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

Eloxatin was first approved in the US in January 2004 for the first-line treatment of advanced carcinoma of the colon or rectum in combination with infusional 5-FU/LV. In August 2002, this combination received approval for second-line treatment of this patient population (i.e., therapy for already treated patients with metastatic colorectal cancer). Oxaliplatin is a third-generation platinum derivative currently marketed by Sanofi-Aventis in more than 60 countries for the treatment of metastatic colorectal cancer. BioHorizon has assigned this emerging chemotherapy agent 65 points for innovation.

American Cancer Society estimates that 106,370 new cases of colon cancer will be diagnosed in the United States in 2004. This represents an incidence of 37/100,000 Americans and results in a burden of illness score of 18. Standard care for most colon cancer patients is surgical resection; however, a significant number of these patients will be candidates for adjuvant chemotherapy regimens designed to reduce the risk of the cancer’s recurrence and/or spread. Demand/diffusion will depend upon the extent to which oncologists integrate Eloxatin into adjuvant regimens. According to company news releases, global sales of Eloxatin rose 54.5 percent to 873 million euros ($1.1 billion) in the first nine months of 2004. Eloxatin earns a demand/diffusion score of 50.

Eloxatin receives a Moderate/High Score of 58. We are recommending commencement of assessment activities as soon as possible. Clients are advised to consult with key prescribing oncologists while reviewing the clinical epidemiology of colorectal
cancer.

Technology Details
Target Disease / Indication: Colorectal Cancer
Technology Classification: Drug
Body System: Gastrointestinal System
Program Area: Medicine/Oncology
Regulatory Status: Approved
BioHorizon Impact Score: 58/100 – Moderate/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

The American Cancer Society estimates that 147 500 new cases of colorectal cancer will be diagnosed in the United States in 2003. This makes colorectal cancer the third most commonly diagnosed cancer and the second leading cause of cancer death in the United States.

According to Genentech, more than 2,000 patients have been treated with Avastin in clinical studies. The current BLA filing is based upon the results of a pivotal 900 patient study of Avastin plus the three other chemotherapy agents comprising the IFL regimen (5-FU/Leucovorin/CPT-11). Genentech reported that Avastin plus the IFL regimen improved median survival by approximately five months, compared to patients treated with chemotherapy alone (20.3 months versus 15.6 months).

Wall Street analysts position Avastin in the 1billion dollar/year sales range. The actual cost per patient treated is not known at this time but new cancer therapies typically cost somewhere in the $12 000 – $20 000 per patient per year range. It is critical to note that these costs will be in addition to the costs of treating metastatic colon cancer with existing chemotherapy regimens as, initially, Avastin will likely be used in addition to the IFL chemotherapy regimen.

If approved, we feel that Genentech’s Avastin has the potential to be a High Impact technology and therefore we recommend oncology programs begin some early assessment activities while watching for the FDA’s decision. Early steps would include the identification of current and predicted metastatic colon cancer patient numbers and some discussion with treating oncologists concerning future plans for Avastin in treatment regimens.

Technology Details
Target Disease / Indication: First Line Therapy in Metastatic Colorectal Cancer
Technology Classification: Drug
Body System: Gastrointestinal System
Program Area: Medicine/Oncology
Regulatory Status: Biologics License Application Submitted to FDA
BioHorizon Impact Score: 70/100 – High