- Treatment with Gilenya
(fingolimod) substantially reduced the debilitating impact of MS,
with significant decreases in key measures of disease activity vs.
interferon beta-1a
- MS severely affects the everyday
lives of children and adolescents with the disease and carries a
significant impact throughout their lifetime
- Gilenya, a leading oral
therapy for relapsing MS, is the only treatment approved by
the US FDA for patients from 10 years of age through to
adulthood
The digital press
release with multimedia content can be accessed here:
Basel, September 12, 2018
- Novartis today announced that The New England Journal of Medicine
(NEJM) has published full results from the landmark Phase III
Gilenya® (fingolimod)
PARADIGMS study, the first-ever controlled, randomized study
specifically designed for children and adolescents (aged 10 to 17)
with relapsing forms of MS (RMS). Children and adolescents with MS
experience more frequent and often more severe relapses than those
seen in adults with MS[1]. The negative effect of relapses on
movement, memory and thinking prevents patients from enjoying their
childhood and adolescent years to the full, often leaving them
feeling isolated and anxious[2]. PARADIGMS met the primary endpoint
of significantly reducing the rate of relapses when compared to
interferon beta-1a intramuscular injections over a period of up to
two years[3]. The study also met several secondary clinical and
imaging endpoints[3].
"I'd like to thank all the children who
participated in the PARADIGMS study, and their families, who have
helped transform the outlook for pediatric patients living with
relapsing MS," said Dr. Tanuja Chitnis, Principle Investigator for
PARADIGMS and Director of the Partners Pediatric Multiple Sclerosis
Center, Massachusetts General Hospital, Boston, US, and Scientist,
Ann Romney Center, Brigham and Women's Hospital, Boston, US. "These
data, published today, will go a long way in helping to advance
knowledge and understanding amongst the MS community of how to
evaluate and treat pediatric patients with MS."
Results from PARADIGMS show that, compared to
interferon beta-1a, Gilenya[3]:
-
Significantly reduced relapse rates by 82%
(p<0.001) and delayed the time to first relapse; an estimated
85.7% of patients treated with Gilenya were relapse-free at 24
months, versus 38.8% of patients treated with interferon beta-1a
(p<0.001)
-
Significantly reduced the number of new or newly
enlarged T2 lesions up to 24 months by 53% (p<0.001). Also, it
significantly reduced the average number of gadolinium enhancing T1
(Gd+) lesions per scan at 24 months by 66.0% (p<0.001). The
number and volume of lesions are associated with increased relapse
rates and disability progression
-
In additional analyses, significantly reduced
the annualized rate of brain volume loss (brain shrinkage) by
40%
The safety profile of Gilenya in this study was
overall consistent with that seen in previous clinical trials in
adults[3].
"PARADIGMS exemplifies Novartis' commitment to
reimagining care for young patients with neurological conditions,"
said Danny Bar-Zohar, Global Head, Neuroscience Development for
Novartis. "It is pioneering in every sense of the word,
demonstrating the collaborative approach taken with all
stakeholders and disciplines to bring the understanding of the
unique attributes of pediatric MS to the next level. Our priority
now is to continue discussions with worldwide health authorities to
bring Gilenya to young patients in need, as soon as possible."
Gilenya is a well-established treatment for MS in
the adult population, having been used to treat more than 255,000
patients in both clinical trials and the post-marketing setting,
with approximately 566,000 years of patient experience[4].
About the Phase III PARADIGMS
study
The Phase III PARADIGMS study (NCT01892722) is a flexible duration
(up to two years), double-blind, randomized, multi-center study to
evaluate the safety and efficacy of oral Gilenya®
(fingolimod) compared to interferon beta-1a in children and
adolescents with a confirmed diagnosis of multiple sclerosis (MS),
followed by a five-year open label extension phase[3]. The study
enrolled 215 children and adolescents with MS, 10 to less than 18
years of age with an Expanded Disability Status Scale (EDSS) score
between 0 and 5.5[3]. Patients were randomized to receive
once-daily oral Gilenya (0.5 mg or 0.25 mg, dependent on patients'
body weight) or intramuscular interferon beta-1a once
weekly[3].
The primary endpoint of the study was the
frequency of relapses in patients treated up to 24 months
(annualized relapse rate)[3]. Secondary endpoints include the
number of new or newly enlarged T2 lesions, gadolinium-enhancing T1
lesions, safety and the pharmacokinetic properties of Gilenya, all
measured throughout the treatment period[3].
