Background

Children have the highest rates of influenza infection and school-aged children are the major vectors for influenza transmission that spread the virus to adults and the elderly in the community, causing substantial socioeconomic impact.1 For these reasons, the U.S. Centers for Disease Control and Prevention (CDC) recommends annual seasonal influenza vaccination for all eligible persons in the U.S., including eligible children aged 6 months through 18 years of age.2 Despite this, vaccination rates for school-aged children 5 to 17 years of age remain low, ranging from 24.6% (healthy) to 34.7% (high-risk) in the 2008-09 influenza season.2

To increase seasonal influenza vaccination rates, stakeholders have explored new immunization strategies including the routine vaccination of school-aged children.3 Previous research has demonstrated that increased vaccination of children could modulate the spread of influenza in the community. Mass vaccination programs in schools have demonstrated both direct benefits to immunized children and indirect benefits to the community including reduced school absenteeism due to influenza.4,5,6

An example of the benefits of influenza vaccination in school settings is:

• The Knox County (Tennessee) Health Department demonstrated program feasibility in a large public school system by vaccinating 24,198 students (56% among elementary schools, 45% among middle schools, and 30% among high schools) and 3,626 school staff from October to December 2005.7 Similarly, three Minnesota county health departments vaccinated 41% of all school children (K-12) in 2006. The study reported that school-based immunization programs offer the potential to achieve higher vaccination coverage of school children at modest cost.8

Past research supports the feasibility and benefits of conducting school-based influenza vaccination programs in terms of increasing vaccination in children, reducing school absenteeism and protecting the community from influenza. To help ensure pandemic preparedness and to establish an infrastructure for seasonal influenza vaccination of children, states should adopt school-based influenza vaccination programs to protect the public health.

1 Neuzil KM, et.al. Illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families. Arch Pediatr Adolesc Med 2002;156:986-991.
2 At http://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0729a1.htm?s_cid=rr59e0729a1_w. August 10, 2010.
3 Longini IM and Halloran ME. Strategy for distribution of influenza vaccine to high-risk groups and children. Am J Epidemiol 2005;161:303-306.
4 Principi N, et al. Socioeconomic impact of influenza on healthy children and their families. Pediatr Infect Dis J. 2003:22:S207-10.
5 Wiggs-Stayer KS, et al. The impact of mass immunization on school attendance. J School Nursing. 2006;22:219-222.
6 Davis MM, King JC, Moag L, et. al. Countywide school-based influenza immunization: direct and indirect impact on student absenteeism. Pediatrics 2008;122:e260-e265.
7 Carpenter LR, Lott J, Lawson BM, et. al. Mass distribution of free, intranasally administered influenza vaccine in a public school system. Pediatrics 2007;120:e172-e178
8 Hull HF, Frauendienst RS, Gundersen ML, et. al. School-based influenza immunization. Vaccine 2008;26:4312-4313.

Download POSITION ON SCHOOL-BASED INFLUENZA VACCINATION PROGRAMS (PDF, 50.7KB)

Background

“Biologics” are complex medicines that are reviewed and approved by the U.S. Food & Drug Agency (FDA) under the provisions of the Public Health Service Act (PHSA) for use in the United States. The “biological standard” for approval requires demonstration that a biologic is “pure, potent, and safe” and that its manufacturing facility is designed to assure the product continues to be pure, potent, and safe. The recent passage of the Patient Protection and Affordable Care Act (PPACA) established a foundation for biosimilars to enter the U.S. marketplace. While the PPACA created a general framework, the law also provides FDA authority to establish rules and guidance that will govern the specific requirements and procedures for reviewing and approving biosimilars.

The terms “biosimilars” (also called “follow-on biologics”) refer to products that are intended to copy previously-approved, innovator biologics and are submitted for approval based on similarity to the innovator product. Biosimilars are fundamentally different from small molecule generic drugs, which are virtually identical versions of innovator products and can readily be characterized by comparison of the exact chemical composition to the innovator product. As such, even without clinical trials to show safety and efficacy, generic drugs are usually designated to be “therapeutically equivalent” with the innovator drug and therefore interchangeable under FDA generic regulations. Conversely, while a biosimilar may be similar to an innovator product, it currently cannot be proven to be identical based on the current state of science. Thus, there are unique and inherent characteristics of biologics that must be considered as FDA establishes a regulatory pathway for biosimilars:

• Biologics are manufactured using live cells and biologics, such as monoclonal antibodies manufactured by MedImmune, are larger and more complex than small molecule drugs.
• Biologics are more difficult to characterize using laboratory techniques and have a more complex manufacturing process.
• Every biologic is different – even slight differences between biosimilars and innovator biologics, including their manufacturing processes, can result in meaningful differences in the safety and efficacy profile of the products.

