BASEL, Switzerland,
May 24, 2019 /PRNewswire/
-- AveXis, a Novartis company, today announced the US
Food and Drug Administration (FDA) has approved
Zolgensma® (onasemnogene abeparvovac-xioi) for the
treatment of pediatric patients less than 2 years of age with
spinal muscular atrophy (SMA) with bi-allelic mutations in the
survival motor neuron 1 (SMN1) gene. Zolgensma is
designed to address the genetic root cause of SMA by providing a
functional copy of the human SMN gene to halt disease progression
through sustained SMN protein expression with a single,
one-time intravenous (IV) infusion. Zolgensma is the first and only
gene therapy approved by the FDA for the treatment of SMA,
including those who are pre-symptomatic at diagnosis.
Check back soon to experience the interactive Multichannel News
Release here:
https://www.multivu.com/players/English/8548551-avexis-fda-approval-zolgensma/
"A diagnosis of SMA is devastating, leaving untreated babies who
have the most severe form with painfully short, highly medicalized
lives, during which they are unable to lift their heads, sit or
roll, have difficulty swallowing and breathing and need 24-hour
care," said Jerry Mendell, M.D.,
principal investigator at the Center for Gene Therapy at The
Abigail Wexner Research Institute of Nationwide Children's Hospital
in Columbus, OH. "In the START
clinical trial we conducted with Zolgensma, all children were alive
at the conclusion of the study and many were able to sit, roll,
crawl, play and some could walk. This level of efficacy, delivered
as a single, one-time therapy, is truly remarkable and provides a
level of unprecedented hope for families battling SMA Type 1. We
now have data four years out from the trial, and we see the
durability of this gene therapy."
"The approval of Zolgensma is a testament to the
transformational impact gene therapies can have in reimagining the
treatment of life-threatening genetic diseases like spinal muscular
atrophy," said Vas Narasimhan, CEO of Novartis. "We believe
Zolgensma could create a lifetime of possibilities for the children
and families impacted by this devastating condition."
SMA is a rare, genetic neuromuscular disease caused by a
defective or missing SMN1 gene. Without a functional
SMN1 gene, infants with SMA lose the motor neurons
responsible for muscle functions such as breathing, swallowing,
speaking and walking.1 Left untreated, muscles become
progressively weaker.1,2 In the most severe form, this
eventually leads to paralysis and ultimately permanent ventilation
or death by age 2 in more than 90% of cases.3 SMA is the
leading cause of genetic infant death.4 Approximately
450 to 500 infants are born with SMA in the US
annually.5,6 It is imperative to diagnose SMA and begin
treatment, including proactive supportive care, as early as
possible to halt irreversible motor neuron loss and disease
progression.7 This is especially critical in the most
severe form where degeneration starts shortly before birth and
escalates quickly.8 With states adding SMA to their
genetic newborn screening panel, babies with SMA can begin to be
widely identified at birth and the ability to have earlier
intervention can be improved.9
"Zolgensma's one-time dose of gene therapy has the potential to
make a truly transformative impact on this life-threatening
disease," said Kenneth Hobby,
president of Cure SMA, a patient advocacy organization dedicated to
the care, treatment and cure of SMA. "Our organization is leading
the way to a world without SMA and we are excited the FDA's
approval of Zolgensma brings patients and families a powerful new
treatment which corrects the underlying cause of the disease."
The approval of Zolgensma is based on data from the ongoing
Phase 3 STR1VE trial and the completed Phase 1 START trial
evaluating the efficacy and safety of a one-time IV infusion of
Zolgensma in patients with SMA Type 1 who showed symptoms of SMA at
<6 months of age, with one or two copies in the STR1VE trial or
two copies in the START trial of the SMN2 backup
gene and who have bi-allelic SMN1 gene deletion or
point mutations.These data show Zolgensma provides unprecedented
rates of survival never seen in the natural history of the disease;
rapid motor function improvement, often within one month of dosing;
and, durable milestone achievement, including the ability to sit
without support, a milestone never achieved in untreated patients.
Safety observations in STR1VE were comparable to those seen in the
START trial. The most commonly observed adverse events were
elevated aminotransferases and vomiting.
"We are grateful to the tenacious researchers, partners and
families who participated in the Zolgensma clinical trials that
helped us achieve this incredible milestone," said Dave Lennon, president of AveXis. "We are proud
to bring this one-time gene therapy to pediatric patients with SMA
and remain committed to advancing the science behind Zolgensma to
transform SMA, as well as other rare genetic diseases."
