BioChem Pharma Inc.'s lamivudine reduced hepatitis B virus (HBV)DNA to undetectable levels in all patients who received therapeuticdoses in a Phase II trial, the Laval, Quebec, company reportedMonday.
Results of the 32-patient, double-blind, randomized, dose-rangingU.S. study were presented in Chicago at the annual meeting of theAmerican Association for the Study of Liver Diseases. Patients,treated for three months and followed for six, received either 25, 100or 300 mg/day.
"It's encouraging, and further trials are warranted," Gervais Dionne,BioChem Pharma's executive vice president, research anddevelopment, told BioWorld. "More clinical trials have to be done."
The drug, being developed in conjunction with London-based GlaxoHoldings plc, was taken into Phase III trials for hepatitis B in Europelast summer, and in Hong Kong, Singapore and Taiwan in the fall.Another Phase II trial, involving six months of treatment and sixmonths of follow-up, is ongoing in Europe and Canada.
Investigators reported at the Chicago meeting that all 22 patientstaking 100 or 300 mg/day of lamivudine had HBV DNA reduced toundetectable levels. Reduction of HBV DNA levels was sustained insix of those 22 patients for the six-month follow-up period.
An earlier Phase II trial of the nucleoside analog involved one-monthtreatment of 62 patients receiving between 5 and 600 mg/day. In thatstudy, 98 percent of those receiving more than 100 mg/day hadreduction of HBV DNA to undetectable levels, Dionne said. "Thetreatment was very good," he said, "but after the treatment there wasa rebound, they came back to baseline."
Five percent of the patients receiving therapeutic doses in that one-month trial remained HBV DNA negative, Dionne said. "Whereas inthis trial [with three-month treatment] 19 percent remained HBVDNA negative."
Half of the patients were refractory to interferon-alpha and half were"therapy naive," or receiving their first treatment.
"In the Phase II trials, the reduction of HBV DNA has beendramatic," Dionne said. "There have been no serious adverseevents." Investigators at the Chicago meeting reported side effects ofheadaches, fatigue, nausea and abdominal pain.
BioChem Pharma invented the antiviral agent and licensedworldwide rights, excluding North America, to Glaxo. In NorthAmerica, lamivudine will be produced by a joint venture of the twocompanies, and sold in Canada by the joint venture and in the U.S.by Glaxo. BioChem Pharma will receive undisclosed royalties.
Dionne said that BioChem Pharma, after consulting with Glaxo,understands that the expected new drug application filing date wouldbe the end of 1996, assuming future trials are positive.
Data on a different formulation of lamivudine, called 3TC, will bepresented Sunday in Glasgow, Scotland. That trial is testing 3TC in acomparative study for HIV. One arm of that Phase II/III double-blindstudy is 3TC in combination with Retrovir, Wellcome plc's approvedHIV drug; the other arm is Retrovir alone.
Wellcome, of London, has an option to negotiate for rights to 3TC. Itis expected to decide whether to exercise those rights or not aftertrial results are reported. n
-- Jim Shrine
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