What we believe

We support a regulatory pathway for biosimilars that is based on patient safety, product efficacy and continued incentives for innovator companies to invest in the development of novel, life-changing biologic medicines. We believe a biosimilars pathway should ensure:

• Appropriate rigorous scientific standards and a robust regulatory review process;
• A determination that biosimilars demonstrate the purity, potency and safety of innovator biologics as proven through human clinical trials and post-market surveillance; and
• Implementation of effective innovator regulatory exclusivity and patent enforcement provisions.

Below is a detailed look at our position:

Patient Safety
Because of the complexities of biologics, we believe that patient safety must be paramount when evaluating the approval of biosimilars. The introduction of biosimilars into the marketplace must ensure the current purity, potency, and safety standards established for innovator products by FDA. In addition, because the manufacturing process can have a significant impact on a biologic’s structure and activity, a regulatory pathway should ensure a rigorous inspection and control process for the manufacture of biosimilars that is similar to the innovator product standards

Clinical Trials
We believe that all biosimilars applicants should be required to conduct clinical trials that demonstrate sufficiently similar product safety, efficacy and immunogenicity relative to the innovator product. Non-clinical methods of characterizing complex biotechnology drugs have not matured to the point where they can substitute for clinical studies. Therefore, to ensure patient safety, it is essential for biosimilar sponsors to demonstrate product safety and efficacy by testing their product in adequate and well-controlled clinical studies. Furthermore, immunogenicity testing in human subjects, an integral part of biologics drug development, is critical to help measure potential adverse immune response to the biosimilar product. Immunogenicity has been associated with allergic or anaphylactic reactions, as well as reduction in efficacy or autoimmunity. We believe the FDA should issue molecule-by-molecule guidance for clinical trials required for biosimilars to account for the particular characteristics of the product.

Post-Market Risk Management Programs
We believe that biosimilars, once approved, should have FDA-approved risk management plans to ensure the products are rigorously monitored for post-market safety and immunogenicity. If biosimilars are approved with less clinical data than innovator biologics, the FDA should ensure that longer-term post-marketing outcomes for biosimilars remain similar to those with the innovator product.

Interchangeability/Substitution
We do not support interchangeability between an innovator biologic and a biosimilar product. Current regulations allow small molecule generic drugs to be designated as “therapeutically equivalent” and dispensed interchangeably with innovator products without physician’s knowledge. Because biosimilars are not identical to innovator biologics, they should not be deemed therapeutically equivalent and dispensed interchangeably for innovator biologics absent clinical trials that adequately demonstrate such interchangeability.

Unique Naming and Product Identification
Because biosimilars are similar to innovator biologics (rather than identical), we believe biosimilars should have a unique common name to distinguish themselves for prescribing, dispensing and pharmacovigilance purposes. In the interest of patient safety, it is critical that any adverse events be accurately traced to the actual product administered so that the manufacturer can take immediate remedial actions.

Patent Rights
Strong patent protection is the cornerstone of preserving incentive for biologics innovation, and a biosimilars approval pathway must establish a fair, transparent and effective system for all parties to quickly resolve any patent disputes.

Incentives for Innovation
Because biologics generally have substantial research, development and manufacturing periods and costs, a significant period of non-patent data exclusivity for innovator biologics must be provided to maintain an environment that fosters discovery of new and innovative biotechnology therapies. Although patent protection is important, this alone may be insufficient to protect the substantial investment made by innovators. For example, a biosimilar may be similar enough to an innovator biologic to receive regulatory approval, but different enough to circumvent the innovator’s patents. We support the provisions in PPACA that provides a base 12-year period of data exclusivity for innovator biologics plus an additional 6 months for pediatric studies.

Next Generation Improved Biologics
We support measures that protect investment in improvements to innovator biologics through extension of data exclusivity and intellectual property protections. This will help encourage continued investment and discovery of enhanced versions of previously-approved biologics that are safer, more effective, easier to administer and more capable of meeting patient needs. Modifications such as changes in amino acid sequences involve fundamental changes to a biologic’s molecular structure, and generally require clinical trials to gain regulatory approval. The vital, step-by-step process for advancing these medicines is dependent upon continued incentives for next generation biologics.

