Tarceva is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor. By inhibiting the addition of phosphate to the EGFR associated tyrosine kinase, Tarceva may interrupt important cellular signaling pathways and thereby suppress cancer cell growth. Astra Zeneca’s Iressa® is an example of an EGFR tyrosine kinase inhibitor already approved by the FDA for use in NSCLC. According to Astra Zeneca’s third quarter financial statements for 2004, sales of Iressa for the first 9 months in the United States were $160,000,000. We have given Tarceva 10 demand/diffusion points and 65 innovation status points.

According to CDC estimates, more than 170,000 people will be diagnosed with lung cancer in the United States in 2004. Anywhere from 75-85% of these will be the non-small cell type, the most common form of lung cancer in the US. In addition, lung cancer is the most common cause of cancer death in the United States accounting for more than 25% of cancer deaths on an annual basis. Using the BioHorizon burden of illness methodology, NSCLC receives a burden of illness rating of 21.

Overall, Tarceva receives a BioHorizon Emerging Health Technology score of 46, placing it in our Moderate Impact Technology category. However, the EGFR tyrosine kinase inhibitors represent true innovation and are likely to see increasing uptake for NSCLC as well as other cancer indications. Health services clients are advised to begin or continue preliminary assessment activities for Tarceva and Iressa this quarter.

Technology Details
Target Disease / Indication: Non-Small Cell Lung Cancer
Technology Classification: Drug
Body System: Respiratory
Program Area: Medicine/Oncology
Regulatory Status: Approved
BioHorizon Impact Score: 46/100 – Moderate

Nabi describes Altastaph as a polyclonal antibody for the prevention and treatment of S. aureus infections in patients at immediate risk for infection or patients with immune systems unable to respond adequately to vaccine. Altastaph is produced by vaccinating healthy volunteers with the company’s StaphVAX vaccine, and then harvesting the anti-staphylococcus antibodies to capsular polysaccharides (protective outer sugar coatings on S. aureus bacteria) from S. aureus types 5 and 8. Nabi reports that these two types account for upwards of 85 % of all S. aureus infections.

The use of specific antibodies for the prevention and treatment of infectious diseases is by no means a novel concept. Specific antibodies are used in the prevention of Hepatitis B, Rabies, RSV and in the treatment of Tetanus and Diptheria. A search of the BioHorizon.com Emerging Health Technology Surveillance System database yields two other antibody-based therapies targeted against S. aureus: Aurexis (Phase 2) and Veronate (Phase 3). We have assigned 45 innovation points to Altastaph.

S. aureus infections are responsible for significant morbidity and mortality in low birth-weight neonates. Estimates of the incidence of VLBW in the United States are in the 14-15/100, 000 population range corresponding to a burden of illness score of 11. Demand/diffusion scoring is difficult at this stage of development; we have assigned the default score of 10.

Altastaph receives a final BioHorizon Emerging Health Technology Impact Score of 28 placing it in our Low Impact Technology category. No assessment activities are recommended for health services clients at this time.

Technology Details
Target Disease / Indication: Staph. Aureus infections
Technology Classification: Drug
Body System: Multiple Systems
Program Area: Medicine/Infectious Disease
Regulatory Status: Phase 2
BioHorizon Impact Score: 28/100 – Low

ABT–874 is a fully human, monoclonal antibody directed against an inflammatory cytokine known as IL-12. IL-12 is a known mediator of inflammation and may be important in Crohn’s disease. Given the inflammatory nature of Crohn’s, many targets related to immune system function are being pursued. Already, approved infliximab targets the tumor necrosis factor, another member of the class of inflammatory cytokines. We have assigned ABT-874 a score of 60 for innovation status.

Crohn’s disease is a chronic, inflammatory disease of the gastrointestinal tract that affects between 500,000 and 1 million Americans. Usually diagnosed before age 30, symptoms include diarrhea, cramping, abdominal pain, weight loss, fever, and in some cases rectal bleeding. There is no cure for Crohn’s disease. Incidence estimates for this disease vary greatly, ranging from 1/100, 000 cases per year to 70/100, 000. Published studies seem to cluster around the 5-10/100, 000 range resulting in a burden of illness score of 10.

We have scored the demand/diffusion variable at 10 resulting in an overall BioHorizon Emerging Health Technology Impact Score of 30, placing ABT-874 in our Low Impact Technology category. No preliminary assessment activities are required at present.

