The daclatasvir-sofosbuvir regimen for the treatment of genotype 1 hepatitis C patients was granted amended Breakthrough Therapy Designation by U.S. Food and Drug Administration (FDA). In the beginning of 2015, the FDA had planned to remove Breakthrough-Therapy Designation for the daclatasvir-sofosbuvir treatment since other therapies were available and had higher success for other genotypes. However, the FDA revised its first decision and decided to continue the development of this therapy for the genotype 1 hepatitis C patients addressed in ALLY-1 Trial due to its promising results.
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Showing posts with label ALLY-1. Show all posts
Showing posts with label ALLY-1. Show all posts
Tuesday, May 26, 2015
Thursday, April 30, 2015
Study results promising for hepatitis C patients awaiting or completing liver transplant
Public Release:
SAN ANTONIO (April 30 2015) -- A number of new, highly effective oral treatments for various types of hepatitis C have been approved in the past few years. However, two groups who have not benefitted from the new treatments are patients with hepatitis C who have advanced liver disease and patients who have received a liver transplant but the advanced liver disease has returned because of hepatitis C.
"The problem for these patients is that unless the hepatitis C is cured, the virus continues circulating in their blood infecting the new liver, usually within a few months of transplant. One-third of them have cirrhosis again within five years," explained Fred Poordad, M.D., clinical professor of medicine and chief of hepatology at The University of Texas Health Science Center at San Antonio.
"This puts these patients back at high risk of dying from chronic hepatitis C or liver disease," said Dr. Poordad, principal investigator of the ALLY-1 study, who presented the results April 25 at The International Liver CongressTM of the European Association for the Study of the Liver (EASL) in Vienna, Austria.
The Phase III clinical trial evaluated a 12-week course of daclatasvir - the new drug being evaluated - combined with sofosbuvir and ribavirin for patients with chronic hepatitis C. Patients accepted into the trial either had a liver transplant with returning hepatitis C or had hepatitis C with advanced cirrhosis (scarring of the liver).
Study results showed an overall cure rate of 94 percent for patients with a liver transplant and returning hepatitis C, and 83 percent for patients with advanced cirrhosis.
The study's primary endpoints also were reached, with 95 percent of post-transplant genotype 1 patients and 82 percent of genotype 1 patients with advanced cirrhosis being cured 12 weeks after treatment. Patients with other genotypes of the disease were enrolled as well, with benefits seen in all groups.
Genotypes are subgroups or strains of a disease, such as hepatitis C. There are many subtypes of hepatitis C based on the geographic regions where the strain is most prevalent. Over time, each strain evolved differently so that treatments are based on the genotype of the disease. For example, genotype 1 is the type of hepatitis C most common in the United States and is the most difficult to treat.
The study regimen was well tolerated and showed few serious side effects. "Transplant patients take a variety of medications to prevent organ rejection that can complicate the treatment of hepatitis C. In ALLY-1, we saw no drug-to-drug interactions between transplant and hepatitis C therapies and no need to make close adjustments to patients' transplant-related drugs while they received the hepatitis C regimen," Dr. Poordad said.
The ALLY-1 study was conducted at five major transplant centers in San Antonio and Houston, Texas; Miami, Fla.; Ann Arbor, Mich., and Seattle, Wash.
Hepatitis C is a liver disease found worldwide that is spread though contact with blood or semen, such as shared drug injection needles, inadequate sterilization of medical equipment, unscreened blood and blood products, accidental needle sticks in the health profession, and sexual intercourse with a person who has hepatitis C. The disease also can be passed from mothers to their children through the birthing process.
According to the U.S. Centers for Disease Control and Prevention, 3.2 million people in the U.S. have chronic hepatitis C, and 70 to 80 percent do not have symptoms. Nonetheless, it is a serious disease that can lead to long-term health problems such as liver damage, liver failure, liver cancer and death. It is often discovered later, after significant liver damage has occurred.
