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Meningitis B vaccine’s high price tag poses a health care conundrum

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Public policy and individual choice 'revisited' 

In October 2014 and January 2015, the Food and Drug Administration licensed two meningococcal serogroup B vaccines for administration in adolescents and young adults aged 10-25 years based on each vaccine's ability to elicit bactericidal antibody against the majority of invasive serogroup B strains and demonstrated safety. Each vaccine represented novel technology that overcame the challenge of both the poor immunogenicity of serogroup B polysaccharide protein conjugates and the potential cross reactivity with fetal brain tissue. In the United States, the vaccine was recommended (category A) for individuals in this age grouping with complement deficiency, anatomic or functional asplenia, outbreaks (when indicated), and for microbiologists. The Centers for Disease Control and Prevention also recommends that physicians consider the MenB vaccine for individuals aged 16-23 years who wish to obtain short-term protection against diverse strains of serogroup B meningococcal disease (category B). The American Academy of Pediatrics encouraged pediatricians to discuss the availability of the MenB vaccines with families. 


The annual incidence of meningococcal disease varied between approximately 0.5-1.5 cases per 100,000 population between 1950 and 1990 - approximately 3,000 cases annually. Between 1990 and 2010, disease caused by the three common serogroups in the United States (B, C, and Y) declined to approximately 0.35 cases per 100,000. Subsequent to the introduction of a tetravalent meningococcal conjugate vaccine (MCV4) further declines - sustained over a longer time period than previously observed - have occurred, reaching a nadir of approximately 400 annual cases. Despite the absence of serogroup B component in MCV4, declines in serogroup B disease were reported in addition to vaccine serogroups C and Y. The biological explanations for the substantial decline in the overall rate of meningococcal disease are unknown. This decline in meningococcal serogroup B disease has created a controversy about implementation of Advisory Committee of Immunization Practices and the AAP and American Academy of Family Physician recommendations reflected in Shefali Luthra's writings.   


There is widespread agreement about the severity of invasive meningococcal disease, the peaks of incidence in infancy and late adolescence, a 10% case fatality rate, an additional 10%-15% morbidity, and the limited number of cases (in the United States) to be prevented by adolescent immunization despite serogroup B being the most common. The effectiveness (greater than 80%) of at least one of these vaccines (MenB-4C) has been established in the United Kingdom, where it is recommended for all infants as part of a three-dose series at 2, 4, and 12 months. The value proposition (number of people immunized to prevent one death), however, is estimated at 1 million vaccinees for each death prevented. 


Some experts believe the small burden of disease that might be prevented by these expensive vaccines requires thoughtful consideration in this era of increasingly limited resources. Others (as cited in the accompanying article) believe the marketing and advertising bend the truth and create fear in the public and conclude the risk is not great enough to warrant universal immunization (called category A by ACIP designation). In contrast, parent groups (especially those including parents of children who had meningococcal serogroup B disease) advocate strongly for a universal approach. For example, Alicia Stillman, director of the Emily Stillman Foundation, feels the current recommendation is "irresponsible" because it leaves so many teens and young adults vulnerable to the disease. The group believes that ACIP has made the menB vaccine to be an "optional item," but there is no requirement to provide the education to the parent and/or patient so they are aware of this option. 


For me, the question is this: Who should decide how we use limited resources? I am reminded of an editorial in the New England Journal of Medicine titled, "The Meningococcal Vaccine - Public Policy and Individual Choices" by Paul Offit, MD, and Georges Peter, MD, that examined this question (N Engl J Med. 2003;349[24]:2353-6). They advocated that parents, if aware, may choose vaccination to protect adolescents and young adults from devastating infection, even if they were required to pay. I believe the CDC foresaw this as likely and moved to recommend individual choice. The wisdom of this was that category B status required MenB vaccine to be covered by insurers, thus preventing a potential divergent uptake, where families that could afford the price would recognize its value and those unable to pay for the vaccine would have no choice but to decline. This is especially relevant as there are not specific risk factors among healthy adolescents to warrant prioritizing one group over another. 


MenB vaccines are valuable but costly tools for the prevention of life-threatening infectious disease. The use of increasingly limited resources, as raised by Dr. Moss and others, is a relevant and important question, and a call for a national dialogue.

 
As new medical breakthroughs increase, seemingly exponentially, how do we resolve the individual versus societal benefit of costly new treatments or preventions? How do we value prevention of life-threatening illness and death in mostly healthy adolescents, compared with treatment of end-stage diseases? These are important conversations that are only in their infancy.  


Abraham Verghese wrote, in his book "Cutting for Stone," that American ambulance crews "salvaged people we'd never see in Missing [fictional hospital in Addis Ababa], because no one would have tried to bring them to a hospital [in Addis Ababa]. Judging someone to be beyond help never crossed the minds of police, firemen, or doctors here" in the United States. We need transparency and a national dialogue to develop consensus about priorities. We need to make sure the discussions are comprehensive and civil - not about pushing grandmothers over cliffs or death panels. Currently, ACIP and AAP have advocated for individual choice and to empower the parent and adolescent to choose after we (clinicians) communicate disease severity, the risk to the adolescent, and adverse events associated with MenB vaccine.  
 
Stephen I. Pelton, MD, is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton disclosed that he has participated in advisory boards on meningitis B vaccines for GlaxoSmithKline and Pfizer, has research grants from Pfizer and Merck, and has spoken at CME events on meningitis B vaccines. 


 


 

 

Four years ago, when meningitis B, an extremely rare but potentially lethal form of the infection, sickened a small number of college students at Princeton and the University of California–Santa Barbara, there was no vaccine against the disease sold in the U.S. Despite its availability abroad, it had never been licensed in the country due to its limited marketability.

