REG - AstraZeneca PLC - Ultomiris accepted for FDA Priority Review for gMG

AstraZenecaAnnouncement

21/12/2021 07:00

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RNS Number : 3208W  AstraZeneca PLC  21 December 2021

21 December 2021 07:00 GMT

 

Ultomiris regulatory submission accepted under FDA Priority Review in the US
for adults with generalised myasthenia gravis

 

Submission based on positive Phase III trial in which Ultomiris significantly
improved functional activities as measured by Myasthenia Gravis-Activities of
Daily Living Profile

 

The supplemental Biologics License Application (sBLA) for Ultomiris
(ravulizumab-cwvz) in adults with generalised myasthenia gravis (gMG) has been
accepted for Priority Review by the US Food and Drug Administration (FDA).

 

The FDA set a Prescription Drug User Fee Act date during the second quarter of
2022, following use of a rare disease priority review voucher by Alexion,
AstraZeneca's Rare Disease group.

 

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that
leads to a loss of muscle function and severe weakness.(1) The diagnosed
prevalence of gMG in the US is estimated at 64,000.(2-10)

 

Marc Dunoyer, Chief Executive Officer, Alexion, said: "Soliris was the first
new treatment approved for this devastating disease in approximately 60 years,
and this filing for Ultomiris demonstrates Alexion's continued commitment to
improve outcomes for patients living with gMG. The Phase III trial shows that
Ultomiris may help a broader range of patients including those with milder
symptoms or who are earlier in their treatment journey."

 

The sBLA submission in the US is based on results from the Phase III trial of
Ultomiris in gMG, which were announced
(https://alexionpharmaceuticalsinc.gcs-web.com/news-releases/news-release-details/alexion-announces-positive-topline-results-phase-3-study)
by Alexion in July 2021, and showed efficacy as early as Week 1 and sustained
for 52 weeks (26 weeks randomised controlled period + 26 weeks of open-label
extension). In the trial, the safety profile of Ultomiris was consistent with
that observed in Phase III trials of Ultomiris in paroxysmal nocturnal
haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS).

 

Regulatory submissions for Ultomiris for the treatment of gMG are also
currently under review with health authorities in the European Union (EU) and
Japan.

 

Notes

 

gMG

gMG is a rare autoimmune disorder characterised by severe muscle weakness. In
gMG, inflammation causes damage at the connection point between nerve cells
and the muscles they control (known as the neuromuscular junction or NMJ).
This damage leads to a breakdown of communication between the brain and
muscles, causing loss of muscle function and severe weakness.(1)

 

About 85% of people with gMG produce specific antibodies that bind to the
surface of the cells at the NMJ.(1) This binding activates the complement
cascade and causes the immune system to attack the NMJ. People with gMG can
suffer from initial symptoms, such as slurred speech, droopy eyelids, double
vision, and lack of balance, which can often lead to more severe symptoms like
choking, impaired swallowing, extreme fatigue and even episodes of respiratory
failure.11,12

 

gMG can occur at any age, but it most commonly begins for women before the age
of 40 and for men after the age of 60.1(3-15)

 

Clinical trial

The global Phase III randomised, double-blind, placebo-controlled, multicentre
26-week trial evaluated the safety and efficacy of Ultomiris in adults with
gMG who were not previously treated with a complement inhibitor medicine. The
trial enrolled 175 patients across North America, Europe, Asia-Pacific and
Japan. Participants were required to have a confirmed myasthenia gravis
diagnosis at least six months prior to the screening visit with a positive
serologic test for anti-AChR antibodies, Myasthenia Gravis-Activities of Daily
Living Profile (MG-ADL) total score of at least 6 at trial entry and
Myasthenia Gravis Foundation of America Clinical Classification Class II to IV
at screening. There was no requirement for prior treatment failure, and
patients could stay on stable standard of care medicines, with a few
exceptions, for the duration of the trial.16

 

Patients were randomised 1:1 to receive Ultomiris or placebo for a total of 26
weeks. Patients received a single weight-based loading dose on Day 1, followed
by regular weight-based maintenance dosing beginning on Day 15, every eight
weeks. The primary endpoint of change from baseline in the MG-ADL total score
at Week 26 was assessed along with multiple secondary endpoints evaluating
improvement in disease-related and quality-of-life measures.

 

Patients who completed the randomised controlled period were eligible to
continue into an open-label extension period evaluating the safety and
efficacy of Ultomiris for up to two years, which is ongoing. At the time of
the preliminary analysis of the open-label extension period, 75 patients had
completed 26 weeks of treatment, for a total of 52 weeks of treatment.