Technology Details
Target Disease / Indication: Crohn’s Disease
Technology Classification: Drug
Body System: Gastrointestinal
Program Area: Medicine/Gastroenterology
Regulatory Status: Phase 2
BioHorizon Impact Score: 30/100 – Low

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

Uncomplicated influenza is characterized by the sudden onset of constitutional and respiratory signs and symptoms. In the majority of patients, recovery is complete after several days; however, in certain individuals, influenza can exacerbate underlying medical conditions. Young children with influenza infection can have initial symptoms mimicking bacterial sepsis with high fevers; influenza infection has also been associated with encephalopathy, transverse myelitis, Reye syndrome, myositis, myocarditis, and pericarditis. Estimates of influenza related deaths sit in the 19,000-36,000 per annum range. A study that modeled influenza-related deaths estimated that an average of 92 deaths occurred among children aged <5 years annually during the 1990's. There were 143 laboratory-confirmed pediatric deaths during the 2003–2004 influenza season; 41% were aged <2 years and 45% of did not have an underlying medical condition. We have assigned a 100 point score to the burden of illness variable.

We believe nasally administered vaccines represent true innovation; however, MedImmune’s FluMist is already approved. Of important note, ID Biomedical’s FluInsure is also in Phase 3 testing. CAIV-T merits a 55/100 score for the innovation status variable. Demand/diffusion scoring is difficult as this year’s flu vaccine shortage due to Fluvirin’s withdrawal highlights. Under normal supply/demand circumstances, intranasal vaccines will be significantly more expensive than injectable influenza vaccines. We maintain our demand/diffusion score of 10 here to remain consistent with FluInsure’s scoring resulting in a score of 60 for CAIV-T. Health services delivery clients should assess current influenza immunization programs looking specifically at the planned role for inhaled intranasal vaccines.

Technology Details
Target Disease / Indication: Influenza
Technology Classification: Drug/Vaccine
Body System: Respiratory
Program Area: Medicine/Infectious Disease
Regulatory Status: Phase 3
BioHorizon Impact Score: 60100 – Moderate/High

According to the CDC, every year between 5 and 20% of Americans develop influenza. This results in an estimated 114, 000 influenza-related hospitalizations and 36, 000 influenza-related deaths annually. Influenza receives a 100/100 score for the Burden of Illness variable.

Biohorizon is currently monitoring one other inhaled Influenza vaccine, MedImmune’s FluMist™, a live-attenuated intranasal vaccine. Demand for FluMist during the 2003-2004 season was significantly lower than expected and in June of 2004, MedImmune announced a 50% price reduction (from approximately 46 to 23 dollars per dose). The company also announced a reduction in production from 4 million doses to 1 to 2 million doses. ID Biomedical’s FluInsure is inactivated vs. live and could have an expanded indication. We have assessed the Demand/Diffusion variable to be 10/100. The Innovation variable is currently scored at 60/100.

Several factors should significantly increase influenza vaccine demand in the 2004-2005 season and beyond. These factors include: the higher than expected pediatric mortality associated with the 2003-2004 A/Fujian strain of influenza; concerns regarding Avian Influenza; the availability of intranasal vaccine delivery as an alternative to intramuscular vaccine delivery; and the CDC’s expanded recommendations for routine immunization of infants 6-23 months of age. If FluInsure receives FDA approval and infants and children are included in the indication, this vaccine could have a major impact on immunization costs. We therefore recommend commencement of preliminary assessment activities and have placed FluInsure in the Moderate/High Impact category with an Impact Score of 63.

Technology Details
Target Disease / Indication: Influenza
Technology Classification: Drug
Body System: Respiratory
Program Area: Medicine/Infectious Disease
Regulatory Status: Phase III
BioHorizon Impact Score: 63/100 –Moderate/ High

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

AVP 13358 is an orally active compound thought to exert its action through decreasing the production of IgE. It is generally accepted that IgE (immunoglobulin epsilon) plays an important role in the inflammatory response that produces many of the signs and symptoms of asthma and other allergic diseases. Other mediators of inflammation, such as IL-4 and IL-5, may also be suppressed by AVP 13358. According to Avanir, pre-clinical data suggests that AVP 13358 suppresses markers of disease in mouse models of asthma, including pulmonary lavage levels of IL-4, IL-5, eosinophils, and lymphocytes as well as expression of CD23 and the IL-4 receptor (IL4R(alpha)) on leukocytes.

