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 daclatasvir plus sofosbuvir. Show all posts
Showing posts with label daclatasvir plus sofosbuvir. Show all posts
Tuesday, May 26, 2015
Thursday, May 7, 2015
Treatment Curing Patients with Advanced Hepatitis C Symptoms
A medical breakthrough tested in San Antonio is opening doors for patients diagnosed with hepatitis C.
The virus can be deadly, but now researchers say they've found a cure for those suffering from advanced stages of the disease.
People like Joey Libby.
Libby was just 15 years old when he was diagnosed with liver failure.
Read more...
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....
Thursday, April 23, 2015
EASL 2015: Daclatasvir-sofosbuvir treatment highly effective in patients with HCV and HIV co-infection
Phase III results revealed today at The International Liver Congress™ 2015 show that once-daily treatment with daclatasvir (DCV) plus sofosbuvir (SOF) resulted in an overall 97% sustained virologic response (SVR) at 12 weeks post-treatment in patients with hepatitis C virus (HCV) and HIV co-infection, including cirrhotic patients.
HIV co-infection more than triples the risk of hepatitis C-related liver disease, liver failure and liver-related death. Co-infection can also complicate the management of HIV infection.
In the ALLY-2 randomised, open-label study, the combination of DCV+SOF was well tolerated and effective across the four different genotypes. Importantly, due to their limited pharmacokinetic interactions with other agents, DCV+SOF was able to work effectively across a broad range of concomitant combination antiretroviral therapy (cART) regimens without compromising HIV virologic control (98% of patients were on cART).
Read more...
HIV co-infection more than triples the risk of hepatitis C-related liver disease, liver failure and liver-related death. Co-infection can also complicate the management of HIV infection.
In the ALLY-2 randomised, open-label study, the combination of DCV+SOF was well tolerated and effective across the four different genotypes. Importantly, due to their limited pharmacokinetic interactions with other agents, DCV+SOF was able to work effectively across a broad range of concomitant combination antiretroviral therapy (cART) regimens without compromising HIV virologic control (98% of patients were on cART).
Read more...
Friday, April 3, 2015
HCV Drugs Alan Franciscus, Editor-in-Chief
BMS Files NDA with FDA
On March 12, 2015 Bristol-Myers Squibb (BMS) announced that the Food and Drug Administration (FDA) had accepted their new drug application (NDA) for the combination of daclatasvir plus sofosbuvir for the treatment of HCV genotype 3. In BMS’s phase 3 studies of genotype 3 patients—101 treatment-naïve, 51 treatment-experienced—the cure rates were 90% and 86% respectively. However, in people who had cirrhosis (F-4) the cure rates were 63% to 73% leaving an unmet need for these patients.
On March 12, 2015 Bristol-Myers Squibb (BMS) announced that the Food and Drug Administration (FDA) had accepted their new drug application (NDA) for the combination of daclatasvir plus sofosbuvir for the treatment of HCV genotype 3. In BMS’s phase 3 studies of genotype 3 patients—101 treatment-naïve, 51 treatment-experienced—the cure rates were 90% and 86% respectively. However, in people who had cirrhosis (F-4) the cure rates were 63% to 73% leaving an unmet need for these patients.
CROI
The Conference on Retroviruses and Opportunistic Infections (CROI) 2015 held in Seattle, WA, had a wealth of information about the treatment of people with HIV and HCV coinfection. Since the introduction of interferon-free therapy the cure rates of HCV in people who are coinfected with HIV and HCV are the same as the cure rates in people who are HCV mono-infected, and importantly the studies presented at CROI reinforce this information.
Daclatasvir/Sofosbuvir
DL Wyles et al., presented “Daclatasvir in Combination with Sofosbuvir for HIV/HCV Coinfection: ALLY-2 Study.” The study included patients with HCV genotype 1 (1a-139 pts; 1b-29 pts), genotype 2 (19 pts), genotype 3 (19 pts) and genotype 4 (3 pts). There were three arms in the study—two arms with 12 weeks treatment duration and one arm with an eight-week treatment period—there were no genotype 4 patients in the eight-week treatment arm. Most of the patients were male (83-91%);
White (56-65%); and there were 29 patients with cirrhosis in the study.
