* 84.7 pct of difficult-to-treat patients cured in trial

* Japan has about 1.2 million patients with chronic hepatitis C

By Bill Berkrot

Nov 2 (Reuters) - Bristol-Myers Squibb Co has filed with Japanese health regulators seeking approval of its experimental all-oral combination of hepatitis C treatments, the U.S. drugmaker said on Saturday.

The submission with Japan's Pharmaceutical and Medical Devices Agency marks the first time that any drugmaker has filed for approval of a hepatitis C treatment regimen that does not include either of the standard older treatments - the injected, difficult-to-tolerate interferon, or ribavirin, a pill.

Gilead Sciences Inc, widely seen as the leader in a crowded race to develop highly effective, interferon-free treatments for the serious liver disease, has sought U.S. approval of its highly regarded anti-viral drug sofosbuvir in combination with ribavirin. A Food and Drug Administration advisory panel last week voted unanimously to recommend its approval.

The Bristol-Myers filing was based on data from a Phase III study of Japanese patients who either could not tolerate interferon, which causes miserable flu-like symptoms, or those who had previously failed to be helped by treatment with the older drugs - a particularly tough-to-treat patient population.

Patients in the trial were given a combination of daclatasvir, from a promising new class of drugs called NS5A inhibitors, and the protease inhibitor asunaprevir for 24 weeks. Those who had no detectable levels of the virus in their blood 24 weeks after completing the therapy were deemed to be cured, a measure known as SVR24, for sustained virologic response.

The overall cure rate in the 222-patient study was 84.7 percent, according to the data to be presented next week at the American Association for the Study of Liver Diseases (AASLD) meeting in Washington.

Of those who were either ineligible for or intolerant of treatment with interferon, the cure rate was 87.4 percent, while 80.5 percent of past nonresponders to the older drugs were deemed cured.

"The Phase III study results of daclatasvir plus asunaprevir are exciting to see, especially in this difficult-to-treat patient population," Kazuaki Chayama, the study's lead investigator from Hiroshima University, said in a statement.

Twenty-eight patients dropped out of the study - a 12.6 percent discontinuation rate - and about 6 percent, or 13 patients, reported serious side effects, primarily elevated liver enzymes, an indication of inflammation.

JAPAN FOCUS

Bristol-Myers has made Japan a particular focus of its all-oral efforts at tackling the hepatitis C virus, which if left untreated can cause cirrhosis, liver cancer or the need for a transplant.