Since its approval in the United States in 2000 Wyeth’s Prevnar vaccine against pneumococcal disease has helped to transform what was thought of as a mature, marginally profitable segment of the pharmaceutical business into a much more dynamic and profitable one. Prevnar has proven to be both effective and innovative while filling an unmet need in the prevention of serious pediatric infections caused by the pneumococcal bacteria. According to CNN Money.com, Prevnar sales surged 24% in 2007 to $2.4 billion, making it the first vaccine to exceed $2 billion in annual sales.

Prevnar has been the only conjugate pneumococcal vaccine available to immunization programs and clinicians throughout North America and European Union looking to prevent pneumococcal disease. However, GSK’s new 10-valent conjugate pneumococcal vaccine (Synflorix) could soon start changing this.

There are two significant differences between Synflorix and Prevnar that our readers should be aware of. First, Prevnar contains antigen from seven different serotypes of pneumococcal bacteria while Synflorix contains antigen from ten different types. The second difference is in the carrier protein that these polysaccharide antigens are attached to. In Prevnar the protein is called CRM-197 and it has been critical in the success of Wyeth’s product. The carrier protein is more than a passive molecule, it greatly enhances the immunogenicity of the vaccine and makes it more effective. In Synflorix, the carrier protein (NTHi) not only does this, but because it is derived from non-typable Haemophilus Influenza bacteria, provides protection against infections with this pathogen as well. GSK has filed for Synflorix approval in the EU and the vaccine has recently been approved for sale in Canada but we have no word on when or even if approval will be sought in the United States.

The story does not end here as Wyeth is countering with an enhanced version of Prevnar that contains protection against thirteen different serotypes of the pneumococcal bacteria and has filed for approval in both the United States and the European Union.

There are some fundamental questions that need to be explored further concerning the safety and effectiveness of these new vaccines, the changing epidemiology of pneumococcal disease, and of course the cost-effectiveness data that is all important to vaccine program planners. Readers should stay tuned as we plan to explore these crtical areas in the coming days. Thanks for joining us today on the BioHorizon.

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

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

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

An Altana executive said the Phase III study, involving nearly 1,800 patients over six months, had shown that patients on a 500-microgram dosage of the drug showed 0.75 exacerbations over the study period compared to 1.13 exacerbations in a placebo group. Exacerbations are defined as an acute worsening of the patient’s condition, leading to treatment with oral steroids or a combination of steroids and antibiotics. In most cases, hospitalization is required.

Daxas is a member of a class of drugs known as phosphodiesterase inhibitors. Phosphodiesterases (PDEs) belong to an important family of proteins that regulate the intracellular levels of cyclic nucleotide second messengers. Targeting PDE with selective inhibitors may offer novel therapeutic strategies in the treatment of various conditions. In the context of respiratory disease, these include asthma and chronic obstructive pulmonary disease (COPD).

COPD refers to a group of diseases that cause airflow blockage and breathing-related problems. It includes emphysema, chronic bronchitis, and in some cases asthma. COPD is a leading cause of death, illness, and disability in the United States. In 2000, 119,000 deaths, 726,000 hospitalizations, and 1.5 million hospital emergency departments visits were caused by COPD. An additional 8 million cases of hospital outpatient treatment or treatment by personal physicians were linked to COPD in 2000.

If approved, Daxas would represent the first PDE inhibitor indicated for the prevention of COPD exacerbations. At this time, the date of Pfizer’s FDA submission is not known. Although we see Daxas as a High Impact Technology, we recommend no assessment activities until Pfizer’s plans for Daxas in North America become clear.

Technology Details
Target Disease / Indication
COPD

Technology Classification
Drug

Body System
Respiratory System

Program Area
Medicine/Respirology

Regulatory Status
Phase III

BioHorizon Impact Score
78/100 – High