Investor Update

Basel, 11 December 2009

Positive interim analysis supports early closure of heart failure trial

Further analysis could promote new paradigm in the management of heart failure

Roche (SIX: RO, ROG; OTCQX: RHHBY) and study investigators at the Massachusetts General Hospital have announced today that active enrollment into the Pro-BNP Outpatient Tailored Congestive Heart Failure Therapy (PROTECT) study (Clinical Trials.gov identifier: NCT00351390) has been stopped early based on a positive interim analysis.

PROTECT, a prospective randomized trial comparing a strategy of aggressive heart failure therapy guided by levels of a cardiac hormone—amino-terminal pro-B type natriuretic peptide (NT-proBNP)—versus standard heart failure treatment without NT-proBNP guidance has been enrolling subjects in the Heart Center at the Massachusetts General Hospital since 2006.

The positive interim analysis suggests a strategy of NT-proBNP guided heart failure care was independently associated with a significant reduction in total cardiovascular events, the primary endpoint of the study, which included relevant cardiac outcomes, such as worsening heart failure, heart failure hospitalization, and cardiovascular death.

Tests for NT-proBNP, a cardiac hormone that is released into the blood when the heart wall is stretched, are developed and marketed by Roche. NT-proBNP was approved by the US Food and Drug Administration (FDA) as an objective marker for the diagnosis and prognosis of heart failure as well as the risk assessment in patients with acute coronary syndrome.¹

Commenting on the trial’s early suspension, lead investigator, Dr James Januzzi, Associate Professor of Medicine at Harvard Medical School and Director of the Cardiac Intensive Care Unit at the Massachusetts General Hospital said: “There are few reasons to stop a trial early, the most compelling of which is unequivocal success.  In the case of PROTECT, the data from interim analysis of the study appear to indicate a significant difference between the treatment arms in favor of the NT-proBNP group.”

Concentrations of NT-proBNP are known to be predictive of future risk in chronic heart failure. However, while therapies for heart failure that improve patient outcomes are known to lower NT-proBNP values, the strategy to actively “guide” heart failure therapy by combining standard clinical titration of medications together with a targeted strategy to lower NT-proBNP values (with the hope to reduce events further than heart failure therapy guided by clinical judgment alone) remains to be proven.

In the PROTECT study, patients with chronic systolic heart failure (left ventricular ejection fraction <40%) were randomized to one of two treatment approaches: a standard-of-care arm, where patients received aggressive guideline-compliant heart failure care, and an NT-proBNP arm, where patients were treated with similar aggressive clinical care, but investigators also aimed to decrease NT-proBNP concentrations to a level below 1,000 pg/mL, a value below which previous studies have shown the cardiovascular event risk in heart failure to be considerably lower.²

“The decision to stop the trial indicates strong potential for the guided therapy approach,” Januzzi continued.  “While previous studies have returned mixed results with respect to the approach of "guided therapy" with natriuretic peptide testing, the reduction in total cardiovascular events in the NT-proBNP arm suggests the important role of this cardiac hormone in the management of heart failure,” he said.

The trial is now closed. Final patient visits will be carried out and final data will be collected to allow a full analysis.  Final results of the study will be presented and published in 2010, once the analysis is complete.

Besides the primary endpoint of total cardiovascular events over a one year period, other endpoints in PROTECT will include effects of NT-proBNP guidance on quality of life, effect of NT-proBNP guided care on cardiac structure and function, and overall costs of care.

It is estimated that as many as five million Americans have heart failure, with 400,000-500,000 new cases/year; the diagnosis carries a mortality rate that exceeds many cancers. Heart failure ranks among the most costly chronic conditions in developed countries, with the burden being greatest among the elderly. Heart failure hospitalization represents a major burden on the health care system.

“Given this rapidly increasing incidence of heart failure, and relative shortage of novel therapies for diagnosis, a new strategy of care utilizing existing therapies including the intention to not only address symptoms, but also to lower NT-proBNP concentrations with the goal of reducing risk in parallel, would not only contribute to better patient outcomes but also likely reduce healthcare costs.”  

“We are excited to see the full results of the trial, and ascertain next steps for proceeding forwards with the concept of biomarker guided heart failure care,” concluded Dr Januzzi.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Group posted sales of 45.6 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

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1) Roche Diagnostics. NT-pro BNP , US Package Insert. 2008
2)Troughton RW, Richards AM. Outpatient Monitoring and Treatment of Chronic Heart Failure Guided by Amino-Terminal Pro–B-Type Natriuretic Peptide Measurement. Am J Cardiol 2008; 101 [suppl]: 72A-75A