Zolgensma will be made available in the US and will be marketed
by AveXis, a Novartis company. OneGene Program™, AveXis'
comprehensive patient support program, provides a dedicated,
personalized support team focused on the needs of each family
throughout the Zolgensma treatment journey. This includes answering
questions about Zolgensma, verifying reimbursement assistance and
coordinating financial assistance programs for eligible patients.
For more information, caregivers and healthcare professionals can
call 1-855-441-GENE (1-855-441-4363).
Outside of the US, Zolgensma has PRIME (PRIority MEdicines)
designation in Europe and is being
reviewed under Accelerated Assessment Procedure, and also has
accelerated Sakigake designation in Japan. In the interim, AveXis has arranged to
make the product available for international markets, subject to
local laws and regulations, as a part of its paid Managed Access
Program via a collaboration with Durbin, a third-party provider.
International inquiries regarding availability of Zolgensma outside
of the US may be made by contacting Durbin at
AveXisMAP@DurbinGlobal.com or +44-20-8869-6506.
AveXis has an exclusive, worldwide license with Nationwide
Children's Hospital to both the intravenous and intrathecal
delivery of AAV9 gene therapy for the treatment of all types of
SMA; has an exclusive, worldwide license from REGENXBIO for any
recombinant AAV vector in its intellectual property portfolio for
the in vivo gene therapy treatment of SMA in humans; an exclusive,
worldwide licensing agreement with Genethon for in vivo delivery of
AAV9 vector into the central nervous system for the treatment of
SMA; and a non‑exclusive, worldwide license agreement with AskBio
for the use of its self‑complementary DNA technology for the
treatment of SMA.
About Zolgensma Clinical Data
The efficacy of
Zolgensma in pediatric patients less than 2 years of age with SMA
with bi-allelic mutations in the SMN1 gene was evaluated in
STR1VE, an open-label, single-arm clinical trial (ongoing), and in
START, an open-label, single-arm, ascending-dose clinical trial
(completed). Patients experienced onset of clinical symptoms
consistent with SMA before 6 months of age. All patients had
genetically confirmed bi-allelic SMN1 gene deletions, two
copies of the SMN2 gene, and absence of the c.859G>C
modification in exon 7 of SMN2 gene (which predicts a milder
phenotype). All patients had baseline anti-AAV9 antibody titers of
≤ 1:50, measured by ELISA. In both trials, Zolgensma was delivered
as a single-dose intravenous infusion.
Efficacy was established on the basis of survival, and
achievement of developmental motor milestones such as sitting
without support. Survival was defined as time from birth to either
death or permanent ventilation. Permanent ventilation was defined
as requiring invasive ventilation (tracheostomy), or respiratory
assistance for 16 or more hours per day (including noninvasive
ventilatory support) continuously for 14 or more days in the
absence of an acute reversible illness, excluding perioperative
ventilation. Efficacy was also supported by assessments of
ventilator use, nutritional support and scores on the Children's
Hospital of Philadelphia Infant Test of Neuromuscular Disorders
(CHOP-INTEND). CHOP-INTEND is an assessment of motor skills in
patients with infantile-onset SMA.
The ongoing clinical trial, STR1VE, enrolled 21 patients (10
male and 11 female) with infantile-onset SMA. Before treatment with
Zolgensma, none of the 21 patients required non-invasive ventilator
(NIV) support, and all patients could exclusively feed orally
(i.e., no need for non-oral nutrition). The mean CHOP-INTEND score
at baseline was 31.0 (range 18 to 47). All the patients received
1.1 × 1014 vg/kg of Zolgensma. The mean age of the 21
patients at the time of treatment was 3.9 months (range 0.5 to 5.9
months).
As of the March 2019 data cutoff,
19 patients were alive without permanent ventilation (i.e.,
event-free survival) and were continuing in the trial, while one
patient died at age 7.8 months due to disease progression, and one
patient withdrew from the study at age 11.9 months. The 19
surviving patients who were continuing in the trial ranged in age
from 9.4 to 18.5 months. By the data cutoff, 13 of the 19 patients
continuing in the trial reached 14 months of age without permanent
ventilation, one of the study's co-primary efficacy endpoints. In
addition to survival, assessment of the other co-primary efficacy
endpoint found that 10 of the 21 patients (47.6%) achieved the
ability to sit without support for ≥ 30 seconds between 9.2 and
16.9 months of age (mean age was 12.1 months). Based on the natural
history of the disease, patients who met the study entry criteria
would not be expected to attain the ability to sit without support,
and only approximately 25% of these patients would be expected to
survive (i.e., being alive without permanent ventilation) beyond 14
months of age. In addition, 16 of the 19 patients had not required
daily NIV use.
