10 years after a rejection, Merck returns to the FDA with a Gardasil 9 age expansion bid

How long is a drugmaker willing to wait on an indication expansion plan? For Merck’s HPV vaccines, that's 10 years.

Merck won the FDA "priority review" designation for an application to expand Gardasil 9 into older populations, about 10 years after the agency struck down a similar attempt for the company's older version of Gardasil. The FDA is expected to deliver a verdict by Oct. 6, 2018.

Gardasil 9 is currently FDA-approved for people 9 through 26 years of age, but Merck is seeking FDA approval to extend its use in women and men ages 27 to 45 for the prevention of certain cancers and diseases caused by the nine HPV strains covered by the vaccine. That’s the exact age group Merck was once eyeing for the quadrivalent shot Gardasil.

Back in 2008, after agreeing to a faster review in the age group, the FDA decided against Merck’s case for an additional Gardasil approval in females 27 to 45. The agency in 2009 issued a second complete response letter for that application, demanding Merck to provide longer-term efficacy data in the age group.

That set of data apparently didn’t turn things around for Merck. In both Gardasil’s and Gardasil 9’s current labels, information about a study on 3,253 women 27 through 45 years of age states that there was "no statistically significant efficacy" demonstrated by the vaccine in preventing high-grade cervical lesions or cervical cancer.

What has changed in the past decade that Merck hopes could convince FDA for a positive decision this time?

Observational and clinical data over the past decade demonstrate that women 27 to 45 are also at risk of acquiring new HPV infections, Merck spokeswoman Pamela Eisele told FiercePharma. Even though many people have already been exposed to HPV at an younger age, they have not been exposed to all nine HPV types targeted by Gardasil 9. Besides, a follow-up of the long-term study with Gardasil in women ages 27-45 showed no additional cases of HPV disease for at least 10 years following vaccination, a result that can be extended to Gardasil 9, she said.

The Gardasil family has in recent years been steadily building up its case at fighting off HPV-related diseases, including cervical, vulvar, vaginal and anal cancers and genital warts. Result released last October from a large-scale phase 3 study in girls and women 16 to 26 years of age showed that protection offered by Gardasil 9 lasts six years. Another one showed the older Gardasil’s protection can last a decade.

An analysis of data from Public Health England this week showed that since the introduction of a HPV vaccination program in 2008, first with GlaxoSmithKline’s bivalent Cervarix, HPV infection incidence in women 16 to 21 has dropped 86%, according to the Independent. Gardasil replaced Cervarix in the U.K.’s program in September 2012.

Because of those positive data and higher rates of uptake and course completion, life science commercial intelligence firm Evaluate recently predicted the vaccine's sales will grow from $2.38 billion in 2017 to $3.28 billion in 2024.