Liver Cancer Drug;FDA Approves Special Protocol Assessment for Phase 3 Trial of Polaris Group's Cancer Therapeutic, ADI-PEG 20
FDA Approves Special Protocol Assessment for Phase 3 Trial of Polaris Group's Cancer Therapeutic, ADI-PEG 20, in the Treatment of Hepatocellular Carcinoma
Polaris Set to Advance Novel Therapeutic Targeting Cancer Metabolism to Pivotal Studies
Ghassan Abou-Alfa, M.D., of Memorial Sloan-Kettering Cancer Center in New York, is the principal investigator of the study.
"ADI-PEG 20 has demonstrated medical benefit in prior studies in multiple indications with a remarkable safety profile," said Dr. Abou-Alfa. "I am delighted to lead this study to explore ADI-PEG 20 as a viable option for patients with advanced liver malignancies."
SPA is a mechanism that allows the FDA and drug developers to reach an agreement prior to study initiation about the design and size of a Phase 3 trial. It will form the primary basis of an efficacy claim in a marketing application.
"The SPA agreement with the FDA is a key step in our plans for the clinical development of ADI-PEG 20," said John Bomalaski, M.D., executive vice president, medical affairs, of Polaris. "We are pleased to move ADI-PEG 20 into a pivotal Phase 3 trial and to be working with such well-established hepatocellular carcinoma experts."
Leo Chen, M.D., the lead investigator of the Phase 2 HCC study in Taiwan, stated, "Our Phase 2 study demonstrated that ADI-PEG 20 was effective and well-tolerated in patients with advanced liver cancer, and we look forward to the opportunity to further assess the efficacy and safety of this drug in a large randomized Phase 3 study."
The lead investigator in China, Shukui Qin, M.D., president of the Chinese Society of Clinical Oncology and chair of the Chinese Liver Cancer Study Group, added, "Approximately half of the liver cancer-related deaths in the world are in China. We have been watching the development of this drug, and we are excited to become an active participant in this pivotal global study."
ADI-PEG 20 is a biologic being developed to treat cancers carrying a major metabolic defect that renders them, unlike normal cells, unable to make arginine internally. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, these cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 works by systemically depleting the external supply of arginine and causes these arginine-dependent cancer cells to die while leaving the normal cells unharmed.
In addition to HCC, multiple other cancers have been reported to have a high degree of arginine-dependency. Early-to-mid-stage clinical trials have yielded positive results in patients with metastatic melanoma, and Phase 2 trials for small cell lung cancer (SCLC) and mesothelioma are currently ongoing. Polaris also plans to initiate clinical studies in prostate cancer, pancreatic cancer, leukemia, lymphoma and sarcoma this year.
About Hepatocellular Carcinoma
Hepatocellular carcinoma (primary liver cancer) is one of the most common cancers worldwide, resulting in approximately 700,000 deaths annually. Infection with hepatitis B or C and alcohol consumption are highly associated with the development of hepatocellular carcinoma. The prognosis for patients with this disease is poor as chemotherapy often does not result in prolonged survival, and liver transplantation only increases the survival of selected patients. Despite all forms of current treatment, life expectancy for most patients is only one year post-diagnosis.
About Polaris Group
Polaris Group is a privately held multinational biopharmaceutical company that specializes in the research and development of protein drugs to treat cancer and other debilitating diseases. The company's lead therapeutic, ADI-PEG 20, is advancing into a pivotal Phase 3 trial for hepatocellular carcinoma. Polaris is also investigating ADI-PEG 20 as a treatment for other arginine-dependent cancers, such as melanoma, prostate cancer, leukemia, lymphoma, sarcoma and pancreatic cancer. In addition to the ADI-PEG 20 project, Polaris is researching and developing other biotherapeutic agents and has a small molecule drug program that utilizes rational structure-based approach to design novel compounds that inhibit the biological function of cancer-related protein targets.
Listed as Recruiting @ http://www.clinicaltrials.gov/
Click Here For Trial Information and Locations; PSI-7977 With Pegylated Interferon and Ribavirin Hepatitis C Virus (HCV) Genotypes 1,4,5,6 (ATOMIC)
The purpose of this study is to assess the safety, tolerability, and efficacy of PSI-7977 administered in combination with pegylated interferon and ribavirin (PEG/RBV) in treatment naive patients with HCV genotypes 1,4,5,6, or indeterminate genotype.
Updated/April 8th ; Verified on April 2011 by Pharmasset
Click Here For Trial Information and Locations; Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3 Condition: Chronic Hepatitis C
Intervention: Drug: PSI-7977 with ribavirin (RBV) with and without Pegylated Interferon (PEG-IFN)
Pharmasset Initiates Phase 2b ATOMIC Trial of PSI-7977 for Multiple HCV Genotypes
PRINCETON, N.J., March 30, 2011 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that screening has begun in a Phase 2b study of PSI-7977, a nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (HCV).
"The trial will evaluate PSI-7977 400mg QD with pegylated interferon and ribavirin in patients with HCV genotype 1, 4, 5 or 6 who have not been treated previously."
"We are encouraged by the early efficacy and safety data being generated with our nucleotide analogs, PSI-7977 and PSI-938," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "The ATOMIC trial is designed to explore 12 and 24 week durations of PSI-7977. The potency, high barrier to resistance, and consistent antiviral activity across genotypes provided the data to support an interferon free dosing period in this trial, as well as enabling us to enroll multiple genotypes in this trial."
