Press Release: New Novartis Entresto(R) real world evidence data shows beneficial impact on quality of life in people living with heart failure

Novartis International AG / New Novartis Entresto(R) real world evidence

data shows beneficial impact on quality of life in people living with

heart failure. Processed and transmitted by Nasdaq Corporate Solutions.

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

-- Entresto reversed trend of worsening New York Heart Association

(NYHA) class - a key measure of the severity of a patient's heart failure

symptoms - improving common physical activity such as exercise and other

daily activities at 90 and 180 days after treatment initiation in a

retrospective database study in patients with heart failure with reduced

ejection fraction (HFrEF) in Germany[1]

-- Entresto significantly reduced levels of NT-proBNP, a key blood marker

associated with cardiovascular risk in patients with heart failure; the

magnitude of the decrease was similar to that observed in the PARADIGM-HF

study[1]

-- Results are consistent with other real world data published in 2017 which

showed Entresto improves NYHA class[2] as well as exercise capacity[2]

-- Majority of patients in this cohort started and stayed on the lowest dose

of Entresto, highlighting the potential to further improve patient

outcomes by increasing treatment to recommended target maintenance dose

-- Data were shared today at the American Heart Association's Scientific

Sessions 2017, building on existing evidence that Entresto has beneficial

effects on the quality of life in addition to reducing cardiovascular

death and heart failure hospitalization

Basel, November 12, 2017 - Novartis today announced new results from a

real-world database study of patients in Germany prescribed Entresto(R)

(sacubitril/valsartan) for heart failure with reduced ejection fraction

(HFrEF). The findings further substantiate the beneficial effect of

Entresto on heart failure symptoms and patients' quality of life

observed in the PARADIGM-HF study and in other real-world cohorts.

Results were presented today as a poster at the American Heart

Association's Scientific Sessions 2017.

"People living with heart failure experience symptoms that severely

limit their physical activities and quality of life," said Shreeram

Aradhye, Chief Medical Officer and Global Head, Medical Affairs,

Novartis Pharmaceuticals. "We are excited to see the growing body of

evidence showing that Entresto has a beneficial effect on the quality of

life in heart failure, in addition to reducing cardiovascular death and

heart failure hospitalization."

The non-interventional, retrospective database study examined changes in

clinical characteristics of 1,643 patients in Germany on Entresto in the

12 months after their first dose. All patients with available data were

analyzed and the results included:

-- The majority of patients had a stable New York Heart Association (NYHA)

class over time. Before Entresto more patients had a trend of worsening

NYHA class. The trend of worsening NYHA was reversed after switching to

Entresto at Day 90 (n=121) and 180 (n=81)[1]. NYHA classification is used

to grade the severity of a patient's heart failure symptoms, with

physicians determining class based on specific criteria (e.g., the level

of discomfort associated with physical activity)

-- There was an approximately 30% mean decrease (-503pg/mg; p<0.001; n=119)

in NT-proBNP, a blood marker used to diagnose heart failure and to

determine prognosis[1]. Levels of NT-proBNP are typically higher in

patients with worse outcomes[3]

-- The majority of patients had a documented first dose of Entresto at the

lowest level (24/26mg twice daily). Of these patients, 36% from the

primary care practices and 41% from the cardiology practices had their

dose up-titrated during follow-up; however, <11% received the target dose

(97/103mg twice daily) at the last recorded prescription

These results are consistent with other real world data published in

2017, which show that Entresto has a beneficial impact on quality of

life:

-- Canada (n=276): 45% of patients switched to Entresto report feeling

better after four weeks, 56% after 12 weeks[4]

-- France (n=200): in patients treated with Entresto improvement in NYHA

class and exercise capacity was observed[2]

These data results were also consistent with post-hoc analyses of the

landmark PARADIGM-HF clinical trial published between 2015 and 2017,

which show that:

-- In surviving patients, treatment with Entresto improved patients' quality

of life, including heart failure symptoms and physical limitations as

compared with enalapril, as measured by KCCQ[5]; this effect is sustained

over 36 months

-- Entresto improved seven out of 10 activities when compared with enalapril,

with the most significant changes in household chores and intimate/sexual

relationships[6]

-- Among patients who had been hospitalized for heart failure, Entresto has

been shown to slow the further decline in health-related quality of life

in approximately half of patients compared to enalapril, as measured by

KCCQ[7]

-- Patients were less likely to have NYHA functional class deterioration on

Entresto compared with enalapril[8]

KCCQ is a self-administered health-related quality of life (HRQL)

measure for HF patients, with higher scores indicating fewer symptoms

and physical limitations associated with HF[5]. The questionnaire

quantifies physical function, symptoms (recent change, frequency and

burden), social function, self-efficacy and knowledge, and quality of

life. Scores are transformed to a range of 0-100, in which higher scores

reflect better health status.

