Merck's newly approved herpes zoster vaccine Zostavax is priced in the middle of the company's cost-effectiveness estimates.

The vaccine's list price is about $150 per dose, according to Merck; the exact price depends on whether the product is purchased as part of a 10-pack ($145.35 per dose) or in single-dose vials ($152.50 per dose).

Zostavax, the first vaccine indicated to prevent the reactivation of varicella zoster virus, was approved May 25 for use in patients age 60 and older. It is administered as a single subcutaneous injection.

A Merck-sponsored study evaluated potential vaccine prices ranging from $125 to $175 per dose.

"Cost-effectiveness ratios for a cohort of vaccine recipients age 60 and above over a range of potential vaccine prices from $125 to $175 per dose were $11,259 to $19,410" per quality-adjusted life years gained, the study abstract states.

"Using a threshold for cost-effectiveness of $50,000/QALY gained, these analyses show that the zoster vaccine is cost-effective over a broad range of scenarios and age cohorts."

Herpes zoster (shingles) is a manifestation of the reactivation of varicella zoster virus, which also causes chickenpox. Postherpetic neuralgia, or long-term nerve pain, is the most common complication of herpes zoster.

Merck found that the number of herpes zoster-related healthcare encounters was reduced in patients who had received the vaccine. Healthcare encounters for vaccinated herpes zoster and postherpetic neuralgia subjects were reduced by 65%. The placebo arm produced a reduction in healthcare encounters of 78%.

"While the rates of HZ-related HCEs reported in the trial were lower than the rates in published epidemiology studies, due to the care required by the protocol, Zostavax was effective in reducing the rates of HCEs" for herpes zoster and postherpetic neuralgia, the abstract states.

"The vaccine could substantially reduce the burden of HZ if these rate reductions were observed in practice."

Merck intends to present Zostavax cost-effectiveness data to the Centers for Disease Control & Prevention's Advisory Committee on Immunization Practices at its June 29 meeting.

ACIP also will review the firm's pending human papillomavirus vaccine Gardasil , which recently received a positive recommendation from an FDA advisory committee (¹ Also see "Gardasil Sails Through Committee; Discussions Center On Labeling Language" - Pink Sheet, 22 May, 2006., p. 3).

According to Merck, Zostavax will be the first vaccine to be covered under Medicare Part D.

Zostavax also will be available as part of a new Merck vaccine assistance program for adults, slated to launch in the third quarter.

Under the program, Merck will offer uninsured adults free vaccines through physicians' offices.

To be eligible, patients must have no insurance coverage and limited income - an annual household income that is less than $19,600 for individuals, $26,400 for couples or $40,000 for a family of four (twice the federal poverty level).

All of Merck's vaccines for adults - Zostavax, Gardasil, M-M-R II (measles, mumps and rubella), Pneumovax 23 (pneumococcal infection), Recombivax HB (hepatitis B), Vaqta (hepatitis A) and Varivax (varicella) - will be covered.

Merck is undertaking a physician education campaign to accompany the Zostavax launch, the firm said; a patient education campaign will follow. According to Merck, Zostavax has a potential market of 50 mil. people in the U.S.

Approval of the vaccine was based on the Shingles Prevention Study of 38,546 people over age 60. The randomized, double-blind, placebo-controlled study was conducted by the Department of Veterans Affairs, the National Institutes of Health and Merck. Patients were followed for a median duration of 3.1 years.

Overall, Zostavax reduced the risk of developing shingles by 51% compared to placebo.

"Vaccine efficacy for the prevention of HZ was highest for those subjects 60-69 years of age and declined with increasing age," labeling notes.

The vaccine was 64% effective in the 60-69 year-old group, dropping to 41% for patients 70-79 and 18% for patients over 80.

Merck also analyzed reduction in postherpetic neuralgia in patients who developed shingles despite vaccination.

"Vaccination with Zostavax reduced the incidence of PHN in individuals 70 years of age and older who developed zoster postvaccination," labeling states. The reduction in PHN was not statistically significant for the 60-69 or 80 and older age groups.

Merck had sought a Zostavax indication for ages 50 and older, but FDA's Vaccines & Related Biological Products Advisory Committee concluded during its December meeting that the results of the company's pivotal trial were insufficient to establish efficacy of the vaccine in patients ages 50-59 (² Also see "Zostavax Clinical Efficacy Trials For 50-59 Year-Olds Needed, Cmte. Says" - Pink Sheet, 19 December, 2005., p. 15).

Merck had hoped to base the indication for use in ages 50-59 on comparable immune responses across the various age cohorts, the efficacy of the vaccine in individuals over 60 and the tolerability of the vaccine. Of the 38,546 subjects participating in the Zostavax study, only 185 individuals under 60 were vaccinated.

The company "would have to present more data, both safety and efficacy data, to pursue" approval for that age group, Center for Biologics Evaluation & Research Office of Vaccines Research & Review Director Norman Baylor said during a May 26 conference call discussing the vaccine's approval.

Merck said it intends to pursue an indication for the 50 and older population and is working with FDA to determine what data are needed to move forward with a supplemental BLA.

Serious adverse experiences with Zostavax occurred at a similar rate to placebo (1.4%). Zostavax is contraindicated in individuals with a history of allergic reactions to components of the vaccine, those on immunosuppressive therapy (including high-dose corticosteroids), patients with immune deficiencies and those with active, untreated tuberculosis. Women who are or may be pregnant should not use the vaccine, labeling adds.

Zostavax safety will be further explored in four required post-marketing studies.

Merck will conduct a randomized, placebo-controlled general safety study in a total of 12,000 patients receiving Zostavax or placebo. Primary safety follow-up for serious adverse experiences will be for 42 days postvaccination, but subjects will be followed for six months.

The trial will be stratified by age - subjects younger than 80 years old and those older than 80 - with a target of 15% enrollment in the older group.

In the pivotal Shingles Prevention Study, 2.2% of subjects age 80 and older had a serious adverse event, compared with 1.1% in the 60-69 group and 1.6% in the 70-79 group.

In the Adverse Event Monitoring Substudy, patients 80 and older had a 5.1% rate of serious adverse events, versus 1.3% in ages 60-69 and 2.2% in ages 70-79.

The general safety study is expected to begin in May 2007 and conclude in November 2010.

Additionally, Merck will conduct a large-scale, 20,000-subject observational post-licensure safety study of Zostavax in a U.S. HMO "to gain further knowledge of the safety of the vaccine in the course of ordinary clinical practice." That trial is slated to begin in January 2007 and conclude in June 2008.

Merck will also evaluate the safety of a high-potency dose of Zostavax in 5,000 subjects. If a high-potency lot is manufactured within three years, "the study will be initiated and a preliminary report will be provided to CBER within 2.5 years of vaccine lot identification."

The company also will conduct a randomized, placebo-controlled, double-blind study to assess the safety of Zostavax in 300 subjects receiving low to moderate maintenance doses of corticosteroids. The corticosteroid study must be completed by September 2007. Merck intends to file an sBLA for use of the vaccine in steroid patients.

Merck submitted the Zostavax BLA (125123) April 25, 2005. The user fee date was extended by three months after the company submitted additional information.

Merck Zostavax Gets Mid-Range Price, Loses Younger Age Group

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