“Gilead is first to throw its hat into direct to consumer marketing for hepatitis C.”
February 24, 2014
Celsion Announces FDA Clearance of the OPTIMA Study - A Pivotal Phase III Trial of ThermoDox in Primary Liver Cancer
Feb. 24, 2014, 8:00 a.m. EST
--Study Developed in Consultation with Clinical Advisors, Statistical Experts and FDA --Compelling Survival Data Supports Development --Trial Advances Global Regulatory Strategy in Key Markets
LAWRENCEVILLE, N.J., Feb. 24, 2014 /PRNewswire/ -- Celsion Corporation CLSN -0.27% announced today that the U.S. Food and Drug Administration (FDA) has reviewed and provided clearance for the Company's planned pivotal, double-blind, placebo-controlled Phase III trial of ThermoDox®, its proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radio frequency ablation (RFA) in primary liver cancer, also known as hepatocellular carcinoma (HCC). The trial design is based on a comprehensive analysis of data from the Company's Phase III HEAT Study, which demonstrated that treatment with ThermoDox resulted in a 55% improvement in overall survival in a substantial number of HCC patients that received an optimized RFA treatment. Celsion expects to launch the study in the first half of 2014.
The Phase III trial, known as the OPTIMA Study, was designed with extensive input from globally recognized HCC researchers and clinicians, and after formal consultation with FDA. The OPTIMA Study is expected to enroll 550 patients globally, with up to 100 sites in the United States, Europe, China and Asia Pacific and will evaluate ThermoDox in combination with RFA, which will be standardized to a minimum of 45 minutes across all investigators and sites for treating lesions 3 to 7 centimeters, versus standardized RFA alone. The primary endpoint for the trial is overall survival (OS). The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).
"ThermoDox appears to hold great promise as a first-line treatment when used in combination with optimized RFA, for primary liver cancer, one of the most deadly and prevalent forms of cancer worldwide," stated Nicholas Borys, MD, Celsion's Chief Medical Officer. "Consistency of the retrospective data emerging from the HEAT Study over the past year has been remarkable, and underscores the potential of ThermoDox to extend survival in primary liver cancer patients. Now informed by critical insights from our HEAT Study, I am confident that the OPTIMA Study is robust, well-designed and well-supported by HCC researchers worldwide. We look forward to initiation and timely completion of this important study."
As reported in January 2014, post-hoc data from the Company's HEAT Study demonstrate that the patient subgroup in the ThermoDox arm whose RFA procedure lasted longer than 45 minutes (285 patients or 63% of single lesion patients), experienced a 55% improvement in overall survival, with a Hazard Ratio of 0.64 (95% CI 0.41 - 1.00) and a P-value = 0.0495. Median overall survival for this subgroup has not yet been reached. Celsion will continue to follow patients in the HEAT Study on a quarterly basis.
"FDA allowance of the Phase III OPTIMA Study represents a significant step forward in our global development strategy for ThermoDox and establishes a clear regulatory pathway that advances our goal of delivering a new treatment option to patients with this devastating and underserved disease," stated Michael H. Tardugno, Celsion's President and CEO. "In parallel with our efforts in the United States, we continue to advance discussions with regulators in other important global markets, including a recent positive meeting with China FDA (CFDA) and near-term plans to meet with European regulatory authorities."
In support of the Company's global regulatory efforts, Celsion recently met with CFDA to discuss the Phase III trial, including minimum patient enrollment requirements supporting ThermoDox's registration in China. Based on those discussions, Celsion is submitting an application for accelerated approval of the study in China. Celsion will expand its clinical site footprint in Europe and plans to meet with the European Medicines Agency (EMA) in the first half of 2014.
The HEAT Study and prior post-hoc analyses were presented at three medical conferences in 2013, including the World Conference on Interventional Oncology in May; the European Conference on Interventional Oncology in June and the International Liver Cancer Association Annual Conference in September. Presentations were made by some of the most highly recognized liver cancer researchers and key HEAT Study investigators. Quarterly overall survival data analyses have been conducted with the full support of these researchers and clinical investigators.
About Celsion Corporation
Celsion is dedicated to the development and commercialization of innovative cancer drugs, including tumor-targeting treatments using focused heat energy in combination with heat-activated liposomal drug technology. Celsion has research, license or commercialization agreements with leading institutions, including the National Institutes of Health, Duke University Medical Center, University of Hong Kong, the University of Pisa, the UCLA Department of Medicine, the Kyungpook National University Hospital, the Beijing Cancer Hospital and the University of Oxford. For more information on Celsion, visit our website: http://www.celsion.com .