In the U.S., people born between 1945 and 1965 have the highest risk of hepatitis C due to higher drug use. People in this age group are urged to have a one-time blood test for hepatitis C to detect the virus and begin receiving treatment, if necessary, before significant liver damage occurs. There is no vaccine to prevent hepatitis C.
Daclatasvir, a drug developed by Bristol-Myers Squibb, was approved in Europe in 2014 for use with other medications for genotypes 1 through 4 for the treatment of chronic hepatitis C in adults. It is also approved in Japan as well as many countries in Central and South America, the Middle East and Asia Pacific. Daclatasvir regimens also have been included in the EASL's recommendations for the treatment of hepatitis C in Europe.
The U.S. Food and Drug Administration is reviewing daclatasvir for possible approval in the United States.
For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook or follow us on Twitter.
The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university's schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways "We make lives better®," visit http://www.
The Texas Liver Institute's mission is to set the standard of excellence in care and innovative research in the field of liver disease. The institute is affiliated with The University of Texas Health Science Center at San Antonio. The physicians are professors and teach at University Hospital of the University Health System and are involved with the liver transplantation program of the University Transplant Center, a partnership of the Health Science Center and the University Health System. For more information, visit http://www.
UT Health Science Center San Antonio doctor presents results of daclatasvir regimen
University of Texas Health Science Center at San Antonio
SAN ANTONIO (April 30 2015) -- A number of new, highly effective oral treatments for various types of hepatitis C have been approved in the past few years. However, two groups who have not benefitted from the new treatments are patients with hepatitis C who have advanced liver disease and patients who have received a liver transplant but the advanced liver disease has returned because of hepatitis C.
"The problem for these patients is that unless the hepatitis C is cured, the virus continues circulating in their blood infecting the new liver, usually within a few months of transplant. One-third of them have cirrhosis again within five years," explained Fred Poordad, M.D., clinical professor of medicine and chief of hepatology at The University of Texas Health Science Center at San Antonio.
"This puts these patients back at high risk of dying from chronic hepatitis C or liver disease," said Dr. Poordad, principal investigator of the ALLY-1 study, who presented the results April 25 at The International Liver CongressTM of the European Association for the Study of the Liver (EASL) in Vienna, Austria.
The Phase III clinical trial evaluated a 12-week course of daclatasvir - the new drug being evaluated - combined with sofosbuvir and ribavirin for patients with chronic hepatitis C. Patients accepted into the trial either had a liver transplant with returning hepatitis C or had hepatitis C with advanced cirrhosis (scarring of the liver).
Study results showed an overall cure rate of 94 percent for patients with a liver transplant and returning hepatitis C, and 83 percent for patients with advanced cirrhosis.
The study's primary endpoints also were reached, with 95 percent of post-transplant genotype 1 patients and 82 percent of genotype 1 patients with advanced cirrhosis being cured 12 weeks after treatment. Patients with other genotypes of the disease were enrolled as well, with benefits seen in all groups.
Genotypes are subgroups or strains of a disease, such as hepatitis C. There are many subtypes of hepatitis C based on the geographic regions where the strain is most prevalent. Over time, each strain evolved differently so that treatments are based on the genotype of the disease. For example, genotype 1 is the type of hepatitis C most common in the United States and is the most difficult to treat.
The study regimen was well tolerated and showed few serious side effects. "Transplant patients take a variety of medications to prevent organ rejection that can complicate the treatment of hepatitis C. In ALLY-1, we saw no drug-to-drug interactions between transplant and hepatitis C therapies and no need to make close adjustments to patients' transplant-related drugs while they received the hepatitis C regimen," Dr. Poordad said.
The ALLY-1 study was conducted at five major transplant centers in San Antonio and Houston, Texas; Miami, Fla.; Ann Arbor, Mich., and Seattle, Wash.
Hepatitis C is a liver disease found worldwide that is spread though contact with blood or semen, such as shared drug injection needles, inadequate sterilization of medical equipment, unscreened blood and blood products, accidental needle sticks in the health profession, and sexual intercourse with a person who has hepatitis C. The disease also can be passed from mothers to their children through the birthing process.
