Press Release: Novartis: AveXis receives FDA approval for Zolgensma(R), the first and only gene therapy for pediatric patients with spinal muscular atrophy (...

Novartis International AG / AveXis receives FDA approval for

Zolgensma(R), the first and only gene therapy for pediatric patients

with spinal muscular atrophy (SMA). Processed and transmitted by West

Corporation. The issuer is solely responsible for the content of this

announcement.

-- SMA is a rare genetic disease that leads to progressive muscle weakness,

paralysis and, when left untreated in its most severe form, permanent

ventilation or death for most patients by age 2[1],[2]

-- Zolgensma (onasemnogene abeparvovec-xioi) is approved for the treatment

of pediatric patients less than 2 years of age with spinal muscular

atrophy (SMA) including those who are pre-symptomatic at diagnosis

-- Zolgensma is designed to address the genetic root cause of SMA by

replacing the defective or missing SMN1 gene to halt disease progression

with a single, one-time infusion

-- Data from the Phase 3 STR1VE trial show prolonged event-free survival,

increases in motor function and significant milestone achievement in

patients with SMA Type 1, consistent with the Phase 1 START trial

-- In the START trial, patients treated with Zolgensma achieved motor

milestones never seen in the natural history of the disease, including

sitting, talking and some patients walking, with no waning of effect

nearly four years post-dosing

Basel, May 24, 2019 - AveXis, a Novartis company, today announced the US

Food and Drug Administration (FDA) has approved Zolgensma(R)

(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.

"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(TM), 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

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May 24, 2019 12:31 ET (16:31 GMT)