By Bill Berkrot
(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.
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.
About 1.2 million people in Japan suffer from hepatitis C. The patients tend to be older than those in other developed countries and about 70 percent have Genotype 1b, a form of the virus with very low response rates to the older treatments.
Several other companies are also developing all-oral hepatitis C treatments, including AbbVie Inc, Merck & Co and Johnson & Johnson, and expect to be able to shorten treatment duration to 12 weeks from the current 24- or 48-week regimens.
Bristol early next year plans to begin Phase III testing of an all-oral, three-drug combination that adds BMS791325 - a non-nucleoside polymerase inhibitor - to the two drugs tested in the Japanese study. The company envisions that its three-drug therapy will involve one combination pill taken twice a day for a 12-week course of treatment.
About 170 million people worldwide are infected with the hepatitis C virus. Some analysts believe the market for all-oral hepatitis C treatments could reach $20 billion as many more people get tested for the virus, given new testing recommendations, very high cure rates, shorter treatment durations and tolerable side effects seen with the newer drugs in clinical trials.
It is believed that tens of thousands of hepatitis C patients have delayed treatment while awaiting the new drugs expected to start reaching the market next year in order to avoid the unpleasant side effects of interferon. Physicians would also like to see regimens that do not require ribavirin, which can cause anemia, rash and other side effects.
(Editing by Matthew Lewis)