By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network
The nucleoside analogue entecavir has been approved by the Food and Drug Administration for treating chronic hepatitis B in adults with decompensated liver disease, the manufacturer announced.
Approval was based on data from an ongoing study that randomized patients with chronic hepatitis B and decompensated liver disease to treatment with entecavir, at a dose of 1 mg once daily, or the nucleotide analogue adefovir (10 mg once daily), according to a statement issued by Bristol-Myers Squibb (BMS).
Entecavir, first approved by the FDA in 2005 for treating chronic hepatitis B in adults with compensated liver disease, is marketed as Baraclude by BMS.
The open label, controlled, phase 3b study enrolled HBeAg-positive or HBeAg-negative patients with chronic hepatitis B and evidence of hepatic decompensation, who had never been treated for hepatitis B virus (HBV) or had been treated predominantly with lamivudine or interferon-alpha; 100 patients were randomized to receive entecavir, 91 to receive adefovir.
At 48 weeks, 57% of the patients in the entecavir arm had an undetectable HBV DNA viral load (less than 300 copies/mL), compared with 20% of those on adefovir, according to BMS. Among the patients with abnormal alanine aminotransferase levels at baseline, more of those treated with entecavir achieved normal levels at 48 weeks, compared with those treated with adefovir (63% vs. 46%, respectively). Loss of hepatitis B surface antigen was seen in 5% of those on entecavir, compared with none of those treated with adefovir.
However, slightly more patients on adefovir (67%) showed improvement, or no worsening, in their Child-Turcotte-Pugh scores, compared with 61% of those on entecavir.
The most common adverse events reported in patients treated with entecavir through 48 weeks were peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%), according to the company statement.
The study is the ETV-048 trial.
Approved in 2002, adefovir (Hepsera) is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Sunday, October 31, 2010
Saturday, October 30, 2010
AASLD/ELAD® Bioartificial Liver/3yr Follow Up Confirm Saftey&Survival Benefit
Three-Year Follow-Up Data Confirm Safety and Survival Benefit in Chinese Liver Failure Patients Treated With ELAD® Bioartificial Liver
Poster presentation scheduled at AASLD November 2nd
Vital Therapies, Inc.
/PRNewswire/ -- Vital Therapies, Inc., (VTI) today announced that a poster is being presented at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston on Tuesday, November 2nd. It confirms that previously reported findings of improved transplant free survival (TFS) in Chinese subjects with acute-on-chronic liver failure (ACLF) treated with the ELAD® bioartificial liver support system are maintained for up to three years.
The poster is titled "3-year follow-up of acute-on-chronic liver failure (ACLF) subjects in randomized, controlled, multicenter trial of ELAD® bioartificial liver support system in 49 Chinese subjects reveals significant transplant-free survival (TFS) benefit." It is being presented by Dr. Michael Millis, Professor of Surgery, University of Chicago, and is coauthored by Drs. Zhongping Duan and Jing Zhang, Beijing You'an Hospital, and Shaojie Xin and Shaoli You, 302 Military Hospital, Beijing.
Previously, it was reported that 84-day follow-up of ACLF subjects enrolled at two liver treatment centers in China showed statistically significant improvements in TFS for ELAD treatment compared with standard of care (SOC). At least three years following enrollment, survivors were consented and underwent a cancer screen and physical exam in accord with a questionnaire.
Of 49 subjects enrolled, 84-day TFS was 21/32 (65.6%) in the ELAD group vs. 7/17 (41.1%) in controls. Three-year TFS was 14/32 (43.8%) in the ELAD group vs. 3/12 (25%) in controls. Of 84-day survivors, 2/21 (9.5%) ELAD and 2/7 (28.6%) controls died, 1/21 (4.8%) ELAD and 0/7 controls were transplanted and 4/21 (19.0%) ELAD and 2/7 (28.6%) controls were lost to follow-up. Survival analysis reveals a statistically significant improvement in TFS (p=0.045, log-rank analysis) for the ELAD treated subjects compared with SOC. Median survival of controls was 37 days, whereas median survival of ELAD treated subjects was at least 3 years. There was no evidence of tumor development in either group.
Dr. Millis commented, "This is the first time that a long term survival benefit has been demonstrated in subjects who recovered following treatment with ELAD. It is highly encouraging to note that those subjects that survive in the short term are able to go on to extended survival without any apparent increase in mortality or morbidity compared with subjects administered standard of care."
Dr. Duan, who served as a principal investigator for the study, commented, "China has about 95 million HBV carriers and chronic hepatitis B patients, and 38 million hepatitis C patients. It is estimated that 0.1%-0.5% of these patients will experience severe hepatitis due to acute hepatocellular necrosis or hypofunction, which results in hepatic insufficiency and hepatic failure. Mortality from this condition still remains around 50%-70% even with comprehensive internal medicine treatment, leading to as many as 400,000 deaths per year in China from acute liver failure. When approved for commercial sale in China, ELAD will be the first bioartificial liver support system proven to improve survival in this population."
In order to confirm these findings from China, VTI is conducting the SILVER (Stabilization In LiVER Failure) trial in the United States, Europe and Saudi Arabia which has achieved 50% of its targeted enrollment. Should this study yield positive findings, these results, along with data from other studies, will form the basis of regulatory filings for future marketing authorization.
