Prevnar - first blockbuster vaccine of the millennium
Prevnar is the first conjugate vaccine to be used for the prevention of invasive pneumococcal disease in infants and young children. The vaccine was approved by the US Food and Drug Administration (FDA) on February 17, 2000, and is now approved in 48 countries. Prevnar achieved sales of more than $600 million in its first year, and total sales have now exceeded $1 billion.
The vaccine helps protect against diseases caused by Streptococcus pneumoniae, also known as pneumococcus. The vaccine - pneumococcal 7-valent conjugate vaccine (diphtheria CRM197 protein) - targets the seven serotypes of pneumococcal bacteria most prevalent in the USA, which are also among the most resistant to antibiotics. Worldwide, more than 1.2 million children die each year as a result of pneumococcal diseases. Approximately 16,000 cases of invasive pneumococcal disease are recorded in the USA each year among children under 5 years of age, and the annual cost to the US health care system is estimated to be $1.5 billion.
Prevnar has been developed and commercialized solely by Wyeth Vaccines; the research programs that led to the development of the vaccine having been initiated in the 1980s. Kevin Reilly, President, Wyeth Vaccines, spoke to Phacilitate about the development and success of Prevnar and discussed the impact of the vaccine for healthcare and for the vaccine industry.
Phacilitate: Prevnar has been a huge success story for Wyeth Vaccines. Do you view this as the first ‘blockbuster’ vaccine?
Reilly: Prevnar is certainly a ‘blockbuster’ in the sense of its importance to children’s health and the speed at which it was embraced by the healthcare community. Using those criteria, you might say that polio vaccine was the first ‘blockbuster.’ HepB vaccine by Merck and Glaxo SmithKline could also be called a ‘blockbuster,’ but Prevnar is one of the most successful vaccines ever introduced in terms of its efficacy and its rapid uptake. And, unlike HepB, it was introduced by a single company.
Phacilitate: The vaccine has achieved massive uptake in a very short time. How did Wyeth Vaccines work with the public health bodies to achieve this?
Reilly: The rapid uptake of Prevnar has, indeed, been unprecedented for a new childhood vaccine. We believe the primary reasons for its success are that we have a very effective vaccine that helps prevent a very serious disease.
From the outset, vaccine and infectious disease experts who directly and indirectly impact the need for a vaccine, as well as its use, recognized the serious morbidity and mortality associated with invasive pneumococcal disease in children. Those experts include the infectious disease research community; the Food and Drug Administration, the Centers for Disease Control and Prevention, the American Academy of Pediatrics and the American Association of Family Physicians; managed care organizations; private pediatricians and other health care professionals.
The awareness and concern of parents and other caregivers (child care providers), should also not be overlooked. Meningitis is a frightening and fairly well recognized disease among consumers, and as such parents were very accepting of this vaccine.
Additionally, and as important, the strong efficacy and safety profile of this vaccine, as demonstrated in one of the largest-ever Phase III clinical trials for a childhood vaccine (38,000 children), established a very solid and early foundation of confidence in the vaccine. That data, first presented at ICAAC in September 1998 by the lead investigators at Northern California Kaiser Permanente (NCKP), included a nearly unprecedented efficacy rate of 100% against invasive pneumococcal disease (IPD) with no significant safety issues. In fact, the trial was halted and unblinded earlier than planned because of the highly favorable outcome. Subsequently, the vaccine’s safety and efficacy profiles were reaffirmed as additional data from the NCKP trial (pneumonia, otitis media) and other trials (Finnish otitis media trial) were reported.
We are currently conducting a Phase IV study involving 60,000 children at NCKP, to corroborate the safety and effectiveness of Prevnar that was demonstrated earlier in Phase III pre-licensure studies.
The medical community as well as the regulatory bodies were eagerly awaiting the arrival of Prevnar. It was the first vaccine to be designated by the FDA for ‘priority review’, meaning that it clearly met an urgent need, and was approved by the FDA less than one year later.
Phacilitate: There have been shortages of vaccine due to massive demand. How has the company coped with the huge requirement for manufacturing capacity, and what is the current situation regarding supply and demand?
Reilly: We planned and intended to achieve rapid acceptance of the vaccine, but the actual uptake surpassed even our most optimistic projections. In the first year of commercial availability, immunization rates hit 90% among infants up to 11 months of age, 60% in the 12-23 month age group, and about 20% in the 24-59 month age group. These rates are unprecedented for a new vaccine.
The gap between supply and demand is narrowing, and we expect it to close during Q2 2002. The actions we have taken to increase our product flow include increasing manpower, addressing compliance issues and resolving a ‘bottleneck’ identified in the post-production process. In the meantime, we are working closely with physicians and the CDC to ensure the best use of available vaccine.
Phacilitate: What has been Wyeth Vaccines’ strategy for commercializing the vaccine?
Reilly: Our strategy for commercializing the vaccine was based on four key issues: first, the scientific facts about the seriousness of IPD; second, the compelling need for an effective prevention in young children; third, the emerging evidence of the effectiveness of Prevnar in preventing IPD; and finally, Wyeth Vaccines’ experience in introducing new vaccines and therapeutic products in the domestic and non-US pediatric marketplace.