Celsion wishes to inform readers that forward-looking statements in this release are made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Readers are cautioned that such forward-looking statements involve risks and uncertainties including, without limitation, unforeseen changes in the course of research and development activities and in clinical trials; the uncertainties of and difficulties in analyzing interim clinical data, particularly in small subgroups; FDA and regulatory uncertainties and risks; the significant expense, time, and risk of failure of conducting clinical trials; HEAT Study data is subject to further verification and review by the HEAT Study Data Management Committee; the need for Celsion to evaluate its future development plans; possible acquisitions or licenses of other technologies, assets or businesses or the possible failure to make such acquisitions or licenses; possible actions by customers, suppliers, competitors, regulatory authorities; and other risks detailed from time to time in the Celsion's periodic reports and prospectuses filed with the Securities and Exchange Commission. Celsion assumes no obligation to update or supplement forward-looking statements that become untrue because of subsequent events, new information or otherwise.
Celsion Investor Contact Jeffrey W. ChurchSr. Vice President and CFO609firstname.lastname@example.org
SOURCE Celsion Corporation
Joint Gladstone-UCSF Study Highlights Novel Reprogramming Method, Offers New Hope for Treating Liver Failure
By Jeff Norris and Anne Holden on February 23, 2014
The power of regenerative medicine now allows scientists to transform skin cells into cells that closely resemble heart cells, pancreas cells and even neurons. However, a method to generate cells that are fully mature—a crucial prerequisite for life-saving therapies—has proven far more difficult. But now, scientists at the Gladstone Institutes and UC San Francisco have made an important breakthrough: they have discovered a way to transform skin cells into mature, fully functioning liver cells that flourish on their own, even after being transplanted into laboratory animals modified to mimic liver failure.
Holger Willenbring, MD, PhD
In previous studies on liver-cell reprogramming, scientists had difficulty getting stem cell-derived liver cells to survive once being transplanted into existing liver tissue. But the Gladstone-UCSF team figured out a way to solve this problem. Writing in the latest issue of the journal Nature, researchers in the laboratories of Gladstone Senior Investigator Sheng Ding, PhD, and UCSF Associate Professor Holger Willenbring, MD, PhD, reveal a new cellular reprogramming method that transforms human skin cells into liver cells that are virtually indistinguishable from the cells that make up native liver tissue.
These results offer new hope for the millions of people suffering from, or at risk of developing, liver failure—an increasingly common condition that results in progressive and irreversible loss of liver function. At present, the only option is a costly liver transplant. So, scientists have long looked to stem cell technology as a potential alternative. But thus far they have come up largely empty-handed.
Sheng Ding, PhD
“Earlier studies tried to reprogram skin cells back into a pluripotent, stem cell-like state in order to then grow liver cells,” explained Ding, one of the paper’s senior authors, who is also a professor of pharmaceutical chemistry at UCSF, with which Gladstone is affiliated. “However, generating these so-called induced pluripotent stem cells, or iPS cells, and then transforming them into liver cells wasn’t always resulting in complete transformation. So we thought that, rather than taking these skin cells all the way back to a pluripotent, stem cell-like state, perhaps we could take them to an intermediate phase.”
This research, which was performed jointly at the Roddenberry Center for Stem Cell Research at Gladstone and the Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, involved using a ‘cocktail’ of reprogramming genes and chemical compounds to transform human skin cells into cells that resembled the endoderm. Endoderm cells are cells that eventually mature into many of the body’s major organs—including the liver.
“Instead of taking the skin cells back to the beginning, we took them only part way, creating endoderm-like cells,” added Gladstone and CIRM Postdoctoral Scholar Saiyong Zhu, PhD, one of the paper’s lead authors. “This step allowed us to generate a large reservoir of cells that could more readily be coaxed into becoming liver cells.”
Next, the researchers discovered a set of genes and compounds that can transform these cells into functioning liver cells. And after just a few weeks, the team began to notice a transformation.
“The cells began to take on the shape of liver cells, and even started to perform regular liver-cell functions,” said UCSF Postdoctoral Scholar Milad Rezvani, MD, the paper’s other lead author. “They weren’t fully mature cells yet—but they were on their way.”
