A Promising First Step for Combination Oral Therapy Against HCV
In a short-term study, use of a protease inhibitor and a polymerase inhibitor together rapidly lowered HCV RNA levels.
Oral hepatitis C virus (HCV) protease inhibitors are expected to be approved in 2011. Adding these agents to standard HCV treatment (peginterferon plus ribavirin) improves the likelihood of sustained virologic response, but the interferon component must be given subcutaneously and has substantial side effects. In the industry-funded INFORM-1 study, researchers explored whether an interferon-free regimen containing two new oral anti-HCV agents — the protease inhibitor danoprevir, plus the nucleoside polymerase inhibitor RG7128 — could successfully suppress HCV replication.
In a short-term study, use of a protease inhibitor and a polymerase inhibitor together rapidly lowered HCV RNA levels.
Oral hepatitis C virus (HCV) protease inhibitors are expected to be approved in 2011. Adding these agents to standard HCV treatment (peginterferon plus ribavirin) improves the likelihood of sustained virologic response, but the interferon component must be given subcutaneously and has substantial side effects. In the industry-funded INFORM-1 study, researchers explored whether an interferon-free regimen containing two new oral anti-HCV agents — the protease inhibitor danoprevir, plus the nucleoside polymerase inhibitor RG7128 — could successfully suppress HCV replication.
Patients with chronic HCV genotype 1 infection but not cirrhosis or HIV infection were randomly assigned to receive placebo (n=14) or one of six different doses of danoprevir plus RG7128 (n=74) for 13 days. Treatment was directly observed in a clinical research unit.
At day 14, patients who received danoprevir plus RG7128 had marked declines in HCV RNA, with the median reduction ranging from 3.7 to 5.2 log10 IU/mL in the different dose groups; some patients achieved undetectable HCV RNA levels. At the highest doses tested, reductions in viral load were similar between patients who were treatment naive and those who had not responded to previous standard-of-care treatment. No phenotypic drug resistance was detected, although one patient with viral rebound did have a clone containing a danoprevir-resistance mutation.
Comment: This study shows that a combination of two oral investigational agents effectively suppresses HCV replication, at least in the short term. There has been an explosion of new direct-acting anti-HCV agents, and promising trial results were reported for many of them at the Liver Meeting this month in Boston. If longer-term studies show that combination therapy with new oral agents can eliminate viral replication, we may be able to cure HCV with pills alone. As an editorialist notes, we are "on the eve of a new era in HCV treatment."
— Rajesh T. Gandhi, MD
Robert G. Gish, MD, and Stephen A. Harrison, MD, FACP, review the most clinically relevant data from this important annual meeting. Registration required.
You can download them here.
Published in Journal Watch Infectious Diseases November 17, 2010
Citation(s):
Gane EJ et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): A randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010 Oct 30; 376:1467.
Medline abstract (Free)
Thomas DL. Curing hepatitis C with pills: A step toward global control. Lancet 2010 Oct 30; 376:1441.
Medline abstract
(Free)
Hepatitis c symptoms usually don't manifest themselves for years and, occasionally, never at all. All sorts of hepatitis involve inflammation of the liver. The harm can be caused by drinking excessive amounts of alcohol, toxins, poisons, and some medications. Hepatitis C is caused by the Hepatitis C Virus (HCV).
Health: Premier asks for 'understanding' of feds' role in agency
"I want, and the people of New Brunswick, deserve assurances on the makeup and structure of Canadian Blood Services," he said.
"The Prime Minister has committed to going back and (getting a) better understanding the relationship between the federal government and Canadian Blood Services and, ultimately, the Province of New Brunswick."
As many as 2,000 Canadians were infected with HIV in the late 1970s and early 1980s and up to 60,000 people contracted hepatitis C in the '80s' and '90s from tainted transfusions and secondary infections from family members.
"I want, and the people of New Brunswick, deserve assurances on the makeup and structure of Canadian Blood Services," he said.
"The Prime Minister has committed to going back and (getting a) better understanding the relationship between the federal government and Canadian Blood Services and, ultimately, the Province of New Brunswick."
As many as 2,000 Canadians were infected with HIV in the late 1970s and early 1980s and up to 60,000 people contracted hepatitis C in the '80s' and '90s from tainted transfusions and secondary infections from family members.
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Pittsburgh-based St. Clair Hospital sent letters to 75 patients after officials discovered that improperly cleaned equipment may have exposed them to blood-borne diseases like HIV or Hepatitis B or C, the Pittsburgh Tribune-River reports.
3 Big Developments Make AIDS Outlook More Hopeful - November 24, 2010
(AP) -- In the nearly 30 years the AIDS epidemic has raged, there has never been a more hopeful day than this. Three striking developments took place Tuesday: U.N. officials said new HIV cases are dropping dramatically worldwide. A study showed that a daily pill already on pharmacy shelves could help prevent new infections in gay men. And the pope opened the way for the use of condoms to prevent AIDS.
Pharmaceutical
Database Shows Who Earned What From Pharmaceutical/Device Companies
Michael O’Riordan
Authors and Disclosures
Michael O’Riordan
Authors and Disclosures
Over the six-month period, the drug and device companies made $35.7 million in payments, with almost half of that money going to physicians, the Boston Globe reported Monday. Dr Mary Ann Asbell, a Cambridge-based physician, earned the most money from the drug and device companies, taking in $194 275, all from Genzyme Corp. Second on the list was cardiologist Dr C Michael Gibson (Beth Israel Deaconess Medical Center, Boston, MA) who earned $188 617 from six different companies, including Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Ortho-McNeil, Schering Corporation, and The Medicines Company.
Tighter Rules on Pills Stalled - November 24, 2010
TALLAHASSEE (The New York Times News Service) -- In their zeal to slow down government regulations, Florida lawmakers have inadvertently halted an effort to regulate so-called "pill mills" that fuel an epidemic of prescription drug abuse.
TALLAHASSEE (The New York Times News Service) -- In their zeal to slow down government regulations, Florida lawmakers have inadvertently halted an effort to regulate so-called "pill mills" that fuel an epidemic of prescription drug abuse.
Superbugs
Superbugs Emerge From the School of Hard Knocks
“It’s the bacterial equivalent of ‘That which doesn’t kill you makes you stronger,’” says biomedical engineer Jim Collins.
“It’s the bacterial equivalent of ‘That which doesn’t kill you makes you stronger,’” says biomedical engineer Jim Collins.
Doctors have long known that an incomplete course of antibiotics can promote resistance, which is why pill bottles often carry a stern warning to “finish all this medication.” Boston University biomedical engineer Jim Collins and colleagues have identified one way in which such resistance can develop. They found that when E. coli were treated with doses of ampicillin too low to kill all of the cells, some of those left alive suffered DNA damage that was hastily—and often inaccurately—patched up. The sloppy repair job left behind mutations, and just by chance, a few of these gave the bugs resistance not only to ampicillin but to two other antibiotics they had never encountered. On the basis of these findings, he plans to search for molecules that can block bacteria’s efforts to patch up their genes.
Bugs can’t hide from the virus hunter
Scientist known as a master at identifying causes of infection. Gustavo Palacios was sequencing the genes from a new strain of Ebola virus found in a bat in Spain — a worrisome development, since the fatal virus has almost never been found outside Africa.
Nick Bexfield of the University of Cambridge had flown from England with a new hepatitis virus that has just broken out in British dogs.
Healthy You
Eat Your Fruits and Veggies
By George Lundberg, MD,
Editor-at-Large, MedPage Today
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