CHMP confirms negative opinion following re-examination of RLX030 - further evidence is required
Novartis aims to resubmit for approval with data from ongoing second Phase 3 study (RELAX-AHF-2)

Basel, - Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) has adopted a negative opinion for the use of RLX030 (serelaxin) in the treatment of acute heart failure (AHF) indicating that further evidence is required for a license to be granted in the EU. This follows the company's request for re-examination after a previous negative opinion was issued in January. Novartis aims to resubmit for approval as soon as additional data is available from the ongoing global trial program, including the 6,300 patient RELAX-AHF-2 study, one of the largest and most robust programs undertaken by a company for an AHF drug.

"We are disappointed that patients in Europe will not have access to RLX030 in 2014 but we believe in the value that RLX030 can bring to patients and are committed to extending the current evidence base to confirm this," said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. "20 million people across the world face poor quality of life and high risk of death from heart failure and it remains our mission to change the course of this disease with our research and development efforts."

Heart failure is a debilitating and potentially life-threatening condition where the heart cannot pump enough blood around the body. This, in most cases, happens because the heart muscle responsible for the pumping action weakens over time or becomes too stiff^[1]. Heart failure is a significant and growing public health concern affecting over 20 million people worldwide^[2],[3] and costing the world economy $45 billion annually.^[3]-[6]

Novartis is committed to research in heart failure with a portfolio including RLX030 for acute heart failure and LCZ696 for chronic heart failure.

About RLX030 and Acute Heart Failure
Patients experiencing an AHF episode have rapidly worsening, life-threatening symptoms requiring urgent hospital treatment, including difficulty breathing and swelling around the body as fluid accumulates in the lungs and tissues. Despite significant progress in other heart conditions, there have been no treatment breakthroughs for AHF in 20 years^[7]. Commonly used medicines only treat the immediate symptoms and have not been proven to have an impact on longer-term outcomes^[8]-[10].

RLX030 is a form of a naturally occurring hormone (human relaxin 2) present in both men and women which rises in women during pregnancy to help the body cope with the additional cardiovascular demands.^[11],[12] It has multiple effects including relaxing the blood vessels and reducing fluid buildup. Some evidence also suggests it can reduce damage to heart and vital organs, which may be of particular importance when considering the cascade of damage that occurs during an AHF episode.^{[2],[13],[14]}

References
^[1] Harrison's 'Principles of Internal Medicine', Seventeenth Edition pages 1442 - 1455
^[2] Gheorghiade M, Pang P, Acute heart failure syndromes, Journal of the American College of Cardiology 2009; 53 (7):557-73
^[3] Go AS, Mozaffarian D, Roger VL, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation. 2014;128:00-00
^[4] Lloyd-Jones et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:e46-215
^[5] Berry et al. Economics of chronic heart failure. Eur J Heart Fail. 2001;3:283291
^[6] Stewart et al. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. 2002;4:361371
^[7] Cowie et al, Acute heart failure - a call to action, The British Journal of Cardiology, 2013, 20(2):S1-S11
^[8] Hunt S et al. Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. Circulation. 2009;119:e391-e479
^[9] McMurray et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787-1847
^[10] Gheorghiade et al. The challenge of acute heart failure syndromes. Am J Cardiol. 2005;96:86G89.
^[11] Teichman S et al. Relaxin, a pleiotropic vasodilator for the treatment of heart failure. Heart Fail Rev. 2009;14:321-329
^[12] Teichman SL et al. Relaxin: Review of biology and potential role in treating heart failure. Curr Heart Fail Rep. 2010;7:75-82
^[13] Teerlink JR, Cotter G, Felker GM, 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.
^[14] Metra M, Cotter G, Davison BA, et al. Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) Development Program. J Am Coll Cardiol. 2013;61:196-206.

Source: Novartis