The Huge Bounty On A Global KillerJoan O'C. Hamilton and Neil Gross
In 1988, Japan's Emperor Hirohito lay ill with cancer. His doctors feared that transfusions he needed would be tainted with the hepatitis C virus (HCV), which then infected about 18% of Japanese blood recipients. So Kusuya Nishioka, one of Japan's leading hepatitis experts and an adviser to the Japan Red Cross, called an old friend--William J. Rutter, chairman of Chiron Corp. in Emeryville, Calif. Rutter sent experimental versions of a test Chiron was developing to screen blood for HCV. Months later, he sent more tests: As heads of state began arriving for the Emperor's funeral, Nishioka needed safe blood in case of emergencies.
Nishioka knows only too well what is news to Americans: Hepatitis, a liver disease caused by one of five or more viruses, is a major public-health threat. It afflicts hundreds of millions of people and kills up to 2 million each year. There may be as many as 300 million carriers of hepatitis B (HBV) alone, 75% in the Far East, including 100 million in China. Now, HBV is spreading in the U.S. In the past decade, its incidence has jumped 77% among Americans aged 15 to 39, and 50% overall. That has boosted it to No.2 among reported cases of sexually transmitted disease, behind gonorrhea--even though there has been an HBV vaccine since 1981. More than a million Americans are chronic carriers of HBV, 300,000 more are infected each year, and 7,000 a year die.
Drugmakers see opportunity in such grim numbers. In just three years, the worldwide market for tests, treatments, and the HBV vaccine has zoomed from less than $500 million to about $4 billion, says analyst Jeffrey Casdin of Oppenheimer & Co. The biggest moneymakers have been gene-spliced alpha interferon, which treats HBV and HCV, and HBV vaccines from Merck & Co. and Smith-Kline Beecham PLC, with sales of $850 million a year.
Now, many more treatments are in the works. SmithKline is awaiting regulatory approval for, and Merck is in the late stages of testing, potential vaccines for hepatitis A. Chiron hopes to be testing an HCV vaccine in the U.S. by yearend, and SmithKline and Genelabs are collaborating on one for hepatitis E. Several biotech companies are developing new forms of interferon, which now racks up annual sales of more than $2 billion worldwide, a quarter of that by market leader Schering-Plough Corp.
Chiron claims HCV screening has prevented a million transmissions worldwide, saving at least $500 million in associated health-care costs. Now, it is developing a new test that measures the amount of HBV and HCV in a patient--which could help in designing better treatments (box). Thanks to tools and data provided by biotech, in short, hepatitis research "is exploding," says Teresa L. Wright, associate professor of medicine at the University of California at San Francisco.
Hepatitis literally means inflammation of the liver. Some strains, such as A and E, are caused by poor sanitation (table). HBV travels in bodily fluids and is transmitted via sex, IV drug use, and from mother to fetus. HCV, precisely identified only in 1987, is more mysterious: It's definitely transmitted by blood and needles, but 40% of those infected have no known risk factors, and it isn't clear if the virus is sexually transmitted.
Hepatitis, which destroys liver tissue's ability to process wastes, may show up first as a flu that lasts for weeks. The immune system eventually overcomes the virus in about 90% of those with HBV. But hepatitis can also kill quickly or become chronic and cause cirrhosis or liver cancer. And catching it late isn't catching it at all: Los Angeles TV producer Trace Percy, 49, learned by letter in 1990 that HBV antibodies were in blood he had donated. He didn't think much of it, but within two years Percy was suffering from advanced cirrhosis. Interferon didn't help--it controls the virus in only 30% to 40% of HBV sufferers and 10% to 20% of HCV victims, and works less well in advanced cases. Percy may need a new liver--and even that isn't a guaranteed cure.
CELEBRITY CASES. Despite misconceptions, hepatitis knows no boundaries of wealth or class. Country singer Naomi Judd has retired from touring with her daughter Wynonna because of chronic hepatitis. Actor Jim Nabors just had a liver transplant in an attempt to beat HBV. Executives traveling any place where hepatitis B is endemic would do well to be vaccinated--especially those who plan to stay long or to be sexually active.