The Phase III PARADIGMS study was conducted in 80
centers in 25 countries, and was designed in partnership with the
US Food and Drug Administration, the European Medicines Agency and
the International Pediatric Multiple Sclerosis Study Group[3].
About Multiple
Sclerosis
Multiple sclerosis (MS) is a chronic disorder of the central
nervous system (CNS) that disrupts the normal functioning of the
brain, optic nerves and spinal cord through inflammation and tissue
loss[5]. In adults, there are three types of MS:
relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and
primary progressive MS (PPMS)[6]. Approximately 85% of people with
MS have RRMS, where the immune system attacks healthy tissue[7]. In
children and adolescents, RRMS accounts for nearly all cases
(approximately 98 percent)[1].
The evolution of MS results in an increasing loss
of both physical and cognitive (e.g. memory) function. This has a
substantial negative impact on the lives of the approximately 2.3
million people worldwide affected by MS, of which between three and
five percent are estimated to be children or
adolescents[7],[8].
About Gilenya
(fingolimod)
Gilenya® (fingolimod)
is an oral disease-modifying therapy (DMT) that is highly
efficacious at controlling disease activity in relapsing multiple
sclerosis (RMS)[9]. Gilenya has a reversible lymphocyte
redistribution effect targeting both focal and diffuse central
nervous system (CNS) damage caused by MS[10],[11]. Long-term
clinical trial and real-world evidence and experience has shown
Gilenya treatment to be convenient for individuals to incorporate
into everyday life, leading to high treatment satisfaction,
long-term persistence, and ultimately, improved long-term outcomes
for people with RMS[12],[13].
Gilenya impacts four key measures of RMS disease
activity: relapses, MRI lesions, brain shrinkage (brain volume
loss) and disability progression[14],[15]. Its effectiveness on all
of these measures has been consistently shown in multiple
controlled clinical studies and in the real-world setting. Studies
have shown its safety and high efficacy to be sustained over the
long term, demonstrating that switching to Gilenya treatment as
early in the disease course as possible can be beneficial in
helping to preserve individuals' function[16],[17].
Gilenya is approved in the US for the first-line
treatment of relapsing forms of MS in adults, and children and
adolescents ages 10 to less than 18 years of age[9]. In the EU,
Gilenya is approved for adult patients with highly-active
relapsing-remitting MS (RRMS) defined as either high disease
activity despite treatment with at least one DMT, or
rapidly-evolving severe RRMS[18]. Gilenya is currently under review
with the European Medicines Agency as a treatment for children and
adolescents with MS.
About Novartis in Multiple
Sclerosis
Alongside Gilenya® (fingolimod,
a modulator of the S1P receptor subtypes 1,3,4 and 5), Novartis'
multiple sclerosis (MS) portfolio includes Extavia®
(interferon beta-1b for subcutaneous injection) which is approved
in the US for the treatment of relapsing forms of MS. In Europe,
Extavia is approved to treat people with relapsing-remitting MS,
secondary progressive MS (SPMS) with active disease and people who
have had a single clinical event suggestive of MS.
Investigational compounds include siponimod
(BAF312, a selective modulator of the S1P receptor subtypes 1 and
5), for SPMS, and ofatumumab (OMB157), a fully human monoclonal
antibody in development for relapsing MS. Ofatumumab targets CD20,
and is currently being investigated in two Phase III pivotal
studies.
In the US, the Sandoz Division of Novartis markets
Glatopa® (glatiramer
acetate injection) 20 mg/mL and 40 mg/mL, generic versions of
Teva's Copaxone®.
*Copaxone® is a
registered trademark of Teva Pharmaceutical Industries Ltd.
