By Lisa Seachrist
WASHINGTON - A new hepatitis B vaccine that combines Ribi ImmunoChem Research Inc.'s monophosphoryl lipid A (MPL) immunomodulator with SmithKline Beecham plc's successful hepatitis B vaccine, Engerix-B, elicits a strong immune response in patients unresponsive to Engerix-B alone.
"It's an extremely exciting time for us here at Ribi," said Kris Dyszynski, director of licensing activities for Hamilton, Mont.-based Ribi. "We've been in this business since 1981, and it's very gratifying to see these immunomodulators show such an effect."
Phase III study results of 120 people who failed to respond to the traditional vaccine showed that those individuals responded to the new vaccine without the need for additional doses. SmithKline Biologicals, a Rixensart, Belgium subsidiary of London-based SmithKline, intends to file a biologics license application (BLA) for the new vaccine by the end of 2000.
SmithKline currently markets the world's most widely used hepatitis B vaccine, Engerix-B, and more than 450 million doses of the vaccine have been delivered to date. However, a number of people simply don't produce an adequate immune response to the vaccine.
Those typically at risk for an inadequate immune response to the vaccine are the elderly, who may have decreased immune function; immunodeficient patients; hemodialysis patients; and some healthy younger low-responders or non-responders, who require doses above the standard three doses to build up adequate protection as measured by the concentration of antibody in the bloodstream.
The new vaccine utilizes SmithKline's novel adjuvant, SBAS4, which is a combination of Ribi's MPL and aluminum salts. Vaccine adjuvants enhance the immune response to an antigen, increasing the chances that the immune system will establish protective antibodies.
Ribi's MPL is an analog of the most immunogenic component of the bacterial cell wall, lipid A. In its natural form, lipid A is too toxic to be used as a vaccine adjuvant. Ribi removed the phosphate group from the end of lipid A, making it an acceptable adjuvant.
SmithKline compared Engerix-B to the new vaccine in 120 people who failed to develop an antibody titer of 10 international units per liter or more following four doses of Engerix-B. Using the new vaccine, one month following the first dose, 78 percent of patients had reached the target antibody titer, compared to 59 percent for the Engerix-B group.
BLA Expected In Second Half Of 1999
The new vaccine outperformed Engerix-B one month after the second dose of vaccine by 96 percent to 76 percent. One month following the final dose, which was given six months following the first dose, 98 percent of patients receiving the new vaccine had achieved the target antibody titer, compared to 81 percent of those receiving Engerix-B.
SmithKline also is evaluating MPL adjuvants in malaria vaccines and genital wart vaccines. Ribi is in the process of filing for approval in Canada for a therapeutic melanoma vaccine, Melacine, which employs MPL and antigens from two melanoma cell lines. The company plans to file a BLA in the U.S. in the second half of 1999.
If SmithKline wins regulatory approval for the new vaccine, Ribi will manufacture MPL for the vaccine and transfer the product to SmithKline for a fee, while also receiving royalty payments on any sales.
Ribi's stock (NASDAQ:RIBI) closed Monday at $2.687, up $0.062. *