Now that the team was encouraged by these initial results in a dish, they wanted to see what would happen in an actual liver. So, they transplanted these early-stage liver cells into the livers of mice. Over a period of nine months, the team monitored cell function and growth by measuring levels of liver-specific proteins and genes.
Two months post-transplantation, the team noticed a boost in human liver protein levels in the mice, an indication that the transplanted cells were becoming mature, functional liver cells. Nine months later, cell growth had shown no signs of slowing down. These results indicate that the researchers have found the factors required to successfully regenerate liver tissue.
“Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising,” added Willenbring, associate director of the UCSF Liver Center and the paper’s other senior author. “In the future, our technique could serve as an alternative for liver-failure patients who don’t require full-organ replacement, or who don’t have access to a transplant due to limited donor organ availability.”
Other scientists who participated in this research include UCSF researchers Jack Harbell, MD, also a lead author on the paper, as well as Aras Mattis, MD, PhD, Alan Wolfe and Leslie Benet, PhD. Funding was provided by the following: the California Institute for Regenerative Medicine, the National Institutes of Health, the German Academic Exchange Service, and the Society of University Surgeons.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with UCSF.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital.
February 24, 2014
BOSTON — Although HIV will dominate the agenda at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), related viruses and infections will also be in the limelight.
Several presentations at the conference, being held from March 3 to 6, will focus on advances in the treatment of hepatitis C virus and the barriers to delivery, and the latest developments in tuberculosis (TB) and human papillomavirus.
Lynn Taylor, MD, from the division of infectious diseases at Miriam Hospital, Brown Medical School, in Providence, Rhode Island, told Medscape Medical News that developments in drugs and policy on the hepatitis C front make this year's discussion particularly important.
"We have seen extraordinary, unprecedented improvement in therapies to cure hep C," she said. "We have the potential to eradicate hep C locally, nationally, globally. The focus of our panel is that there's nothing in place yet, on any significant scale, to enhance delivery."
Dr. Taylor described a "crisis" in the United States because baby boomers who never knew they were infected are now discovering it in advanced form. "Seventy-five percent of Americans who have hep C don't even know they have it," she said.
“Ten years ago, you were considered a charlatan if you said hep C was curable.”
Last year, because of the prevalence of hepatitis C in baby boomers, the Centers for Disease Control and Prevention revised its guidelines to recommend a 1-time screening for everyone born from 1945 to 1965, in addition to risk-based screening. In December 2013, the European Association for the Study of the Liver revised its clinical practice guidelines on the management of hepatitis C; they will be presented in April before the International Liver Congress.
Dr. Taylor said she is "thrilled" to see the increased attention on hepatitis C at the conference.
"Ten years ago, you were considered a charlatan if you said hep C was curable," she said.
The conference, the most significant HIV research meeting in the world, will attract more than 4000 leading international HIV/AIDS researchers. The goal is to provide a forum for researchers to translate their findings into direct progress in HIV.
Conference to Draw More Than 4000 Researchers
Last year's conference was abuzz with the news that a 2-year-old Mississippi girl, born with HIV and treated early with antiretroviral drugs, had been functionally cured and no longer had detectable levels of the virus, despite not taking medication for 10 months.
This year, speakers will provide updates on the progress toward a cure for HIV, and look at what is standing in the way of getting there.
Adeeba Kamarulzaman, MBBS, from the University of Malaya in Kuala Lumpur, Malaysia, said she will explain some positive changes for drug users in the HIV fight in countries such as Malaysia.
She will also speak about the impact of the "epidemic of incarceration" and its effects on HIV, as well as coinfection with TB and hepatitis C, she told Medscape Medical News. She will highlight the increase in methamphetamine use and its relation to HIV risk behaviors, particularly in men who have sex with men.
TB is also getting attention at the conference. There will be presentations on the resistance, persistence, monitoring, and control of the disease; the use of novel imaging technology to monitor treatment response; and population-level control of HIV-related TB.
The prevention and treatment of HIV infection in infants will be addressed, as will the short- and long-term consequences of antiretroviral exposure during pregnancy and breast-feeding.
In addition, the outbreak of invasive meningococcal disease that affected men who have sex with men in New York City from 2010 to 2013 will be discussed.
Infectious Disease Special Edition
ISSUE: FEBRUARY 2014 | VOLUME: 1
by Kate O'Rourke
Many clinicians are ecstatic about the recent approval of sofosbuvir (Sovaldi, Gilead Sciences) for patients with hepatitis C virus (HCV) infection. At The Liver Meeting 2013, several presentations provided new insight into just how sofosbuvir will perform in clinical practice.
