0K9E Novartis Ag

 
TIDMNOVN 
 
 
   -- FDA placed a partial hold on AVXS-101 intrathecal clinical trials for SMA 
      patients based on findings in a small pre-clinical animal study 
 
   -- Adverse events that might be expected from the pre-clinical findings have 
      not been seen in a thorough review of human safety data from all 
      available sources to date 
 
   -- Zolgensma(R) (onasemnogene abeparvovec-xioi) also known as AVXS-101 
      intravenous administration is not impacted and remains available in the 
      US 
 
   -- Novartis is working with FDA to determine next steps to release partial 
      hold and resume dosing in the AVXS-101 intrathecal trials 
 
 
   Basel, October 30, 2019 -- Novartis today announced the United States 
Food & Drug Administration (FDA) placed a partial hold on clinical 
trials for intrathecal administration of AVXS-101. The announcement 
follows an AveXis communication to health authorities and clinical trial 
investigators based on findings from a small, AveXis-initiated 
pre-clinical study in which animal findings showed dorsal root ganglia 
(DRG) mononuclear cell inflammation, sometimes accompanied by neuronal 
cell body degeneration or loss. This partial hold by the FDA does not 
impact marketed Zolgensma(R) or AVXS-101 intravenous (IV) clinical 
trials. 
 
   AveXis is studying AVXS-101 intrathecal administration in patients with 
spinal muscular atrophy (SMA) Type 2. The partial hold impacts 
enrollment in the high dose cohort of the STRONG trial, an ongoing, 
open-label, dose-comparison, multi-center trial designed to evaluate the 
efficacy, safety and tolerability of one-time intrathecal administration 
of AVXS-101. The low and mid dose cohort enrollment has previously been 
completed and interim results have been presented. 
 
   The clinical significance of the DRG inflammation observed in this 
pre-clinical animal study is not known and was not seen in prior animal 
studies with AVXS-101. DRG inflammation can be associated with sensory 
effects. Of note, we have completed a thorough review of human safety 
data from all available sources to date and no adverse effects related 
to sensory changes have been seen in AVXS-101 intrathecal or Zolgensma. 
We are working with health authorities to confirm further guidance to 
clinical investigators. 
 
   We will continue to closely monitor for any reports of related safety 
events in patients. We remain confident that the overall benefit-risk 
profile for patients on treatment is favorable and we continue to 
advance our AVXS-101 intravenous clinical studies. We will work 
diligently with FDA to identify any additional actions necessary to 
resume dosing in the AVXS-101 intrathecal clinical trials. 
 
   AveXis and Novartis remain committed to researching and developing gene 
therapies for SMA, a rare and devastating genetic disease. 
 
   About AVXS-101 Intrathecal Administration 
 
   Investigational IT administration of AVXS-101 is currently being 
evaluated in patients with SMA Type 2 in a Phase 1/2 clinical trial. 
 
   Zolgensma in the United States 
 
   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: 
https://urldefense.proofpoint.com/v2/url?u=https-3A__www.avexis.com_content_pdf_prescribing-5Finformation.pdf&d=DwMF3g&c=ZbgFmJjg4pdtrnL2HUJUDw&r=tKuCXoagkLE-x_MsM3ESu7LA2UIGoHHFs7VJV4YomwM&m=8GupuZL87ZveFYkG4fRvDDO6hgbx14h30QcQYFXuqV8&s=reQzy4H_g_HyWbmkUpZki5hUjMyq4SuaxDDQBBllucQ&e= 
for Zolgensma, including Boxed Warning for Acute Serious Liver Injury. 
 
   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.[3],[4] The incidence of SMA is 
approximately 1 in 10,000 live births and it is the leading genetic 
cause of infant mortality.[1],[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.[5] More than 30% of patients with 
SMA Type 2 will die by age 25.2 
 
   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 "working with," "next steps," "resume," "studying," "ongoing," 
"will," "confident," "continue," "to advance," "committed," "currently," 
"being evaluated," "potential," "can," "plan," "expect," 
"investigational," or similar terms, or by express or implied 
discussions regarding potential marketing approvals for intrathecal 
administration of AVXS-101, or new indications or labeling for Zolgensma, 
or regarding potential future revenues from such investigational and 
approved 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 intrathecal administration of AVXS-101 or Zolgensma 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 108,000 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]   Farrar MA, et al. Ann Neurol. 2017;81(3):355-368. 
 
   [2]   Darras BT, Finkel RS Spinal Muscular Atrophy. Chapter 25 - Natural 
History of Spinal Muscular Atrophy. October 2017. 
 
   [3]   Anderton RS and Mastaglia FL. Expert Rev Neurother. 
2015;15(8):895-908. 
 
   [4]   National Organization for Rare Disorders (NORD). Spinal Muscular 
Atrophy. http://rarediseases.org/rarediseases/spinal-muscular-atrophy/. 
Accessed October 9, 2018. 
 
   [5]   Finkel RS, et al. Neurology. 2014;83(9):810-7. 
 
   Novartis Media Relations 
 
   E-mail: media.relations@novartis.com 
 
 
 
 
Eric Althoff                          Samantha Schwarz 
 Novartis US External Communications   Senior Director, Corporate Communications, AveXis 
 +1 646 438 4335 (mobile)              +1 312 925 6315 (mobile) 
 eric.althoff@novartis.com             sschwarz439@avexis.com 
 
   Antonio Ligi 
 
   Novartis Global External Communications 
 
   +41 61 324 1374 (direct) 
 
   antonio.ligi@novartis.com 
 
   Novartis Investor Relations 
 
   Central investor relations line: +41 61 324 7944 
 
   E-mail: investor.relations@novartis.com 
 
 
 
 
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