About ELAD and the SILVER Trial
The SILVER protocol enrolls subjects with chronic liver disease who have been hospitalized as a result of an event, such as an infection or an episode of bleeding, which has caused deterioration of their liver function (acute-on-chronic liver failure, ACLF). The trial is designed to explore whether the use of ELAD in this setting can prevent continued deterioration of liver function, called progression, and thus improve survival. The trial design uses a well-established measure of liver function called the MELD score to define the status of liver function. Treatment with ELAD, along with standard of care, is compared with standard of care alone. The time to either death or deterioration of liver function by a pre-specified amount is measured. It is postulated that the use of ELAD may extend the time to progression and improve survival in this rapidly progressing patient population.
ELAD is a biologic liver support system using a proprietary line of allogeneic human liver cells refined by several leading cell experts. The cells are stable, immortal, can be grown in unlimited quantities and retain their hepatocyte (liver cell) characteristics. About one pound of cells is used for each treatment. The cells are grown in specially designed cartridges at VTI's cell culture facility and used to treat the patient for up to ten days.
About Vital Therapies, Inc.
Vital Therapies, Inc. (VTI) is based in San Diego, California, with a wholly owned subsidiary in Beijing, China. VTI is developing the first human liver cell-based Extracorporeal Liver Assist System (ELAD). ELAD could provide support for patients with severe liver failure by processing toxins and also synthesizing proteins and metabolites that are key products of normal human liver function. ELAD is in investigational clinical trials and VTI completed a pivotal trial and filed for market approval in China in September 2007. For additional information visit http://www.vitaltherapies.com/ or contact Terry Winters, PhD, CEO, Vital Therapies at +1 858 673 6840.
ELAD is a trademark of Vital Therapies, Inc.
SOURCE Vital Therapies, Inc.
http://www.kansascity.com/2010/10/13/2311093/three-year-follow-up-data-confirm.html
AASLD:Scientists grow human livers in laboratory
Scientists grow human livers in laboratory
WINSTON-SALEM, N.C. – Saturday, Oct. 30, 2010 – Researchers at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center have reached an early, but important, milestone in the quest to grow replacement livers in the lab. They are the first to use human liver cells to successfully engineer miniature livers that function – at least in a laboratory setting – like human livers. The next step is to see if the livers will continue to function after transplantation in an animal model.
The ultimate goal of the research, which will be presented Sunday at the annual meeting of the American Association for the Study of Liver Diseases in Boston and published in an upcoming issue of the journal Hepatology, is to provide a solution to the shortage of donor livers available for patients who need transplants. Laboratory-engineered livers could also be used to test the safety of new drugs.
“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, Ph.D., professor of regenerative medicine and project director. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”
Pedro Baptista, PharmD, Ph.D., lead author on the study, said the project is the first time that human liver cells have been used to engineer livers in the lab. “Our hope is that once these organs are transplanted, they will maintain and gain function as they continue to develop,” he said.
The engineered livers, which are about an inch in diameter and weigh about .20 ounces, would have to weigh about one pound to meet the minimum needs of the human body, said the scientists. Even at this larger size, the organs wouldn’t be as large as human livers, but would likely provide enough function. Research has shown that human livers functioning at 30 percent of capacity are able to sustain the human body.
To engineer the organs, the scientists used animal livers that were treated with a mild detergent to remove all cells (a process called decellularization), leaving only the collagen “skeleton” or support structure. They then replaced the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels.
The cells were introduced into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. This network of vessels remains intact after the decellularization process. The liver was next placed in a bioreactor, special equipment that provides a constant flow of nutrients and oxygen throughout the organ.
After a week in the bioreactor system, the scientists documented the progressive formation of human liver tissue, as well as liver-associated function. They observed widespread cell growth inside the bioengineered organ.
The ability to engineer a liver with animal cells had been demonstrated previously. However, the possibility of generating a functional human liver was still in question.
The researchers said the current study suggests a new approach to whole-organ bioengineering that might prove to be critical not only for treating liver disease, but for growing organs such as the kidney and pancreas. Scientists at the Wake Forest Institute for Regenerative Medicine are working on these projects, as well as many other tissues and organs, and also working to develop cell therapies to restore organ function.
Bioengineered livers could also be useful for evaluating the safety of new drugs. “This would more closely mimic drug metabolism in the human liver, something that can be difficult to reproduce in animal models," said Baptista.
Co-researchers were Dipen Vyas, B.Pharm., M.S., Zhan Wang, M.D., Ph.D. and Anthony Atala, M.D., director of the institute.
http://www.wfubmc.edu/News-Releases/2010/Researchers_Engineer_Miniature_Human_Livers_in_the_Lab.htm
Media Relations Contacts:
Karen Richardson: krchrdsn@wfubmc.edu, 336-716-4453
WINSTON-SALEM, N.C. – Saturday, Oct. 30, 2010 – Researchers at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center have reached an early, but important, milestone in the quest to grow replacement livers in the lab. They are the first to use human liver cells to successfully engineer miniature livers that function – at least in a laboratory setting – like human livers. The next step is to see if the livers will continue to function after transplantation in an animal model.
The ultimate goal of the research, which will be presented Sunday at the annual meeting of the American Association for the Study of Liver Diseases in Boston and published in an upcoming issue of the journal Hepatology, is to provide a solution to the shortage of donor livers available for patients who need transplants. Laboratory-engineered livers could also be used to test the safety of new drugs.
“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, Ph.D., professor of regenerative medicine and project director. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”
Pedro Baptista, PharmD, Ph.D., lead author on the study, said the project is the first time that human liver cells have been used to engineer livers in the lab. “Our hope is that once these organs are transplanted, they will maintain and gain function as they continue to develop,” he said.
The engineered livers, which are about an inch in diameter and weigh about .20 ounces, would have to weigh about one pound to meet the minimum needs of the human body, said the scientists. Even at this larger size, the organs wouldn’t be as large as human livers, but would likely provide enough function. Research has shown that human livers functioning at 30 percent of capacity are able to sustain the human body.
