
Investor Relations
Antje Witte =C2=A0 =C2=A0 =C2=A0 =C2=A0=C2=A0
T +32.2.559.94.14=C2=A0
antje.witte@ucb.com
About Generalized Myasthenia Gravis (gMG)
Myasthenia gravis is a rare disease impacting more than 700,000 people worl=
dwide.^11 People living with gMG can experience a variety of symptoms, incl=
uding drooping eyelids, double vision, difficulty swallowing, chewing and t=
alking, as well as severe muscular weakness that can result in life threate=
ning weakness of the muscles of respiration.^3, 4
gMG is a chronic and unpredictable auto-immune disease in which pathogenic =
autoantibodies can impair synaptic transmission at the neuromuscular juncti=
on (NMJ) by targeting specific proteins on the post-synaptic membrane. This=
disrupts the ability of the nerves to stimulate the muscle and results in =
a weaker contraction.^4,12=C2=A0gMG can occur in any race, although previou=
s studies have shown that women are more often impacted than men.^13,14=C2=
=A0 Most patients with gMG have pathogenic IgG antibodies that disrupt the =
transmission of nerve impulses to muscles in the NMJ and some activate the =
complement cascade.^15=C2=A0 Complement-mediated destruction via MAC format=
ion is a key mechanism causing damage at the NMJ and is the key driver of d=
isease in AChR-Ab+ gMG.
About the zilucoplan RAISE study ^6,7
The RAISE study (NCT04115293) is a multi-center, Phase 3, randomized, doubl=
e-blind, placebo-controlled study to confirm the efficacy, safety, and tole=
rability of zilucoplan in patients with AChR-Ab+ gMG. Patients were randomi=
zed in a 1:1 ratio to receive daily subcutaneous (SC) doses of 0.3 mg/kg zi=
lucoplan or placebo for 12 weeks.
The primary endpoint for the RAISE study is change from baseline to Week 12=
in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. Second=
ary endpoints include change in the Quantitative Myasthenia Gravis (QMG) sc=
ore, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Qualit=
y of Life 15 revised (MG-QoL15r) score from baseline to Week 12, =C2=A0time=
to rescue therapy, the proportion with minimal symptom expression (MSE) (d=
efined as MG-ADL of 0 or 1), the proportion with a =E2=89=A53-point reducti=
on in MG-ADL and the proportion with a =E2=89=A55-point reduction in QMG wi=
thout rescue therapy, all measured at Week 12. The secondary safety endpoin=
t is incidence of TEAEs. Patients who completed the 12 week RAISE trial had=
the possibility to enter the open label extension study, RAISE-XT.=C2=A0
For more information about the trial visit https://clinicaltrials.gov/ct2/s=
how/NCT04115293.=C2=A0
About Zilucoplan=C2=A0
Zilucoplan is a once-daily SC, self-administered peptide inhibitor of compl=
ement component 5 (C5 inhibitor) under clinical development by UCB in gMG. =
As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the ne=
uromuscular junction through its targeted dual mechanism of action.^9 In 20=
19, the US FDA granted orphan drug designation to zilucoplan for the treatm=
ent of myasthenia gravis.^1 Orphan designation was granted in 2022 by the E=
uropean Commission to zilucoplan for the treatment of myasthenia gravis.^2
The safety and efficacy of zilucoplan have not been established and it is n=
ot currently approved for use in any indication by any regulatory authority=
worldwide.
About Rozanolixizumab
Rozanolixizumab is an SC administered, humanized monoclonal antibody that s=
pecifically binds, with high affinity, to human neonatal Fc receptor (FcRn)=
. It has been designed to block the interaction of FcRn and Immunoglobulin =
G (IgG), accelerating the catabolism of antibodies and reducing the concent=
ration of pathogenic IgG autoantibodies.^16,15
Rozanolixizumab is under clinical development with the aim of improving the=
lives of people with pathogenic IgG-autoantibody-driven autoimmune disease=
s. In 2019, the US FDA granted orphan drug designation to rozanolixizumab f=
or the treatment of myasthenia gravis.^17 Orphan designation was granted in=
2020^18 by the European Commission for rozanolixizumab to the treatment of=
myasthenia gravis.