Conclusion
As new, innovative biologics and biosimilars enter the marketplace, AstraZeneca and MedImmune believe patient safety and product efficacy are of utmost importance. As a result, we support the development of a regulatory pathway for biosimilars that is based on patient safety, product efficacy and incentives for innovation. We will continue to monitor policy discussions and proposed regulations as the FDA moves forward in establishing a biosimilars pathway, and share our expertise and views where appropriate.

Download POSITION ON BIOSIMILARS (PDF, 34KB)

Since joining the company in 2006, Peter has been a major contributor to the growth of MedImmune. He has overseen the development of the global marketing and portfolio organizations, as well as managing the broader commercial, corporate development and strategy functions. He has also been accountable for MedImmune Ventures, a corporate development investment group.  In addition to being a member of the MedImmune Executive Team, Peter has led the cross-functional Brand Management Team and been a member of the Product Development Committee.

Greenleaf stated: “I am very excited about the future of MedImmune – and the role that biologics will play in achieving AstraZeneca’s long term success. I look forward to working closely with my colleagues from across the broader company.”

Prior to MedImmune, Greenleaf was at Centocor, Inc., where he served as franchise vice president, responsible for sales, marketing, strategic planning and business development. Previously, he served in sales and marketing capacities with Boehringer Mannheim Corporation and US Healthcare, Inc. He has a bachelor of science degree from Western Connecticut State University and a master’s degree in business administration from St. Joseph’s University.

About MedImmune

MedImmune, the worldwide biologics business for AstraZeneca PLC (LSE: AZN.L, NYSE: AZN), has approximately 3,300 employees worldwide and is headquartered in Gaithersburg, Maryland. For more information, visit MedImmune’s website at www.medimmune.com

“MedImmune is dedicated to conducting ground-breaking research on the prevention of respiratory syncytial virus (RSV) and influenza in children,” said Alexander A. Zukiwski, M.D., executive vice president and chief medical officer. “We believe the data being presented at the conference may help advance innovative healthcare solutions for these important causes of respiratory infections in children.”

MedImmune abstracts to be presented at IDSA on RSV include:

• Prophylaxis Utilizing Nebulized Motavizumab, a Monoclonal Antibody Against Fusion Protein of Respiratory Syncytial Virus (RSV) Zhang J, et al. Poster Session: October 30, 2009; 12:30 – 2:00 PM; Poster Hall A / Poster # 608

BACKGROUND: Respiratory syncytial virus (RSV) infection is the primary cause of pneumonia and bronchiolitis in young children, and also causes disease in older adults. This study evaluated the prophylactic use of nebulized motavizumab, an investigational anti-RSV humanized monoclonal antibody against RSV fusion protein, in cotton rats. The findings suggest that prophylaxis with nebulized motavizumab may inhibit RSV infection and spread in the lungs and may provide an alternative to the current intramuscular antibody delivery.

MedImmune abstracts to be presented at IDSA on influenza include:

• A Postmarketing Evaluation of the Frequency of Use and Safety of Live Attenuated Influenza Vaccine Use in Unapproved Children Less Than 59 Months of Age Tennis P, et al. Poster Session: October 31, 2009; 12:30-2:00 PM; Hall A / Poster #1179

BACKGROUND: In September 2007, the approval of live attenuated influenza vaccine (LAIV) was expanded for use in children between 24 and 59 months in age. The vaccine was not approved for use in children younger than 24 months, or for use in children with asthma or recurrent wheezing, or those with altered immunocompetence. This study evaluates the usage and safety of the vaccine in those patient populations younger than 59 months of age that were not in the approved indication. The study found that healthcare providers appear to be complying with the indications for the use of LAIV in children <5 years, and no adverse safety outcomes were detected in the small number of children in unapproved groups who received the vaccine.

• Whole Genome Transcriptional Analysis of the Early Immune Responses Induced by Live Attenuated and Inactivated Influenza Vaccines in Young Children Zhu W, et al. Poster Session: October 31, 2009; 12:30-2:00 PM; Hall A / Poster #1181

BACKGROUND: This study examined the early genomic immune response to live attenuated and inactivated vaccines in previously unvaccinated children 12 to 35 months of age. Among LAIV recipients, an increase in interferon (a natural anti-viral immune protein) production was seen, which may partly explain previous clinical study observations of LAIV-induced protection against illness in the first 2 weeks after administration.

• Influenza-Associated Antibiotic Use in Children Receiving Live Attenuated Influenza Vaccine Compared With Inactivated Influenza Vaccine Belshe R, et al. Poster Session: October 31, 2009; 12:30-2:00 PM; Hall A / Poster #1180

BACKGROUND: Influenza illness in children commonly results in the unnecessary use of prescription antibiotics. This analysis evaluated the efficacy of live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV) in preventing antibiotic use in children ranging from six months to 17 years in age. Overall, there was less influenza-associated antibiotic use in LAIV recipients due to a lower rate of culture-confirmed influenza with LAIV.