According to the U.S. Centers for Disease Control and Prevention, 3.2 million people in the U.S. have chronic hepatitis C, and 70 to 80 percent do not have symptoms. Nonetheless, it is a serious disease that can lead to long-term health problems such as liver damage, liver failure, liver cancer and death. It is often discovered later, after significant liver damage has occurred.
In the U.S., people born between 1945 and 1965 have the highest risk of hepatitis C due to higher drug use. People in this age group are urged to have a one-time blood test for hepatitis C to detect the virus and begin receiving treatment, if necessary, before significant liver damage occurs. There is no vaccine to prevent hepatitis C.
Daclatasvir, a drug developed by Bristol-Myers Squibb, was approved in Europe in 2014 for use with other medications for genotypes 1 through 4 for the treatment of chronic hepatitis C in adults. It is also approved in Japan as well as many countries in Central and South America, the Middle East and Asia Pacific. Daclatasvir regimens also have been included in the EASL's recommendations for the treatment of hepatitis C in Europe.
The U.S. Food and Drug Administration is reviewing daclatasvir for possible approval in the United States.
###
For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook or follow us on Twitter.
The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university's schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways "We make lives better®," visit http://www.
The Texas Liver Institute's mission is to set the standard of excellence in care and innovative research in the field of liver disease. The institute is affiliated with The University of Texas Health Science Center at San Antonio. The physicians are professors and teach at University Hospital of the University Health System and are involved with the liver transplantation program of the University Transplant Center, a partnership of the Health Science Center and the University Health System. For more information, visit http://www.
Saturday, April 25, 2015
EASL 2015: ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)
- 97% of post-transplant patients with HCV genotype 1a achieved cure
- 91% of post-transplant patients with HCV genotype 3 achieved cure
- No need seen to alter existing transplantation medication regimens
Saturday, April 25, 2015 10:00 am EDT
(PRINCETON, N.J., APRIL 25, 2015) – Bristol-Myers Squibb Company (NYSE:BMY) today announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV. The data was presented as a late-breaker at The International Liver Congress™ 2015, the 50th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria from April 22-26.
“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine, Chief, Hepatology, University of Texas Health Science Center and VP, Academic and Clinical Affairs Texas Liver Institute. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”
The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).
The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorize disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites (the build-up of fluid in the abdomen), hepatic encephalopathy (confusion or altered level of consciousness due to the liver’s inability to remove toxins from the blood), and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.
Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.
In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks.
HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY program, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations and is at the center of Bristol-Myers Squibb’s HCV research focus. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during EASL 2015.
Additionally, EASL issued 2015 Hepatitis C treatment guidelines that include a regimen of daclatasvir+sofosbuvir as the first 12-week treatment for patients with genotype-3 virus. The EASL guidelines now list daclatasvir+sofosbuvir regimens as options for treating all HCV genotypes and for use with patients coinfected with HCV/HIV. (Guidelines available here.)
Other Bristol-Myers Squibb presentations at The International Liver Congress included data from compassionate use programs in the EU that add to the real-world clinical evidence informing the use of daclatasvir-based regimens to treat patients with HCV conditions posing high unmet medical needs.
“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”
About ALLY-1: Study Design
This Phase III open-label clinical trial enrolled treatment-naïve and treatment-experienced patients with HCV infection of any genotype in 2 cohorts: advanced cirrhosis (n=60) and post-liver transplant with HCV recurrence (n=53). All patients received daclatasvir 60 mg plus sofosbuvir 400 mg once-daily with ribavirin initially dosed at 600 mg/d (with potential for adjustment based on hemoglobin levels and creatinine clearance) for 12 weeks. Patients receiving a variety of immunosuppressive agents were permitted. In the cirrhosis cohort, patients transplanted during treatment could receive 12 weeks of extended treatment immediately post-transplant, regardless of treatment duration before transplant. The primary endpoint was the SVR12 rate (defined as HCV RNA <LLOQ (25 IU/mL) at post-treatment week 12) among genotype 1 patients in each cohort.
Read complete press release here....
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