Asthma is a chronic disease of the lungs characterized by recurring episodes of wheezing, breathlessness, chest tightness, and nighttime or early morning coughing. According to CDC surveillance data during 1980-1996, asthma prevalence in the United States has increased. Between 1995 and 1999, the rate of outpatient visits and emergency department visits for asthma has also increased, while the rates of hospitalization and death decreased. In 1996, an estimated 14.6 million persons (54.6/1,000 population) reported asthma during the previous 12 months in 1996. The pharmaceutical market for asthma therapeutics is estimated to be well in excess of 3 billion dollars per annum in the United States.

The Biohorizon Emerging Health Technology Database contains 49 technologies listing asthma as their main disease indication. 11 of these are in Phase I of development, and 25 are at the Phase II stage or beyond. While the Phase I clinical trial results for AVP 13358 are encouraging, this technology requires no preliminary assessment activities by health services delivery clients at this time.

Technology Details
Target Disease / Indication: Asthma
Technology Classification: Drug
Body System: Respiratory System
Program Area: Medicine/Respirology
Regulatory Status: Phase I
BioHorizon Impact Score: 50/100 – Moderate

Enbrel is a protein that is thought to exert its action through the binding and subsequent inactivation of a naturally produced cytokine known as Tumor necrosis factor (TNF). TNF is produced by the body’s immune system, and in patients with psoriasis and other autoimmune diseases, certain immune cells increase production of TNF. This increased TNF activity is thought to be critical in mediating the overactive immune response that causes the tissue damage that is a hallmark of psoriasis and rheumatoid arthritis. Amgen has indicated that approximately 234,000 patients have already been treated with Enbrel worldwide. Amgen reports total sales of Enbrel for 2003 in the 1.3 billion dollar range

The true incidence of psoriasis in the United States is difficult to determine. Estimates of prevalence suggest that approximately 4.5 million people are affected by psoriasis with approximately one third of these suffering from the ‘plaque’ type of the disease. Psoriasis is characterized by the development of red, itchy skin plaques that are often painful and disfiguring.

Enbrel satisfies all Biohorizon criteria for High Impact Technologies: it is an innovative therapy, it has diffused rapidly, it has demonstrated efficacy in clinical trials, and with this most recent approval, it is indicated for more prevalent conditions. In light of the psoriasis indication, clients should begin or revisit assessment activities at this time.

Technology Details
Target Disease / Indication: Psoriasis
Technology Classification: Drug
Body System: Integumentary System
Program Area: Medicine/Dermatology
Regulatory Status: Approved
BioHorizon Impact Score: 76/100 – High

The intial May 2003 FDA approval of Iressa was based upon data from Phase II trials that showed that 13.6 % of patients had achieved a minimum 50% tumor shrinkage. Patients in these trials had received Iressa after disease progression following failure of both platinum-based and docetaxel chemotherapies. The NEJM and Science publications essentially attempt to provide a molecular explanation for why some patients respond so well to Iressa and others experience absolutely no response whatsoever. The concept of targeted cancer therapy, although clearly in the early stages of its development, will certainly be advanced because of these findings.

Iressa is an orally active epidermal growth factor receptor (EGFR) inhibitor. EGFR is expressed in cancerous cells of the lung. When stimulated, it is thought to play a role in cancer cell proliferation, metastasis, and tumor resistance to chemo and radiotherapies. Iressa is thought to exert its effect by inhibiting EGFR and preventing it from activating damaging cell signaling pathways.

There will be in excess of 145,000 new cases of lung cancer diagnosed in the United States this year, and in excess of 150,000 deaths due to this disease. Of these, 80-85% will be NSCLC. Most patients are in the advanced stage of the disease at the time of diagnosis and are offered chemotherapy.

Iressa is the first EGFR inhibitor approved for use in the United States. Until the NEJM and Science online publications were released, its low rate of tumor response diminished the drug’s overall efficacy. However, the screening of candidates for specific EGFR mutations may dramatically increase effectiveness in health systems. As such, Biohorizon recommends commencement of organization specific assessment activities in the near term.

Technology Details
Target Disease / Indication: Non Small Cell Lung Cancer
Technology Classification: Drug
Body System: Respiratory System
Program Area: Medicine/Oncology
Regulatory Status: Approved
BioHorizon Impact Score: 70/100 – High