* Drug cuts cardiovascular death, hospitalisations by fifth
* Has been little progress in heart failure in past decade
* Novartis sees multibillion-dollar sales opportunity
* Glowing review of drug in New England Journal of Medicine
(Adds further comment from investigators, reaction)
By Ben Hirschler
BARCELONA, Aug 30 A new medicine from Novartis
could replace drugs that have been central to treating
heart failure for a quarter of century, after proving remarkably
effective in reducing deaths in a keenly awaited study.
The experimental treatment, known at LCZ696, cut the risk of
both cardiovascular death and admissions to hospital by a fifth,
boosting hopes for a product seen as a multibillion-dollar
seller - thanks, in part, to its expected premium price.
"Given the survival advantage of LCZ696 over currently
available drugs, once this drug becomes available, it would be
difficult to understand why physicians would continue to use
traditional (drugs) ... for the treatment of heart failure,"
said Milton Packer of the University of Texas.
Packer was joint-principal investigator on the study with
John McMurray of the University of Glasgow, who called the
There has been little progress for more than a decade in
treating chronic heart failure, in which the heart fails to pump
enough blood around the body, so there is excitement about the
new medicine among both doctors and investors.
The study, comparing LCZ696 to an older drug already known
to improve survival, was stopped early five months ago because
the benefit to patients was overwhelmingly positive - but the
size of the effect was only disclosed on Saturday at the annual
meeting of the European Society of Cardiology (ESC), the world's
largest cardiology congress.
ESC officials flagged the PARADIGM-HF trial as a highlight
of the five-day event in Barcelona and Piotr Ponikowski of the
Medical University of Wroclaw, who was not involved in the
trial, urged a fast-track review of treatment guidelines given
the "striking" finding.
Novartis is looking to LCZ696 to revive its fortunes as the
blood pressure pill Diovan faces generic competition. As a
result, the data on the product is widely viewed as the most
important catalyst for the stock over the remainder of 2014.
"This result is better than we ever could have anticipated,"
the company's pharmaceuticals head David Epstein told Reuters.
In addition to reducing deaths and hospital admissions, the
drug also made patients feel measurably better, underscoring the
case for it to replace existing treatments and bolstering
expectations for multibillion-dollar sales, he said.
In the study - the largest ever undertaken in heart failure,
involving more than 8,400 patients - LCZ696 was tested against
enalapril, a so-called ACE inhibitor drug.
Patients who took LCZ696 were 20 percent less likely than
those on enalapril to die of cardiovascular causes and were also
21 percent less likely to be admitted to hospital, according to
results presented at congress and also published online by the
New England Journal of Medicine (NEJM).
The relative risk reduction for a composite of both, which
was the primary measure for the trial, was also 20 percent.
Industry analysts had been expecting a risk reduction with
LCZ696 of between 15 percent and the low 20s percent.
Around 32 patients had to be treated with LCZ696 to prevent
one cardiovascular death - and Epstein said this suggested there
would be approximately 90,000 fewer deaths a year in the United
States and Europe if patients were switched to the new drug.
WIDE SPECTRUM OF PATIENTS
In a glowing NEJM editorial, Mariell Jessup, a heart failure
expert at the University of Pennsylvania, said the beneficial
effects of the drug could apply to a wide spectrum of patients,
even those receiving the best current therapy.
"PARADIGM-HF may well represent a new threshold of hope for
patients with heart failure," she wrote.
The size of the benefit is critical in determining how
broadly LCZ696 will be used. Unlike a heart attack, heart
failure develops progressively but the prognosis is poor.
LCZ696 is a two-in-one pill, taken twice a day, combining
Diovan's active ingredient valsartan and another class of drug
called a neprilysin inhibitor.
In terms of side effects, patients on LCZ696 suffered more
low blood pressure and non-serious swelling but less kidney
impairment, high potassium and cough than the enalapril group.
Analyst forecasts for LCZ696 have been climbing in recent
months and the consensus for sales in 2019 - four years after
its expected launch - currently stands at $1.9 billion,
according to Thomson Reuters Cortellis.
Still, analysts have found it hard to predict the drug's
potential pending the detailed data, prompting some to adopt a
cautious stance while others see sales well above $5 billion.
Deutsche Bank analysts have predicted the drug could
eventually sell as much as $10 billion a year, assuming it works
across two broad groups of heart failure patients.
While the PARADIGM-HF study targeted patients with reduced
ejection fraction, where the heart muscle does not contract
effectively, Novartis is also starting a trial in a
similar-sized group with preserved ejection fraction, where the
ventricles do not relax as they should.
Heart failure affects about 26 million people across the
United States and Europe.
Epstein said LCZ696 could reach the market by the third
quarter of 2015. He declined to comment on how much it would
cost, although he said there would be a strong economic case for
its use since it would save money by reducing hospital visits.
Analysts at Bernstein believe it could be priced at around
$7 a day in the United States and $4 in Europe, where drug
prices are lower. They noted there was very little in the
pipelines of other companies in terms of competing products.
(Editing by Tom Pfeiffer and Louise Heavens)