About the Phase 2b ATOMIC Trial
This Phase 2b trial is planned to enroll approximately 300 patients with chronic HCV genotype 1 who have not been treated previously. The primary endpoint of the trial will be the safety and tolerability of PSI-7977 in combination with peginterferon and ribavirin over 12 or 24 weeks. The trial will be conducted in the U.S. Patients will be randomized (1:2:3) into the following arms:
PSI-7977 400mg QD with peginterferon and ribavirin for 12 weeks;
PSI-7977 400mg QD with peginterferon and ribavirin for 24 weeks;
PSI-7977 400mg QD with peginterferon and ribavirin for 12 weeks, followed by either PSI-7977 400mg QD monotherapy for 12 weeks or PSI-7977 400mg QD plus ribavirin for 12 weeks.
HCV GT1 patients will be stratified by IL28B status and baseline HCV RNA to ensure balance across cohorts. An additional 25 treatment-naïve patients with HCV genotype 4, 5, 6 or indeterminate genotype, will receive PSI-7977 400mg QD with peginterferon and ribavirin for 24 weeks.
Additional details on this and all Pharmasset trials can be found at http://www.clinicaltrials.gov/
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates. Mericitabine (RG7128, MCB), a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys® plus Copegus® and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys® and Copegus®, all conducted through a strategic collaboration with Roche. PSI-7977 is our unpartnered uracil nucleotide analog currently dosing in three Phase 2 studies in patients with HCV genotypes 1 through 6, including studies with abbreviated duration or no interferon. PSI-938 is our unpartnered guanosine nucleotide analog which recently completed a 14-day monotherapy and combination study with PSI-7977. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Pegasys® and Copegus® are registered trademarks of Roche.
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 613-4181
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
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OctoPlus' licensee Biolex presents Phase IIb results at EASL showing reduced rates of depression in HCV patients treated with Locteron
* Reuters is not responsible for the content in this press release.
Thu Mar 31, 2011 3:46am EDT
Locteron's next-generation controlled-release mechanism is designed to provide key tolerability and dosing advantages over currently marketed interferons
Locteron may address one of the most significant side effects associated with the use of current interferon products in the treatment of HCV
OctoPlus N.V. ("OctoPlus" or the "Company") (Euronext: OCTO) announces that its licensee Biolex Therapeutics will present today final results from the Locteron® Phase IIb clinical study at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. These data show substantially reduced rates of depression in patients treated with Locteron, compared to current HCV treatments.
Jan Egberts, CEO of OctoPlus, comments: "These positive final results from the Phase IIb clinical study with Locteron further confirm the long term benefits of Locteron's controlled release mechanism and even show a significant advantage in depression related side effects. Our PolyActive technology has enabled the development of an interferon alpha with a significantly improved side effect profile, achieving both a 50% reduction in flu-like adverse events and substantially lower rates of depression, compared to conventional interferon treatments. In combination with its reduced injection frequency, these benefits clearly position Locteron as the interferon of choice for future hepatitis C treatments."
The following information was taken directly from Biolex' press release (see http://www.biolex.com/ ).
Results demonstrating reduced rates of depression from its SELECT-2 Phase 2b trial of Locteron® for the treatment of hepatitis C are being presented today at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. In SELECT-2, patients treated with Locteron within the expected commercial dose range experienced substantially lower rates of depression and depressive symptoms than patients treated with the PEG-Intron® control. Locteron, the only controlled-release interferon alpha, is designed to offer key tolerability and dosing advantages over currently marketed pegylated interferons and serve as a core component of new combination therapies as the treatment of hepatitis C evolves to triple- and quad-drug regimens.
In a survey of hepatitis C patients published in the Journal of Viral Hepatitis in 2010, depression was cited as the number one adverse event impacting patient adherence to treatment, and studies have shown that patients who develop depression during treatment have a reduced chance of achieving a cure. The expected progression of treatment for hepatitis C to triple and quad regimens with potentially shorter durations of treatment are unlikely to eliminate the problem of depression as the SELECT-2 results presented today show that the majority of all episodes of depression occur by the 12th week of treatment.
Locteron is administered once every other week and requires half as many injections as the currently marketed pegylated interferons, each of which are injected once per week. In SELECT-2, three different doses of Locteron were studied (320, 480 and 640 µg). All three doses of Locteron in SELECT-2 demonstrated viral kinetics and sustained virologic response (SVR) rates that were comparable with or exceeded the PEG-Intron control while also achieving a statistically significant reduction in flu-like adverse events and lower use of concomitant medications. The Company expects the commercial dose of Locteron to be in the 320 to 480 µg range as the SVR rates for these two doses were comparable with or exceeded the control, and the tolerability advantages (including lower discontinuation rates due to adverse events) were greatest within this dose range.
In SELECT-2, depression was assessed by two methods, including patient self reporting using a validated instrument and adverse event assessment performed by medical personnel at the clinical sites during weekly visits by the patients. The SELECT-2 results demonstrated that patients experienced depression early in the study, with 75% of cases occurring within the first 12 weeks of the trial under each of the reporting methodologies. Under both reporting methodologies, depression was less frequent for the Locteron doses encompassing the expected commercial dose range compared to the PEG-Intron control.
Throughout the 48 weeks of treatment in SELECT-2, patients self reported their status using the Beck Depression Inventory (BDI), one of the most widely used instruments for measuring the severity of depression. Higher BDI scores indicate more severe depressive symptoms. Mean BDI scores peaked by week 12 of treatment for all Locteron doses and for the PEG-Intron control group. The increase in peak mean BDI scores was substantially less for all three Locteron doses compared to the PEG-Intron group. In addition, the results demonstrated that fewer patients reported scores greater than 16 using the BDI (the threshold for mild depression) in the 320 and 480 µg Locteron dose groups compared to the PEG-Intron group.
Click on the link below for the full press release including tables.
Click here for the press release in PDF format
EASL;CTS-1027 Plus Pegasys/Riba geno 1 null-responder 24-week interim results in hepatitis C patients
Conatus Pharmaceuticals Presents Results From a Phase 2 Clinical Trial of CTS-1027 in HCV Genotype 1 Null-Responders
By Conatus Pharmaceuticals Inc.