About the German Disease Analyzer Study

This non-interventional, retrospective database study, 'Dosing patterns

and evolution of clinical parameters in patients prescribed

sacubitril/valsartan in Germany,' was initiated to assess dosing

patterns and the evolution of clinical parameters in patients who were

prescribed Entresto(R) (sacubitril/valsartan) in the primary care or

cardiology setting in Germany. Patients aged 18 and above were

identified via electronic medical records from the German IMS(R) Disease

Analyzer database, which contained data from 1,095 primary care

practices and 43 cardiology practices at the time of the study. The

study period was January 1, 2016 to December 31, 2016, with a maximum

look-back period to January 1, 2015.

The study population included 1,643 patients with a subset of patients

having available data for analysis (n=119 evaluated for impact on

NT-proBNP and n=121 evaluated for impact on NYHA classification trend).

About the PARASAIL study

The PARASAIL study, 'Patient reported outcomes from the Canadian real

world experience use of sacubitril/valsartan in patients with heart

failure and reduced ejection fraction (HFrEF),' is an ongoing,

multi-center, open-label, prospective, post-approval (Phase IV) study

being conducted in 302 patients with HFrEF at 32 study sites across

Canada. It aims to characterize the tolerability, safety and therapeutic

effectiveness of Entresto(R) (sacubitril/valsartan) 97/103mg twice daily

in Canadian patients with HFrEF.

In addition to primary and secondary efficacy and safety endpoints, the

study included pre-specified exploratory endpoints to evaluate heart

failure symptoms and quality of life (QoL): changes in Patient Global

Assessment (PGA - a seven-point patient self-evaluation scale that

determines how a patient feels at subsequent visits compared with

baseline), Minnesota Living with Heart Failure Questionnaire (MLHFQ - a

validated questionnaire representative on how heart failure is impacting

key dimensions of QoL) and EuroQoL questionnaire (EQ-5D - an instrument

consisting of five domains [morbidity, self-care, usual activity, pain,

and anxiety and depression among patients] and a visual analogue scale

to assess the current health status of patients) from baseline to weeks

four, 12 and 24.

The interim analysis of this study evaluated these pre-specified

exploratory endpoints in the first 276 patients who completed their

initial 12 weeks of Entresto treatment. Results showed early signs of

improvement in two of the three validated QoL questionnaires: nearly

half of the patients reported feeling better (using PGA questionnaire)

and there was a significant improvement in MLHFQ scores. No changes were

detected based on the EQ-5D score.

These results were published in the September 2017 supplement of the

European Journal of Heart Failure. 2017;19: p34.

About the France Study

The study 'Results of a single center experience on 200 consecutive

patients treated with Entresto(R) (sacubitril/valsartan),' evaluates

results from a monocentric cohort of 200 consecutive heart failure with

reduced ejection fraction (HFrEF) patients treated with Entresto.

Between October 2015 and September 2016, 200 patients received Entresto;

180 were evaluated one month after introduction, 157 three months after,

and 99 after six months of follow up.

Entresto was initiated at half dosage or less depending on the fragility

of the patient (78% at 49mg/51 mg twice daily and 22% at 24/26mg twice

daily). Patients attended a first follow-up appointment after one month

of treatment, and if tolerance was good, the dosage was increased. At

three months, 82% of patients received the target dose of 97/103mg.

After one month of treatment, functional class improved significantly

with 4.5% New York Heart Association (NYHA) 1, 81% NYHA 2, and 14.5%

NYHA 3 (p= <0.001), as the 6-minute walk distance (511 vs 461m, p

<0.0001). These improvements occurred from the first month of treatment

with the half dosage of Entresto and were still significantly present

after six months of follow up.

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November 12, 2017 13:30 ET (18:30 GMT)