To engineer the organs, the scientists used animal livers that were treated with a mild detergent to remove all cells (a process called decellularization), leaving only the collagen “skeleton” or support structure. They then replaced the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels.
The cells were introduced into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. This network of vessels remains intact after the decellularization process. The liver was next placed in a bioreactor, special equipment that provides a constant flow of nutrients and oxygen throughout the organ.
After a week in the bioreactor system, the scientists documented the progressive formation of human liver tissue, as well as liver-associated function. They observed widespread cell growth inside the bioengineered organ.
The ability to engineer a liver with animal cells had been demonstrated previously. However, the possibility of generating a functional human liver was still in question.
The researchers said the current study suggests a new approach to whole-organ bioengineering that might prove to be critical not only for treating liver disease, but for growing organs such as the kidney and pancreas. Scientists at the Wake Forest Institute for Regenerative Medicine are working on these projects, as well as many other tissues and organs, and also working to develop cell therapies to restore organ function.
Bioengineered livers could also be useful for evaluating the safety of new drugs. “This would more closely mimic drug metabolism in the human liver, something that can be difficult to reproduce in animal models," said Baptista.
Co-researchers were Dipen Vyas, B.Pharm., M.S., Zhan Wang, M.D., Ph.D. and Anthony Atala, M.D., director of the institute.
http://www.wfubmc.edu/News-Releases/2010/Researchers_Engineer_Miniature_Human_Livers_in_the_Lab.htm
Media Relations Contacts:
Karen Richardson: krchrdsn@wfubmc.edu, 336-716-4453
Many Have A New Chance At Treating Hepatitis C
Jasper Cropsey New doors may open in treating hepatitis C
(Note all links in this article incorporated by this blog)
Bloomberg News
Bristol-Myers Squibb Co. and Gilead Sciences 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."
About 200 million people worldwide have hepatitis C, an analysis at Dartmouth Medical School in 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 of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Whitehouse Station-based Merck & Co. sells a form called PegIntron.
Two new hepatitis C options that may be introduced next year are telaprevir, from Vertex Pharmaceuticals Inc. and New Brunswick-based Johnson & Johnson, and boceprevir, from Merck. 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.
Bloomberg News
Bristol-Myers Squibb Co. and Gilead Sciences 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."
About 200 million people worldwide have hepatitis C, an analysis at Dartmouth Medical School in 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 of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Whitehouse Station-based Merck & Co. sells a form called PegIntron.
Two new hepatitis C options that may be introduced next year are telaprevir, from Vertex Pharmaceuticals Inc. and New Brunswick-based Johnson & Johnson, and boceprevir, from Merck. 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.
.
,
Telaprevir/Boceprevir/Similar Cure Rates/Shorter Treatment Duration
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, Mass. "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, Minn.
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, Mass. "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, Minn.
.
Homo musculus: Researchers Create a "Humanized" Mouse for Liver Disease Studies
"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."
Bristol-Myers 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.
"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."
Bristol-Myers 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.
.
See trial status
.
,
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; Medivir AB of Huddinge, Sweden; Idenix Pharmaceuticals Inc. of Cambridge, Mass.; and Inhibitex Inc. of Alpharetta, Ga.
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."
AASLD/2010 Telaprevir 3 Studies Showed Superior SVR (Viral Cure)Regardless of Race/Stage Of Liver Disease
http://www.nj.com/business/index.ssf/2010/10/new_doors_may_open_in_treating.html
AASLD/2010 Telaprevir 3 Studies Showed Superior SVR (Viral Cure)Regardless of Race/Stage Of Liver Disease
New Data From Phase 3 Studies Showed Superior SVR (Viral Cure) Rates Achieved with Telaprevir-Based Combination Therapy in People with Hepatitis C, Regardless of Race or Stage of Liver Disease
Industry updates: Oct 30, 2010
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from its Phase 3 studies of people with genotype 1 chronic hepatitis C who have not been treated previously. In these studies, the majority of people achieved superior sustained viral response (SVR or viral cure) rates with a telaprevir-based combination regimen, compared to current therapies, regardless of race/ethnicity or stage of liver fibrosis (factors known to limit response to current hepatitis C treatments). Patients in the ADVANCE and ILLUMINATE studies were given telaprevir with pegylated-interferon and ribavirin for the first 12 weeks of the studies, followed by treatment with pegylated-interferon and ribavirin alone for a total of either 24 weeks or 48 weeks based on their response to treatment at weeks 4 and 12. Final data from the Phase 3 ADVANCE and ILLUMINATE studies are being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which takes place in Boston October 29 to November 2.
“In our Phase 3 program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “The results of the ADVANCE and ILLUMINATE studies represent a major milestone in the development of telaprevir and offer hope for doctors and the millions of people living with hepatitis C who need new and more effective medicines.”
Vertex Pharmaceuticals Incorporated is developing telaprevir in collaboration with Tibotec and Mitsubishi Tanabe Pharma.
Results from ADVANCE & ILLUMINATE
Overall in ADVANCE, 75% of people treated with a telaprevir-based combination regimen for 12 weeks, followed by an additional 12 or 36 weeks of pegylated-interferon and ribavirin alone, achieved SVR, compared to 44% of people treated with 48 weeks of pegylated-interferon and ribavirin alone. New data from this study showed that 62% of African Americans/Blacks achieved SVR with telaprevir compared to 25% of African Americans/Blacks who were treated with pegylated-interferon and ribavirin alone. Additionally, 62% of people with advanced liver fibrosis or cirrhosis (scarring of the liver) achieved SVR with telaprevir compared to 33% who were treated with pegylated-interferon and ribavirin alone.