Published: Thursday, Mar. 31, 2011 - 12:08 pm
SAN DIEGO, March 31, 2011 -- /PRNewswire/ -- Conatus Pharmaceuticals Inc. announced today 24-week interim results from a clinical trial with CTS-1027 in combination with Peginterferon Alpha-2a (Pegasys®) and ribavirin (Copegus®) in a treatment experienced, hepatitis C virus (HCV) null-responder patient population. Null-responder patients are the most difficult to treat patient population and are clinically defined as those patients failing to achieve an early virologic response (EVR) when undergoing treatment with the current standard of care (SOC; pegylated interferon and ribavirin). EVR is defined as at least a 2 log decline in HCV-RNA by week 12 of SOC treatment. The CTS-1027-04 clinical trial enrolled 67 HCV genotype 1 null-responder patients. The clinical trial is a single arm and open label design with sustained viral response (SVR; no detectable virus 24 weeks after the end of treatment) as its primary end point. At week 12, 51% (31/61) of patients receiving 15 mg twice a day of CTS-1027 in addition to standard doses of Pegasys® and Copegus® achieved an EVR on a per protocol (PP) basis. HCV-RNA was below quantifiable limit (BQL) in 5 patients (8.2%, PP) at week 12 and increased to 17 patients (34%, 17/50, PP) at week 24. This clinical trial is ongoing and final SVR results are expected in 2011.
Data from the CTS-1027-04 clinical trial were presented at the 46th annual meeting of the European Association for the Study of the Liver (EASL) held in Berlin, Germany, as Abstract 468. The full abstract is available at http://www.conatuspharma.com/ .
Consistent with expectations, the majority of patients tested for genetic analysis of IL-28B (95%, 58/61) carried the CT or TT allelic variant. Patients possessing these genetic variants are predicted to be less responsive to the antiviral actions of interferon.
"Most other approaches to treat HCV infection are direct-acting anti-viral drugs whose activity is directed against virus proteins or enzymes with the objective of reducing the production of virus in infected cells. CTS-1027, by comparison, is distinctly different in that its activity is hypothesized to facilitate the immune clearance of virus-infected cells and decrease the frequency of new infections, both of which are of key importance in curing HCV infections," said Alfred P. Spada, Ph.D., Senior Vice President of R & D of Conatus.
"Clearance of infected cells is a slow but essential process to achieving a sustained viral response. It is intriguing to observe this significant improvement in viral load reduction at such a low dose of CTS-1027. A recently initiated Phase 2b clinical trial (CTS-1027-05) will test CTS-1027 at higher doses in combination with Pegasys® and Copegus® in the null-responder patient population," said Steven J. Mento, Ph.D., President and CEO of Conatus.
Conatus Pharmaceuticals Inc. is a privately-held biopharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease and oncology. Conatus' lead drug candidate, CTS-1027 is in multiple Phase 2 clinical trials for the treatment of hepatitis C virus (HCV). Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the sale of Idun to Pfizer. For additional information, please visit www.conatuspharma.com.
Pegasys® and Copegus® are registered trademarks of F. Hoffman-La Roche, Inc.
SOURCE Conatus Pharmaceuticals Inc.
New Data Suggests Liver Experts Should Exercise Caution When Prescribing Novel Antiviral HCV Drugs
Data presented at the International Liver CongressTM highlight the fact that new novel antiviral compounds for the treatment of hepatitis C virus (HCV) must be prescribed and monitored by experts and specialists to ensure resistance is minimised.1,2,3,4,5,6
Several studies observed the rapid onset of HCV resistance in patients treated with NS3-protease, NS5b-polymerase and NS5a inhibitors. Although these direct anti-virals are effective in both treatment-naive HCV patients and those who've been previously unresponsive to current treatment options, the development of resistant viral variants may cause problems in the future. In fact, two studies found HCV strains resistant to novel antiviral compounds pre-existed in patients who had never previously been exposed to the new antiviral compounds. In these patients, the variants were selected out by treatment.
Professor Heiner Wedemeyer, EASL's Secretary General, said: "While the regulatory approval of these new treatments is a highly anticipated milestone in HCV therapy, these studies show that care must be taken in the prescription and use of the new compounds. What we want to avoid is a rapid spread of HCV resistance within the patient population, which could drastically lower the effectiveness of the new drugs."
The current standard of care for chronic HCV is the combination of pegylated interferon-alfa and ribavirin, but only 40-54% of patients infected with HCV genotype 1 achieve a sustained virological response (SVR).7,8 Novel antiviral therapeutics are much sought after to treat patients who don't respond to the current standard of care. As such, a large number of new drugs for HCV are at various stages of preclinical and clinical development.9
However, as each new copy of the HCV genome exhibits - on average - one nucleotide change per replication cycle, HCV's replication machinery allows the virus to quickly come up with mutations that render it resistant to antiviral drugs. This is a major concern for successful anti-HCV therapy. 10
NS3 protease inhibitors block the function of the HCV NS3 protease, an enzyme essential for HCV's replication. NS5A replication complex inhibitors block the function of HCV nonstructural protein 5A, a multifunctional protein essential for HCV replication.10
1 McPhee F et al. Charactarizaion of virologic escape in HCV gentotype 1 null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052. Abstract presented at The International Liver CongressTM 2011
2 Chevaliez S et a. Molecular characterization of HCV resistance to telaprevir by means of ultra-deep pyrosequencing: pre-existing resistant variants and dynamics of resistant populations. Abstract presented at The International Liver CongressTM 2011
3 Hebner C et al. Emergence and persistence of ns5b mutations following combination treatment with tegobuvir (gs-9190) plus standard of care--long-term follow-up from the phase iib study gs-us-196-0103. Abstract presented at The International Liver CongressTM 2011
4 Zeuzem S et al. Boceprevir Resistance-Associated Variants (RAVs) are observed more frequently in HCV (gt1)-infected Patients with poor response to peginterferon alfa- 2B/ribavirin. Abstract presented at The International Liver CongressTM 2011 (1621)
5 Svarovskaia E et al. Abundant minority drug-resistant ns3 mutants detected by deep sequencing in hcv patients as early as 24 hours after initiating antiviral treatment. Abstract presented at the international liver congresstm 2011 (1773)
6 Sullivan J et al. Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials. (1783)
7 Fried M.W et al. "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection." New England Journal of Medicine 347.13 (2002): 975-82
8 Hadziyannis S J et al. "Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C - A randomized study of treatment duration and ribavirin dose." Annals of Internal Medicine 140.5 (2004): 346-55.
