Bristol seeks Japan approval of all-oral hepatitis C treatment


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

* Japan has about 1.2 million patients with chronichepatitis C

By Bill Berkrot

Nov 2 (Reuters) - Bristol-Myers Squibb Co has filedwith Japanese health regulators seeking approval of itsexperimental all-oral combination of hepatitis C treatments, theU.S. drugmaker said on Saturday.

The submission with Japan's Pharmaceutical and MedicalDevices Agency marks the first time that any drugmaker has filedfor approval of a hepatitis C treatment regimen that does notinclude 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 acrowded race to develop highly effective, interferon-freetreatments for the serious liver disease, has sought U.S.approval of its highly regarded anti-viral drug sofosbuvir incombination with ribavirin. A Food and Drug Administrationadvisory panel last week voted unanimously to recommend itsapproval.

The Bristol-Myers filing was based on data from a Phase IIIstudy of Japanese patients who either could not tolerateinterferon, which causes miserable flu-like symptoms, or thosewho had previously failed to be helped by treatment with theolder drugs - a particularly tough-to-treat patient population.

Patients in the trial were given a combination ofdaclatasvir, from a promising new class of drugs called NS5Ainhibitors, and the protease inhibitor asunaprevir for 24 weeks.Those who had no detectable levels of the virus in their blood24 weeks after completing the therapy were deemed to be cured, ameasure known as SVR24, for sustained virologic response.

The overall cure rate in the 222-patient study was 84.7percent, according to the data to be presented next week at theAmerican 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, while80.5 percent of past nonresponders to the older drugs weredeemed cured.

"The Phase III study results of daclatasvir plus asunaprevirare exciting to see, especially in this difficult-to-treatpatient population," Kazuaki Chayama, the study's leadinvestigator from Hiroshima University, said in a statement.

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


Bristol-Myers has made Japan a particular focus of itsall-oral efforts at tackling the hepatitis C virus, which ifleft untreated can cause cirrhosis, liver cancer or the need fora transplant.

About 1.2 million people in Japan suffer from hepatitis C.The patients tend to be older than those in other developedcountries and about 70 percent have Genotype 1b, a form of thevirus with very low response rates to the older treatments.

Several other companies are also developing all-oralhepatitis C treatments, including AbbVie Inc, Merck &Co and Johnson & Johnson, and expect to be ableto shorten treatment duration to 12 weeks from the current 24-or 48-week regimens.

Bristol early next year plans to begin Phase III testing ofan all-oral, three-drug combination that adds BMS791325 - anon-nucleoside polymerase inhibitor - to the two drugs tested inthe Japanese study. The company envisions that its three-drugtherapy will involve one combination pill taken twice a day fora 12-week course of treatment.

About 170 million people worldwide are infected with thehepatitis C virus. Some analysts believe the market for all-oralhepatitis C treatments could reach $20 billion as many morepeople get tested for the virus, given new testingrecommendations, very high cure rates, shorter treatmentdurations and tolerable side effects seen with the newer drugsin clinical trials.

It is believed that tens of thousands of hepatitis Cpatients have delayed treatment while awaiting the new drugsexpected to start reaching the market next year in order toavoid the unpleasant side effects of interferon. Physicianswould also like to see regimens that do not require ribavirin,which can cause anemia, rash and other side effects.

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