###

Additional information about the 2009 IDSA conference can be found at http://www.idsociety.org/IDSA2009.htm.

About FluMist®

FluMist® (Influenza Vaccine Live, Intranasal) is a vaccine indicated for active immunization of individuals two to 49 years of age against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

FluMist is contraindicated in individuals with history of hypersensitivity to eggs, egg proteins, gentamicin, gelatin or arginine or with life- threatening reactions to previous influenza vaccinations, and in children and adolescents receiving concomitant aspirin or aspirin-containing therapy.

Do not administer FluMist to children less than two years of age due to an increased risk of hospitalization and wheezing that was observed in clinical trials. FluMist should not be administered to any individual with asthma and to children less than five years of age with recurrent wheezing unless the potential benefit outweighs the potential risk. Do not administer FluMist to individuals with severe asthma or active wheezing.

If Guillain-Barre syndrome has occurred with prior influenza vaccination or if an individual is immunocompromised, the decision to give FluMist should be based on careful consideration of the potential benefits and risks. FluMist should not be administered to individuals with underlying medical conditions predisposing them to wild-type influenza infection complications unless the potential benefit outweighs the potential risk. FluMist should be given to a pregnant woman only if clearly needed.

Most common adverse reactions (occurring in 10 percent or more of individuals receiving FluMist and at a rate at least five percent higher than in those receiving placebo) are runny nose or nasal congestion in recipients of all ages, fever more than 100 degrees F in children two to six years of age, and sore throat in adults.

FluMist may not protect all individuals receiving the vaccine. FluMist is for intranasal administration only.

Please see complete Prescribing Information for FluMist, call 1-877-FLUMIST (1-877-358-6478) or visit http://www.medimmune.com/pdf/products/flumist_pi.pdf for additional information.

About MedImmune, Inc.

MedImmune, the worldwide biologics business for AstraZeneca PLC (LSE: AZN.L, NYSE: AZN), has approximately 3,100 employees worldwide and is headquartered in Gaithersburg, Maryland. With an advancing pipeline of promising candidates, MedImmune aims to be the next revolutionary force in biotechnology by delivering life-changing products, industry-leading performance, and a tireless commitment to improving patient health. For more information, visit MedImmune’s website at www.medimmune.com.

Background

Most state Medicaid drug reimbursement formulas are “one size fits all” in that they do not distinguish between biologics and chemical-based pharmaceuticals, nor do they fully recognize the extensive level of support services needed for patients using biologics. It is critical that states change this approach and recognize the unique nature of biologics and implement separate reimbursement mechanisms for biologics, since any reduction in reimbursement for biologics under existing Medicaid reimbursement formulas may result in inadequate compensation for patient support services and thereby reduce patient access to biologics; decrease the number of participating specialty distributor providers; and ultimately, increase costs to the state due to patients’ failure to obtain all necessary prescribed therapies.

Biotechnology drugs, or biologics, offer new hope to patients by providing novel therapies to treat unmet medical needs and debilitating health conditions. Biologics are complex medicines that are markedly different than most traditional chemistry-based pharmaceutical drugs in how they are developed, manufactured, stored, delivered and administered.

• Biologics consist of large, protein-based molecules that are manufactured using living organisms, and as such, are far more complex to produce than small molecule products.
• Biologics are generally prescribed by physician specialists (e.g., oncologists, rheumatologists, dermatologists, pediatricians, etc.) and historically target hard-to-treat diseases for which there are few, if any, effective therapeutic or preventive options.
• Biologics are most commonly administered via injection or infusion.
• Biologics are usually shipped by specialty distributors directly to the healthcare provider to ensure the proper storage and handling (referred to as maintaining proper “cold chain”) from manufacturer to the end user.
• Biologics require a variety of critical support services (often provided by the specialty distributors) to help ensure successful patient outcomes, including:
  • coordination of the drug’s delivery with scheduled patients’ visits to the provider;
  • patient tracking services (requiring compilation of data from several sources) to ensure patients receive follow-up doses as prescribed;
  • patient counseling and compliance education; and
  • educational services and product information for healthcare providers and office staff.



Policy Position Current on October 1, 2009

Download POSITION ON STATE MEDICAID DRUG REIMBURSEMENT FOR BIOLOGICS (PDF, 30.4KB)