Healthcare Industry News: amlodipine besylate
News Release - May 17, 2006
Novartis Announces Efficacy Data on New Investigational High Blood Pressure Therapies at The American Society of Hypertension Annual MeetingStudies show Rasilez(R) (aliskiren), investigational agent in a new class of direct renin inhibitors, provides significant blood pressure reductions, sustained over 24 hours
New Exforge(R) (amlodipine besylate/valsartan) data show dual mechanism of action lowered systolic blood pressure up to 43 mm Hg in patients with stage 2 high blood pressure; majority of patients reach blood pressure goal
Diovan(R)(valsartan) data evaluating potential impact on lowering an important marker of inflammation, high sensitivity C-reactive protein, to be presented on Friday
EAST HANOVER, N.J., May 17 (HSMN NewsFeed) -- Data demonstrating the blood pressure efficacy of two new investigational high blood pressure medicines being developed by Novartis Pharmaceuticals Corporation were presented today at the American Society of Hypertension, Inc., Annual Scientific Meeting and Exposition (ASH 2006) in New York. In addition, on Friday, the results of Val-MARC (Valsartan-Managing blood pressure Aggressively and evaluating Reductions in hsCRP) with currently available Diovan®/Diovan HCT® will also be presented. Val-MARC evaluates the effects of Diovan on high sensitivity C-reactive protein (hsCRP), an important marker for inflammation. In total, there will be more than 30 abstracts with new data on currently marketed and investigational agents within the company's hypertension portfolio presented at the ASH 2006 meeting.
"High blood pressure -- and its consequences -- is the world's number one killer, estimated to affect nearly one billion people. The overwhelming numbers of patients who remain uncontrolled despite treatment speaks to the urgent need for more therapeutic options," said James Shannon, M.D., Head of Development, Novartis Pharma AG. "Data presented at ASH 2006 shows our commitment to expand our investigations for additional benefits of Diovan and to develop new agents to help physicians get their patients to blood pressure goal."
Investigational agents Rasilez® (aliskiren) and Exforge® (amlodipine besylate/valsartan) are under regulatory review in the United States.
If approved, Rasilez, developed with Speedel, would be the first effective oral direct renin inhibitor. It acts within the Renin System, which is central to blood pressure regulation. By directly inhibiting the system's point of activation -- renin -- Rasilez decreases the activity of the Renin System, as measured by plasma renin activity (PRA).
Exforge is a potential new treatment for high blood pressure. Exforge utilizes two complementary mechanisms of action, calcium channel blockade with amlodipine and angiotensin receptor blockade with valsartan, both agents being the number one prescribed medications in their respective classes.
The trade names Rasilez and Exforge are currently pending regulatory approval.
Newly released aliskiren data highlights:
POSTER # P-228 "The novel oral renin inhibitor aliskiren provides effective blood pressure control in patients with hypertension when used alone or in combination with hydroclorothiazide"
Alberto Villamil, M.D., Fundapres, Las-Heras, Buenos Aires, Argentina
A randomized, double-blind eight-week multifactorial study of 2,776 patients who received aliskiren at 75 mg, 150 mg or 300 mg, hydrochlorothiazide (HCTZ) or placebo showed that aliskiren provides effective blood pressure control in people with high blood pressure when used alone or in combination with HCTZ. Aliskiren significantly reduced mean sitting systolic and diastolic blood pressure. The combination of aliskiren and HCTZ lowered blood pressure more effectively than either agent alone. Aliskiren 300 mg in combination with HCTZ 25 mg reduced diastolic blood pressure by 21.2 mm Hg and systolic levels by 14.3 mm Hg. Similarly, this combination resulted in a 76.9% responder rate defined as patients who reached a diastolic blood pressure of less than 90 mm Hg and/or a decrease of at least 10 mm Hg.
"This study showed that aliskiren is an effective treatment for high blood pressure when given alone, and provided additional blood pressure reductions when combined with HCTZ," commented study author Alberto Villamil, M.D., Fundapres, Las-Heras, Buenos Aires, Argentina. "The additive effect is particularly promising because when aliskiren and HCTZ were used together, blood pressure dropped significantly more than with either agent individually."
POSTER #209 "Once-daily aliskiren provides effective, smooth 24-hour blood pressure control in patients with hypertension"
Jerry Mitchell, M.D., Texas Center for Drug Development, Houston
A randomized, double-blind, multicenter, placebo-controlled study of 672 people with mild-to-moderate high blood pressure given either aliskiren 150 mg, 300 mg or 600 mg once a day or placebo showed that once-daily aliskiren provides sustained blood pressure control throughout a 24-hour dosing period.
Ambulatory systolic and diastolic blood pressure measured over 24 hours was lowered significantly. With aliskiren 300 mg, the trough-to-peak ratio for lowering diastolic blood pressure was 0.98, indicating that reductions were consistent over 24 hours without loss of effect. The trough-to-peak ratio was 0.64 with aliskiren 150 mg and 0.86 with the 600 mg dosage.
"Sustained control is particularly important because during a 24-hour period, blood pressure fluctuates and surges in the early morning," said lead study investigator Jerry Mitchell, M.D., Texas Center for Drug Development, Houston. "Patients need to control blood pressure around the clock, and our study shows that aliskiren can provide that control."