9 Shiffman M L. "Treatment of hepatits C in 2011:what can we expect?" Curr.Gastroenterol.Rep. 12 (2010): 70-75
10 Raffaele De Francesco and Giovanni Migliaccio (2005). Challenges and successes in developing new therapies for hepatitis C. Nature, 436, 953-960
The International Liver Congress
Investigational Direct-Acting Antiviral BMS-790052 Plus PEG-Interferon Alfa and Ribavirin Achieved Up to 92% Sustained Virologic Response in Phase II Dose-Ranging Study of Treatment-Naïve Hepatitis C Patients
Adverse event profile of regimen containing BMS-790052 was consistent with that of treatment with PEG-Interferon alfa and ribavirin alone
PRINCETON, N.J.--(BUSINESS WIRE)--Mar 31, 2011 -
Bristol-Myers Squibb Company (NYSE: BMY) today announced results from a Phase II clinical trial in which treatment with the investigational direct-acting antiviral (DAA) BMS-790052, an NS5A replication complex inhibitor, in combination with PEG-Interferon alfa and ribavirin (RBV), achieved sustained virologic response 12 weeks post-treatment (SVR12) in up to 92% of treatment-naïve patients chronically infected with hepatitis C (HCV) genotype 1 (10 mg dose arm, n=12). Adverse events and serious adverse events were consistent with those reported in the PEG-Interferon alfa and ribavirin arm and were comparable across all doses of BMS-790052. These data were reported today for the first time in a late-breaker poster session at the International Liver Congress, the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.
“There currently exists a medical need for new medicines or new combinations of medicines for hepatitis C patients as many hepatitis C patients have limited success on the currently available treatments,” said Stanislas Pol, MD, PhD, Professor of Hepatology at Université Paris V (René Descartes), Paris, France and head of the Hepatology unit at Cochin Hospital, Paris, France. “The results of this study warrant further clinical investigation of adding Bristol-Myers Squibb's investigational compound BMS-790052 to the current medicines to evaluate its potential to address this unmet treatment need.”
The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR) defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. BMS-790052 plus PEG-interferon alfa and ribavirin achieved higher rates of SVR12 compared to PEG-interferon alfa and ribavirin alone, across all BMS-790052 treatment groups [BMS-790052: 60 mg: 83% (10/12 patients), 10 mg: 92% (11/12 patients), 3 mg: 42% (5/12 patients); PEG-interferon alfa/RBV: 25% (3/12 patients)].
Adverse events (AEs) and serious adverse events (SAEs) were comparable across study arms and were consistent with the safety profile of PEG-Interferon alfa and ribavirin therapy. Four patients discontinued due to AEs in the BMS-790052 60 mg group for a diverse set of adverse events. All four patients had undetectable viral load at the time of study discontinuation and three of these patients achieved SVR12. No new on-treatment SAEs were reported beyond study week 24.
Grade 3 to 4 adverse events for BMS-790052 treatment groups and placebo were BMS-790052: 60 mg: 33.3%, 10 mg: 25%, 3 mg: 8.3%; PEG-interferon alfa/RBV: 41.7%. Two patients (one receiving 3 mg BMS-790052 and one receiving 60 mg BMS-790052) experienced anemia (hemoglobin <9 g/dL). Erythropoietin use was comparable between BMS-790052 treatment groups (one to three patients per arm) and the placebo treatment group (two patients). The use of filgrastim (G-CSF) in the study groups was: BMS-790052: 60 mg: 0%, 10 mg: 25%, 3 mg: 16.7%; PEG-interferon alfa/RBV: 16.7%. Other adverse events, occurring in at least four patients (33.3%) in any cohort include: fatigue (BMS-790052: 60 mg: 50%,10 mg: 50%, 3 mg: 58.3%; placebo: 75%), neutropenia (BMS-790052: 60 mg: 16.7%,10 mg: 33.3%, 3 mg: 25%; placebo: 41.7%), nausea (BMS-790052: 60 mg: 33.3%,10 mg: 33.3%, 3 mg: 41.7%; placebo: 50%), vomiting (BMS-790052 60 mg: 33.3%, 10 mg: 8.3%, 3 mg: 16.7%; placebo: 0%), and headache (BMS-790052: 60 mg: 25%, 10 mg: 75%, 3 mg: 58.3%; placebo: 25%).
About the Study
This double-blind study randomized 48 treatment-naïve HCV genotype 1-infected patients 1:1:1:1 (n=12/arm) to receive one of three doses of BMS-790052 (3 mg, 10 mg, or 60 mg) or placebo once daily, in combination with PEG-interferon alfa-2a and ribavirin for 48 weeks. The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR) defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. Primary endpoint data were previously reported at EASL 2010 in Vienna, Austria.
