By: Peter Loftus
Published: November 3, 2013
An experimental Merck & Co. vaccine appeared to provide broader protection against a cancer-causing virus than the company’s Gardasil shot in clinical trials.
Merck said the study results support its plan to submit the new vaccine, code-named V503, for U.S. regulatory approval by year’s end, which could lead to market launch next year at the soonest. Merck expects health-care providers to eventually switch to V503 if the product receives marketing approval. Some analysts expect its annual sales could exceed $1 billion.
“The case for using V503 is even stronger than the case for using Gardasil, which was already strong,” said Roger Perlmutter, head of Merck’s research and development unit. Dr. Perlmutter has singled out V503 as one of the programs Merck will focus on as it overhauls its R&D unit in a bid to recover from a series of setbacks.
Gardasil, launched in 2006, was the first vaccine to protect against human papillomavirus, or HPV, a sexually transmitted virus that can cause cervical cancer in women and other less-common types of cancer in males and females. The U.S. Centers for Disease Control and Prevention recommends HPV vaccination of boys and girls ages 11 and 12, though it is approved to be given to people ages 9 to 26. GlaxoSmithKline also sells an HPV vaccine called Cervarix.
Gardasil is designed to protect against four strains of HPV, two of which are believed to be responsible for about 70% of all cervical cancer cases. The other two strains are the primary culprits in causing genital warts. But Gardasil doesn’t protect against many other strains of HPV, some of which can also cause cervical and other cancers.
To close the gap, Merck designed V503 to protect against nine HPV strains, adding five cancer-causing HPV types to the four included in Gardasil. This wider set is believed to account for nearly 90% of all cases of cervical cancer globally, said Alain Luxembourg, director of clinical research for adult vaccines in Merck’s R&D unit.
Merck ran clinical trials to test the new vaccine’s safety and efficacy, and results are being presented at an HPV- focused medical meeting in Florence, Italy, this week. One study enrolled more than 14,000 women ages 16 to 26, who received either Gardasil or V503 in three doses over six months. The goal was to demonstrate V503 was comparable to Gardasil in protecting women against the four HPV strains common to both vaccines, and superior to Gardasil in protecting against the five additional strains in V503.
For the four HPV strains common to both vaccines, the study compared immune responses as measured in blood tests, and found V503 to be comparable to Gardasil. The researchers used immune response as the key measure because the rates of disease caused by these four HPV strains were too low in both groups to provide a meaningful comparison.
For the five HPV strains not covered by Gardasil, researchers compared the rates of precancerous lesions caused by those five strains. The study found that V503 reduced the incidence of these lesions by about 97% compared with Gardasil.
Merck said it couldn’t test the efficacy of V503 in virginal adolescents because they generally haven’t yet been exposed to HPV. So researchers measured immune responses in boys and girls ages 9 to 15 and compared them to the immune responses seen in women ages 16 to 26. The study concluded the responses were comparable across the nine HPV types targeted by V503, which Merck hopes will demonstrate to health authorities that the vaccine is effective in adolescents.
The rates of adverse events among V503 recipients were generally similar to those for Gardasil, though V503 subjects had a higher incidence of injection-site problems such as pain and redness than Gardasil subjects, 90.8% versus 85.1%. Safety concerns have occasionally dogged Gardasil, particularly reports of fainting after receiving the shot. But the CDC has concluded the vaccine is safe and effective.
Analysts from Leerink Swann estimate V503 sales could reach $1.9 billion by 2018, though it would cannibalize sales of Gardasil. Merck reported $1.6 billion in Gardasil sales last year, but Leerink predicts that would fall to $525 million by 2018.
Some health experts say an HPV vaccine with broader coverage would be an important advance. “We should be able to prevent more cervical cancer if that vaccine is given,” said Jessica Kahn, professor of pediatrics in the division of adolescent medicine at Cincinnati Children’s Hospital Medical Center. She wasn’t involved in the studies of V503.
It’s unclear, however, whether an HPV vaccine with broader protection would help improve vaccination rates, which have flattened out in the U.S. Public health experts say family physicians and pediatricians aren’t recommending HPV vaccination as strongly as other vaccines given to adolescents, such as the shot for tetanus, diphtheria and pertussis.
There is little research to suggest that a vaccine protecting against additional HPV strains would significantly improve vaccination rates, said Anne Schuchat, head of immunization programs at the CDC. Still, she said she welcomed industry research on improving HPV vaccines.
*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.