Response-guided therapy was used in ADVANCE, whereby patients whose virus was undetectable at weeks 4 and 12 of treatment with telaprevir-based therapy were eligible to reduce their treatment time by half – from 48 weeks to 24 weeks. ILLUMINATE was designed to confirm both the use of response-guided therapy and to evaluate whether there was any benefit in extending therapy from 24 weeks to 48 weeks in people who met these criteria. In ADVANCE and ILLUMINATE, 58% and 65% of people, respectively, met these criteria for 24-week total treatment. In ILLUMINATE there was no benefit in extending therapy to 48 weeks.
In ILLUMINATE, 72% of people overall achieved SVR with telaprevir-based therapy. New data from this study showed that 60% of African Americans/Blacks and 63% of people with advanced liver fibrosis or cirrhosis achieved SVR with telaprevir-based therapy in the overall study analysis. Of African Americans/Blacks whose virus was undetectable at weeks 4 and 12, 88% of people achieved SVR in both the 24-week and 48-week randomized treatment arms. There was no control arm of pegylated-interferon and ribavirin alone in ILLUMINATE.
The safety and tolerability profile of telaprevir was consistent in both trials, with low discontinuation rates of all drugs during the telaprevir treatment phase due to adverse events.
“Less than half of people with the most common form of hepatitis C - genotype 1- achieve a viral cure with currently approved medicines, and factors such as race and extent of liver fibrosis can further limit cure rates to less than a third,” said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, at New York-Presbyterian Hospital/Weill Cornell Medical Center, and the Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College. “After treatment with telaprevir-based combination therapy in the ADVANCE study, 75% of people overall achieved a viral cure. Importantly, 62% of African Americans/Blacks and people with extensive liver disease achieved a viral cure – nearly twice as many as those who received pegylated-interferon and ribavirin alone.”
+ RVR: rapid viral response; undetectable (<25>
All patients received 12 weeks TVR combined with PEGASYS (PEG) and Copegus (RBV) plus either an additional 12 or 36 weeks with PEG/RBV alone.
* Reflects people whose hepatitis C virus was undetectable (<25>
Discontinuation (%) of all drugs during the telaprevir treatment phase
ADVANCE
12-week telaprevir
Industry updates: Oct 30, 2010
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from its Phase 3 studies of people with genotype 1 chronic hepatitis C who have not been treated previously. In these studies, the majority of people achieved superior sustained viral response (SVR or viral cure) rates with a telaprevir-based combination regimen, compared to current therapies, regardless of race/ethnicity or stage of liver fibrosis (factors known to limit response to current hepatitis C treatments). Patients in the ADVANCE and ILLUMINATE studies were given telaprevir with pegylated-interferon and ribavirin for the first 12 weeks of the studies, followed by treatment with pegylated-interferon and ribavirin alone for a total of either 24 weeks or 48 weeks based on their response to treatment at weeks 4 and 12. Final data from the Phase 3 ADVANCE and ILLUMINATE studies are being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which takes place in Boston October 29 to November 2.
“In our Phase 3 program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “The results of the ADVANCE and ILLUMINATE studies represent a major milestone in the development of telaprevir and offer hope for doctors and the millions of people living with hepatitis C who need new and more effective medicines.”
Vertex Pharmaceuticals Incorporated is developing telaprevir in collaboration with Tibotec and Mitsubishi Tanabe Pharma.
Results from ADVANCE & ILLUMINATE
Overall in ADVANCE, 75% of people treated with a telaprevir-based combination regimen for 12 weeks, followed by an additional 12 or 36 weeks of pegylated-interferon and ribavirin alone, achieved SVR, compared to 44% of people treated with 48 weeks of pegylated-interferon and ribavirin alone. New data from this study showed that 62% of African Americans/Blacks achieved SVR with telaprevir compared to 25% of African Americans/Blacks who were treated with pegylated-interferon and ribavirin alone. Additionally, 62% of people with advanced liver fibrosis or cirrhosis (scarring of the liver) achieved SVR with telaprevir compared to 33% who were treated with pegylated-interferon and ribavirin alone.
Response-guided therapy was used in ADVANCE, whereby patients whose virus was undetectable at weeks 4 and 12 of treatment with telaprevir-based therapy were eligible to reduce their treatment time by half – from 48 weeks to 24 weeks. ILLUMINATE was designed to confirm both the use of response-guided therapy and to evaluate whether there was any benefit in extending therapy from 24 weeks to 48 weeks in people who met these criteria. In ADVANCE and ILLUMINATE, 58% and 65% of people, respectively, met these criteria for 24-week total treatment. In ILLUMINATE there was no benefit in extending therapy to 48 weeks.
In ILLUMINATE, 72% of people overall achieved SVR with telaprevir-based therapy. New data from this study showed that 60% of African Americans/Blacks and 63% of people with advanced liver fibrosis or cirrhosis achieved SVR with telaprevir-based therapy in the overall study analysis. Of African Americans/Blacks whose virus was undetectable at weeks 4 and 12, 88% of people achieved SVR in both the 24-week and 48-week randomized treatment arms. There was no control arm of pegylated-interferon and ribavirin alone in ILLUMINATE.
The safety and tolerability profile of telaprevir was consistent in both trials, with low discontinuation rates of all drugs during the telaprevir treatment phase due to adverse events.