Discovered by Bristol-Myers Squibb through a genomics approach, BMS-790052 is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C. BMS-790052 is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials. BMS-790052 is currently in Phase II development.
About Hepatitis C1
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with blood. An estimated 170 million people worldwide are infected with hepatitis C. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, 20 percent will progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a curable disease.
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 the compound described in this release will move from exploratory development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. 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, 2010, 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.
1 World Health Organization. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html.
Accessed March 9, 2011.
Contact: Bristol-Myers Squibb Company
Cristi Barnett, 609-252-6028
John Elicker, 609-252-4611
New Drugs for Hepatitis C on the Horizon
With the promise of two new drugs to fortify the current treatment protocol, doctors see promise of a better-tailored cocktail, similar to HIV treatments, to beat back this common and often debilitating infection
By Katherine Harmon
March 30, 2011
Some 3.2 million Americans have chronic hepatitis C, an infection that can linger in the body for years before producing symptoms. It can eventually lead to serious liver scarring and cancer. And most infections in the U.S. are the disease's particularly tough breed, known as genotype 1, which has a cure rate of less than 40 percent with the best current treatment.
Two new drugs for this type, however, are now racing toward approval by the U.S. Food and Drug Administration, which could come as soon as late May. Both compounds are protease inhibitors and are expected to hit the market at about the same time. At EASL, the european liver meeting I am at some striking news about other drugs will emerge today & I will report it later today.
Hepatitis C is spread through contact with blood and occasionally other bodily fluids, and 65 to 70 percent of people infected with the disease are unaware that they have it, according to John Ward, director of the Division of Viral Hepatitis at the U.S. Centers for Disease Control and Prevention. In the U.S. about one in 30 baby boomers has hepatitis C, and one in four people with HIV has the infection, he noted at a 2010 talk. The disease is responsible for some $33.3 billion in medical costs each year.
"We've been waiting for these drugs for a long time," says Darryn Potosky, a hepatologist at the University of Maryland Medical Center, who often has to tell patients they face steep odds of beating the disease.
If the new drugs come to market, patients would take one or the other in addition to the current two-drug treatment regimen. "It seems hepatitis C therapy is moving in the direction of HIV therapy, with multiple drug cocktails," Potosky says. And with that come "hopes that we can tailor treatments to patients."
Two new studies of one of the drugs, boceprevir, will be published in the March 31 issue of the New England Journal of Medicine. Both phase III trials were funded by Schering-Plough (now part of Merck), which makes the drug. There have not yet been any studies comparing boceprevir and the other new protease inhibitor, telaprevir (made by Vertex), but given the drugs' similarity, experts say they both seem promising.
In the new boceprevir trials, adding the drug to the current standard treatment (of interferon and ribavirin) effectively doubled the percentage of patients who were able to suppress the virus-an effect called sustained viral response, which is a mark of being effectively "cured."
"Patients with hepatitis C genotype 1 infection can anticipate a significant therapeutic advance," says Donald Jensen, a professor of medicine at the University of Chicago Medical Center, who wrote an editorial on the new research for the same issue of NEJM. But because these new drugs will each need to be used in combination with the existing two-drug regimes, they "will be associated with more side effects and more complexity."
Long road to safety
Doctors have long hoped for a safe and effective drug to beat hepatitis C (HCV) genotype 1-which, among strains of the disease, is "the most common and the hardest to treat at the same time," Potosky says. Some 70 to 80 percent of people infected with hepatitis C in the U.S. have this type.
With excitement building for these new drugs to arrive in the market, those who have been working on the problem have not forgotten that getting to this point "has been painstakingly slow," says Stuart Gordon of Henry Ford Hospital in Detroit, who coauthored one of the new studies.
Just finding the right compounds was challenging, he notes. An early protease-inhibitor contender, made by Boehringer Ingelheim, was found to be too toxic, and "many of the HCV polymerase inhibitors had to stop their development because of unacceptable side effects," Gordon notes.
And because the new treatment regime must be shown to be better than the current standard of care, which is a 48-week course, "the sheer time involved in conducting these large trials" made for slow going. But a payoff might be near.
One new trial, of 1,097 patients with hepatitis C genotype 1 who had never been treated, found that after 24 or 44 weeks of adding boceprevir to their drug regimen some two-thirds of non-black patients showed they were effectively suppressing the virus. The drug combo was not as effective for black patients, who are less likely to have a gene alteration that is linked to responsiveness to one of the drugs. But adding boceprevir still boosted response rates in these patients from 23 percent to more than half in the 44-week treatment group.
In the other trial, 403 patients with the disease who had not responded to traditional treatment-either showing no improvement or relapsing-were studied. Adding boceprevir to the standard treatment for 32 or 44 weeks resulted in sustained viral response rates in 59 and 66 percent of patients, respectively, compared with 38 percent in the control group.
The studies were both somewhat unusual in that they started patients out with a month-long lead-in period in which patients received the two drugs already available-before boceprevir was introduced to some groups. This "allowed some prediction capability of both subsequent response as well as risk of developing resistant variants," Jensen explains.
Early studies showed that although a protease inhibitor given on its own was very effective initially, it often led to resistant strains of the virus in a matter of days, Gordon says. Even with interferon and ribavirin, resistance "remains a concern," he says. To keep it to a minimum, "clinicians must follow such patients very closely during therapy because if the viral level starts to rise after initially declining, then the protease inhibitor must be stopped to prevent the development of even more resistant strains."
Potosky notes that the extent of resistance will only become clear with time-and as more people take the new drugs. And just as they monitor HIV patients for telltale resistance patterns, doctors should be able to detect early signs of resistance in people being treated for hepatitis C as well.