DL Wyles et al., presented “Daclatasvir in Combination with Sofosbuvir for HIV/HCV Coinfection: ALLY-2 Study.” The study included patients with HCV genotype 1 (1a-139 pts; 1b-29 pts), genotype 2 (19 pts), genotype 3 (19 pts) and genotype 4 (3 pts). There were three arms in the study—two arms with 12 weeks treatment duration and one arm with an eight-week treatment period—there were no genotype 4 patients in the eight-week treatment arm. Most of the patients were male (83-91%);
White (56-65%); and there were 29 patients with cirrhosis in the study.
The cure rates were 97% in genotype 1, and 100% in genotypes 2, 3, and 4 in the groups treated for 12 weeks. In the groups treated for eight weeks, the cure rates fell to 76%. There was no impact based on genotype or type of prior treatment response.
Comments: These are remarkable cure rates regardless of genotype, viral load, and other factors at least in the 12-week group. Based on this data 8 weeks of Daclatasvir plus sofosbuvir is not effective.
An unmet medical need is treatment of people with genotype 3 with cirrhosis—this information was not available. Additionally, there were very few genotype 3 patients in the study to draw any conclusions.
Given the results of Harvoni (below) the niche for this combination may be narrow. However, it was noted that, if approved, adjusting the dosing would be easier since these drugs are dosed separately especially for some people on HIV medications.
Harvoni
S Naggie et al., present data from “Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected with HCV and HIV-1: ION-4.” This study was a phase 3 clinical trial of Harvoni (sofosbuvir/ledipasvir) for the treatment of HCV genotype 1 and 4 in people who are coinfected with HIV and hepatitis C. A total of 335 patients were included in the trial—75% were genotype 1a; 23% genotype 1b; 2% genotype 4. The study included 45% treatment-naïve patients, 55% treatment-experienced patients, and 20% of the patients had compensated cirrhosis. The mean age of the patients was 52yo; 82% were male, 34% were Black.
S Naggie et al., present data from “Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected with HCV and HIV-1: ION-4.” This study was a phase 3 clinical trial of Harvoni (sofosbuvir/ledipasvir) for the treatment of HCV genotype 1 and 4 in people who are coinfected with HIV and hepatitis C. A total of 335 patients were included in the trial—75% were genotype 1a; 23% genotype 1b; 2% genotype 4. The study included 45% treatment-naïve patients, 55% treatment-experienced patients, and 20% of the patients had compensated cirrhosis. The mean age of the patients was 52yo; 82% were male, 34% were Black.
The overall cure rate was 96%. There was little difference in cure rates between treatment naïve and treatment experienced (95% vs. 97%) and those with and without cirrhosis (94% vs. 96%). There was a difference in cure rates between Blacks (90%) and non-Blacks (99%). The most common side effects were headache, fatigue and diarrhea.
Gilead is trying to determine the difference in the cure rates between Blacks and non-Blacks. They have ruled out drug concentration levels in the blood and the possible interaction of the HIV medications. During the question and answer period there were a couple of interesting comments about the lower response rates in Blacks:
- Perhaps Black patients coinfected with HIV and HCV may need to be treated longer
- Previous clinical trials have had lower Black patient populations that may not have given us a true picture of treatment cure in Blacks—more Blacks are needed in clinical trials period. In the days of pegylated interferon and ribavirin therapy the cure rates were much lower.
Gilead stated that they are planning to file a New Drug Application (NDA) with the FDA based on the phase 3 data for the treatment of HCV in people with HIV.
Comments: Impressive cure rates and low side effects regardless of prior treatment response or degree of liver damage. Once we learn more about the reason for the lower response rates in Blacks we will keep our readers informed.
Delaying Treatment = More Deaths
Everyone is trying to come to terms with the impact of treating people who are the sickest. Lately, there have been studies showing this approach may not be cost effective. It certainly isn’t patient centered or tied to improving the quality of life for people living with hepatitis C. A study presented at CROI—“Impact of Deferring HCV Treatment on Liver-Related Events in HIV+ Patients, by C Zahnd et al.”—sheds some light on the long-term health risk of delaying treatment.
Everyone is trying to come to terms with the impact of treating people who are the sickest. Lately, there have been studies showing this approach may not be cost effective. It certainly isn’t patient centered or tied to improving the quality of life for people living with hepatitis C. A study presented at CROI—“Impact of Deferring HCV Treatment on Liver-Related Events in HIV+ Patients, by C Zahnd et al.”—sheds some light on the long-term health risk of delaying treatment.
