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

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

Zenapax is a humanized IgG1 antibody produced by recombinant DNA technology. It binds to a lymphocyte receptor known as the IL-2 receptor and impacts this cell’s role in the immune response. Zenapax is approved for the prevention of renal allograft rejection.

The estimated number of people reporting at least one asthma attack during the past 12 months in the United States is about 11.1 million or 40.7/1000 US population.

While the preliminary Phase II data looks intriguing, Biohorizon considers Zenapax to be at a relatively early stage in development. Injectable immunotherapies for asthma, at least in their current form, would likely be niche products, at best, in the asthma market. We have designated Zenapax as a Moderate Impact technology; we do not see any need for clients to plan for Zenapax’s diffusion in the near term.

Technology Details
Target Disease / Indication
Asthma

Technology Classification
Drug/Humanized Monoclonal Antibody

Body System
Respiratory System

Program Area
Medicine/Respirology

Regulatory Status
Phase II

BioHorizon Impact Score
50/100 – Moderate