Adding boceprevir also increased the amount of side effects patients experienced. More than 40 percent of subjects taking this third drug required treatment for anemia in one of the studies, and in the other, severe anemia led doctors to decrease dosage in some 20 percent of subjects. Even though some of these cases were serious, few patients dropped out of treatment.
With boceprevir and telaprevir likely in the home stretch to reach potentially millions of hepatitis C patients in the U.S., doctors and researchers are now turning their focus to the many challenges that remain.
Aside from keeping resistance low and dialing down side effects, the next steps are to try to simplify the treatment regimen. "Everyone wants to get rid of interferon and ribavirin because both have toxicity that make them often difficult to tolerate," Gordon notes. Interferon also currently is usually administered via injection, so moving to an all-oral, once-a-day dosing would make treatment better and more consistent.
Gordon also looks forward to finding ways to help special populations of patients, including those who have HIV, end-stage liver disease or renal disease, as well as children, "who are currently not eligible for our current therapies."
From the New York Journal Of Medicine
Related A Better Way to Unbind Prometheus? Boceprevir for the Treatment of Chronic Hepatitis C Infection
EASL Telaprevir Improved SVR Rates in People Whose Prior Treatment For Hepatitis C Was Unsuccessful
EASL; EARLY RESULTS SHOW BENEFITS IN USING ACUTE KIDNEY INJURY CRITERIA (AKIN) FOR THE DIAGNOSIS OF CIRRHOTIC PATIENTS
Early results show benefits in using acute kidney injury criteria (AKIN) for the diagnosis of cirrhotic patients
EARLY RESULTS SHOW BENEFITS IN USING ACUTE KIDNEY INJURY CRITERIA (AKIN) FOR THE DIAGNOSIS OF CIRRHOTIC PATIENTS
Recent study may change future approach to diagnosis
Berlin, Germany, 31 March 2011: The first clinical study investigating the use of the AKIN criteria (Acute Kidney Injury Network) in cirrhosis has shown significant benefits that have the potential to change future diagnosis, according to results from a Spanish study1 presented today at the International Liver CongressTM. As screening and differential diagnosis is becoming increasingly important in relation to managing health service provision, if these results are confirmed in larger studies, the AKIN criteria has the potential to replace current screening and diagnosis criteria in hospitalised cirrhotic patients. This prospective study aimed to assess the value of the AKIN criteria in predicting outcomes in hospitalised cirrhotic patients.
Out of 300 patients admitted to hospital for complications of cirrhosis 88 (29%) developed renal failure according to the AKIN criteria. Three-month survival of these patients was 38%, compared with 87% of patients who did not develop renal failure (p< 0.01). Renal failure in cirrhosis is currently defined as serum creatinine greater than 1.5 mg/dL. According to the study investigators this definition has two shortcomings: firstly it represents a very low glomerular filtration rate (GFR), and secondly it may not detect significant changes in GFR because it does not take into account variations in creatinine values. In contrast, the AKIN criteria is much more sensitive and considers renal failure as an increase in serum creatinine greater than or equal to a 0.3ml/dL (≥50% increase) compared to baseline within 48 hours. Mark Thursz, EASL’s Vice-Secretary commented: “Liver disease is associated with a high mortality due to renal failure, especially in end stage cirrhosis. As experts and clinicians in the field of hepatology, defining more sensitive tests that help to identify patients at risk of renal failure or death earlier is critical to enable us to intervene and ensure the patient has the best possible outcome”.
Furthermore, when the AKIN criteria were combined with the current definition of renal failure, patients meeting the AKIN criteria in whom serum creatinine reached a peak value of >1.5 mg/dL (n=60) had a significantly lower survival compared to patients with a peak value ≤ 1.5 mg/dL (n=28) (29% vs 58%, respectively; p=0.026). Out of the 300 patients, 30 patients had serum creatinine >1.5 mg/dL but did not meet the AKIN criteria. However, three-month survival of these patients was 80%.
EASL; Fluvastatin Enhances Chronic Hepatitis C Treatment Response In Combination With Pegylated Interferon-Alpha And Ribavirin
Fluvastatin Enhances Chronic Hepatitis C Treatment Response In Combination With Pegylated Interferon-Alpha And Ribavirin
First Vaccine for Viral Hepatitis C Could Become a Reality
FLUVASTATIN ENHANCES CHRONIC HEPATITIS C TREATMENT RESPONSE IN COMBINATION WITH PEGYLATED INTERFERON-ALPHA AND RIBAVIRIN
Well-known statin could be recycled as HCV therapy supplement
Berlin, Germany, Thursday 31 March 2011: /PRNewswire/ — New data presented today at the International Liver CongressTM confirm the antiviral activity of fluvastatin – commonly used as a cholesterol-lowering treatment – in patients with chronic hepatitis C (HCV).1
Patients had improved early and sustained virological response (EVR and SVR) when treated with the current standard of care – pegylated Interferon-alpha and ribavirin (PegIFNα/RBV) – and fluvastatin. The results show patients receiving fluvastatin and PegIFNα/RBV achieve higher rates of EVR and SVR – 75.96% and 63.46% – to those receiving placebo and PegIFNα/RBV – 61.9% and 49.52% respectively.
EASL’s Secretary General, Professor Heiner Wedemeyer, said: “We know that metabolic syndrome (MS), the main treatment indication for statins, is associated with severe fibrosis and lower treatment responses in chronic HCV patients.2 The confirmation that the combination of fluvastatin and PegIFNα/RBV could provide better clinical outcomes for those patients with co-morbid chronic HCV and MS is very exciting for clinicians."
Even in patients without MS, the study shows that responses to treatment are still higher in patients treated with fluvastatin and PegIFNα/RBV (EVR 85.36% versus 71.42% and SVR 74.39% vs. 58.44).
