Human Genome Sciences To Test New Delivery Method for HCV Interferon
     By Scott Henley of the Wall St. Journal / Help

NEW YORK -- Human Genome Sciences Inc. (HGSI), a gene-discovery company, is poised to start human testing of a new technology for delivering biotech drugs that could reduce its business risk, boost prospects for all sorts of biotech drugs, and help treat the epidemic of hepatitis C--if it works.

The new technology links interferon, a natural protein that is used to treat hepatitis C and other ills, with albumin, a common blood protein (and the protein found in egg white). The combination allows interferon to stay in the bloodstream for weeks instead of hours.

The first test of the drug in humans could begin any day now. While these clinical trials will take several years to complete, success would mark a vast improvement in the lives of hepatitis C patients. Currently they endure three injections a week with standard therapy or in the best case weekly shots with an interferon chained to a waxy chemical that the Food and Drug administration approved in January.

For Human Genome Sciences, based in Rockville, Md., the new drug represents an addition to its basic strategy of developing drugs from genes discovered by company researchers. Several protein drugs that HGS scientists found are already in clinical testing, including one called repifermin that promises to speed healing of persistent skin ulcers.

But the new technology could be applied to any protein drug, not just those that HGS discovers. Being able to use this albumin technology to enhance already existing drugs "increases opportunities while decreasing risk," says William Haseltine, chairman and chief executive of HGS. "You don't generally hear about biotech companies talking about reducing risk. But it's good work if you can get it."

HGS acquired the technology, not through its laboratories, but when it bought closely held Principia Pharmaceutical Corp. last September for $120 million in stock, equivalent to less than 2% of the outstanding stock of HGS at the time.

HGS and Principia executives first met at a scientific conference last year. They discussed ways to bring albumin to bear on the protein drug portfolio of HGS. Besides reducing injections for patients, the system for making albumin-linked proteins could greatly simplify the notoriously inefficient methods for manufacturing protein drugs today.

But HGS also learned that Principia had plans to develop improved versions of proven protein drugs, such as human growth hormone, that will soon come off patent. Sensing rich potential in Principia's approach, HGS dropped its original plan to license the albumin know-how and decided to buy the company outright.

Patients with hepatitis C could be the first to realize the fruits of this albumin technology. Nearly four million Americans are infected with the hepatitis C virus that causes few symptoms until serious liver damage has already occurred. It is the leading cause of liver failure and the most common reason for liver transplants. Like HIV, the AIDS virus, the hepatitis C virus has proved impossible to eliminate and can only be contained by life-long administration of a combination of drugs including interferon, an immune-system booster.

Sadly, the current drug cocktail works in less than half of hepatitis patients. Even when effective, the interferon can cause flu-like side effects, including severe fever and chills, that lead many patients to stop treatment. Interferon lasts only a matter of hours after injection. Thus, relatively large doses must be given to keep enough of the drug in the blood to tackle the virus. Unfortunately, these large doses are thought to cause the unpleasant side effects. And even at large doses, the blood levels of interferon quickly drop below the optimum concentration needed to combat the virus.

But the HGS interferon may dramatically reduce these symptoms and improve effectiveness of the treatment by keeping a steady dose of the drug in patients' blood for weeks at a time.

The trick up HGS's sleeve is a patented brewer's yeast that was genetically modified to produce a human form of albumin, a blood protein that is a natural transporter of other proteins throughout the body. Scientists at HGS insert the gene for interferon inside the yeast's DNA. Fermenters, like those used to brew beer, are then filled with the modified yeast to produce prodigious quantities of the immune booster fused to the albumin protein.

If the HGS interferon succeeds in humans, the albumin carrier could be used to ferry all kinds of gene-based protein medicines throughout the body, enhancing both their safety and effectiveness. The need for a better way to administer drugs like interferon is strong because the dawning gene age is spurring discovery of scores of potential protein treatments. That's because one of the fastest ways to make a drug from a genetic discovery is to simply use a protein made by the gene as a medicine. But proteins must be injected because they either don't survive the journey through stomach acid or can't be absorbed by the blood vessels surrounding the intestine. Thus, many in biotech are closely watching HGS's promising experiment with albumin to make protein drugs tolerable.

The protein-linking technology is so promising, says HGS Chairman Dr. Haseltine, "I think it could double the value of the company."

Risks abound, however. The human immune system might perceive the albumin-interferon combination as foreign and then produce antibodies that inactivate the drug. Further, in some patients interferon causes nettlesome side effects, such as severe depression, that could last weeks instead of days with the ultra-long-acting HGS interferon.

"Toxicity has to be the same or less," says Robert Brown, Jr., a liver specialist at New York-Presbyterian Hospital in New York, who is unconnected to the HGS research. Otherwise, he says, the benefit of the long half-life could instead turn out to be a big problem.