“I think sofosbuvir is the cat’s meow,” said Sammy Saab, MD, MPH, professor of medicine and surgery and head of outcomes research in hepatology at the David Geffen School of Medicine, University of California, Los Angeles.
“It’s a drug that has no resistance or incremental adverse effects. It is very well tolerated, very safe, very efficacious and there are no significant drug interactions with it. I think it is going to revolutionize the way we treat hepatitis in this country and around the world.”
Traditional Risk Factors Fade Away
According to studies presented at The Liver Meeting, many factors traditionally thought to portend poor outcomes in HCV patients may not have an effect with sofosbuvir. One study was a retrospective analysis of 982 patients with HCV infection (genotypes 1-6) in four Phase III trials: FISSION, POSITRON, FUSION and NEUTRINO. Patients were treated with sofosbuvir plus ribavirin, with or without pegylated interferon (IFN). Sustained virologic response (SVR) rates were analyzed according to gender, age (<65 vs. ≥65 years), interleukin-28 B (IL28B) genotype, body mass index (<30 vs. ≥30 kg/m2), race (black vs. non-black), viral load (HCV RNA <107 vs. ≥107 copies/mL), opiate replacement status and cirrhosis. Of these factors, only male gender and the presence of cirrhosis were consistently predictive of worse outcomes; the difference between cirrhotics and noncirrhotics existed but was not large. In the NEUTRINO trial, for example, 80% of cirrhotics versus 92% of noncirrhotics achieved SVR at week 12. Also, IL28B genotype status was only predictive of SVR in the NEUTRINO trial.
Sofosbuvir in combination with ribavirin also works well and causes less toxicity than IFN-based regimens in HCV patients who are coinfected with HIV. In the PHOTON-1 trial, 182 treatment-naive patients with HCV genotype 1, 2 or 3 and stable HIV disease, some of whom had cirrhosis, were evaluated. SVR rates at week 12 were 81% in HCV genotype 2 patients and 67% in HCV genotype 3 patients. Among the 19 patients not acheiving SVR at week 12, relapse was confirmed in 12 patients and data were missing for six patients. HCV genotype 1 patients received 24 weeks of treatment and had an SVR rate of 76%. Sofosbuvir was coadministered effectively with multiple HIV antiretroviral regimens, including inhibitors of HIV-1 protease, reverse transcriptase and integrase; it had no adverse effect on HIV status or antiretroviral therapy.
“The IFN-free regimen of sofosbuvir plus ribavirin resulted in high SVR 12 rates in HCV treatment-naive, HIV-infected patients with HCV genotype 1, 2 or 3 coinfection,” said Mark Sulkowski, MD, medical director of the Viral Hepatitis Center in the Divisions of Infectious Diseases and Gastroenterology & Hepatology, and professor of medicine at the Johns Hopkins School of Medicine, in Baltimore, who presented the study. “SVR 12 rates were similar to those observed in patients with HCV mono-infection.”
Data from the COSMOS trial suggested that HCV genotype 1 null responders may be a lot easier to treat with the combination of sofosbuvir plus simeprevir (Olysio, Janssen) than with first-generation direct-acting antiviral agents. In this Phase II trial, investigators evaluated 167 patients in two cohorts. In cohort 1, patients with METAVIR scores of F0 to F2 who were prior null responders to IFN with ribavirin received 12 or 24 weeks of treatment with sofosbuvir plus simeprevir, with or without ribavirin. In an intent-to-treat (ITT) analysis of the data, these patients achieved SVR rates at week 12 of 79% to 96%. Cohort 2 included treatment-naive patients and prior null responders with METAVIR scores of F3 to F4; they received 12 weeks of treatment with sofosbuvir plus simeprevir, with or without ribavirin. These patients achieved SVR rates at week 4 of 96% to 100%, based on an ITT analysis. The treatments were characterized as generally well tolerated.
“The findings in this interim analysis suggest that the addition of ribavirin to simeprevir plus sofosbuvir may not be needed to achieve high rates of SVR in this patient population,” said Ira Jacobson, MD, chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medical College, New York City, who presented the data. “Anemia and bilirubin increases were predominantly limited to the ribavirin-containing treatment arms.”
