BiDil is a fixed dose, combination therapy consisting of 37.5 mg of hydralazine hydrochloride and 20 mg of isosorbide dinitrate per tab taken three times daily. Although hydralazine and isosorbide dinitrate are both approved for use in several cardiovascular indications, their use together in a fixed dose format for the treatment of CHF is unique and merits an innovation score of 65. Nitric oxide is important in myocardial remodeling. BiDil may exert its therapeutic effect as both a source and preserver of nitric oxide in the heart.

Estimates of the prevalence of congestive heart failure range from 3 to 5 million Americans. We use an incidence of 400, 000 new diagnoses per annum; this translates into a burden of illness variable value of 35. Congestive heart failure results from an impairment in pump function in which the heart fails to maintain the circulation of blood adequately. In the New York Heart Association’s functional classification of CHF, class III is characterized by a marked limitation in normal physical activity. Class IV is defined by symptoms at rest or with any physical activity.

If approved, we expect significant demand/diffusion of this emerging technology. The integration of BiDil into the CHF therapeutic armamentarium will create an increase in the pharmacologic treatment cost per patient per year. BiDil will be added to existing patient specific therapeutic regimens. We have assigned the demand/diffusion variable a value of 30 and an overall BioHorizon Emerging Health Technology Impact Score of 53. If FDA approval occurs, we intend to recommend early assessment activities.

Technology Details
Target Disease / Indication: Congestive Heart Failure
Technology Classification: Drug
Body System: Cardiovascular System
Program Area: Medicine/Cardiology
Regulatory Status: Phase 3
BioHorizon Impact Score: 53/100 – Moderate

Prasugrel is an oral antiplatelet drug that may prevent platelet activation by blocking adenosine diphosphate receptors on the platelet surface. When activated, these receptors allow for a protein in the blood known as fibrin to link platelets together, creating a ‘plug’ or ‘clump’ of platelets that can produce a critical vessel blockage and cause a heart attack. Other anti-platelet treatments currently available include ASA, the thienopyridines-clopidogrel (Plavix), and ticlopidine as well as the glycoprotein IIb/IIIa inhibitors abciximab and tirafibrin. We have assigned prasugrel 50/100 for innovation as a new drug in an existing class of oral antiplatelet drugs.

BioHorizon believes that demand/diffusion parameters for oral anti-platelet drugs are increasing. Bristol Myers Squibb, the manufacturers of Plavix™, recently reported a 23% increase in U.S. prescriptions and a nine month total sales figure of in excess of 900 million dollars. Depending on the forthcoming efficacy and adverse event data, prasugrel could compete in this market. We have assigned this technology a demand/diffusion score of 20/100.

The overall BioHorizon Emerging Health Technology Impact Score is 47/100, currently placing prasugrel in our Moderate Impact Technology category. No preliminary assessment activities are recommended for health services clients at this time.

Technology Details
Target Disease / Indication: Acute Coronary Syndrome
Technology Classification: Drug
Body System: Cardiovascular System
Program Area: Medicine/Cardiology
Regulatory Status: Phase 3
BioHorizon Impact Score: 47/100 – Moderate Impact

Zocor is a so-called ‘statin’ lipid lowering agent that exerts its action by inhibiting an enzyme known as HMG-CoA., which plays a critical role in cholesterol synthesis. The clinical benefit of Zocor in reducing death due to CHD, MI, and decreasing the need for invasive coronary procedures in patients with elevated cholesterol levels is well established. Unlike Zocor, Zetia works by inhibiting the absorption of dietary cholesterol from the small intestine. Data demonstrating Zetia’s ability to significantly decrease morbidity and mortality from coronary artery disease has not been produced.

According to the American Heart Association, in excess of 100 million Americans presently have total blood cholesterol levels above 200 mg/dl. In addition, fewer than 50% of patients who would benefit from cholesterol lowering treatments are actually receiving them. Some analysts expect Vytorin to eventually attain annual sales of up to $8 billion.

Given that Vytorin is comprised of two already approved drugs, a positive FDA decision is anticipated. Combination therapies are almost always less expensive than the cost of their constituents purchased separately, so potentially Vytorin would not drive up cost of per patient treatment. However, Vytorin will most certainly be more costly than the individual statin drugs that in some cases it is likely to replace. Clinicians might choose Vytorin when they are striving for more aggressive lipid control or when patients are inadequately controlled on a statin alone. Both of these scenarios would see the cost of treatment significantly increase on a per patient basis and forms the underlying rationale for our recommendation that clients should begin preliminary assessment activities for Vytorin in anticipation of FDA approval.

Technology Details
Target Disease / Indication: Hyperlipidemia
Technology Classification: Drug
Body System: Cardiovascular System
Program Area: Medicine/Cardiology
Regulatory Status: Phase III
BioHorizon Impact Score: 81/100 – High

Ranexa is believed to exert its effect on the heart by partial inhibition of fatty acid oxidation (pFOX inhibition). Pre-clinical studies have suggested that pFOX inhibition alters heart myocardial cell metabolism in such a way as to increase its efficiency and, in effect, to require less oxygen to do a given amount of work.

Angina as a disease occurs when an imbalance exists between the heart’s energy demands and the coronary vasculature’s ability to deliver oxygen. Chronic angina is usually associated with coronary artery disease (CAD) and is characterized by repeated, often debilitating episodes of chest pain. The American Heart Association reports that 6.8 million Americans suffer more than 700 million angina attacks per year in the United States. Current anti-anginal therapies include beta-blockers, calcium channel blockers, and nitroglycerin.

CV Therappeutics has yet to complete or publicly release the results of the pivotal Phase III trials required for FDA approval of Ranexa. However, given the high incidence and prevalence of chronic angina in North America, innovative technologies effective in treating this condition have the potential to significantly alter, if not transform, the anti-anginal landscape. Bearing this in mind, Biohorizon has designated Ranexa as a High Impact Technology but is recommending no preliminary assessment activities until more clinical trial data become available.

Technology Details
Target Disease / Indication: Chronic Angina
Technology Classification: Drug
Body System: Cardiovascular System
Program Area: Medicine/Cardiology
Regulatory Status: Phase III
BioHorizon Impact Score: 75/100 – High

In excess of five million Americans are treated for coronary artery disease each year. Most of these patients (about 80%) are treated medically, however, in excess of 1million patients will require more invasive procedures like Coronary Artery Bypass Grafting (CABG) or angioplasty. Among those patients receiving stents, 15-20% will require repeat treatment for restenosis. The CYPHER stent, approved for U.S. marketing in April 2003, has been used to treat approximately 500,000 patients in more than 80 countries worldwide. Industry analysts value the drug-eluting stent market in the 3-4 billion dollar per annum range. The actual direct cost increase associated with CYPHER compared to a bare metal stent is significant. Each CYPHER stent costs in the $2500 to $3000 range. This represents an increase of 200-300% over the per unit costs of a bare metal stent. It is duly noted that the significant decrease in restenosis rates and therefore revascularization procedures may ultimately reduce the cost per patient treated by a given health services organization.

The CYPHER stent is currently in our High Impact Technology category. All clients with significant cath-lab operations should commence or continue assessment activities as soon as possible.

Technology Details
Target Disease / Indication: Coronary Artery Disease
Technology Classification: Combination Drug/Device
Body System: Cardiovascular System
Program Area: Medicine/Cardiology
Regulatory Status: Approved
BioHorizon Impact Score: 86/100 – High