“Less than half of people with the most common form of hepatitis C - genotype 1- achieve a viral cure with currently approved medicines, and factors such as race and extent of liver fibrosis can further limit cure rates to less than a third,” said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, at New York-Presbyterian Hospital/Weill Cornell Medical Center, and the Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College. “After treatment with telaprevir-based combination therapy in the ADVANCE study, 75% of people overall achieved a viral cure. Importantly, 62% of African Americans/Blacks and people with extensive liver disease achieved a viral cure – nearly twice as many as those who received pegylated-interferon and ribavirin alone.”
* 12 weeks of telaprevir (TVR), Pegasys ® (PEG, pegylated-interferon alfa-2a) and Copegus ® (RBV, ribavirin) followed by 12 or 36 weeks of only PEG and RBV, based on response to treatment at week 4 and week 12
** 8 weeks of telaprevir (TVR) Pegasys (PEG, pegylated-interferon alfa-2a) and Copegus (RBV, ribavirin) followed by 16 or 40 weeks of only PEG and RBV, based on response to treatment at weeks 4 and 12
*** 48 weeks of PEG and RBV
** 8 weeks of telaprevir (TVR) Pegasys (PEG, pegylated-interferon alfa-2a) and Copegus (RBV, ribavirin) followed by 16 or 40 weeks of only PEG and RBV, based on response to treatment at weeks 4 and 12
*** 48 weeks of PEG and RBV
+ RVR: rapid viral response; undetectable (<25>
Relapse rates were 9% (27/314), 9% (28/295) and 28% (64/229) in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm, respectively
.
“Many patients today are not motivated to begin hepatitis C therapy given the year-long treatment time and low cure rates with approved therapies,” said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health. “Data from the ILLUMINATE study are extremely promising and showed that high viral cure rates and shorter treatment duration may be possible for the majority of people who have not been treated previously.
.
All patients received 12 weeks TVR combined with PEGASYS (PEG) and Copegus (RBV) plus either an additional 12 or 36 weeks with PEG/RBV alone.
* Reflects people whose hepatitis C virus was undetectable (<25>
” Additional Data at AASLD Results from the EXTEND study are also being presented at the meeting. EXTEND is a long-term follow-up study of patients who received telaprevir-based regimens in the PROVE Phase 2 clinical trials and was designed to evaluate whether people maintain their SVR (viral cure) over time and to observe changes in hepatitis C viral resistance variants in those telaprevir-treated patients who had not achieved SVR. The results showed that after an average of two years of follow-up, SVR rates with telaprevir were durable in 99% (122/123) of patients with SVR who took part in the trials. Among patients who did not achieve SVR and who had resistant variants at the start of the EXTEND study, 89% (50/56) no longer had detectable variants. Safety & Tolerability Results from ADVANCE and ILLUMINATE The safety and tolerability results of telaprevir-based combination regimens were consistent in the ADVANCE and ILLUMINATE studies. Treatment discontinuation rates of all drugs due to adverse events during the telaprevir treatment phase in the ADVANCE study were low in the telaprevir arms (7% to 8%) and the control arm (4%). The most common adverse events (>25% of people) reported in both studies, regardless of treatment arm, were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, influenza-like symptoms and pyrexia. The majority of these adverse events were mild to moderate.
To optimize each patient’s opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the drugs was recommended if discontinuation of treatment was necessary due to adverse events. Investigators were not required to discontinue the use of all three drugs at once, and, for example, patients may have continued on pegylated-interferon and ribavirin after discontinuing telaprevir only.
To optimize each patient’s opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the drugs was recommended if discontinuation of treatment was necessary due to adverse events. Investigators were not required to discontinue the use of all three drugs at once, and, for example, patients may have continued on pegylated-interferon and ribavirin after discontinuing telaprevir only.
Discontinuation (%) of all drugs during the telaprevir treatment phase
ADVANCE
12-week telaprevir
arm ...............................................7%
8-week telaprevir
8-week telaprevir
arm................................................. 8%
Control Arm.................................... 4%
ILLUMINATE*
Total .................................................7%
*There was no control arm in ILLUMINATE
In ADVANCE, discontinuation of telaprevir or placebo only due to adverse events during the telaprevir treatment phase occurred in 11% of people in the 12-week telaprevir arm, 7% of people in the 8-week telaprevir arm and 1% of people in the control arm. In ILLUMINATE, 12% of people overall discontinued telaprevir only due to adverse events during the telaprevir treatment phase.
Discontinuation of all drugs due to either rash or anemia was low in both studies (1% to 3%). Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. Ninety-two percent and 95% of rash was mild to moderate in ADVANCE and ILLUMINATE, respectively. Rash was managed with the use of topical corticosteroids and antihistamines, and anemia was primarily managed by reducing the dose of ribavirin. The use of erythropoiesis-stimulating agents (ESAs) were not allowed in any of the Phase 3 clinical studies.
Planned NDA Submission and Additional Phase 3 Analysis
Three Phase 3 studies, ADVANCE, ILLUMINATE and REALIZE will form the basis of the clinical portion of the telaprevir New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA), which is expected to be complete in the fourth quarter of 2010.
Phase 3 REALIZE Trial
REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
Control Arm.................................... 4%
ILLUMINATE*
Total .................................................7%
*There was no control arm in ILLUMINATE
In ADVANCE, discontinuation of telaprevir or placebo only due to adverse events during the telaprevir treatment phase occurred in 11% of people in the 12-week telaprevir arm, 7% of people in the 8-week telaprevir arm and 1% of people in the control arm. In ILLUMINATE, 12% of people overall discontinued telaprevir only due to adverse events during the telaprevir treatment phase.
