Vitae Initiates Phase 1 Trial Of Novel Renin Inhibitor

Main Category: Cardiovascular / Cardiology
Also Included In: Clinical Trials / Drug Trials;  Heart Disease
Article Date: 23 Sep 2009 - 1:00 PDT

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Vitae Pharmaceuticals, Inc., an integrated discovery and development company, announced that it has initiated a Phase 1 clinical trial of its novel cardiovascular agent, VTP-27999.

VTP-27999 is a novel, proprietary renin inhibitor discovered and advanced by Vitae. "Renin inhibition offers a powerful approach to blood pressure control because renin is the first and rate limiting enzyme in the primary biochemical pathway for regulating the body's blood pressure", said Richard Gregg, MD, chief scientific officer at Vitae. "Also, renin is found in critical organs throughout the body such as the heart, brain and kidney. By inhibiting renin directly, VTP-27999 should provide superior end organ protection versus currently available drug classes." Recently published human biomarker data support that conclusion1,2. Additional biomarker studies and several long-term morbidity and mortality trials3 are currently underway with another drug in the class, involving approximately 35,000 patients. This effort makes renin inhibition one of the most intensely studied therapeutic modalities in cardiovascular medicine today.

The Phase 1 trial is a randomized, double blind, placebo controlled study evaluating VTP-27999 in healthy volunteers. The primary objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of VTP-27999 in order to determine doses to be used in subsequent studies. Additionally, Vitae will evaluate pharmacodynamic markers of the biological activity of VTP-27999.

VTP-27999 selectively targets the aspartyl protease enzyme renin, which is the key enzyme regulating the renin-angiotensin pathway, implicated in hypertension. An extremely challenging target, renin has been the focus of industry-wide discovery efforts for more than three decades, with success coming only recently amongst a handful of companies including Vitae.

VTP-27999 Preclinical Data

"VTP-27999 has demonstrated a best-in-class profile", continued Dr. Gregg. "It is extremely potent and selective, with picomolar inhibitory activity against renin and a PK profile supporting once daily dosing. In preclinical testing, VTP-27999 has demonstrated significant and sustained reductions in blood pressure. More importantly, it has clearly shown beneficial end organ protection effects and enhanced survival in animal models of hypertension."

VTP-27999 has a relatively simple synthetic structure and is highly bioavailable, unlike other members of the renin inhibitor class. The compound was discovered by Vitae scientists using the company's proprietary structure-based design platform. Vitae plans to present its preclinical data for VTP-27999 early in 2010.

About Renin

Renin is an enzyme secreted by the kidney in response to a decrease in blood pressure and circulating blood volume. It plays an important role in the regulation of blood pressure and has been a broadly pursued but extremely difficult target to drug within the pharmaceutical industry for many years. Within the bloodstream, renin initiates a series of reactions in the renin-angiotensin system to induce vascular constriction and increase vascular resistance, correspondingly increasing blood pressure. Suppression of the renin angiotensin system using angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blocker (ARB) drug therapies has been shown to reduce blood pressure and associated renal and cardiovascular events.

About Hypertension and End-Organ Diseases

Hypertension is a common disorder characterized by high blood pressure. Hypertension causes stress on the heart, blood vessels and vital organs such as the kidney and brain. Patients with high blood pressure have a significantly greater risk of heart attack, stroke, renal disease, aortic aneurysms, left ventricular hypertrophy and heart failure. Hypertension is a major contributing cause of disease and death worldwide. More than one in three Europeans and North Americans over the age of 35 have hypertension - an estimated 70 million people in the U.S. currently suffer from hypertension and the number is expected to grow to 100 million over the next decade. More than half of those on current therapies remain insufficiently controlled, indicating a clear need for new and more effective treatment options.

References

1. Parving, HH, et al. Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy. N Eng J Med 2008;358:2433-46

2. Fisher, N D.L., et al. Renal and Hormonal Responses to Direct Renin Inhibition With Aliskiren in Healthy Humans. CIRCULATION 2008; 177: 3190-3205

3. Novartis Press Release: June 2008;

4. Vitae Pharmaceuticals Press Release: October 15, 2007;

5. Vitae Pharmaceuticals Press Release: June 15, 2009;

Source
Vitae Pharmaceuticals

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