HBV is on the rise in America partly because some primary-care doctors and pediatricians don't take it seriously enough. According to the Centers for Disease Control in Atlanta, all adolescents are at high risk for HBV if they're sexually active. CDC officials argue that it's easier to inoculate them as babies than to get them in for shots when they're older. Experts say, however, that many doctors ignore CDC directives to immunize newborns--and aren't aggressive in inoculating teens.
The bottom line is that only 1% of 28 million single Americans between ages 11 and 34 are vaccinated against HBV, with predictable results. "Historically, HBV was only recognized among certain segments, like gay men and drug users," says Miriam J. Alter, chief epidemiologist for the hepatitis branch of the CDC. Now, "it's well entrenched in the general population." In Hong Kong, by contrast, a six-year push to vaccinate children is showing results: New HBV cases there dropped from 4,357 in 1992 to 1,274 in 1993.
The race to cure hepatitis is getting crowded. Biogen Inc. and Amgen Inc. are testing other forms of interferon--called beta and consensus, respectively--to see if they'll destroy more virus with fewer side effects. SciClone Pharmaceuticals Inc. in San Mateo, Calif., has won approval in Singapore for a drug that stimulates the body's immune system to fight HBV. Protein Design Labs Inc. in Mountain View, Calif., is doing early testing of an antibody-based drug that seeks out and disables circulating hepatitis viruses in the blood. Agouron, Gilead Sciences, and ICN Pharmaceuticals, among others, are chasing drugs they hope can stop hepatitis B and C from replicating inside cells. "Everybody wants to treat this disease," says Chiron's Rutter. "The size of the market indicates the need for it."
There are even interesting nondrug experiments. Cryopharm Corp. in Pasadena, Calif., is testing molecules called "psoralens" that insert themselves into a virus, then disable it when it's exposed to light. These chemicals might help rid donor blood supplies of contamination--for which current tests are good but less than 100% accurate.
"UNDERPUBLICIZED." There are so many approaches to hepatitis because it is such a complex disease. It may or may not be accompanied by jaundice, which can make it hard to diagnose. The different strains are distinct, linked only by their infection of the liver. Transmission patterns vary, as do the body's immune responses. And there are other peculiarities: "We know that mother to child transmission [of HBV] is very high in Asia, while it is rare in the U.S. and Europe," says Japan's Nishioka.
Some researchers complain that hepatitis takes a backseat to AIDS in some countries: It's "enormously underpublicized," says professor Wright, and underfunded, too. That's ironic, since experts say HBV, for example, is 100 times as infectious as HIV: It can live on a dry surface for a week. Even in Japan, where hepatitis has infected 2% of the population, or 3 million people, and kills more than 20,000 a year, the government's priorities seem askew. Hepatitis expert Ichiro Tomizawa at the Infectious Disease Control Div. of Japan's Health Ministry notes that AIDS, which afflicts a total of 20,000 Japanese, gets 100 times the research funding of hepatitis.
That seems unlikely to change. And so many people carry the hepatitis virus that it will take huge doses of education and vaccine to curb this killer. For the foreseeable future, it seems, hepatitis will be a major market for drugmakers--and a huge threat to public health.
THE TYPES OF HEPATITIS
All strains have essentially the same symptoms: jaundice, fever, nausea, lethargy, itching, and elevated liver-enzyme levels. But each has radically different effects on the body.
A Infects about 30,000 Americans
annually, mainly through contact with contaminated food and water. A test
is available but no treatment, though vaccines are nearly ready. Travelers
to high-risk regions can get immune globulin shots for short-term
B Spreads via sex, IV drugs, or other
exchange of bodily fluids, such as mother to infant. A test is available,
as are vaccines from Merck and SmithKline.
Accounts for 90% of cases contracted via blood transfusion. Half of the
170,000 people infected in the U.S. each year develop chronic hepatitis,
which leads to cirrhosis and liver cancer. May also be spread sexually.
There's no vaccine yet.
C Occurs in concert with B. U.S.
incidence is unknown, but mortality is high. Occurs mainly in multiple
blood- transfusion recipients. There's no screening test, no vaccine, and
no treatment except interferon, with mixed results.
D Waterborne virus spread by fecal
contamination. Occurs mostly in developing countries. Is more severe than
A, killing 1% to 2% of those infected and 20% of pregnant women who
X Hepatitis strains that don't fit any existing category have been isolated,
most of them outside the U.S.