Scientific evidence supporting an absolute need to immunize against meningitis B still falls short. The risk of contracting it is smaller than that of being involved in a car crash.

But the headlines prompted by those 13 campus cases – which resulted in one death and one double amputation – helped reshape the financial prospects for a vaccine.

Today, two brand-name vaccines, both with price tags of more than $300, are widely advertised on television and touted as a smart investment for parents who love their college-bound kids.

“As moms, we send our kids out into the world, full of hope,” says a mother in the ad for Bexsero, sold by pharmaceutical giant GlaxoSmithKline, as her son loads up the car to go off to college.

Says another voice, “And we don’t want something like meningitis B getting in their way.”

Courtesy CDC


Analysts expect the two vaccines to generate annually at least hundreds of millions of dollars in global sales.

As new crops of students head to college, some physicians and other industry experts, though, are growing uneasy about the role of marketing in leveraging parental fears to sell the MenB vaccine – as well as ever more expensive vaccines that prevent quite rare illnesses. A complete Bexsero series costs $320; a competing vaccine, Trumenba, costs $345.

“Parents believe their children are susceptible to this terrible condition, and [drugmakers] use that fear to get parents to take action,” said Adrienne Faerber, a lecturer at the Dartmouth Institute for Health Policy and Clinical Practice who researches drug marketing.

The advertising, especially when coupled with news coverage, puts parents in a quandary left unresolved by federal vaccination guidelines and university requirements.

The Centers for Disease Control and Prevention recommends doctors consider the meningitis B vaccine for people ages 16-23 years on an individual basis. This recommendation – ranked as a category B – is not as universal as the approach applied to illnesses such as measles or human papillomavirus vaccines or even the “quadrivalent” vaccine for meningitis A, C, W, and Y, which all students must get.

Meanwhile, insurers generally cover it as part of preventive care. Still, most universities don’t require the vaccine but simply list it as an option for families to consider.

The resulting messages can confuse parents.

“There is perhaps, with all the marketing and advertising, some bending of the truth, and perhaps a little bit of creating fear – again recognizing that meningitis disease is a very severe disease,” said William Moss, a professor at Johns Hopkins Bloomberg School of Public Health who specializes in vaccines and global children’s health. “[The risk] is not a large enough problem to warrant routine vaccination.”

In recent years, drugmakers’ interests have begun to expand beyond the relatively cheap, broadly used immunizations – such as a tetanus shot or the children’s hepatitis A vaccine – to new, much pricier ones for less common infections.

These newer treatments have the potential to transform what’s long been a less lucrative side of drug production, manufacturing vaccines, into a major cash cow. But since the newer vaccines are regarded as less crucial than, say, preventing measles – and are often not required – marketing has become a big part of the sales equation.

Bexsero and its competitor, Trumenba, offer clues into how this scenario plays out.

Both vaccines got accelerated approval by the Food and Drug Administration in 2015 and 2014 respectively, following the Princeton and UCSB outbreaks.

Meningitis B does not spread readily from person to person. It requires close physical contact, like kissing or sharing utensils. It can be fatal but is treatable with antibiotics if caught early. Caused by the B serogroup of the meningococcal infection, it tends to appear in rare-scatter, slowed, self-limited outbreaks on college campuses. The standard meningitis vaccine doesn’t prevent it.

After new cases at Princeton and UC Santa Barbara kept appearing over many months, the CDC arranged for an emergency import of Bexsero. All students on those campuses got the shots, and there were no more cases.

Now the drugmakers are urging all parents to be proactive. Last year, Pfizer put more than $21 million into paid advertisements for the vaccine, according to figures kept by Kantar Media, a firm that tracks multimedia advertising. GlaxoSmithKline put in just about $79,000.

Those figures don’t account for other efforts such as meningitis awareness and ongoing social media campaigns done by GlaxoSmithKline, a “substantial effort” that “wasn’t cheap,” said Sriram Jambunathan, who heads GlaxoSmithKline’s meningococcal franchise in the United States. They also don’t include Pfizer’s investments in similar activities.

Already, industry analysts forecast Bexsero could bring in global revenue north of $1 billion per year by 2022. Trumenba is expected to earn Pfizer $880 million by that time.

But the industry’s gain may come at the expense of efficient health care spending and inflated consumer concern.

First, there’s the relative rarity of meningitis B. The CDC has estimated fewer than 300 cases occur in the United States per year, and some medical experts interviewed suggested the number may be closer to 50 or 60.

“As a mom, I would say, if my kid got this disease, and I had had the opportunity to prevent it, and I didn’t, I would kill myself,” said Martha Arden, a practicing physician and the medical director of Mount Sinai Adolescent Health Center’s school-based health program in New York City. “But the odds are small. It’s much more dangerous to send a kid out skiing than it is to not give the vaccine.”

Jambunathan said the price tag is warranted given the resources needed to bring Bexsero to market. Similar vaccines, he added, are comparably priced, and firms won’t necessarily want to develop these pharmaceuticals if they aren’t sure they can recoup their investment.

For parents who opt for the vaccines, there are caveats. Researchers don’t know, for instance, how long its immunity lasts. Many noted it also doesn’t cover all strains of the infection, so its efficacy in the United States is uncertain (there are different strains in different parts of the world).

And the cost of vaccination, while substantial, isn’t immediately felt by consumers because the treatment usually is covered without having to pay out-of-pocket. But the price tag may contribute to increasing premium costs.

In a world where there already aren’t enough health care dollars to address every possible harm, many experts noted, other health concerns might be a smarter investment.

Still, the price tag might not cause parents to blink. “When it’s your child or one case you know about, suddenly the health economic arguments feel difficult to have,” Jambunathan said.
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