Phase 3 results boost rotavirus vaccine developed in India

In a phase 3 trial, a rotavirus vaccine that was developed by an Indian company with help from an international partnership showed about the same efficacy as existing rotavirus vaccines, raising hope that it will offer another affordable option for developing countries, according to reports published yesterday in The Lancet.

The manufacturer, Bharat Biotech, has committed to making the vaccine available to the public sector at less than $1 a dose for a three-dose series, according to a commentary accompanying the trial report.

The vaccine was developed from a nonpathogenic rotavirus strain, called 116E, that was discovered in India in 1985, according to a companion "viewpoint" article written by some of the study authors. Investigators found that it generated immune responses that protected infants from pathogenic rotavirus strains.

Tested in 4,500 infants

In the randomized trial, conducted at three sites in India, the vaccine was administered to about 4,500 infants, while about 2,200 others received a placebo.

The authors report that 71 cases of severe rotavirus gastroenteritis occurred in 4,752 person-years in the vaccine group, versus 76 events in 2,360 person-years in the placebo group. They calculated that overall vaccine efficacy against severe rotavirus gastroenteritis was 53.6% (95% confidence interval [CI], 35.0% to 66.9%; P = .0013) and that efficacy against the condition in the first year of life was 56.4% (95% CI, 36.6% to 70.1%; P < .0001).

The incidence of severe rotavirus gastroenteritis per 100 person-years was 1.5 in the vaccine group versus 3.2 in the placebo group, the report says. The team estimated that to prevent one severe rotavirus gastroenteritis episode, 55 infants (95% CI, 37-97) needed to be immunized.

On the safety side, the prevalence of immediate, solicited, and serious adverse events was similar in the vaccine and placebo groups, according to the report. Six cases of intussusception were reported in the vaccine group and two in the placebo group, all after the third dose. There were 25 deaths in the vaccine group and 17 in the placebo group, but none were believed to be related to the vaccine.

Comparable to licensed vaccines

In the accompanying commentary, two South African experts, Shabir A. Madhi, MD, PhD, and Umesh D. Parashar, MD, MPH, write that the vaccine's efficacy in the trial was similar to that of the two licensed rotavirus vaccines in developing countries. For example, the monovalent vaccine, Rotarix (GlaxoSmithKline), had 50% efficacy in Malawi, while the pentavalent vaccine, Rotateq (Merck), showed 64% efficacy in low-income African countries, they said.

Although the new vaccine's efficacy appears modest, it could yield substantial benefits, given the "tremendous health burden of severe rotavirus gastroenteritis in India and other low-income countries," according to Madhi and Parashar, who work for South Africa's National Health Laboratory Service.

India has an estimated 75,000 to 122,000 rotavirus deaths per year, or about a quarter of the global total, according to the viewpoint article by Maharaj A. Bhan, MD, and others. Bhan is the senior author of the vaccine study.

The article explains that the vaccine is the product of a team effort that involved investigators from 13 institutions and financial support from a public-private partnership that included the Indian government, Bharat Biotech, the nonprofit global health organization PATH, and academic institutions. PATH is supported by the Bill & Melinda Gates Foundation, the article notes.

The piece also describes the vaccine as "the first totally new vaccine in recent memory to be developed entirely in India," from a key clinical observation through basic research and product development. "This process opposes the often cited bias from big pharma that local manufacturers cannot pursue independent research, develop good manufacturing practices, and produce a novel product," the authors add.

They say the 116E isolate was initially developed into a vaccine candidate by a team of Indian and American physicians through the Indo-US Vaccine Action Programme, supported by Indian and US government agencies. Bharat Biotech became involved in 1998.

As for the cost, Madhi and Parashar write that GAVI (the Global Alliance for Vaccines and Immunization) buys the two licensed vaccines at discounted prices of $2.50 per dose for a two-dose series and $3.50 per dose for a three-dose series. The doses are distributed to low-income countries, which pay $0.40 for a full series of either vaccine.

But the viewpoint article asserts that the supply of the existing vaccines has been insufficient, and leaders in developing countries fear that when subsides end in 5 years, the prices will rise out of reach.

Madhi and Parashar write that the new vaccine "provides an alternative model of risk and cost sharing to develop life-saving vaccines that are effective, safe, and affordable for use in low income countries."

Bhandari N, Rongsen-Chandola T, Bavdekar A, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial. Lancet 2014 Mar 12. (Early online publication) [Abstract]

Madhi SA, Parashar UD. 116E rotavirus vaccine development: a successful alliance. (Comment) Lancet 2014 Mar 12. (Early online publication) [Introduction]

Bhan MK, Glass RI, Ella KM, et al. Team science and the creation of a novel rotavirus vaccine in India: a new framework for vaccine development. (Viewpoint). Lancet 2014 Mar 12 (Early online publication) [Introduction]

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