Discontinuation of all drugs due to either rash or anemia was low in both studies (1% to 3%). Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. Ninety-two percent and 95% of rash was mild to moderate in ADVANCE and ILLUMINATE, respectively. Rash was managed with the use of topical corticosteroids and antihistamines, and anemia was primarily managed by reducing the dose of ribavirin. The use of erythropoiesis-stimulating agents (ESAs) were not allowed in any of the Phase 3 clinical studies.
Planned NDA Submission and Additional Phase 3 Analysis
Three Phase 3 studies, ADVANCE, ILLUMINATE and REALIZE will form the basis of the clinical portion of the telaprevir New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA), which is expected to be complete in the fourth quarter of 2010.
Phase 3 REALIZE Trial
REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
These data suggest that prior treatment response is a better predictor of SVR than a 1 log10 reduction at week 4 and that prospectively defined null responders and those patients with a less than 1 log10 reduction in HCV RNA at week 4 of a lead-in represent different patient populations. About the Telaprevir Development Program To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies.
Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously (ADVANCE and ILLUMINATE) as well as people who had been treated before but did not achieve a viral cure (REALIZE). A fact sheet on the Phase 3 telaprevir development program is available at http://www.vrtx.com/aasld2010.html
Phase 3 ADVANCE Trial The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naïve patients. The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. As part of a response-guided design, people in the telaprevir-based treatment arms who had undetectable HCV RNA at weeks 4 and 12 of treatment were eligible to receive a total of 24 weeks therapy. Patients who did not meet the response-guided criterion but were undetectable at week 24, received 48 weeks of total therapy.
Phase 3 ILLUMINATE Trial The ILLUMINATE trial was a supplemental Phase 3 study designed to evaluate whether there was any benefit in extending therapy from 24 to 48 weeks in people whose hepatitis C was undetectable at weeks 4 and 12 of therapy. The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups, evaluated by a non-inferiority analysis.
Phase 3 REALIZE Trial REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. About Hepatitis C Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and blood of people with the disease.2
According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, 4,5,6 or viral cure.1 Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11 Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
About Vertex Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with other pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline. Lexiva is a registered trademark of the GlaxoSmithKline group of companies. PEGASYS® and COPEGUS® are a registered trademarks of Hoffman-La Roche. References: 1 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40. 2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010. 3 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed.
Updated January 11, 2010. Accessed May 25, 2010. 4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965. 5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982. 6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593. 7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115). 8 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW.
Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521. 9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755. 10 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684. 11 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm .
Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc. 12 Picchio G, et al. Discrepancies between definitions of null response to treatment with peginterferon alfa-2a and ribavirin: Implications for new HCV drug development. [poster 289]. In: Program and Abstracts of the 2010 International Liver Conference by the European Association for the Study of Liver Disease. . Athens, Greece: April 2010. 13 United States Food and Drug Administration.
Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral .
Updated
September 14, 2010. Accessed September 14, 2010. Special Note Regarding Forward-looking Statements This press release contains forward-looking statements, including statements regarding (i) the data from ILLUMINATE being extremely promising and (ii) the expectation that the Company’s NDA for telaprevir will be completed in the fourth quarter of 2010. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that Vertex could experience unforeseen delays in submitting the NDA for telaprevir and/or obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; that future outcomes from clinical trials of telaprevir may not be favorable; and that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based combination therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex’s website at http://www.vrtx.com/ /. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN)
AASLD:Telaprevir/Boceprevir/Similar Cure Rates/Shorter Treatment Duration
Vertex, Merck Drugs Help More with Faster Cure for Hepatitis C in Studies
By Michelle Fay Cortez
-
Bloomberg Great Site For Up To Date News On HCV Drugs
Oct 30, 2010 9:00 AM ET
Vertex Pharmaceuticals Inc. and Merck & Co. said their experimental drugs for hepatitis C cured more patients than traditional treatment, and many people were able to take a shorter, less toxic course of therapy.
Telaprevir
Two-thirds of patients given Vertex’s telaprevir were able to cut their treatment time in half to six months, and about 90 percent were cured, two studies funded by the Cambridge, Massachusetts-based company found.
Boceprevir
Nearly half of those given boceprevir in studies from Whitehouse Station, New Jersey-based Merck were able to reduce their treatment times to six months to nine months, with similar high rates of cure.
The findings presented today at the American Association for the Study of Liver Disease meeting in Boston will help usher in a new era of treatment for hepatitis C, doctors say. The chronic condition affects nearly 4 million Americans and 200 million people worldwide, according to the National Institutes of Health. The companies plan to file for U.S. regulatory approval of the drugs by the end of the year.
“The current standard of care is long and it’s not easy to take,” said Michael Charlton, director of the Mayo Clinic’s liver transplant program in Rochester, Minnesota. “The appeal of the new drugs is the shorter treatment, and you get there quicker with telaprevir,” he said in a telephone interview.
Standard Treatment
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over time. Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. The yearlong treatment causes aches and pains similar to the flu that may last the entire year of treatment and cures about half of those who can tolerate it.
Roche Holding AG of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck sells a form called PegIntron.
Telaprevir will capture about three-fourths of the demand for the new medicines, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview. The drug, which Vertex is developing with New Brunswick, New Jersey-based Johnson & Johnson, will generate about $2.6 billion annually by 2013, he said.
http://www.bloomberg.com/news/2010-10-30/vertex-merck-drugs-help-more-with-faster-cure-for-hepatitis-c.html
By Michelle Fay Cortez
-
Bloomberg Great Site For Up To Date News On HCV Drugs
Oct 30, 2010 9:00 AM ET
Vertex Pharmaceuticals Inc. and Merck & Co. said their experimental drugs for hepatitis C cured more patients than traditional treatment, and many people were able to take a shorter, less toxic course of therapy.
