By Jim Shrine
Special To BioWorld Today
An FDA advisory panel unanimously recommended approval of BioChem Pharma Inc. and Glaxo Wellcome plc's Epivir (lamivudine) for chronic hepatitis B.
Approved in November 1995 under the name 3TC for HIV, Epivir is expected to receive marketing clearance for the hepatitis B virus (HBV) by the end of the year. If approved, it will be called Epivir-HBV in the U.S. and would entail a daily oral administration of 100 mg.
David Crossen, senior biotechnology analyst at Montgomery Securities, in San Francisco, called Epivir for hepatitis B "a reasonably important advance, but not a huge breakthrough. It will have an impact, but that [impact] should become greater as additional drugs are introduced for use in combination therapy."
Lamivudine, a nucleoside analogue reverse transcriptase inhibitor, received its first marketing clearance for HBV in August, when the drug was approved for sale in the Philippines. Since then, approvals have been granted in New Zealand and Pakistan. In most countries outside the U.S., the drug is called Zeffix.
Applications are pending in more than 30 countries, including the European Union, Japan and Canada, with approval expected in most by the end of the year, Crossen said.
Recommendation No Surprise, Says Crossen
The antiviral compound was discovered by BioChem Pharma, of Laval, Quebec, and licensed to London-based Glaxo in 1990. The terms of the agreement for HBV are the same as those for HIV: Glaxo has worldwide development, manufacturing and marketing rights (outside of Canada), and pays BioChem Pharma a royalty on sales. In the first six months of this year, 3TC sales totaled US$398 million. BioChem Pharma said its royalties, along with revenues from a joint marketing agreement in Canada, were US$46.6 million for the same period.
Crossen said Tuesday's recommendation by the FDA's Antiviral Drugs Advisory Committee was expected. "It had to be approved," he said.
"It was interesting," Crossen added, "the extent to which the panel raised concerns about the durability of response, and especially the emergence of resistance. It was very telling that they likened the state of therapy for the hepatitis B virus with the approval of this drug to the early days of single therapy against HIV, which I think is a realistic assessment.
"The drug has a profound effect on a minority number of patients," Crossen said. "Resistance is going to become a very complicated issue. Combination therapy will have to become the norm in this area over time, as more drugs are approved."
The standard therapy for hepatitis B infection now is alpha interferon injection. The daily, oral formulation of Epivir would have advantages in price and lessened side effects. BioChem Pharma said there are about 350 million people worldwide with chronic HBV infection, 1 million of whom are in the U.S., and about one-third are expected to develop serious progressive liver disease. Epivir-HBV, which interferes with viral replication, is designed to reduce the level of infection. The drug was tested in controlled studies of 967 chronic HBV patients and resulted in improved liver histology, more frequent hepatitis B "e" antigen seroconversion and more normalized serum alanine aminotransferase concentrations compared to placebo.
The vast majority of HBV patients are outside Europe and the U.S., about 95 percent, Crossen estimated. BioChem Pharma said 75 percent of the world's chronic HBV carriers live in Southeast Asia and the Western Pacific regions.
"It's impossible to know how effective Glaxo will be in these markets," Crossen said. "Reaching the Asian population will not be easy."
Crossen estimated the price of the drug for HBV will be about $1,500 per year, which he described as a 50 percent premium to the HIV price, given that the dose is one-third of that used by HIV patients. "But $1,500 is still a lot less than alpha interferon, which is $6,000 per year," he said.
Sales, according to Crossen, are estimated at $150 million the first year after approval, $300 million the second year and $450 million the third year. He said the numbers are guesswork, justified only by the U.S. and European markets, since Asian penetration is hard to gauge. BioChem Pharma will receive royalties of 12 percent in all markets outside the U.S., where royalties are 15 percent, he said.
BioChem Pharma's stock (NASDAQ:BCHE) was not traded Tuesday because of the pending news. The company's shares closed Wednesday at $17.437, down $0.187. *