Merck & Co. discontinues HIV vaccine trials

Vaccination in a phase II clinical trial of Merck & Co.'s investigational HIV vaccine (V520) is being discontinued because interim analysis of the STEP study shows it was not effective.

The Merck vaccine candidate is a mixture of three components, each made with a weakened version of a common virus (adenovirus type 5), that serves as a carrier, along with three synthetically produced HIV genes known as gag, pol and nef.

The STEP study was a multicentre, randomised, double-blind, placebo-controlled phase II test-of-concept clinical trial. The trial enrolled 3,000 HIV-negative volunteers from diverse backgrounds between 18 and 45 years of age at high risk of HIV infection.

The study evaluated two primary efficacy endpoints: whether the vaccine prevented HIV infection and whether it reduced the amount of virus in those who developed infection. As planned, an interim efficacy analysis was conducted in the approximately 1,500 volunteers expected to have the best response to the vaccine because they had low levels of pre-existing immunity to adenovirus 5.

The vaccine did not prevent infection: in volunteers who received at least one dose of the three-dose vaccine series, 24 cases of HIV infection were observed in the 741 volunteers who received vaccine and 21 cases of HIV infection were observed in the 762 participants in the placebo group. In the subgroup who had received at least two vaccinations and who were HIV negative for at least the first 12 weeks of the trial, 19 cases of HIV infection were observed in the 672 volunteers who received vaccine and 11 cases were observed in the 691 volunteers who received placebo.

In addition, the vaccine did not reduce the amount of virus in the bloodstream of those who became infected; HIV RNA levels approximately 8 to 12 weeks after diagnosis of infection were similar in the vaccine and the placebo arms. The geometric means of the HIV RNA levels in the blood of infected individuals, the standard measure of ongoing HIV replication, were approximately 40,000 copies/mL in the vaccine group and approximately 37,000 copies/mL in the placebo group. Additional analyses will be conducted on the entire study population and will be shared with the scientific community.

Study volunteers were followed for approximately 13 months. Overall adverse event rates were generally similar among the two groups, except for a higher rate of local injection-site related reactions in the vaccine group.

"Sadly, developing an effective AIDS vaccine remains one of the most challenging tasks facing modern medicine," said Dr Peter S. Kim, president, Merck Research Laboratories. "Merck's 20-year HIV research programme has led to improved scientific understanding of HIV and to true breakthrough medicines. We are committed to studying the data closely and sharing it with the scientific community to inform the on-going search for an effective HIV vaccine."