Telaprevir
Two-thirds of patients given Vertex’s telaprevir were able to cut their treatment time in half to six months, and about 90 percent were cured, two studies funded by the Cambridge, Massachusetts-based company found.
Boceprevir
Nearly half of those given boceprevir in studies from Whitehouse Station, New Jersey-based Merck were able to reduce their treatment times to six months to nine months, with similar high rates of cure.
The findings presented today at the American Association for the Study of Liver Disease meeting in Boston will help usher in a new era of treatment for hepatitis C, doctors say. The chronic condition affects nearly 4 million Americans and 200 million people worldwide, according to the National Institutes of Health. The companies plan to file for U.S. regulatory approval of the drugs by the end of the year.
“The current standard of care is long and it’s not easy to take,” said Michael Charlton, director of the Mayo Clinic’s liver transplant program in Rochester, Minnesota. “The appeal of the new drugs is the shorter treatment, and you get there quicker with telaprevir,” he said in a telephone interview.
Standard Treatment
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over time. Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. The yearlong treatment causes aches and pains similar to the flu that may last the entire year of treatment and cures about half of those who can tolerate it.
Roche Holding AG of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck sells a form called PegIntron.
Telaprevir will capture about three-fourths of the demand for the new medicines, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview. The drug, which Vertex is developing with New Brunswick, New Jersey-based Johnson & Johnson, will generate about $2.6 billion annually by 2013, he said.
http://www.bloomberg.com/news/2010-10-30/vertex-merck-drugs-help-more-with-faster-cure-for-hepatitis-c.html
AASLD:TMC435 PILLAR study in treatment-naive patients/ genotype 1
Week-24 Interim Results From Phase 2b PILLAR Study to be Presented as Late-Breaker at AASLD
- Data show high antiviral activity, safety and tolerability comparable to placebo
BOSTON, Oct. 30 /PRNewswire/ -- Tibotec Pharmaceuticals (Tibotec) announced today the company will present the results of a Week-24 planned interim analysis of the phase 2 response-guided PILLAR study in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA., USA. The data will be presented as part of a late-breaker oral presentation on Monday, November 1.
The results showed that in the four TMC435 treatment groups between 79 and 86 percent of patients were able to stop all therapy at Week-24, according to the response criteria defined in the study protocol. There were no relevant differences for adverse events between TMC435 treatment groups and placebo. TMC435, a hepatitis C protease inhibitor, dosed once daily (q.d.) is being developed jointly by Tibotec Pharmaceuticals and Medivir.
The PILLAR study [Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen] (TMC435-C205; NCT00882908) is an ongoing, five-arm, global phase 2b randomized, double-blind, placebo controlled study in 386 treatment-naive patients. TMC435 was administered in doses of 75mg or 150mg q.d. for either 12 weeks or 24 weeks in combination with 24 weeks of peg-interferon and ribavirin (PR). Patients in the placebo arm receive 24 weeks of placebo plus peg-interferon and ribavirin followed by 24 additional weeks of peg-interferon and ribavirin treatment. The primary endpoint of the study is sustained virologic response at Week-72 (SVR24). The PILLAR study is being conducted in 13 countries in Europe, North America, and Australasia.
- Data show high antiviral activity, safety and tolerability comparable to placebo
BOSTON, Oct. 30 /PRNewswire/ -- Tibotec Pharmaceuticals (Tibotec) announced today the company will present the results of a Week-24 planned interim analysis of the phase 2 response-guided PILLAR study in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA., USA. The data will be presented as part of a late-breaker oral presentation on Monday, November 1.
The results showed that in the four TMC435 treatment groups between 79 and 86 percent of patients were able to stop all therapy at Week-24, according to the response criteria defined in the study protocol. There were no relevant differences for adverse events between TMC435 treatment groups and placebo. TMC435, a hepatitis C protease inhibitor, dosed once daily (q.d.) is being developed jointly by Tibotec Pharmaceuticals and Medivir.
The PILLAR study [Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen] (TMC435-C205; NCT00882908) is an ongoing, five-arm, global phase 2b randomized, double-blind, placebo controlled study in 386 treatment-naive patients. TMC435 was administered in doses of 75mg or 150mg q.d. for either 12 weeks or 24 weeks in combination with 24 weeks of peg-interferon and ribavirin (PR). Patients in the placebo arm receive 24 weeks of placebo plus peg-interferon and ribavirin followed by 24 additional weeks of peg-interferon and ribavirin treatment. The primary endpoint of the study is sustained virologic response at Week-72 (SVR24). The PILLAR study is being conducted in 13 countries in Europe, North America, and Australasia.
Patients receiving TMC435 were allowed to stop all treatment at week 24 when a) HCV RNA levels less then 25 IU/mL at week 4 and b) HCV RNA < 25 IU/mL levels at weeks 12, 16 and 20. Patients who did not meet the above response-guided criteria continued with peg-interferon and ribavirin until Week-48. TMC435 demonstrated potent antiviral activity, at week 4 (rapid virologic response (RVR)) and at week 12 (complete early virologic response (cEVR)) HCV RNA was undetectable (<25IU/ml) for the majority of patients. The viral breakthrough rate was 4.9 percent in the TMC435 treatment groups.
"Chronic infection with HCV is a leading cause of cirrhosis, liver cancer, and liver transplantation worldwide," said Dr Michael W. Fried M.D., lead clinical investigator and Professor of Medicine, Director of Hepatology, University of North Carolina at Chapel Hill. "We are extremely encouraged by these data for TMC435."