Results from the LONESTAR-2 trial echoed results of other trials showing the high efficacy of sofosbuvir in prior null responders and patients with cirrhosis. This trial tested 12 weeks of treatment with sofosbuvir plus pegylated IFN and ribavirin in treatment-experienced patients with HCV genotype 2 or 3 infection. HIV and HBV coinfected patients were excluded from the trial, but 50% of the study population had compensated cirrhosis. In patients with HCV genotype 2 (n=23), 93% of cirrhotics and 100% of noncirrhotics achieved SVR at week 12. In HCV genotype 3 patients, the presence of cirrhosis did not affect outcomes, and 83% of patients achieved SVR at week 12.
“Sofosbuvir plus pegylated IFN/ribavirin for 12 weeks demonstrated high efficacy in treatment-experienced genotype 2/3 patients who have historically low response rates and limited treatment options,” said Eric Lawitz, MD, vice president of scientific and research development at The Texas Liver Institute and clinical professor of medicine at the San Antonio University of Texas Health Science Center, who presented the study. “SVR rates were similar in patients with and without cirrhosis.”
Different Treatment Duration for Patients With HCV Genotypes 2 and 3
Although many of the traditional factors that predict treatment response in HCV patients do not seem to apply to sofosbuvir, there does seem to be a difference in response among HCV genotypes. In general, clinicians are accustomed to treating patients with HCV genotype 2 or 3 similarly, but these two groups respond differently to sofosbuvir.
In Phase III trials, response rates have been higher in patients with HCV genotype 2 after 12 weeks of treatment with sofosbuvir plus ribavirin. The VALENCE trial originally set out to test 12 weeks of treatment with sofosbuvir plus ribavirin in patients with HCV genotype 2/3, but investigators amended the trial after recognizing that the two types of patients might respond to treatment differently; the 250 patients with HCV genotype 3 ultimately received 24 weeks of treatment. Among genotype 3 patients without cirrhosis, response rates were 94% in treatment-naive patients and 87% in treatment-experienced patients; genotype 3 patients with cirrhosis had response rates of 60%.
More evidence that longer therapy is better for HCV genotype 3 patients came from data presented at a meeting of the FDA Sofosbuvir Review team on Oct. 25.
“The FDA did an elegant analysis of the effect of treatment duration with sofosbuvir–ribavirin in genotype 3–infected patients,” Dr. Sulkowski said. “[They] presented very convincing data that a 24-week duration of sofosbuvir–ribavirin should be the standard for all genotype 3–infected patients.”
The FDA analysis combined data from the FISSION, POSITRON, FUSION and VALENCE trials. In both treatment-naive and treatment-experienced patients with HCV genotype 3, SVR rates dramatically rose and relapse rates fell when treatment was increased from 12 weeks to 24 weeks (Table).
As a result, when the FDA approved sofosbuvir in December, the agency approved a 12-week treatment regimen in patients with HCV genotype 2 and a 24-week regimen in patients with genotype 3, both in combination with ribavirin. The FDA also approved a 12-week regimen of sofosbuvir in combination with ribavirin and IFN for patients with HCV genotypes 1 and 4.
Dr. Saab has served as a consultant and on the speakers’ bureaus for Boehringer Ingelheim, Genentech, Gilead Sciences, Janssen, Merck, and Vertex Pharmaceuticals. Dr. Sulkowski has received consulting fees from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck and Vertex. Dr. Jacobson has received grants or research support and has served as a member of a speaker’s bureau or as a consultant/advisor for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Idenix Pharmaceuticals, Janssen, Merck, Novartis, Roche/Genentech and Vertex. Dr. Lawitz has served on advisory committees or review panels for AbbVie, Achillion, BioCryst Pharmaceuticals, Biotica, Enanta, Idenix, Janssen, Merck, Novartis, Santaris, Theravance and Vertex; he has received grant and research support form AbbVie, Achillion, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Idenix, Intercept, Janssen, Merck, Novartis, Presidio, Roche, Santaris Pharma and Vertex.