The researchers in the study used a model to predict health outcomes from the Swiss HIV Cohort Study to simulate HIV/HCV patients from the time of acute infection through chronic infection and fibrosis stages using the Metavir system for staging fibrosis/cirrhosis (F0 through F4), decompensated cirrhosis, liver cancer, and death. They assumed that 100% of patients were treated with interferon-free therapies and of these patients 90% were cured.
The highlights of their findings included:
- If patients were treated one month or 1 year after diagnosis—3% would die from liver-related deaths
- If HCV treatment was delayed until later stages, the percentages of patients who were predicted to die dramatically increased: Treated at F-2 a 5% death rate; treated at F-3 a 10% death rate; treated at F-4 a 25% death rate.
http://hcvadvocate.org/news/newsLetter/2015/advocate0415.html#3
Thursday, March 12, 2015
Bristol-Myers Squibb Announces Acceptance of New Drug Application for Investigational Daclatasvir for FDA Review for the Treatment of Hepatitis C Genotype 3
The NDA contains data to support approval for daclatasvir in combination with sofosbuvir; would be the first 12-week regimen specifically for the treatment of hepatitis C genotype 3
The application is based on a Phase III clinical trial which tested a 12-week, ribavirin-free regimen and resulted in sustained virologic response (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced genotype 3 HCV patients
“The daclatasvir-based NDA seeks to address a high-unmet patient need that still exists despite recent hepatitis C treatment advances. Approximately 9-12% of HCV patients in the U.S. have genotype 3. That’s thousands of individuals in the U.S. who historically have had limited treatment options requiring at least 24 weeks of treatment,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “We also are continuing clinical trials to determine the potential of daclatasvir-based regimens in treating a range of other high unmet-need patients, including those coinfected with HIV, HCV patients with decompensated cirrhosis, and HCV recurrence in post-transplant patients.”
Genotype 3 is estimated to affect 54.3 million people worldwide, and is the second most common hepatitis C genotype after genotype 1 (83.4 million). The more aggressive nature of genotype 3 lies in the damage it causes to the liver, as it is associated with progressive disease, increased rates of steatosis and a disproportionately increased risk of hepatocellular carcinoma.
In the ALLY-3 study, the daclatasvir and sofosbuvir combination regimen was well tolerated, with no deaths, treatment-related serious adverse events, or discontinuations due to adverse events. The most frequent side effects (≥5%) were headache (19.7%), fatigue (19.1%), nausea (11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain and arthralgia (both 5.3%). Additionally, there were 17 (11.2%) treatment failures, with 16 relapses post-treatment and 1 rebound at the end of treatment. There were no viral breakthroughs in this ribavirin-free regimen.
About ALLY-3: Study Design
This Phase III open-label clinical trial enrolled 152 genotype 3 HCV patients; 101 treatment-naïve patients and 51 treatment-experienced patients in 2 cohorts each received daclatasvir 60 mg and sofosbuvir 400 mg once daily for 12 weeks, with 24 weeks of follow-up. The primary endpoint was SVR12 rates, defined as HCV RNA < LLOQ target detected or not detected at follow-up week 12 in treatment-naïve and treatment-experienced patients.
Read complete press release here
Combo Hepatitis C Genotype 3 Tx To Be Reviewed By FDA
Bristol-Myers Squibb announced that the Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) of daclatasvir in combination with sofosbuvir for the treatment of chronic hepatitis C (HCV) genotype 3.
The initial NDA now includes data from the ALLY-3 trial (n=152), a Phase 3 open-label study in which patients received daclatasvir 60mg + sofosbuvir 400mg once daily for 12 weeks with 24 weeks of follow-up. The study demonstrated high cure rates for the combination therapy with sustained virologic response 12 weeks after treatment (SVR12) seen in 90% of treatment-naive genotype 3 HCV patients, and in 86% of treatment-experienced patients. SVR12 rates were seen in 96% of non-cirrhotic genotype 3 patients, regardless of treatment history.
Read more...
The initial NDA now includes data from the ALLY-3 trial (n=152), a Phase 3 open-label study in which patients received daclatasvir 60mg + sofosbuvir 400mg once daily for 12 weeks with 24 weeks of follow-up. The study demonstrated high cure rates for the combination therapy with sustained virologic response 12 weeks after treatment (SVR12) seen in 90% of treatment-naive genotype 3 HCV patients, and in 86% of treatment-experienced patients. SVR12 rates were seen in 96% of non-cirrhotic genotype 3 patients, regardless of treatment history.