Comparison of the results of the ongoing clinical trial to
available natural history data of patients with infantile-onset SMA
provides primary evidence of the effectiveness of Zolgensma.
The completed clinical trial, START, enrolled 15 patients (6
male and 9 female) with infantile-onset SMA, 3 in a low-dose cohort
and 12 in a high-dose cohort. At the time of treatment, the mean
age of patients in the low-dose cohort was 6.3 months (range 5.9 to
7.2 months), and 3.4 months (range 0.9 to 7.9 months) in the
high-dose cohort. The dosage received by patients in the low-dose
cohort was approximately one-third of the dosage received by
patients in the high-dose cohort. However, the precise dosages of
Zolgensma received by patients in this completed clinical trial are
unclear due to a change in the method of measuring Zolgensma
concentration, and to decreases in the concentration of stored
Zolgensma over time. The retrospectively-estimated dosage range in
the high-dose cohort is approximately 1.1 × 1014 to 1.4
× 1014 vg/kg.
By 24 months following Zolgensma infusion, one patient in the
low-dose cohort met the endpoint of permanent ventilation; all 12
patients in the high-dose cohort were alive without permanent
ventilation. None of the patients in the low-dose cohort were able
to sit without support, or to stand or walk; in the high-dose
cohort, 9 of the 12 patients (75.0%) were able to sit without
support for ≥ 30 seconds, and 2 patients (16.7%) were able to stand
and walk without assistance. Comparison of the results of the
low-dose cohort to the results of the high-dose cohort shows a
dose-response relationship that supports the effectiveness of
Zolgensma.
About Zolgensma® (onasemnogene
abeparvovec-xioi)
Zolgensma (onasemnogene abeparvovec-xioi)
is a proprietary gene therapy approved by the US Food and Drug
Administration for the treatment of pediatric patients less than 2
years of age with spinal muscular atrophy (SMA) with bi-allelic
mutations in the survival motor neuron 1 (SMN1) gene. Zolgensma is
designed to address the genetic root cause of SMA by providing a
functional copy of the human SMN gene to halt disease progression
through sustained SMN protein expression with a single,
one-time intravenous (IV) infusion. Zolgensma represents the
first approved therapeutic in a proprietary platform to treat rare,
monogenic diseases using gene therapy. The therapy is also under
regulatory review and anticipated to receive approval in
Japan and the European Union later
this year.
About Spinal Muscular Atrophy (SMA)
SMA is a severe neuromuscular disease characterized by the loss of
motor neurons leading to progressive muscle weakness and paralysis.
SMA is caused by a genetic defect in the SMN1 gene
that codes SMN, a protein necessary for survival of motor
neurons.1,2 The incidence of SMA is approximately 1 in
10,000 live births and it is the leading genetic cause of infant
mortality.2,4 The most severe form of SMA is Type 1, a
lethal genetic disorder characterized by rapid motor neuron loss
and associated muscle deterioration, resulting in mortality or the
need for permanent ventilation support by 24 months of age for more
than 90 percent of patients if left
untreated.3
Indication
Zolgensma (onasemnogene abeparvovec-xioi)
is an adeno-associated virus vector-based gene therapy indicated
for the treatment of pediatric patient less than 2 years of age
with spinal muscular atrophy (SMA) with bi-allelic mutations in the
survival motor neuron 1 (SMN1) gene.
Limitation of Use:
The safety and effectiveness of repeat administration of Zolgensma
have not been evaluated.
The use of Zolgensma in patients with advanced SMA (e.g.,
complete paralysis of limbs, permanent ventilator dependence) has
not been evaluated.
Important Safety Information
Acute Serious Liver Injury
Acute serious liver injury and elevated aminotransferases can occur
with Zolgensma. Patients with pre-existing liver impairment
may be at higher risk. Prior to infusion, assess liver function of
all patients by clinical examination and laboratory testing (e.g.,
hepatic aminotransferases [aspartate aminotransferase and alanine
aminotransferase], total bilirubin and prothrombin time).
Administer systemic corticosteroid to all patients before and after
Zolgensma infusion. Continue to monitor liver function for at least
3 months after infusion.
Thrombocytopenia
Transient decreases in platelet
counts, some of which met the criteria for thrombocytopenia, were
observed at different time points after Zolgensma infusion. Monitor
platelet counts before Zolgensma infusion and on a regular basis
afterwards.
