PRESS RELEASE: Novartis' serelaxin (RLX030) improved symptoms and mortality across multiple subgroups of patients with acute heart failure[1],[2]

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-2 of 3- 02 Sep 2013 12:01:00 UTC  PRESS RELEASE: Novartis' serelaxin (RLX030) improved symptoms and mortality across multiple subgroups of patients with acute heart failure[1],[2]

Novartis International AG / Novartis' serelaxin (RLX030) improved symptoms and mortality across multiple subgroups of patients with acute heart failure[1],[2] . Processed and transmitted by Thomson Reuters ONE. The issuer is solely responsible for the content of this announcement.

-- New analysis of RELAX-AHF published in the European Heart Journal and presented as a late breaker at the European Society of Cardiology congress[1],[2]

-- If approved, RLX030 has the potential to be the first treatment breakthrough for AHF patients in 20 years[3],[4]

Basel, September 2, 2013 - Results from a new analysis of the Phase III RELAX-AHF study published today in the European Heart Journal and presented as a late breaker at the European Society of Cardiology (ESC) congress in Amsterdam indicate that the investigational medicine RLX030 consistently improved symptoms and mortality across multiple subgroups of patients with acute heart failure (AHF) assessed in the trial[1],[2].

The addition of RLX030 to conventional treatment led to improvements in breathlessness (dyspnea) and mortality at 6 months across all pre-specified subgroups including those with renal impairment (eGFR<50ml/min), the elderly (>=75 years) and patients with atrial fibrillation,[1],[2] although the small numbers of patients in each group limit the statistical conclusions that can be drawn. AHF patients require urgent treatment so prompt decision-making to stop heart failure worsening is crucial in spite of patients often having diverse clinical profiles.

"Treatment of AHF is largely unchanged since the 1970s and with RLX030 Novartis aims to bring the first therapy shown to improve longer-term outcomes to patients," said David Epstein, Division Head of Novartis Pharmaceuticals. "This new analysis adds to the overall results from RELAX-AHF that showed intervention with RLX030 is key to halting the downward spiral of organ damage that occurs during an AHF episode".

Each year around 3.5 million AHF episodes happen in the US and EU alone[5]; this is expected to increase further as the population ages. Every AHF episode contributes to a downward spiral of worsening heart failure and damage to vital organs, such as the heart and kidneys, which decreases the chance of the patient surviving another episode[6]. There is an urgent need for new treatments that help relieve patients' symptoms and protect the vital organs against damage during an AHF episode, as well as have the potential to increase life expectancy in the AHF patient population.

Results from RELAX-AHF previously presented in 2012 demonstrated that RLX030 reduced the risk of death by more than one-third (37%) compared with conventional treatment at six months[7]. RLX030 is currently the only drug for which a reduction in all-cause mortality has been observed in patients with AHF in a major study[7].

RLX030 is currently being assessed by health authorities around the world including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of AHF. In June 2013 the FDA granted RLX030 Breakthrough Therapy designation status, recognizing its potential to address a serious unmet medical need[8].

Study details

Results from the full analysis of RELAX-AHF were presented at the American Heart Association congress in November 2012. RELAX-AHF was an international randomized, double-blind study involving 1,161 patients and was designed to compare the efficacy and safety profile of RLX030 to placebo in addition to standard therapy for the treatment of AHF. RLX030 was given within 16 hours of hospitalization (mean 7.8 hours) in the form of an intravenous infusion (30 mcg per kg per day) for 48 hours in addition to conventional therapy for AHF. The study had two primary endpoints using different scales to measure reduction in breathlessness (dyspnea). The visual analog scale (VAS) showed a significant benefit up to day five (p=0.0075), whereas the Likert scale (a baseline-related short-term assessment of dyspnea relief) did not reach significance at 6, 12 and 24 hours (p=0.702)[1]. As one of the primary endpoints was met the study was positive according to protocol criteria[7].

Analysis of additional endpoints showed that patients who received RLX030 had a 37% reduction in the risk of mortality at 6 months after an AHF episode compared with those who received conventional treatment[7]. RLX030 also significantly reduced heart failure worsening up to day 14 (p=0.026) thereby decreasing the need for intensified treatment, as well as reducing the mean length of stay in hospital by 0.9 days (p=0.039) and in the intensive/cardiac care unit by 0.4 days (p=0.029)[7]. The study did not meet secondary endpoints including days alive and out of hospital up to day 60 (p=0.438), and cardiovascular death or re-hospitalization due to heart or kidney failure up to day 60 (p=0.862)[7]. RELAX-AHF showed that the side effects of RLX030 were comparable to conventional therapy and the drug was generally well tolerated[7].

