FDA GIVES MIXED REVIEW FOR EXPERIMENTAL SHINGLES VACCINE

Merck's experimental vaccine Zostavax reduces the risk of shingles infection and mitigates pain associated with the condition, but does not reduce the incidence of shingles-related deaths or hospitalizations, according to FDA briefing documents released recently.

Merck is seeking approval of Zostavax (varicella virus vaccine live) to prevent the shingles virus, known as herpes zoster (HZ), which causes outbreaks of small, rash-like blisters on the skin. The virus, which is most common in older people, causes postherpetic neuralgia (PHN), a condition characterized by persistent, long-term nerve pain. Roughly 1 million people develop shingles annually.

An FDA review of clinical data included in Merck's biologic license application (BLA) showed that Zostavax reduced the incidence of HZ in patients 60 and older by 51 percent and the incidence of PHN by 67 percent.

However, FDA staff noted that Zostavax appeared to be less effective in older patients. There is "a consistent trend toward progressive loss of vaccine efficacy in prevention of [shingles] with increasing age, although the numbers of subjects and cases of [shingles] occurring at the oldest ages are relatively small," the documents state. For example, Zostavax reduced the incidence of HZ by 64 percent in patients 60-69 years old, but only by 38 percent in subjects 70 years of age and older.

The review also revealed that Zostavax's potency may wane over time. "The study report shows a trend of decreasing efficacy in all three major efficacy endpoints (HZ incidence, PHN incidence and burden-of-illness) over the first three years following vaccination," the documents state. However, the reviewers acknowledged that the data was difficult to interpret because only a small proportion of subjects were examined three years after taking the vaccine.

Although Zostavax proved effective against shingles infection and postherpetic neuralgia, FDA scientists noted that the drug was not associated with a reduction in deaths or hospitalizations. No significant difference between the Zostavax and placebo groups was observed in terms of deaths, hospitalizations, use of pain medications or interference with daily activities, the briefing documents state.

In addition, the FDA's clinical reviewer pointed to possible flaws in the Zostavax study protocols, noting that because Merck studied relatively healthy people, its research "may not provide an adequate opportunity to evaluate whether the vaccine had any impact" on shingles-related hospitalizations or other severe complications.