Bristol-Myers Squibb Co. and Gilead Sciences (GILD) Inc., makers of the top-selling combination pills for AIDS, are trying to duplicate their success to combat another evasive virus, hepatitis C.
The companies are among about a dozen that are developing drug cocktails more effective, less toxic and easier to take than current therapy. Hints of which blends may work will emerge next week, in research presented at a Boston meeting of the American Association for the Study of Liver Disease.
The pill combinations are designed to cure the liver-destroying hepatitis C virus without using interferon, a decades-old shot that causes a year of flu-like symptoms and works in only half of patients. While the virus outsmarted new mixtures in preliminary tests, study continues because the first blends to succeed will dominate a market that, according to Decision Resources Inc., may total $8 billion a year by 2014.
“We are trying to duplicate the paradigm that revolutionized HIV therapy well over a decade ago, and apply those lessons learned to hepatitis C,” said Ira Jacobson, medical director of the Center for the Study of Hepatitis C, a New York-based program of Rockefeller University, Weill Cornell Medical College, and New York-Presbyterian Hospital. “My belief is if we suppress it profoundly enough, the virus will eventually wither away and be eradicated in the liver.”
The shares of New York-based Bristol-Myers decreased 9 cents to $26.90 at 4 p.m. in New York Stock Exchange composite trading. Gilead, of Foster City, California, fell 19 cents to $39.67 in Nasdaq Stock Market composite trading.
200 Million People
About 200 million people worldwide have hepatitis C, an analysis at Dartmouth Medical School in Hanover, New Hampshire, found. The disease often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over the course of years or decades.
Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. Roche Holding AG (ROG) of Basel, Switzerland sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey sells a form called PegIntron.
Two new hepatitis C options that may be introduced next year are telaprevir, from Cambridge, Massachusetts-based Vertex Pharmaceuticals Inc. (VRTX) and New Brunswick, New Jersey-based Johnson & Johnson (JNJ), and boceprevir, from Whitehouse Station, New Jersey-based Merck & Co. The drugs are similar to the family of AIDS medicines called protease inhibitors that prevent viruses from replicating. Both are used with interferon and ribavirin.
The combinations are expected to generate more than $3 billion in sales annually by 2013, with telaprevir accounting for $2.6 billion, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview.
The new antiviral combinations are oral drugs, not injections, and may have the potential to cure patients who haven’t benefitted from the older products, Liang said.
“Both clinicians and patients would prefer drugs that lack the side effects of interferon and ribavirin,” said Alexandra Makarova, an analyst at Decision Resources, a research company in Burlington, Massachusetts, in a telephone interview. “If the combination of direct antivirals will allow doctors to exclude interferon and ribavirin, it could spoil the party for those regimens.”
Research hasn’t identified the optimal oral combination for hepatitis C. Initial reports show treatment with just one pill or low-dose combinations aren’t enough to keep the virus in check, and investigators are building more, and more-powerful, combinations. The U.S. Food and Drug Administration, which initially rejected efforts to study treatments without interferon and ribavirin, has now let trials begin.
The ability to create liver cells from stem cells, breed mice that are better models for hepatitis C, and isolate cells from human livers infected with the virus are making it easier to identify and pull together the best cocktails before they are tested in humans, said Michael Charlton, director of the liver transplant program at the Mayo Clinic in Rochester, Minnesota.
“The door may be opening to more innovative combinations of oral therapies,” said Charlton, who sees a new patient every 30 minutes, on average, when working in Minneapolis. “There is still a tremendous second and third wave of drug combinations that are being explored,” he said in a telephone interview.
Bristol-Myers (BMY) will present results at the Boston meeting from second-stage tests combining an experimental protease inhibitor, similar to those used for AIDS, with a pill from new family of virus-fighting medicines. The two ingredients, called BMS-790052 and BMS-650032 stopped working in as little as three weeks. Adding interferon and ribavirin to the two-drug cocktail suppressed the virus for as long as three months.
Gilead will report outcomes from a monthlong study of its experimental protease inhibitor, GS-9256, with a second new drug, GS-9190, which is in a different family of medicines.
Adding ribavirin alone delayed or reduced the breakthrough virus, the study found. Vertex stopped a low-dose combination of telaprevir and its experimental drug VX-222 after the virus broke through during the first month of treatment. A higher-dose combination is undergoing tests.
The combination approach is being pursued by biotechnology companies, among them Pharmasset Inc. of Princeton, New Jersey; Medivir AB (MVIRB) of Huddinge, Sweden; Idenix Pharmaceuticals Inc. of Cambridge, Massachusetts; and Inhibitex Inc. of Alpharetta, Georgia.
Merck is developing several oral hepatitis C drugs internally, while looking for outsiders to become partners on its compounds, said Lisa Pedicone, global director of scientific affairs for the company’s hepatitis C products.
A combination of two oral drugs from Roche and Pharmasset was able to keep the virus in check during an initial 13-day study. The combination includes a protease inhibitor and another medicine polymerase inhibitor.
“We need to be bringing the people who have all these agents together to sit down at the same table,” Charlton said. “It takes someone with deep resources to develop a multidrug cocktail.”
Preliminary data suggest that a new family of medicines known as nucleoside-based polymerase inhibitors, which block an enzyme the virus needs to thrive, may be a key player in the drug combinations, Leerink’s Liang said. Pharmasset and Idenix are among the few companies working with those drugs, making them desirable partners or potential takeover targets, he said.
“This is like the early days of HIV,” said Stuart Ray, director of the infectious-diseases fellowship training program at Johns Hopkins University School of Medicine in Baltimore. “We are trying to weigh the safety of getting these drugs when they are first available, against the risk of waiting when we know liver disease is likely to be progressing in all of our patients.”
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