Bristol-Myers Squibb Receives U.S. FDA Breakthrough Therapy Designation for All-Oral Daclatasvir Dual Investigational Regimen for Chronic Hepatitis C
- FDA grants Designation request for investigational daclatasvir (DCV) and asunaprevir (ASV) combination therapy for treatment of genotype 1b chronic hepatitis C (HCV) infection
- Marks second Breakthrough Therapy Designation for a daclatasvir-based regimen; 3DAA regimen granted Designation in 2013
Monday, February 24, 2014 8:30 am EST
"The FDA’s decision to grant Breakthrough Therapy Designation for our DCV Dual Regimen (daclatasvir and asunaprevir combination therapy) marks the second time that the FDA has granted the Designation to a daclatasvir-based regimen, further underscoring its potential to help address the high unmet needs of the HCV patient population"
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that the U.S. Food and Drug Administration (FDA) has granted its investigational DCV Dual Regimen (daclatasvir and asunaprevir) Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b chronic hepatitis C infection (HCV). The designation is based on data from the company’s ongoing Phase III clinical trial program evaluating the all-oral combination regimen of DCV, an investigational NS5A replication complex inhibitor, and ASV, an investigational NS3 protease inhibitor, without ribavirin.
According to the FDA, Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
“The FDA’s decision to grant Breakthrough Therapy Designation for our DCV Dual Regimen (daclatasvir and asunaprevir combination therapy) marks the second time that the FDA has granted the Designation to a daclatasvir-based regimen, further underscoring its potential to help address the high unmet needs of the HCV patient population,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “This is an important milestone for Bristol-Myers Squibb as we continue our strategic focus on the development of innovative medicines to address areas of high unmet medical need, where potential expedited review can make a critical difference for patients.”
Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the U.S. Many of these people have been living with HCV for decades, putting them at heightened risk for developing serious, potentially life-threatening liver disease.
New data from Bristol-Myers Squibb’s ongoing Phase III clinical program studying the DCV Dual Regimen is anticipated to be presented at an upcoming scientific forum. Data from a separate daclatasvir and asunaprevir Phase III trial in Japanese patients with HCV genotype 1b who were either interferon-ineligible/intolerant or non-responders (null and partial) to interferon-based therapies served as the basis for a regulatory filing in Japan in October 2013.
Bristol-Myers Squibb also recently announced that the European Medicines Agency (EMA) validated the company’s marketing authorization application (MAA) for the use of daclatasvir for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4. The application seeks the approval of daclatasvir for use in combination with other agents for the treatment of chronic hepatitis C and will be reviewed under an accelerated regulatory review.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, 20 percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer.
About Bristol-Myers Squibb’s HCV Portfolio
Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as a foundational agent for multiple direct-acting antiviral (DAA) based combination therapies.
In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/ asunaprevir/BMS-791325) received FDA Breakthrough Therapy Designation, which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic treatment naïve and experienced patients, as well as cirrhotic treatment naïve and experienced patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.
In addition, enrollment has begun for the Phase III ALLY Program, in which daclatasvir in combination with sofosbuvir, is being studied in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients and patients infected with HCV genotype 3.
Other compounds in the pipeline include:
- Asunaprevir (ASV) is an investigational NS3 protease inhibitor for hepatitis C which has been studied as a component of DCV-based treatment regimens
- BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase III development for hepatitis C as a component of DCV-based treatment regimens
- Peginterferon lambda is an investigational type III interferon that has the potential to offer an alternative to peginterferon alfa in patients for whom an interferon-based regimen is required or preferred
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that DCV or any other compounds mentioned in this release will receive regulatory approval or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Bristol-Myers Squibb Company
Ranya Dajani, 609-252-5330
Ryan Asay, 609-252-5020
Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients
J Hepatol. 2014 Mar;60(3):530-7. doi: 10.1016/j.jhep.2013.11.009. Epub 2013 Nov 19.
BACKGROUND & AIMS: Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75-80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens.
METHODS: A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs).
RESULTS: Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of $15,709/QALY at baseline cost of oral therapy. The ICER remained below $50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease.
CONCLUSIONS: Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.
Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
KEYWORDS: BOC, CHC, CMS, Centers for Medicare and Medicaid Services, Cost-effectiveness analysis, DAA, F0, F1, F2 or F4, GT, HCV, HIV, ICER, IFN, IFN, BV, DAA, Interferon-free oral treatment, Markov model, NADAC, National Average Drug Acquisition Cost, QALYs, RBV, SVR, TVR, Triple therapy, WAC, boceprevir, chronic hepatitis C, direct, acting antiviral agent, genotype, hepatitis C, immunodeficiency virus, incremental cost, effectiveness analysis, mild fibrosis, moderate or advanced fibrosis, pegylated, interferon alpha, quality, adjusted life years (a standard metric that incorporates both length and quality of life), ribavirin, sustained virologic response, telaprevir, wholesale acquisition cost
PMID: 24269472 [PubMed - in process]