In this subgroup analysis the effects of RLX030 versus conventional treatment were similar across multiple pre-specified groups with respect to the primary dyspnea endpoints, 60-day composite outcomes, and 180-day mortality[1],[2], although due to the small numbers of patients in each subgroup the study is underpowered to draw conclusions about individual groups. Subgroups included age, sex, race, geographic region, estimated glomerular filtration rate, time from presentation to randomization, baseline systolic blood pressure, history of diabetes, atrial fibrillation, ischemic heart disease, cardiac devices and intravenous nitrates at randomization.

About RLX030 and Novartis' commitment to heart failure

RLX030 is a form of a naturally occurring hormone (human relaxin-2), present in both men and women[9], although its levels rise in pregnant women to help the body cope with the additional cardiovascular demands during pregnancy[10]. Another Novartis compound called LCZ696, an angiotensin receptor neprilysin inhibitor, is the first in a new class of drugs being evaluated for the treatment of chronic heart failure. A robust clinical development program including two global phase III studies (PARAGON-HF and PARADIGM-HF) is underway to fully assess the efficacy and safety profile of LCZ696[11],[12].

About heart failure

Heart failure is a debilitating and potentially life-threatening condition where the heart cannot pump enough blood around the body. More than 20 million people suffer from heart failure worldwide and this number is increasing[13],[14]. The condition is often fatal when patients have one or repeated AHF episodes. As an AHF episode approaches, patients become severely breathless and incapacitated and may rapidly gain weight due to fluid build-up in the lungs and around the body. Every AHF episode results in a downward spiral of worsening health and damage to vital organs, such as the heart and kidneys, which decreases the chance of the patient surviving another episode[6].

Patients experiencing an AHF episode require immediate treatment, making AHF the most common cause of hospitalization in patients over 65 years[15],[16]

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as "potential," "investigational," "aims, " "expected," "being assessed," "Breakthrough Therapy," "commitment," "being evaluated," "underway," or similar expressions, or by express or implied discussions regarding potential approvals for RLX030 or LCZ696, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that RLX030 or LCZ696 will be approved for sale in any market, or at any particular time. Nor can there be any guarantee that such products will achieve any particular levels of revenue in the future. In particular, management's expectations regarding such products could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. 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 provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, (MORE TO FOLLOW) Dow Jones Newswires

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-3 of 3- 02 Sep 2013 12:01:00 UTC  PRESS RELEASE: Novartis' serelaxin (RLX030) -2-
over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

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References

[1] Metra et al. Administration of serelaxin to patients with acute heart failure: are there any differences across RELAX-AHF subgroups? Clinical Trial Update Hot Line I: Updates on hypertension, heart failure and diabetes; Abstract 3478. European Society of Cardiology 2013.

[2] Metra et al. Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX- AHF. Eur Heart J 2013 Sept 2; ePub ahead of print (doi: 10.1093/eurheartj/eht371).

[3] Cowie et al. Acute heart failure - a call to action. Br J Cardiol 2013;20(2):S1-S11.

[4] Felker et al. Clinical trial of pharmacological therapies in acute heart failure syndromes, Circ Heart Fail 2010;3:314-325.

[5] Novartis, data on file: approximately 1.86 million diagnosed events in the US and 1.6 million in the top 5 EU countries.

[6] Mosterd A, Hoes A. Clinical epidemiology of heart failure. Heart 2007;93:1137-1146.

[7] Teerlink et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013;381:29-39.

[8] FDA. Frequently Asked Questions: Breakthrough Therapies. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm accessed 13 August 2013.

[9] Teichman et al. Relaxin, a pleiotropic vasodilator for the treatment of heart failure. Heart Fail Rev 2009;14:321-329.

[10] Teichman et al. Relaxin: Review of biology and potential role in treating heart failure. Curr Heart Fail Rep 2010;7:75-82.

[11] Solomon S. PARAMOUNT: Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in patients with heart failure and preserved ejection fraction: Primary results from the PARAMOUNT study. ESC Presentation at European Society of Cardiology, August 26, 2012.

[12] ClinicalTrials.gov: Prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in patients with heart failure (PARADIGM-HF). http://clinicaltrials.gov/ct2/show/NCT01035255. Accessed August 2012.

[13] Roger et al. Heart disease and stroke statistics--2012 update : A report from the American Heart Association. Circulation 2012;125:e2-e220.

[14] Dickstein et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008;29:2388-2442.

[15] Forman et al. Influence of age on the management of heart failure: Findings from Get With the Guidelines-Heart Failure (GWTG-HF). Am Heart J 2009;157:1010-1017.

[16] Healthcare Cost and Utilization Project 2009 (http://www.hcup-us.ahrq.gov/reports/factsandfigures/2009/pdfs/FF_2009_exhibit2_4.pdf)

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