Read more...
Saturday, February 28, 2015
Combos Cure HCV in Almost All With HIV Co-infection
Just 12 weeks of treatment eliminated hepatitis C virus in HIV patients.
SEATTLE -- Two drug combinations aimed at hepatitis C (HCV) yielded almost perfect cure rates in patients also infected with HIV, researchers reported here at the 2015 Conference on Retroviruses and Opportunistic Infections.
When the drugs were given for 12 weeks, 96% to 98% of patients had undetectable HCV 12 weeks after the end of therapy -- the so-called SVR12, which is regarded as a cure.
The only blot on the horizon was a 76% SVR12 rate when the combination of daclatasvir and sofosbuvir (Sovaldi) was given for just 8 weeks, reported David Wyles, MD, of the University of California San Diego.
Read more...
Thursday, February 26, 2015
ALLY Trial Demonstrates 97% Hepatitis C Cure Rates Among Patients Coinfected with HIV After Ribavirin-Free Investigational 12-Week Regimen of Daclatasvir and Sofosbuvir
Daclatasvir-sofosbuvir 12-week regimen resulted in:
Thursday, February 26, 2015 3:15 pm EST
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from ALLY-2, a Phase III clinical trial evaluating the investigational once-daily combination of daclatasvir and sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) coinfected with HIV – a patient population that historically has been challenging to treat in large part due to potential drug-drug interactions between the therapy regimens used to treat each infection.
“The results of ALLY-2 signal that nearly all HIV-HCV coinfected patients in the study could be cured of hepatitis C with a 12-week regimen on daclatasvir and sofosbuvir,” said David Wyles, M.D., ALLY-2 Lead Investigator and Associate Professor of Medicine in the Department of Medicine, Division of Infectious Diseases at the University of California San Diego. “The trial demonstrated the dosing flexibility afforded by the daclatasvir-sofosbuvir regimen did not require alteration of HIV medications because of potential drug-drug interactions. This is a paramount consideration for clinicians treating this patient population.”
Among ALLY-2 patients treated for 12 weeks (treatment-naïve and -experienced), 97% (n=149/153) achieved cure (sustained virologic response 12 weeks after treatment; SVR12). The study met the primary endpoint, with 96% (n=80/83) of treatment-naïve genotype 1 patients achieving SVR12. Treatment with daclatasvir in combination with sofosbuvir in this study showed high SVR rates, with no discontinuations due to adverse events, and no serious adverse events related to study medications throughout the treatment phase.
“While substantial strides have been made in the battle against hepatitis C, a significant number of patients with complicated disease and treatment histories need additional treatment options to help them achieve hepatitis C cure,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “The ALLY-2 results show that daclatasvir paired with sofosbuvir produced high cure rates in this trial regardless of the coinfected patients’ HCV genotype.”
According to the Centers for Disease Control and Prevention (CDC), about one quarter of HIV-infected persons in the United States - approximately 300,000 people - are also infected with hepatitis C, and HCV infection progresses more rapidly to liver damage in people living with HIV.
In ALLY-2, high SVR rates occurred among all patients treated for 12 weeks, regardless of prior treatment experience, HCV genotype, cirrhosis status, concurrent combination antiretroviral therapy regimen, or race. African-American patients comprised 34% of study participants; in this patient demographic, SVR12 rates were 98% (n=49/50). ALLY-2 also included an 8-week arm; 38 of 50 treatment-naïve patients with HCV achieved SVR12. However, study investigators concluded that further studies are needed to assess the potential of shorter-duration, all-oral treatment regimens.
Additional safety data demonstrated a low rate of Grade 3/4 lab abnormalities in the study: INR (1%), AST (0.5%), Tbili (4%), Lipase (3%).
About ALLY-2: Study Design
This Phase III open-label clinical trial randomized 151 treatment-naïve and 52 treatment-experienced HCV (genotypes 1-4) patients coinfected with HIV-1 on a broad range of antiretroviral regimens, into 3 cohorts. Among treatment-naïve patients, one cohort received daclatasvir 30, 60, or 90 mg (dose adjusted for concomitant antiretroviral therapy) plus sofosbuvir 400 mg once daily for 12 weeks, and another received the same dosage and combination for 8 weeks.
