By Lisa Seachrist
Phase III clinical results of BioChem Pharma Inc.'s lamivudine show that the drug effectively slows liver damage cause by hepatitis B virus (HBV) infections, as well as reduces the level of virus in the blood stream.
Discovered by BioChem Pharma, of Laval, Quebec, lamivudine is the nucleoside analogue antiviral drug 3TC in a dosage designed for the treatment of HBV infection. Glaxo Wellcome, of London, licensed it from BioChem Pharma and is steering its development. Glaxo intends to file for regulatory approval in Asia later this year, with filings in the U.S. and Europe sometime in the first half of 1998. BioChem Pharma has a marketing partnership with Glaxo in Canada, where a first half of 1998 filing also is likely.
"These clinical results are very important for BioChem Pharma," Christine Lennon, vice president for corporate communications, said. "It really shows that the company can discover products that have clinical benefit."
The licensing agreement with Glaxo Wellcome is likely to produce substantial royalties to BioChem Pharma once the product is on the market. "These data are extremely important," analyst Marc Ostro, with UBS Securities, in New York, told BioWorld Today. "This is likely to be a $2 billion-a-year product for Glaxo and by way of their agreement, a huge future impact for BioChem Pharma's bottom line."
BioChem Pharma's (BCHXF) stock closed at $23 per share Thursday, down $1.50 on the news.
HBV is transmitted via blood and bodily fluids where it infects liver cells and begins replicating. The virus itself doesn't appear to cause any direct damage to the liver. Instead, it is the body's immune response that causes the inflammation and scarring associated with HBV infections.
Most adults eventually develop antibodies that clear the infection, but about 5 percent to 10 percent of newly infected adults and 90 percent of children infected at birth do not eliminate the virus and develop chronic infections which may lead to serious liver disease and liver cancer. Worldwide, 300 million to 350 million people * mostly in Asia * are chronic carriers of HBV and 1 million to 2 million deaths result from HBV every year.
Currently, HBV is treated with the injected immune stimulant alpha interferon in the hopes of ramping up the immune system to fight and clear the virus. The treatment, however, doesn't directly affect viral replication.
"Active chronic hepatitis B infections are potentially the biggest unmet medical need," Ostro said. "And, as such, it is a huge, huge market."
Lamivudine blocks viral replication, which in turn lessens the amount of HBV in the liver and in the bloodstream. Presumably, this reduction in viral load slows the body's immune response and lessens the progressive damage to the liver that leads to cirrhosis and liver cancer.
In their Phase III trial, Glaxo tested 100 mg doses and 25 mg doses of lamivudine vs. placebo in 358 patient with chronic HBV infection in Hong Kong, Singapore and Taiwan for one year. During that time, the company monitored liver histology (the amount of damage as determined by liver biopsy), the presence of hepatitis B e antigen and the level of HBV DNA in the blood stream. The company presented the results of the study at the annual meeting of the European Association for the Study of the Liver, in London.
Patients treated with lamivudine had significant improvements in liver histology compared to placebo. Sixty-seven percent of those receiving the 100 mg dose and 59 percent of those on the 25 mg dose had improvements in liver histology compared to only 30 percent of the patients receiving the placebo. In addition, those on lamivudine were less likely to have liver deterioration (7 percent on the 100 mg dose, and 10 percent on the 25 mg dose, compared to 32 percent on the placebo).
"This study really shows that lamivudine has an effect on the liver where the damage is happening," Lennon noted.
The presence of HBeAG in the blood is associated with active viral replication. Seroconverting * clearing the antigen from the bloodstream * is associated with clinical remission of the disease. Sixteen percent of patients on the 100 mg dose seroconverted and showed no HBV DNA in their bloodstream as compared to 4 percent in the placebo group.
"These results bode very well for lamivudine because these patients were very difficult to treat," Lennon said. "Some had been infected for as long as decades."
Ostro noted that the results of the clinical trial were "spectacular," and will allow Glaxo to fulfill its stated goal of filing in Asia by the end of this year. *