The safety and efficacy of rozanolixizumab have not been established and it=
is not approved for use in any indication by any regulatory authority worl=
dwide.
About UCB in Rare Diseases=C2=A0
At UCB, we don=E2=80=99t just see patients or population sizes, we see peop=
le in need. Through decades of serving the neurology and immunology communi=
ties, we have improved lives with impactful medicines and by enhancing the =
social and emotional well-being of patients. As a continuation of our herit=
age, we are now expanding our efforts to tackle rare neurological and immun=
ological diseases where current options offer little hope, including invest=
igational treatments for gMG, myelin oligodendrocyte glycoprotein antibody-=
associated disease (MOG-AD) and autoimmune enteropathy (AIE).
About UCB=C2=A0
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company =
focused on the discovery and development of innovative medicines and soluti=
ons to transform the lives of people living with severe diseases of the imm=
une system or of the central nervous system. With more than 7,600 people in=
approximately 40 countries, UCB generated revenue of =E2=82=AC5.3 billion =
in 2020. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twi=
tter: @UCB_news
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1. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/o=
pdlisting/oopd/detailedIndex.cfm?cfgridkey=3D699319. Accessed October 2022
2. Data on file.
3. Hansen JS, et al. Mortality in myasthenia gravis: A nationwide populatio=
n-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77.
4. Myasthenia Gravis Foundation of America. Clinical Overview of MG. https:=
//myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed August 202=
2=C2=A0
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eness of common drugs in its treatment: a systematic review and meta-analys=
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. Accessed September 2022.
6. Vu T, et al. Efficacy and safety of zilucoplan in myasthenia gravis: Res=
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2022.
7. Weiss MD, et al, Quality of life outcomes in RAISE: A double-blind rando=
mized, placebo-controlled study of zilucoplan in gMG. Oral presentation. MG=
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9. Howard J, et al. Clinical Effects of the Self-administered Subcutaneous =
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ebo-Controlled, Multicenter Clinical Trial. JAMA Neurol 2022 1;77(5)
10. ClinicalTrials.gov. 2022. A Study to Test Efficacy and Safety of Rozano=
lixizumab in Adult Patients With Generalized Myasthenia Gravis. https://cli=
nicaltrials.gov/ct2/show/NCT03971422. Accesed October 2022=C2=A0
11. Chen J, et al. Incidence, mortality, and economic burden of myasthenia =
gravis in China: A nationwide population-based study. Lancet Reg Health Wes=
t Pac: 2020;5:100063.
12. National institute of Neurological Disorders and Stroke. 2022. Myasthen=
ia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-shee=
t. Accessed October 2022.
13. Dong D, et al. Gender differences in quality of life among patients wit=
h myasthenia gravis in China. Health and Quality of Life Outcomes 2020 18;2=
96
14. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasth=
enia.org/MG-Education/MG-Quick-Facts Accessed October 2022
15. Smith B, et al. Generation and characterization of a high affinity anti=
-human FcRn antibody, rozanolixizumab, and the effects of different molecul=
ar formats on the reduction of plasma IgG concentration. MAbs. 2018;10:1111=
-30.
16. Kiessling P, et al. The FcRn inhibitor rozanolixizumab reduces human se=
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14:eaan1208).
17. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/=
opdlisting/oopd/detailedIndex.cfm?cfgridkey=3D669918. Accessed August 2022
18. European Medicines Agency, EU/3/20/2272: Orphan designation for the tre=
atment of myasthenia gravis https://www.ema.europa.eu/en/medicines/human/or=
phan-designations/eu3202272. Accessed August 2022=C2=A0
GenericFile
Zilucoplan FDA EMA Regulatory Filing Press Release FINAL 14 Nov 2022 For Is=
sue (https://mb.cision.com/Public/18595/3666193/811eb96fd5f8797a.pdf)
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