Novartis investigational renin inhibitor Aliskiren offers once-daily, dose-dependent blood pressure reductions

Main Category: Hypertension
Article Date: 11 Mar 2005 - 16:00 PDT

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Study also demonstrates a safety and tolerability profile for Aliskiren comparable to placebo -

Data published in the March issue of the journal Circulation 1 indicates a significant dose-dependent response with the antihypertensive agent Aliskiren vs. placebo and another antihypertensive, irbesartan. Aliskiren (SPP100) is potentially the first in a new class of orally active renin inhibitors in development for treating hypertension with the potential for improved end organ protection.

"These data support results from earlier studies and provide additional evidence regarding Aliskiren's potential as a useful antihypertensive agent for people with mild-to-moderate hypertension," said lead investigator Alan Gradman, MD, Chief, Division of Cardiovascular Diseases, The Western Pennsylvania Hospital, Pittsburgh, Penn.

In the eight-week study investigators compared the antihypertensive efficacy and safety of Aliskiren with an active comparator, the angiotensin receptor II blocker irbesartan and placebo. Six hundred and fifty-two patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure ¡Ý95 and <110 mm Hg) were randomized to oral once-daily Aliskiren at 150, 300, or 600 mg doses, irbesartan 150 mg or placebo. All doses of Aliskiren effectively lowered trough (level before next dose is administered) mean sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP). DBP reductions for Aliskiren 150 mg, 300 mg, 600 mg were 9.3mm, 11.8mm, and 11.5mm Hg respectively while SBP reductions were 11.4mm, 15.8mm, and 15.7mm respectively. As with other Aliskiren trials, this study demonstrated dose-dependent efficacy up to the 300 mg dose of Aliskiren.

According to Joerg Reinhardt, Head of Development, Novartis Pharma AG, "People with cardiovascular disease/hypertension are still not being adequately treated to prevent detrimental outcomes. With its unique effect on renin, Aliskiren may offer a new treatment option that goes beyond blood pressure lowering and that will potentially offer further protection for the heart and kidney as well. We continue to be encouraged and look forward to exploring the full potential of the agent."

Suppression of the renin angiotensin system (RAS) using angiotensin converting enzyme inhibitors and angiotensin II receptor blockers has been widely shown to treat hypertension and reduce cardiovascular events. Aliskiren's novel mechanism of action offers a new way to address the RAS by inhibiting renin and reducing plasma renin activity (PRA), thereby optimizing RAS suppression. Other therapies which act on the RAS provide incomplete suppression due to indirect pathways and compensatory feedback mechanisms which in turn result in increased PRA.

Aliskiren treatment was well tolerated at all doses in the study. The most commonly reported events were headache, dizziness and diarrhea. The incidence of adverse events and discontinuations due to adverse events was relatively low and was similar to that observed with the placebo or irbesartan treatment.

The phase III clinical trial program for Aliskiren as monotherapy and in combination with other antihypertensive therapies is ongoing. The development of Aliskiren is driven by Novartis' cardiovascular and metabolic research and development program. Novartis is a worldwide leader in cardiovascular care and in the treatment of a variety of metabolic disorders.

Novartis discovered Aliskiren and licensed it to Speedel, a privately-held biopharmaceutical company in 2000. After completion of phase I and II trials by Speedel, Novartis exercised a call-back option in 2002 and is now solely responsible for development and commercialization of Aliskiren.

The foregoing release contains forward-looking statements that can be identified by terminology such as "potentially", "potential", "may offer", "look forward", or similar expressions, or by discussions regarding potential regulatory approvals for or potential future revenue from Aliskiren. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Aliskiren to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Aliskiren will be approved for any indications or labelling in any market. Neither can there be any guarantee that Aliskiren will ever be sold or achieve any particular level of revenue in any market. In particular, management's expectations regarding Aliskiren could be affected by, among other things, additional analysis of Aliskiren clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; 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, and other risks and factors referred to in the Company'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 AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved sales of USD 28.2 billion and a net income of USD 5.8 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

PRESS RELEASE

References

1 Gradman AH, Schmieder RE, Lins RL, et al. Aliskiren, a Novel Orally Effective Renin Inhibitor, Provides Dose-Dependent Antihypertensive Efficacy and Placebo-Like Tolerability in Hypertensive Patients. Circulation. 2005;111:1012-1018.

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