"Today, healthcare professionals have to be mindful when considering health provision and treatment costs. We cannot overlook the importance of opportunities to maximise more affordable drugs’ potential to complement the current standard of care for chronic HCV management," said Professor Wedemeyer.
This new study concludes that the synergistic effects between fluvastatin and PegIFNα/RBV shows lipid lowering drugs may favour HCV clearance and be useful as a chronic HCV treatment, irrespective of the presence of metabolic syndrome.
Notes to Editors
About the study
In the double-blind pilot study, 209 treatment naïve HCV genotype 1b patients were given either PegIFNα/RBV and 20 mg of fluvastatin (104 patients) or PegIFNα/RBV and 20 mg of placebo (105 patients) for 48 weeks. Study medication was administered for 72 weeks (48 weeks in association with PegIFN-ribavirin plus 24 weeks in follow-up) in all patients, irrespective their lipid profile.
Both EVR and SVR are makers of a drug’s efficacy as an HCV treatment: EVR is measured by detectable HCV RNA at week 4, but undetectable HCV RNA at week 12, maintained to the end of treatment; SVR is measured by undetectable HCV RNA 24 weeks after the end of treatment.
Fluvastatin has previously shown promise as an HCV treatment: a 2008 study of 31 patients found the drug exhibited antiviral activity against HCV, although the authors described the effect as modest, variable, and often short-lived.3
Fluvastatin is a statin, a class of drug that improves blood cholesterol levels primarily by inhibiting a liver enzyme called HMG Co-A reductase, thus reducing the liver's ability to make cholesterol.4
About metabolic syndrome
Metabolic syndrome (MS) is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. It is also linked with a higher risk to develop severe fibrosis in chronic HCV patients.2
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL’s main focus on education and research is delivered through numerous events and initiatives, including:
The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
Journal of Hepatology published monthly
Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Travis Taylor: Onsite tel: +44 7843 069 451
Vicky O'Conner: Offsite tel: +44 20 7331 5342
1. Georgescu, E. et al. Potential enhancement of both early (EVR) and sustained (SVR) virological response by fluvastatin in chronic hepatitis C trated [sic] with standard pegifn-ribavirin therapy. A pilot study. Abstract presented at The International Liver CongressTM 2011
2. Tsochatzis E et al. Metabolic syndrome is associated with severe fibrosis in chronic viral hepatitis and non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2008 Jan 1;27(1):80-9. Epub 2007 Oct 5
3. Bader T, Fazili J, Madhoun M, et al. (April 2008). Fluvastatin Inhibits Hepatitis C Replication in Humans. Am. J. Gastroenterol. 103 (6): 1383. doi:10.1111/j.1572-0241.2008.01876.x. PMID 18410471
4. http://heartdisease.about.com/cs/cholesterol/a/statins.htm. Accessed 16.03.2011
TRANSGENE : Announces Completion of Enrolment in HCVac (Phase II Trial) of TG4040 for the Treatment of Chronic Hepatitis C
Transgene S.A. (Paris:TNG)(Euronext Paris: FR0005175080) announces that, with 154 patients randomized and treated, the enrolment of patients in the phase II HCVac trial is now complete. This study explores the combination of TG4040 (MVA-HCV) with standard of care (Pegylated-Interferon ?2a and Ribavarin) in treatment naive patients with chronic genotype 1 hepatitis C.
The patients were recruited in five countries in Europe, in the United States and in Israel, and were randomized in the three arms of the study (one control arm without TG4040 and two experimental arms). HCVac investigates the efficacy and safety of two different schedules of administration of TG4040 administered in subcutaneous injections at the dose of 107 pfu in combination with the standard of care.
HCVac will measure the proportion of patients who achieve complete Early Virologic Response (cEVR), i.e. have no detectable viral load 12 weeks after the beginning of the treatment. These data will be available during the fourth quarter of 2011. The study will also measure the patients' Sustained Virologic Response (SVR), i.e. the treatment's long term effects on the viral load, up to 24 weeks after the end of the treatment, as well as TG4040's ability to elicit an immune response. An additional expected outcome of the study is to identify molecular biomarkers related to TG4040 efficacy in combination with the standard of care. Final data are expected in the fourth quarter of 2012.
"We look forward to obtaining the first results of the study in order to begin preparing the next steps of the development of this promising product candidate for the treatment of patients suffering from chronic hepatitis C, a disease with a growing incidence and which is becoming a public health concern even in the most economically developed countries." stated Philippe Archinard, Chairman and CEO of Transgene.
Transgene's TG4040 vaccine candidate is a recombinant vector based on the MVA virus carrying and expressing three of the major non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus ("HCV"). The MVA vector is a highly attenuated strain of vaccinia virus, which has been tested extensively in humans as a vaccine against smallpox and is known to strongly stimulate innate and adaptive immune responses to antigens.
About TG4040 clinical development program
Phase I clinical results in 39 treatment naïve genotype 1 HCV patients showed that the product is safe and well tolerated at all dose levels tested. Immunological analyses on 15 treatment naive patients were encouraging and supported the expected mechanism of action of TG4040 which aims at inducing an effective HCV-specific T cell based immune response, able to control viral replication.
About chronic hepatitis C
Hepatitis C currently represents a major public health concern. The population chronically infected with HCV in the world is estimated at 170 to 200 million and hepatitis-C-related deaths at approximately 470,000 annually. Peak of prevalence of HCV-related diseases is expected to occur in 2025-2030 in developed countries.
HCV infection leads to liver diseases such as fibrosis, cirrhosis and liver carcinoma, which are the prime indications for liver transplants. The current standard of care for patients infected with the HCV genotype 1 (a combination of Pegylated Interferon ? and Ribavirin) is lengthy, often poorly tolerated and effective in only approximately 50% of patients completing therapy. In addition, a substantial number of patients never receive therapy. Therefore, there is a strong medical need for new alternative approaches, including combination therapies.