As background, the primary infectious pathogens that can cause bacterial meningitis are Hemophilus influenzae type b (Hib), pneumococcus and meningococcus. During the 1990s, the incidence of meningitis caused by Hib rapidly declined due in large part to HibTiter, a Hib conjugate vaccine we introduced in 1990. In fact, it has now been virtually eliminated in the USA and S. pneumoniae has emerged as the leading cause of bacterial meningitis in young children. Since the currently available polysaccharide vaccines were ineffective in children younger than two years, there was clearly a compelling need for an effective vaccine to prevent the morbidity and mortality associated with this disease among young children.
So, from the outset, we were confident that an effective, safe prevention would be commercially successful in the USA and international market. Our efforts, which started in the 1980s, became focused on developing a vaccine to prevent infection from the seven strains (or serotypes) of S. pneumoniae that were the most prevalent in the USA and most resistant to treatment. A grant from the NIH in the early stages played an important role in facilitating inclusion of all seven serotypes in the vaccine. Our confidence in the favorable safety profile and efficacy of the vaccine was assured throughout the early clinical trials. It was overwhelmingly solidified when the Phase III outcomes of the NCKP pivotal trial demonstrated nearly 100% efficacy for the vaccine in young children, and a favorable safety profile.
With that evidence, our commercialization strategy became focused on effectively and quickly communicating these facts to the primary audiences both inside and outside the healthcare community. This was where Wyeth Vaccines’ experience and expertise in marketing played a significant role. Approvals and endorsements for the vaccine surfaced quickly from within the regulatory and medical sectors (FDA, which granted ‘fast track’ status; CDC/ACIP, AAP and AAFP, all of whom issued favorable recommendations), and we effectively secured support within the critical insurance/managed care arena.
Awareness and support also emerged from organizations such as the Meningitis Foundation of America, the National Child Care Association, the National Association of Child Care Professionals, the National Medical Association and related groups who urged rapid approval and acceptance of the vaccine. The combined voices from these groups amplified the urgency of universal immunization coverage.
These are some of the key factors that have contributed to the record success of the vaccine in the US market, and to our successful international strategies that have resulted in approvals in 48 countries in a short period of time.
Phacilitate: How did Wyeth Vaccines approach globalization of Prevnar?
Reilly: This vaccine is a global product with significant sales potential worldwide. The primary factors driving commercial success domestically are also driving the globalization of this vaccine. Those factors include recognition of the compelling need for an effective prevention of IPD - due to the significant morbidity and mortality associated this disease worldwide and the declining treatment options resulting from increasing antibiotic resistance – and, the vaccine’s demonstrated favorable safety profile, efficacy and cost-effectiveness.
While Wyeth is globalizing the vaccine using its own internal resources, there have been significant contributions from both the public and private research communities during development. The NIH, for instance, provided a key support grant to facilitate inclusion of additional serotypes at a pivotal point in development, and the NIH is supporting ongoing studies of the vaccine in adults.
Our commercial globalization efforts have been highly successful. The vaccine is approved in 48 countries and has been commercially launched in 24 countries (as of October 2001) including most of Europe, Latin America, Canada and Australia. The product was approved in the European Union for IPD in infants and toddlers, as it is in the USA. In some other countries, it is indicated for IPD, otitis media and pneumonia in children up to nine years of age (Australia, Switzerland, The Netherlands, Argentina, Brazil, Canada, Chile and Columbia).
Additionally, applications are under active review in a host of other countries including South Africa (filed August 2000); Eastern Europe, Middle East and many Asian countries (filed Q1 2001). Approvals are expected throughout 2002.
Phacilitate: There has been some concern regarding the cost of Prevnar – each child requires four shots with a cost of approximately $60 per injection. How has Wyeth Vaccines justified the cost of vaccination?
Reilly: The cost of immunizing children with Prevnar, as recommended, is actually less than the cost to society of children getting IPD. That does not even include the cost-savings that might be realized from preventing the transmission of the disease from one infected child to an unvaccinated child or elderly person. It also doesn’t include the possible cost-savings associated with reduction in antibiotic use or the reduction of the need to develop new, more expensive antibiotics to treat IPD because the bacteria is growing increasingly resistant to our currently available antibiotics.
The evidence underlying this belief is the rapid acceptance of the vaccine as soon as it was available. The compliance rates within one year of market introduction were equal to, or exceeded, those of any other routinely recommended pediatric vaccine in the USA.
We have found that once parents learn about how devastating IPD can be and how widespread the bacteria is, they tend to view any argument opposing immunization with Prevnar as weak and unconvincing. The rapid uptake proves that physicians and parents alike, as well as managed care organizations and insurance companies, agree that immunization with Prevnar is not only critical for children, but also cost-effective.
Phacilitate: What impact will the success of Prevnar will have for your company and, more widely, for society?
Reilly: Prevnar has contributed strongly to the growth of the division. Global company sales exceed $1 billion and are expected to continue to grow as the vaccine is introduced in new markets. Acceptance of Prevnar and its impact on disease is helping shift conventional wisdom back to thinking that prevention is indeed a better strategy than management of disease - especially in light of the proliferation of antibiotic-resistant strains of pneumococci. The success of Prevnar has confirmed the value that the company placed in investing in its development prior to approval.
Looking at the big picture, if we can prevent pneumococcal meningitis and other serious pneumococcal diseases in children, then we have made a significant contribution to the health and prosperity of future generations. As a company, we feel privileged to be a part of that. Speaking more broadly for Wyeth Vaccines, Prevnar is the first of many life-saving or life-enhancing vaccines that we hope to introduce to help prevent serious diseases and create a healthier world.