The goal of HCV treatment is to achieve SVR24, which means the virus remains undetectable in patients' blood six months after they have finished treatment. Patients who achieve SVR are considered cured. The current standard of care for HCV, pegylated interferon combined with ribavirin, may cause debilitating side effects(1) and cures only about half of patients starting therapy for the first time.(1)
The most common adverse events were headache and fatigue, 46 percent and 42 percent in the TMC435 groups and 51 percent and 47 percent in the placebo group respectively. There were no clinically significant differences in frequency of rash, anemia or gastrointestinal events between the TMC435 groups and placebo. Most AEs were mild to moderate in severity. AEs leading to treatment discontinuation were reported in 7.1 percent of patients in TMC435 arms and 7.8 percent in placebo arm.
In laboratory parameters, significant decreases in transaminases (ALT and AST) were observed in all treatment groups. Small and transient bilirubin elevations (direct and indirect) were seen in the TMC435 150mg dose groups.
"With a strong heritage in virology, Tibotec is committed to improving the lives of those impacted by HCV through the development of innovative new treatment regimens," said Greg Fanning PhD, head of hepatitis C research and development at Tibotec. "TMC435 is an important component of our growing HCV pipeline and we are encouraged by the results of the interim analysis presented at the AASLD meeting."
TMC435 is also being studied in HCV genotype-1 treatment-experienced patients who have failed treatment with peg-interferon and ribavirin. The ASPIRE study (Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients; TMC435-C206; NCT00980330) is an ongoing global phase 2b randomized, double-blind, placebo controlled study in 463 patients.
In addition to the late-breaker oral presentation described above, data on TMC435 has been presented in 4 posters at AASLD:
278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." M.T. Huisman
812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." O. Lenz
895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2–6." C. Moreno
1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." V. Sekar
About HCV
HCV is a blood-borne infectious disease that affects the liver.(1) With an estimated 170 million people infected worldwide(1) and three to four million people newly infected each year,(2) HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant worldwide.(3) Discovering and developing new treatments is very important to improving the standard of care for the millions of people living with this disease.
About Tibotec Pharmaceuticals
Tibotec Pharmaceuticals is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need. Tibotec Pharmaceuticals is a subsidiary of Johnson & Johnson.
(1) World Health Organization (2002). Hepatitis C. Retrieved October 26, 2010 from http://www.who.int/csr/disease/hepatitis/Hepc.pdf.
(2) Hepatitis C: Global Prevalence. Weekly Epidemiological Record. 1997;72 : 341-8. Retrieved October 26, 2010 from http://www.who.int/docstore/wer/pdf/1997/wer7246.pdf.
(3) Roche B, Samuel D., Villejuif, France. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat. 2007 Nov;14. Suppl 1:89-96
"Chronic infection with HCV is a leading cause of cirrhosis, liver cancer, and liver transplantation worldwide," said Dr Michael W. Fried M.D., lead clinical investigator and Professor of Medicine, Director of Hepatology, University of North Carolina at Chapel Hill. "We are extremely encouraged by these data for TMC435."
The goal of HCV treatment is to achieve SVR24, which means the virus remains undetectable in patients' blood six months after they have finished treatment. Patients who achieve SVR are considered cured. The current standard of care for HCV, pegylated interferon combined with ribavirin, may cause debilitating side effects(1) and cures only about half of patients starting therapy for the first time.(1)
The most common adverse events were headache and fatigue, 46 percent and 42 percent in the TMC435 groups and 51 percent and 47 percent in the placebo group respectively. There were no clinically significant differences in frequency of rash, anemia or gastrointestinal events between the TMC435 groups and placebo. Most AEs were mild to moderate in severity. AEs leading to treatment discontinuation were reported in 7.1 percent of patients in TMC435 arms and 7.8 percent in placebo arm.
In laboratory parameters, significant decreases in transaminases (ALT and AST) were observed in all treatment groups. Small and transient bilirubin elevations (direct and indirect) were seen in the TMC435 150mg dose groups.
"With a strong heritage in virology, Tibotec is committed to improving the lives of those impacted by HCV through the development of innovative new treatment regimens," said Greg Fanning PhD, head of hepatitis C research and development at Tibotec. "TMC435 is an important component of our growing HCV pipeline and we are encouraged by the results of the interim analysis presented at the AASLD meeting."
TMC435 is also being studied in HCV genotype-1 treatment-experienced patients who have failed treatment with peg-interferon and ribavirin. The ASPIRE study (Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients; TMC435-C206; NCT00980330) is an ongoing global phase 2b randomized, double-blind, placebo controlled study in 463 patients.
In addition to the late-breaker oral presentation described above, data on TMC435 has been presented in 4 posters at AASLD:
278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." M.T. Huisman
812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." O. Lenz
895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2–6." C. Moreno
1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." V. Sekar
About HCV
HCV is a blood-borne infectious disease that affects the liver.(1) With an estimated 170 million people infected worldwide(1) and three to four million people newly infected each year,(2) HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant worldwide.(3) Discovering and developing new treatments is very important to improving the standard of care for the millions of people living with this disease.
About Tibotec Pharmaceuticals
Tibotec Pharmaceuticals is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need. Tibotec Pharmaceuticals is a subsidiary of Johnson & Johnson.
(1) World Health Organization (2002). Hepatitis C. Retrieved October 26, 2010 from http://www.who.int/csr/disease/hepatitis/Hepc.pdf.
(2) Hepatitis C: Global Prevalence. Weekly Epidemiological Record. 1997;72 : 341-8. Retrieved October 26, 2010 from http://www.who.int/docstore/wer/pdf/1997/wer7246.pdf.
(3) Roche B, Samuel D., Villejuif, France. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat. 2007 Nov;14. Suppl 1:89-96
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