What's New
New Drugs, Dosing Highlight New Approaches to Hepatitis C
The Center for the Study of Hepatitis continues to be actively involved in both clinical and basic science research in an effort to identify new treatments for patients infected with the hepatitis C virus (HCV).
A multidisciplinary approach is central to efforts at the Center, which is a collaborative endeavor of Weill Cornell clinicians and researchers at NewYork-Presbyterian Hospital along with colleagues at NewYork-Presbyterian Hospital/Columbia University Medical Center and researchers at Rockefeller University.
Clinical trials are conducted at a high level of quality using an extensive infrastructure.
The Center is involved in a broad spectrum of trials ranging from Phase 1 (first in human) to the full gamut of later-stage trials—encompassing Phase I through Phase IV studies.
Clinical investigators at the Center are also working with industry to help design early phase trials for drug testing, including first-in-human studies.
"We have nurse practitioners and nurses who are coordinators for our trials and work directly with our patients, and we have an extensive administrative and technical support staff," said Ira M. Jacobson, MD.
In January 2007, according to Dr. Jacobson, a large space on the Digestive Disease floor of the new Weill-Greenberg Center was set aside to house the staff needed to support the administration and execution of clinical trials for hepatitis C.
"Ongoing and anticipated trials include those focusing on HCV protease and polymerase inhibitors, drugs with other novel mechanisms of action, and refinements of the currently used drugs interferon and ribavirin, such as albumin-bound interferon and taribavirin," said Dr. Jacobson.
Antiviral agents included in the HCV trials program are telapravir (VX-950), bocepravir (SCH-503034), HCV-796, GS-9190, and others.
Faculty members focused on hepatitis C and working in the new Weill-Greenberg Center, adjacent to NewYork-Presbyterian Hospital/Weill Cornell Medical Center, have built a large referral practice attracting patients from the surrounding New York metropolitan area.
Several years ago Andrew Talal, MD, MPH, founded a liver clinic that specializes in the care of patients with HCV and patients who are coinfected with HIV/HCV.
Dr. Talal has recently published novel findings derived from patient samples obtained at his clinic (J Acquir Immune Defic Syndr 2007;45:262-268).
Other clinicians at the Center who see a large volume of patients with HCV include Dr. Jacobson, Maya Gambarin, MD, and Samuel Sigal, MD.
Dr. Sigal is also a member of the Center for Liver Disease and Transplantation at NewYork-Presbyterian Hospital.
In addition, Brian Edlin, MD, performs nat ionally recognized epidemiologic studies on hepatitis C.
| Table. Sustained Virologic Response With Ribavirin |
|---|
| Ribavirin (mg/d) | All, (%) | Genotype 1, (%) |
Genotype 1 With High Viral Load, (%) | Genotypes 2 and 3, (%) |
| 800 to 1400, weight-based dose | 44 | 34 | 32 | 62 |
| 800, fixed dose | 41 | 29 | 27 | 60 |
NewYork-Presbyterian Hospital served as the central site in the WIN-R trial, the largest United States hepatitis C study to date.
More than 4,900 patients at 225 centers nationwide took part in the WIN-R trial.
The study led to a number of important findings, noted Dr. Jacobson, who served as principal investigator and was joined by co-principal investigator Robert Brown, Jr, MD, of NewYork-Presbyterian Hospital/Columbia University Medical Center and Medical Director of the Center for Liver Disease and Transplantation, which has a thriving clinical trials program in viral hepatitis and in other areas of hepatology, including transplantation.
The WIN-R study found that weight-based dosing of ribavirin resulted in significantly higher rates of sustained virologic response than using a flat dose of ribavirin (44% vs. 41%; P=0.01).
This was particularly true for patients with HCV genotype 1 (34% vs. 29%; P=0.004).
The findings also revealed that 24 weeks of treatment was as effective as the standard 48 weeks of treatment for patients with HCV genotype 2 or 3.
The shorter course of therapy also had better tolerability.
Several publications derived from the WIN-R study are expected to be published in the peerreviewed literature shortly.
"The philosophy here is similar to the philosophy behind weight-based dosing of chemotherapy," noted Dr. Brown.
"We knew that weight-based dosing in hepatitis C therapy was important, because of
the potential impact fat in the liver can have on disease progression and drug absorption.
It just hadn't been proved.
What we essentially found is that the additional risk for drug toxicity incurred with weight-based dosing is worth it given the increased efficacy."
When it comes to scientific research efforts, NewYork-Presbyterian Hospital continues to work closely with the Laboratory of Virology and Infectious Diseases at Rockefeller University, which focuses on HCV studies and is under the direction of Charles Rice, PhD.
Research efforts include a current collaborative study examining whether patients with undetectable virus who complete treatment with interferon and ribavirin are cured or whether tiny traces of the virus can still be found.
Other ongoing collaborative studies involving Dr. Rice and Lynn Dustin, PhD, at Rockefeller University, are examining how the immune system interacts with the HCV.
Because HCV-associated end-stage liver disease is the leading indication for liver transplantation in the United States, studies to better understand how the virus affects the liver are also ongoing.
NewYork-Presbyterian Hospital's liver transplant program performed more liver transplants in 2006 than any other hospital in the New York metropolitan area.
Researchers at NewYork-Presbyterian/Weill Cornell and the Center for Liver Disease and Transplantation at NewYork-Presbyterian/Columbia have spearheaded efforts to acquire large samples of liver tissue from transplant patients at the Columbia site to determine the percentage of liver cells that are infected and the viral count in infected cells.
The acquired specimens are sent to colleagues at Rockefeller University.
"These are precious samples because they yield large amounts of tissue as opposed to small liver biopsy specimens," said Dr. Jacobson.
In addition, researchers at NewYork-Presbyterian/Columbia are also studying several new agents for the treatment of hepatitis C, including the protease inhibitor VX-950, potentially the first oral HCV treatment, and a drug Dr. Brown calls "the next big step forward."
Robert S. Brown, Jr., MD, MPH, is Medical Director, Center for Liver Disease and Transplantation, and Chief, Division of Abdominal Organ Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center, and is Associate Professor of Medicine and Pediatrics at Columbia University College of Physicians and Surgeons.
Ira M. Jacobson, MD, is Chief, Division of Gastroenterology and Hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and is Vincent Astor Professor of Clinical Medicine and Medical Director of the Center for the Study of Hepatitis C at Weill Cornell Medical College.
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