 

Ultomiris( )

Ultomiris (ravulizumab), the first and only long-acting C5 complement
inhibitor, offers immediate, complete, and sustained complement inhibition.
The medication works by inhibiting the C5 protein in the terminal complement
cascade, a part of the body's immune system. When activated in an uncontrolled
manner, the complement cascade over-responds, leading the body to attack its
own healthy cells. Ultomiris is administered intravenously every eight weeks
or, for paediatric patients less than 20kg, every four weeks, following a
loading dose. Ultomiris is approved in the US for the treatment of adults
and children (one month of age and older) with PNH; in the EU for adults, as
well as for children (with a body weight of 10kg or above) and adolescents
with PNH who experience haemolysis with clinical symptom(s) indicative of high
disease activity, as well as for individuals who are clinically stable after
having been treated with Soliris for at least the past six months; and in
Japan as a treatment for adults with PNH. It is also approved in the US for
aHUS to inhibit complement-mediated thrombotic microangiopathy in adult and
paediatric (one month of age and older) patients, in the EU for the treatment
of adults and children with a body weight of at least 10kg with aHUS, as well
as in Japan for adults and children with aHUS.

 

Alexion

Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on
rare diseases, created following the 2021 acquisition of Alexion
Pharmaceuticals, Inc. As a leader in rare diseases for nearly 30 years,
Alexion is focused on serving patients and families affected by rare diseases
and devastating conditions through the discovery, development and
commercialisation of life-changing medicines. Alexion focuses its research
efforts on novel molecules and targets in the complement cascade and its
development efforts on haematology, nephrology, neurology, metabolic
disorders, cardiology and ophthalmology. Headquartered in Boston,
Massachusetts, Alexion has offices around the globe and serves patients in
more than 50 countries.

 

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts
For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   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.

2.   Fang, F., Sveinsson, O., Thormar, G., Granqvist, M., Askling, J.,
Lundberg, I. E., . . . Piehl, F. (2015). The autoimmune spectrum of myasthenia
gravis: a Swedish population-based study. J Intern Med, 277(5), 594-604.
doi:10.1111/joim.12310

3.   Grob, D., Brunner, N., Namba, T., and Pagala, M. (2008). Lifetime
course of myasthenia gravis. Muscle Nerve 37: 141-149.

4.   Suh, J., Goldstein, J. M., & Nowak, R. J. (2013). Clinical
Characteristics of Refractory Myasthenia Gravis Patients. The Yale Journal of
Biology and Medicine, 86(2), 255-260.

5.   Joensen P. (2014). Myasthenia gravis incidence in a general North
Atlantic isolated population. Acta Neurol Scand 130: 222-228.

6.   Lefter, S., Hardiman, O., and Ryan, AM. (2016). A population-based
epidemiologic study of adult neuromuscular disease in the Republic of Ireland.
Neurology 88:304-313.

7.   Pallaver, F., Riviera, A. P., Piffer, S., Ricciardi, R., Roni, R.,
Orrico, D., & Bonifati, D. M. (2011). Change in myasthenia gravis
epidemiology in Trento, Italy, after twenty years. Neuroepidemiology, 36(4),
282-287. doi:10.1159/000328863

8.   Santos, E., Coutinho, E., Moreira, I., Silva, A. M., Lopes, D., Costa,
H., . . . Goncalves, G. (2016). Epidemiology of myasthenia gravis in Northern
Portugal: Frequency estimates and clinical epidemiological distribution of
cases. Muscle Nerve, 54(3), 413-421. doi:10.1002/mus.25068

9.   Robertson, NP., Deans, J., and Compston DAS. (1998). Myasthenia gravis:
a population based epidemiological study in Cambridgeshire, England. J Neurol
Neurosurg Psychiatry, 65:492-496.

10.  Zieda, A., Ravina, K., Glazere, I., Pelcere, L., Naudina, M. S.,
Liepina, L., . . . Kenina, V. (2018). A nationwide epidemiological study of
myasthenia gravis in Latvia. Eur J Neurol, 25(3), 519-526.
doi:10.1111/ene.13535

11.  Myasthenia Gravis Fact Sheet. (2020, April 27). National Institutes of
Neurological Disorders and Stroke. Available here
(https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet)
. Accessed October 2021.

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.  Myasthenia Gravis. National Organization for Rare Disorders (NORD).
Available here (https://rarediseases.org/rare-diseases/myasthenia-gravis/) .
Accessed October 2021.

14.  Howard, J. F. (2015). Clinical Overview of MG. Available here
(https://myasthenia.org/Professionals/Clinical-Overview-of-MG) . Accessed
October 2021.

15.  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.

16.  ClinicalTrials.gov. Safety and Efficacy Study of Ravulizumab in Adults
With Generalized Myasthenia Gravis. NCT Identifier: NCT03920293. Available
online. Accessed November 2021

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

 

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