The treatment-experienced cohort also received daclatasvir 30, 60, or 90 mg plus sofosbuvir 400 mg once daily for 12 weeks. Daclatasvir was dose-adjusted to accommodate concomitant antiretrovirals: 30 mg with ritonavir-boosted PIs, 90 mg with NNRTIs except rilpivirine. All cohorts had follow-up through post-treatment week 24. The primary endpoint was the SVR12 rate among genotype 1 treatment-naïve patients after 12 weeks of treatment. Patients with cirrhosis were permitted.
Read complete press release here:
- 96% hepatitis C cure rate among patients with HVC genotype 1 disease (n=80/83)
- 100% hepatitis C cure rate among patients with HCV genotype 2, 3 and 4 disease (n=26/26)
Thursday, February 26, 2015 3:15 pm EST
"The ALLY-2 results show that daclatasvir paired with sofosbuvir produced high cure rates in this trial regardless of the coinfected patients’ HCV genotype."
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from ALLY-2, a Phase III clinical trial evaluating the investigational once-daily combination of daclatasvir and sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) coinfected with HIV – a patient population that historically has been challenging to treat in large part due to potential drug-drug interactions between the therapy regimens used to treat each infection.
“The results of ALLY-2 signal that nearly all HIV-HCV coinfected patients in the study could be cured of hepatitis C with a 12-week regimen on daclatasvir and sofosbuvir,” said David Wyles, M.D., ALLY-2 Lead Investigator and Associate Professor of Medicine in the Department of Medicine, Division of Infectious Diseases at the University of California San Diego. “The trial demonstrated the dosing flexibility afforded by the daclatasvir-sofosbuvir regimen did not require alteration of HIV medications because of potential drug-drug interactions. This is a paramount consideration for clinicians treating this patient population.”
Among ALLY-2 patients treated for 12 weeks (treatment-naïve and -experienced), 97% (n=149/153) achieved cure (sustained virologic response 12 weeks after treatment; SVR12). The study met the primary endpoint, with 96% (n=80/83) of treatment-naïve genotype 1 patients achieving SVR12. Treatment with daclatasvir in combination with sofosbuvir in this study showed high SVR rates, with no discontinuations due to adverse events, and no serious adverse events related to study medications throughout the treatment phase.
“While substantial strides have been made in the battle against hepatitis C, a significant number of patients with complicated disease and treatment histories need additional treatment options to help them achieve hepatitis C cure,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “The ALLY-2 results show that daclatasvir paired with sofosbuvir produced high cure rates in this trial regardless of the coinfected patients’ HCV genotype.”
According to the Centers for Disease Control and Prevention (CDC), about one quarter of HIV-infected persons in the United States - approximately 300,000 people - are also infected with hepatitis C, and HCV infection progresses more rapidly to liver damage in people living with HIV.
In ALLY-2, high SVR rates occurred among all patients treated for 12 weeks, regardless of prior treatment experience, HCV genotype, cirrhosis status, concurrent combination antiretroviral therapy regimen, or race. African-American patients comprised 34% of study participants; in this patient demographic, SVR12 rates were 98% (n=49/50). ALLY-2 also included an 8-week arm; 38 of 50 treatment-naïve patients with HCV achieved SVR12. However, study investigators concluded that further studies are needed to assess the potential of shorter-duration, all-oral treatment regimens.
Additional safety data demonstrated a low rate of Grade 3/4 lab abnormalities in the study: INR (1%), AST (0.5%), Tbili (4%), Lipase (3%).
About ALLY-2: Study Design
This Phase III open-label clinical trial randomized 151 treatment-naïve and 52 treatment-experienced HCV (genotypes 1-4) patients coinfected with HIV-1 on a broad range of antiretroviral regimens, into 3 cohorts. Among treatment-naïve patients, one cohort received daclatasvir 30, 60, or 90 mg (dose adjusted for concomitant antiretroviral therapy) plus sofosbuvir 400 mg once daily for 12 weeks, and another received the same dosage and combination for 8 weeks.
The treatment-experienced cohort also received daclatasvir 30, 60, or 90 mg plus sofosbuvir 400 mg once daily for 12 weeks. Daclatasvir was dose-adjusted to accommodate concomitant antiretrovirals: 30 mg with ritonavir-boosted PIs, 90 mg with NNRTIs except rilpivirine. All cohorts had follow-up through post-treatment week 24. The primary endpoint was the SVR12 rate among genotype 1 treatment-naïve patients after 12 weeks of treatment. Patients with cirrhosis were permitted.
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