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.

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

rPA is a recombinant, synthetic protein that is postulated to prevent the complications of anthrax infection by inducing antibodies that bind to and neutralize potent anthrax toxins. The only currently available vaccine for anthrax in the United States is AVA, which requires a primary series of three subcutaneous injections given 2 weeks apart, followed by three additional subcutaneous injections given at 6, 12, and 18 months. Annual booster injections of the vaccine are recommended thereafter.

In December 1997, the U.S. Department of Defense announced a plan to vaccinate all U.S. military personnel with AVA. As of April 2000, 425,976 service members had received 1,620,793 doses of anthrax vaccine under the DoD’s Anthrax Vaccine Immunization Program. In October/November 2001, approximately 10,000 persons were advised to take 60 days of post exposure prophylaxis because of potential exposure to anthrax in several U.S. states as a result of a bioterror attack. 22 cases of anthrax resulted from this intentional release of Bacillus anthracis.

While data released by VaxGen for rPA102 looks promising, it is very preliminary in nature. Ideally, the next anthrax vaccine would have an improved safety and efficacy profile when compared to AVA as well as the benefit of a simplified dosing schedule. As for the degree of impact of an anthrax vaccine, the ongoing assessments by the U.S. government and its Advisory Committee on Immunization Practice concerning the potential risk of an anthrax outbreak are critical. Currently, Biohorizon maintains its Moderate Impact Technology designation for rPA102 and recommends no specific assessment activities for this vaccine.

Technology Details
Target Disease / Indication: Anthrax
Technology Classification: Drug/Vaccine
Body System: Multiple Systems
Program Area: Medicine/Infectious Disease
Regulatory Status: Phase II
BioHorizon Impact Score: 48/100 – Moderate