Disclaimer
This press release contains forward-looking statements within the
meaning of the United States Private Securities Litigation Reform
Act of 1995. Forward-looking statements can generally be identified
by words such as "potential," "can," "will," "plan," "expect,"
"anticipate," "look forward," "believe," "committed,"
"investigational," "pipeline," "launch," or similar terms, or by
express or implied discussions regarding potential marketing
approvals, new indications or labeling for the investigational or
approved products described in this press release, or regarding
potential future revenues from such products. You should not place
undue reliance on these statements. Such forward-looking statements
are based on our current beliefs and expectations regarding future
events, and are subject to significant known and unknown risks and
uncertainties. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect,
actual results may vary materially from those set forth in the
forward-looking statements. There can be no guarantee that the
investigational or approved products described in this press
release will be submitted or approved for sale or for any
additional indications or labeling in any market, or at any
particular time. Nor can there be any guarantee that such products
will be commercially successful in the future. In particular, our
expectations regarding such products could be affected by, among
other things, the uncertainties inherent in research and
development, including clinical trial results and additional
analysis of existing clinical data; regulatory actions or delays or
government regulation generally; global trends toward health care
cost containment, including government, payor and general public
pricing and reimbursement pressures; our ability to obtain or
maintain proprietary intellectual property protection; the
particular prescribing preferences of physicians and patients;
general political and economic conditions; safety, quality or
manufacturing issues; potential or actual data security and data
privacy breaches, or disruptions of our information technology
systems, and other risks and factors referred to in Novartis AG's
current Form 20-F on file with the US Securities and Exchange
Commission. Novartis is providing the information in this press
release as of this date and does not undertake any obligation to
update any forward-looking statements contained in this press
release as a result of new information, future events or
otherwise.
About Novartis
Novartis is reimagining medicine to improve and extend people's
lives. As a leading global medicines company, we use innovative
science and digital technologies to create transformative
treatments in areas of great medical need. In our quest to find new
medicines, we consistently rank among the world's top companies
investing in research and development. Novartis products reach
nearly 1 billion people globally and we are finding innovative ways
to expand access to our latest treatments. About 125 000 people of
more than 140 nationalities work at Novartis around the world. Find
out more at www.novartis.com.
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References
[1] Waldman A et al. Pediatric multiple
sclerosis. Neurology. 2016; 87(9): S74-S81.
[2] MS Society. Children and MS.
https://www.mssociety.org.uk/what-is-ms/types-of-ms/ms-in-children#MS%20and%20school
(link is external). Accessed September 2018.
[3] Chitnis T et al. Trial of Fingolimod versus
Interferon Beta-1a in Pediatric Multiple Sclerosis. NEJM 2018;
379(11): 1017-1027.
[4] Novartis data on file.
[5] PubMed Heath. Multiple Sclerosis
(MS). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001747/
(link is external). Accessed September 2018.
[6] MS Society. Types of MS.
https://www.mssociety.org.uk/what-is-ms/types-of-ms (link is
external). Accessed September 2018.
[7] Multiple sclerosis International Federation.
Atlas of MS 2013.
https://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf
(link is external). Accessed September 2018.
[8] Patel Y et al. Pediatric multiple sclerosis.
Ann Indian Acad Neurol. 2009; 12(4): 238-245.
[9] Gilenya US Prescribing Information.
https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/gilenya.pdf
(link is external). Accessed September 2018.
[10] Brinkmann V et al. FTY720 (fingolimod) in Multiple
Sclerosis: therapeutic effects in the immune and the central
nervous system. Br J Pharmacol. 2009; 158(5): 1173-1182.
[11] De Stefano N et al. Effect of fingolimod on diffuse
brain tissue damage in relapsing-remitting multiple sclerosis
patients. Mult Scler Relat Disord. 2016; 7: 98-101.
[12] Warrender-Sparkes M et al. The effect of oral
immunomodulatory therapy on treatment uptake and persistence in
multiple sclerosis. Mult Scler. 2016; 22(4): 520-532.
[13] Khatri B et al. Comparison of fingolimod with interferon
beta-1a in relapsing-remitting multiple sclerosis: a randomised
extension of the TRANSFORMS study. Lancet Neurol. 2011; 10(6):
520-529.
[14] Giovannoni G et al. "No evident disease activity": The
use of combined assessments in the management of patients with
multiple sclerosis. Mult Scler. 2017. Doi
10.1177/1352458517703193.
[15] De Stefano N et al. Effect of Fingolimod on Brain Volume
Loss in Patients with Multiple Sclerosis. CNS Drugs. 2017; 31(4):
289-305.
[16] Kappos L et al. Inclusion of brain volume loss in a
revised measure of 'no evidence of disease activity' (NEDA-4) in
relapsing-remitting multiple sclerosis. Mult Scler. 2016; 22(10):
1297-1305.
[17] Lizac N et al. Highly active immunomodulatory therapy
ameliorates accumulation of disability in moderately advanced and
advanced multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017;
88(3): 196-203.
[18] Gilenya EMA Summary of Product Characteristics.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002202/WC500104528.pdf
(link is external). Accessed September 2018.
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