In the clinical trial program, Rasilez consistently showed tolerability similar to placebo up to 300 mg (within the expected therapeutic dose range). The most commonly reported adverse events for Rasilez include diarrhea, headache and nasopharyngitis (inflammation of the nose). All drugs that act directly on the renin angiotensin system carry a warning that they should not be used in pregnant women due to the risk of injury and even death to the fetus.
Newly released amlodipine besylate/valsartan data highlights:
POSTER # 217 "Comparative safety and blood pressure (BP)-lowering efficacy of a combination of amlodipine + valsartan and lisinopril + hydrochlorothiazide (HCTZ) in patients with stage 2 hypertension"
Don Poldermans, M.D., of Erasmus Medisch Centrum, Netherlands
In a multi-center, randomized study of 130 patients with stage 2 high blood pressure (at least 110 mm Hg), patients treated with amlodipine besylate/valsartan achieved an average reduction of 35.8 mm Hg in systolic blood pressure compared to 31.8 mm Hg in patients treated with a lisinopril/HCTZ combination. In addition, a sub-group of patients with systolic blood pressure of at least 180 mm Hg experienced an average systolic blood pressure reduction of 43 mm Hg when treated with amlodipine
besylate/valsartan compared to a 31.2 mm Hg reduction in patients receiving the lisinopril/HCTZ combination.
"Reductions in average systolic blood pressure ranging from 35 mm Hg to 43 mm Hg were clinically significant in the amlodipine besylate and valsartan arm," said Don Poldermans, M.D., Erasmus Medisch Centrum, Netherlands. "We were particularly impressed by the drug's efficacy in patients having a systolic blood pressure over 180 mm Hg. People with high systolic blood pressure are at an elevated risk of cardiovascular events."
Importantly, 80% of patients treated with amlodipine besylate/valsartan for six weeks reached the mean sitting diastolic blood pressure goal of under 90 mm Hg. The average drop in diastolic blood pressure was 28.6 among patients treated with amlodipine besylate/valsartan, which was numerically higher than the 27.6 reduction among those treated with lisinopril/HCTZ.
Both treatment regimens were well tolerated. Adverse events were seen in 26 patients treated with amlodipine besylate/valsartan and 21 patients receiving the lisinopril/HCTZ combination. Most events were mild to moderate in severity and were not suspected to be study drug related. The most common adverse events in the amlodipine besylate/valsartan group were headache and peripheral edema, while diarrhea and pharyngitis were most frequently reported in the lisinopril/HCTZ arm.
The NDA filing was based on a robust clinical trial program involving more than 5,000 hypertension patients. The program included five controlled trials in which more than 2,600 patients received amlodipine besylate/valsartan once daily. A single daily dose of amlodipine besylate/valsartan provided clinically significant blood pressure reductions and was well tolerated.
Adverse events observed in the NDA clinical trials were transient and mild in nature. The most common side effects in these placebo-controlled clinical trials that occurred at a higher incidence in amlodipine besylate/valsartan patients than placebo were peripheral edema, nasopharyngitis, upper respiratory tract infections and dizziness. The incidence of peripheral edema was statistically lower in patients treated with amlodipine besylate/valsartan than in patients treated with amlodipine besylate monotherapy. All drugs that act directly on the renin angiotensin system carry a warning that they should not be used in pregnant women due to risk of injury and even death to the unborn child.
About the Diovan Val-MARC study:
POSTER: "Val-MARC (Valsartan-Managing blood pressure Aggressively and evaluating Reductions in hsCRP)" (Results Presentation on Friday, May 19)
Paul Ridker, M.D., Brigham and Women's Hospital, Boston
Lead investigator Paul Ridker, M.D., Brigham and Women's Hospital, Boston, will present findings from the Val-MARC trial during a hotline session and press conference on Friday, May 19. The study looks at the blood pressure reduction of Diovan and its potential effects on the inflammatory marker high sensitivity C-reactive protein (hsCRP). HsCRP is a measure of inflammation commonly found in patients at increased risk for heart attack, stroke or death. The trial also examines the potential of Diovan HCT, including two new high dose strengths recently approved by the US Food and Drug Administration, in helping hard-to-treat patients with stage 2 high blood pressure achieve target blood pressure goals. Val-MARC involved 700 primary care clinics in the US with diverse hard-to-treat blood pressure patients, including African Americans, Hispanics, those with diabetes, and the elderly.
This release contains certain "forward-looking statements" relating to Novartis Pharmaceuticals Corporation's business, which can be identified by the use of forward-looking terminology such as "being developed," "will," "commitment," "if approved ... would be," "potential," "can provide," "expected," or similar expressions, or by express or implied discussions regarding potential marketing approvals of Rasilez or Exforge, potential additional indications or labeling for Diovan, or potential future sales of these products. Such statements reflect the current views of Novartis Pharmaceuticals Corporation with respect to future events and are subject to certain risks, uncertainties and assumptions. There can be no guarantee that any current or future regulatory filings will satisfy the FDA's or other health authorities' requirements for these products; that Rasilez or Exforge will be approved for sale in any market; that Diovan will be approved for any additional indications or labeling; or that any of these products will reach any particular sales levels. In particular, management's expectations regarding these products could be affected by, among other things, unexpected clinical trial results, including additional analysis of existing clinical data, or new clinical data; 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; increased 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 U.S. 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.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS ) -- a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis AG is the only company with leadership positions in both patented and generic pharmaceuticals. Novartis AG is strengthening its medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 91,000 people and operates in over 140 countries around the world. For more information, please visit http://www.novartis.com.
Source: Novartis Pharmaceuticals
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