Press Release: Novartis receives complete response letter from U.S. FDA for inclisiran

-- The U.S. Food and Drug Administration (FDA) has not raised any concerns

related to the efficacy or safety of inclisiran. The complete response

letter is due to unresolved facility inspection-related conditions

-- No onsite inspection was conducted of the single third-party facility in

question. If a facility inspection is needed, FDA will define an approach

once safe travel may resume based on public health need and other factors

-- Novartis will work with FDA and the third-party manufacturing facility in

Europe to complete the inclisiran review, to bring this potential

first-in-class siRNA to patients in the U.S. as quickly as possible

Basel, December 18, 2020 -- The U.S. Food and Drug Administration (FDA)

has issued a complete response letter (CRL) regarding the new drug

application (NDA) for inclisiran, a potential treatment for

hyperlipidemia in adults who have elevated low-density lipoprotein

cholesterol (LDL-C) while being on a maximum tolerated dose of a statin

therapy. The FDA stated that the agency cannot approve the NDA by the

Prescription Drug User Fee Act (PDUFA) action date of December 23, 2020,

due to unresolved facility inspection-related conditions. The conditions

will be conveyed to the European manufacturing facility within 10

business days. The third-party facility is responsible for drug product

manufacturing. Satisfactory resolution of the unresolved facility

inspection-related conditions is required before the Novartis NDA may be

approved. No onsite inspection was conducted. If it is determined that a

facility inspection is needed to approve the application, the FDA will

define an approach for scheduling once safe travel may resume based on

public health need and other factors.

"Novartis is confident in the quality of the regulatory submission for

inclisiran, which includes a robust body of evidence related to efficacy

and safety. We look forward to meeting with the FDA and our third-party

manufacturing partner to discuss the feedback received and next steps,"

said John Tsai, Head Global Drug Development and Chief Medical Officer,

Novartis. "We are committed to bringing this potential first-in-class

small interfering RNA cholesterol-lowering treatment to patients as soon

as possible."

The European Commission (EC) recently granted Novartis marketing

authorization for Leqvio(R) (inclisiran) in Europe on December 11, 2020.

About inclisiran

Inclisiran (KJX839) is the first and only small interfering RNA (siRNA)

therapy to reduce low-density lipoprotein cholesterol (LDL-C) levels via

an RNA interference (RNAi) mechanism of action and could help improve

outcomes for patients with atherosclerotic cardiovascular disease

(ASCVD), a deadly form of cardiovascular disease(1-3). With two doses a

year and effective and sustained LDL-C reduction, inclisiran works as a

complement to statins. Inclisiran works differently from other therapies

by preventing the production of the target protein in the liver,

increasing hepatic uptake of LDL-C and clearing it from the

bloodstream(3). Inclisiran is dosed initially, again at 3 months, and

then once every 6 months. In three clinical trials, patients taking

inclisiran maintained LDL-C reduction throughout each 6-month dosing

interval(1,2). Administered in-office as a subcutaneous injection,

inclisiran is expected to integrate seamlessly into a patient's

healthcare routine(1,2).

In the Phase III trials, inclisiran was well-tolerated(1,2). The most

common adverse events reported (>=3% of patients treated with inclisiran

and occurring more frequently than placebo) were injection site reaction,

arthralgia, urinary tract infection, diarrhea, bronchitis, pain in

extremity and dyspnea(1,2). Among those, injection site reactions were

the most frequent ones. Those were generally mild and none were severe

or persistent(1,2).

Novartis has obtained global rights to develop, manufacture and

commercialize inclisiran under a license and collaboration agreement

with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

About Novartis in Cardiovascular-Renal-Metabolism

Bending the curve of life requires addressing some of society's biggest

public health concerns. Novartis has an established and expanding

presence in diseases covering the heart, kidney and metabolic system. In

addition to essential treatment Entresto(R) (sacubitril/valsartan),

Novartis has a growing pipeline of potentially first-in-class molecules

addressing cardiovascular, metabolic and renal diseases.

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 "will," "may," "as quickly as possible," "potential," "confident,

" "look forward," "committed," "potential," "as soon as possible,"

"could," "expected," "investigational," "pipeline," "launch," or similar

terms, or by express or implied discussions regarding potential

marketing approvals, new indications or labeling for inclisiran and the

other investigational and 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

inclisiran will be approved for sale in the United States, or if

approved, at any particular time. Neither can there be any guarantee

that inclisiran or the other 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 inclisiran and such other products could be

affected by, among other things, regulatory actions or delays or

government regulation generally; the uncertainties inherent in research

and development, including clinical trial results and additional

analysis of existing clinical data; 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, economic and business

conditions, including the effects of and efforts to mitigate pandemic

diseases such as COVID-19; safety, quality, data integrity 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 800 million people globally

and we are finding innovative ways to expand access to our latest

treatments. About 110,000 people of more than 140 nationalities work at

Novartis around the world. Find out more at https://www.novartis.com.

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References

1. Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in

patients with elevated LDL cholesterol. N Engl J Med. 2020;382:1507-1519.

doi:10.1056/NEJMoa1912387.

2. Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the treatment of

heterozygous familial hypercholesterolemia. N Engl J Med.

2020;382(16):1520-1530. doi:10.1056/NEJMoa1913805.

3. Stoekenbroek RM, Kallend D, Wijngaard PL, et al. Inclisiran for the

treatment of cardiovascular disease: the ORION clinical development

program. Future Cardiol. 2018;14(6):433--442.

# # #

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Novartis External Communications Global Head, Cardio-Renal-Metabolism

+41 61 324 2279 (direct) Communications

E-mail: anja.von_treskow@novartis.com +41 79 510 8756 (mobile)

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December 18, 2020 16:50 ET (21:50 GMT)