The U.S. Food and Drug Administration has again withheld approval for the use of Merck & Co Inc.'s (MRK.N) Gardasil cervical cancer vaccine by women aged 27 to 45, asking for longer-term clinical data. The drugmaker has confirmed the report on Friday.

The health regulator recommended Merck submit data when a 48-month study on a test group has been completed. Merck shares fell more than 3 percent in midday trading.

It is the second time the controllers have said no to Merck on Gardasil for women this age. One of Merck's most successful newer products, Gardasil was approved in 2006 for preventing cervical cancer and genital warts in females between the ages of 9 and 26. It works by preventing infection with the sexually transmitted human papillomavirus (HPV), which causes cervical cancer.

"Gardasil's effectiveness drops sharply once females have been exposed to HPV and this is probably the genesis of the problem with the older female population that Merck has been pushing for in this new application," Sanford Bernstein analyst Tim Anderson said in a research note.

Moreover, because effectiveness is naturally lower in older females, Merck could have difficulty convincing insurers to cover Gardasil in that group should it be approved for them, Anderson added. Additionally, there are questions about how enthusiastic insurers will be about paying for it in the older set. There’s already been debate about whether it’s worth the money.

The FDA letter does not affect the use of the drug in the approved age group, or Merck's recently filed application to expand use to males, the company said. Anderson expressed uncertainty about the FDA's eventual decision on Gardasil's use in males and about its sales potential in that population.

Merck on Friday also stood by its 2009 sales and earnings targets of Gardasil (forecasted at $1.4 billion to $1.6 billion), and expects to provide a response to the agency in the fourth quarter of this year