Gary Calton believes his tiny Baltimore biotechnology venture, AuRx Inc., has the long-sought-after vaccine for herpes, the viral disease that is infecting Americans at an accelerating pace. If he's wrong, his company could become another of the many that have tried and failed in the quest.
But Calton is so bullish on his privately held company's vaccine that he has sunk more than $600,000 of his own money into the project.
"No one has seen a vaccine that does what ours can do," said Calton. "This darn thing works. It's an incredible drug."
A preliminary laboratory study on guinea pigs found that the vaccine not only blocked transmission of the form of the virus that can cause painful genital sores but also reduced lesion outbreaks in infected animals, he said. A vaccine that provides ,, that double-barreled shot of protection and treatment in humans would prove enormously valuable and stand a good chance of generating huge sales.
An estimated one in five Americans 12 and older, about 45 million people, have genital herpes, according to a 1997 study published in the New England Journal of Medicine. Some of those infected don't know it because they've never had lesion outbreaks, herpes experts say.
Developing a safe and effective vaccine for genital herpes remains one of the most elusive Holy Grails in medicine.
Some of the world's leading vaccine-development companies -- and more than a few upstarts such as AuRx -- are spending big money trying to be the first to develop a marketable vaccine.
Since the 1950s, an estimated 20 vaccine candidates have been developed and found to be duds.
The reason is that the complexity of the herpes virus. Its DNA has as many as 84 different genes compared with the four or five found in most viruses, said Laure Aurelian, a University of Maryland virologist and professor of pharma cology. The more genes an organism has, the more sophisticated it is considered to be, explained Aurelian. She has committed 30 years to herpes virus research and developed the vaccine that AuRx hopes to market.
"Herpes is a very complex virus. It's been around for 2,500 years, so it's a brilliant survivor, very smart," said Aurelian. "To me it's a stimulating adversary. It tells me secrets it hasn't told anyone else."
It was one of those secrets that provided the clue for the experimental vaccine she and AuRx have beene working on.
Aurelian found that the virus contains what is known as an oncogene, a gene that could trigger cancer tumors.
The role of the gene has been a mystery to scientists for years. Aurelian found that when the the oncogene was removed, the virus no longer replicated rapidly and triggered an immune response in guinea pigs.
More importantly, the altered virus had a therapeutic effect in 14 of 15 guinea pigs that had herpes. They no longer suffered lesion outbreaks.
"I was shocked, but not as shocked as others," said Aurelian. "Like I said, herpes doesn't behave like a regular virus, and you have to have a respect for that if you are going to try to develop a vaccine."
She hopes to conduct more studies soon to determine why the vaccine triggered this therapeutic effect.
Aurelian's discoveries are an example of how a new generation of herpes vaccine developers have been aided in the quest by advances in molecular biology that are helping scientists understand the mysterious structure and life of the virus.
Calton, 54, founded AuRx (its name is a play on the chemical symbol for gold, Au), after he licensed marketing rights to the vaccine from the University of Maryland. Aurelian is a vice president of AuRx.
Private stock offering
The company is seeking through a private stock offering to raise $2.4 million to $4.5 million to fund further development, including human safety trials.
That data could help lasso a big licensing deal with a major vaccine developer.
Calton believes such a deal would at least match the $17 million agreement Cantab Pharmaceuticals Ltd. of Britain landed in March with Glaxo Wellcome PLC for its experimental herpes vaccine. Cantab's animal data showed that its vaccine prevents transmission of the disease.
A vaccine that is also palliative would be even more attractive.
"You want to prevent transmission, but the Holy Grail here is a vaccine that would be therapeutic for those already with it. That's 45 million people we know would want such a vaccine," Calton said.
Calton, a former research executive with Rhone-Poulenc S.A. and W. R. Grace & Co., isn't surprised that private investors are squeamish. He's the first to acknowledge that the drug industry is filled with tales about those who have tried and failed in the quest to develop an effective herpes vaccine.
For example, Chiron Corp. spent an estimated $50 million developing a genital herpes vaccine, but shelved the project in November 1996 after disappointing results from a large human trial.
Based on the biotechnology company's strong animal data for the vaccine, Wall Street had considered the drug a potential flagship product for the company.
Calton and his four-person company -- he, his wife, Sandra, Aurelian and a gene researcher -- have plenty of other competition in the race to develop the first preventive herpes vaccine.
Along with Glaxo Wellcome, SmithKline Beecham PLC is aggressively pursuing a herpes vaccine.
SmithKline's vaccine is being tested in a large-scale clinical trial on partners of people already infected to determine whether it prevents transmission, said Richard Koenig, a company spokesman. The company expects to find out later this year whether the vaccine is effective.
Several small biotechnology concerns such as AuRx also are developing preventive or therapeutic herpes vaccines. They include Malvern, Pa.-based Apollon Inc. and Alexandria, Va.-based Cel-Sci Corp., which has its research facilities in Baltimore.
Other companies, including Gilead Sciences Inc., are attempting develop topical treatments called microbicides that would prevent transmission by destroying the virus in much the way spermicides work.
The reason for the high interest is simple.
A vaccine -- especially one that would prevent transmission and kill the virus or reduce outbreaks in those already infected -- could be an instant blockbuster. Sales could top more than $250 million a year in the United States alone, experts estimate.
As yet, no way has been found to cure herpes. The virus goes into a latent stage in the ganglia of the nerves, emerging when triggered by stress, acidic foods and other factors.
Valtrex and Zovirax, powerful antiviral drugs, can reduce symptoms of the disease during outbreaks. Zovirax, marketed by Glaxo Wellcome, had sales of more than $1.3 billion last year, further evidence of the potential market for an effective vaccine.
"Some people say the disease is now so widespread that there's no stopping it without a vaccine," said Nancy Herndon, patient advocate for the American Social Health Association, which is based in Research Triangle Park, N.C.
But Herndon and other herpes experts are wary of generating false hope for the vaccines in development.
"For years, everyone was very excited about the Chiron vaccine. The animal studies looked very promising," said Herndon. "People really got burned up when it failed. I guess what it proves is that mice are not men."
Pub Date: 8/02/98