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nutrition). The mean CHOP-INTEND score at baseline was 31.0 (range 18 to

47). All the patients received 1.1 × 10[1][4] 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 × 10[1][4] to 1.4 ×

10[1][4] 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(R) (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:

https://www.avexis.com/content/pdf/prescribing_information.pdf 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

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