Elevated Troponin-I
Transient increases in cardiac
troponin-I levels (up to 0.176 mcg/L) were observed following
Zolgensma infusion in clinical trials. The clinical importance
of these findings is not known. However, cardiac toxicity was
observed in animal studies. Monitor troponin-I before
Zolgensma infusion and on a regular basis for at least 3
months afterwards.
Adverse Reactions
The most commonly observed adverse
reactions (incidence ≥5%) were elevated aminotransferases and
vomiting.
Please read full Prescribing Information for Zolgensma,
including Boxed Warning for Acute Serious Liver Injury.
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 "designed to," "to halt," "hope," "can," "could,"
"possibilities," "potential," "leading," "excited," "milestone,"
"committed," "will," "PRIME (Priority Medicines) designation,"
"Accelerated Assessment Procedure," "accelerated Sakigake
designation," "anticipated," "plans," or similar terms, or by
express or implied discussions regarding potential marketing
approvals, new indications or labeling for Zolgensma and for the
investigational 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 Zolgensma and the investigational 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 and requirements for increased
pricing transparency; 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 AveXis
AveXis, a Novartis company, is dedicated to developing and
commercializing novel treatments for patients suffering from rare
and life-threatening neurological genetic diseases. Our initial
product, Zolgensma, is a proprietary gene therapy approved by the
US Food and Drug administration for the treatment of pediatric
patients with SMA less than 2 years of age with spinal muscular
atrophy (SMA) with bi-allelic mutations in the survival motor
neuron 1 (SMN1) gene. In addition to developing Zolgensma to
treat all forms of SMA, AveXis also plans to develop other novel
treatments for rare neurological diseases, including Rett syndrome
and a genetic form of amyotrophic lateral sclerosis caused by
mutations in the superoxide dismutase 1 (SOD1) gene. For
additional information, please visit www.avexis.com.
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 more
than 750 million people globally and we are finding innovative ways
to expand access to our latest treatments. About 105 000 people of
more than 140 nationalities work at Novartis around the
world. Find out more at www.novartis.com.
Novartis is on Twitter. Sign up to follow @Novartis at
http://twitter.com/novartis
For Novartis multimedia content, please visit
www.novartis.com/news/media-library
For questions about the site or required registration, please
contact media.relations@novartis.com
References
- Anderton RS and Mastaglia FL. Expert Rev Neurother.
2015;15(8):895-908.
- National Organization for Rare Disorders (NORD). Spinal
Muscular Atrophy.
http://rarediseases.org/rarediseases/spinal-muscular-atrophy/.
Accessed October 9, 2018.
- Finkel RS, et al. Neurology. 2014;83(9):810-7.
- Farrar MA, et al. Ann Neurol. 2017;81(3):355-368.
- Data on file.
- Verhaart IEC, Robertson A, et al. J Neurol. 2017
Jul;264(7):1465-1473.
- Soler‐Botija C, et al. Brain.
2002;125(7):1624-1634.
- Swoboda KJ, et al. Ann Neurol. 2005; 57(5):704-712.
- Administration HRaS. Recommended Uniform Screening Panel
(RUSP). 2018;
https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html.
Accessed October 30, 2018, 2018.
Novartis Media
Relations
|
E-mail:
media.relations@novartis.com
|
|
Eric
Althoff
Novartis External
Communications
+1 646 438 4335
(mobile)
eric.althoff@novartis.com
|
Farah Bulsara
Speer
VP, Corporate
Communications, AveXis
+1 312 543 2881
(mobile)
fSpeer259@avexis.com
|
|
|
|
|
Novartis Investor
Relations
|
Central investor
relations line: +41 61 324 7944
|
E-mail:
investor.relations@novartis.com
|
|
Central
|
|
North
America
|
|
Samir Shah
|
+41 61 324
7944
|
Richard
Pulik
|
+1 862 778
3275
|
Pierre-Michel
Bringer
|
+41 61 324
1065
|
Cory
Twining
|
+1 862 778
3258
|
Thomas
Hungerbuehler
|
+41 61 324
8425
|
|
|
Isabella
Zinck
|
+41 61 324
7188
|
|
|
View original
content:http://www.prnewswire.com/news-releases/avexis-receives-fda-approval-for-zolgensma-the-first-and-only-gene-therapy-for-pediatric-patients-with-spinal-muscular-atrophy-sma-300856654.html
SOURCE Novartis Pharmaceuticals