Transgene is a France-based biopharmaceutical company focused on the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The Company has four compounds in Phase II clinical trials: TG4010, JX594/TG6006, TG4001/RG3484 and TG4040 and one compound in Phase I clinical trial: TG4023. Transgene has entered into strategic collaborative agreements for the development of two of its immunotherapy products:
An option agreement with Novartis for an exclusive license to develop TG4010 for the treatment of various cancers, including non small cell lung cancer (NSCLC)
An in-licensing agreement with US-based Jennerex Biotherapeutics, Inc., to develop and market JX594 (JX594/TG6006), an oncolytic product.
Transgene has bio-manufacturing capacities for viral-based vectors. Additional information about Transgene can be found at www.transgene.fr.
This press release contains forward-looking statements referring to the clinical testing and development of Transgene's product candidates. Clinical testing and successful product development depend on a variety of factors, including the timing and success of future patient enrolment and the risk of unanticipated adverse patient reactions. Results from future studies with more data may show less favorable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. For further information on the risks and uncertainties involved in the testing and development of Transgene's product candidates, see Trangene's Document de Référence on file with the French Autorité des marchés financiers on its website at http://www.amf-france.org and Transgene's website at www.transgene.fr .
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REG-Novartis first-in-class antiviral DEB025 achieved sustained viral response in 76% of patients with chronic hepatitis C, new phase II study shows
* Reuters is not responsible for the content in this press release.
Thu Mar 31, 2011 11:30am EDT
DEB025 plus standard of care (pegylated-interferon alfa 2a/ribavirin) showed superior viral cure vs standard of care alone (p=0.008)
A cyclophilin inhibitor, DEB025 belongs to a new class of medicines that limit hepatitis C virus replication and have the potential to reshape hepatitis C therapy
Phase III study with DEB025 commenced recently with previously untreated patients infected by the most common form of hepatitis C virus
Basel, March 31, 2011 - Novartis announced today that a Phase II study with the first-in-class antiviral DEB025 (alisporivir) met its primary endpoint for achieving viral cure (24 weeks after stopping treatment) in 76% of patients with chronic hepatitis C. The study involved nearly 300 previously untreated patients infected with the most common form of hepatitis C virus (HCV), the genotype 1 (G1).
The data were presented today at the European Association for the Study of the Liver (EASL) congress in Berlin, Germany. The findings show that 76% of G1 chronic hepatitis C patients treated with DEB025 plus standard of care (pegylated-interferon alfa 2a/ribavirin) achieved superior viral cure (known as sustained viral response, or SVR) compared to 55% of patients on standard of care alone (p=0.008). Treatment with DEB025 demonstrated a low incidence of adverse events, with discontinuation rates comparable between treatment groups.
"Hepatitis C is difficult to treat and current therapies are only effective in about half of patients infected with the most prevalent genotype of HCV," said Stefan Zeuzem, Professor of Medicine at the Goethe University Hospital in Frankfurt, Germany, and the study's principal investigator. "These results are exciting because a large majority of patients achieved sustained viral response with DEB025, with some who also benefited from a shorter duration of treatment compared to standard therapy."
DEB025 is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the virus directly, DEB025 is a host targeting antiviral (HTA) that targets so-called host proteins which are essential for the replication of HCV. As these proteins play a key role in the replication of all types of HCV, DEB025 may offer an effective treatment option for a broad range of HCV forms. In other clinical trials, DEB025 has also shown effective antiviral activity against other common HCV genotypes (G2, G3 and G4).
"There is a critical need for more effective drugs to treat chronic hepatitis C, and Novartis is dedicated to developing medicines that will reduce the burden of this disease for patients and physicians," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "DEB025 has a new mode of action that may stop the virus from replicating and could reshape the future approach to treatment of hepatitis C."
More than 170 million people worldwide are infected with HCV, which can cause serious liver disease leading to cirrhosis, liver cancer, and in some cases death. HCV is a blood borne virus that predominantly affects the liver,. As an RNA (ribonucleic acid) virus, it mutates much more than DNA (deoxyribonucleic acid) viruses. This ability to change makes it harder for the immune system to clear (or eliminate) the virus. There are six major variations of HCV, known as genotypes and labelled from G1 to G6.
The study presented at EASL was a 48-week, global, double-blind, randomized, placebo-controlled trial in G1 treatment-naïve chronic hepatitis C patients. It evaluated the efficacy and safety of DEB025 combined with pegylated-interferon alfa 2a/ribavirin (PegIFN/RBV) vs. PegIFN/RBV alone. The primary endpoint was sustained viral response after 24 weeks (SVR24).
Transient and reversible increase in bilirubin was observed in association with the initial DEB025 loading dose. A small proportion of patients (4.2%) had a transient increase in bilirubin more than five times the upper limit of normal (ULN), but this was not associated with liver damage.
A pivotal Phase III study with DEB025 commenced recently to evaluate the efficacy and safety of DEB025 combined with standard of care and enrolling previously untreated HCV G1 patients. Other Phase II studies are ongoing in other patient populations i.e., G1 treatment-experienced patients and G2 and G3 treatment-naive patients.
Novartis in-licensed DEB025 from Debiopharm Group(TM), an independent biopharmaceuticals company based in Switzerland, under an agreement which gives Novartis exclusive worldwide development, manufacturing and marketing rights (excluding Japan).
The foregoing release contains forward-looking statements that can be identified by terminology such as "potential," "exciting," "may," "dedicated," "will," "could," "launched," or similar expressions, or by express or implied discussions regarding potential marketing submissions or approvals for DEB025, or the potential timing of any such submissions or approvals, or regarding potential future revenues from DEB025. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with DEB025 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that DEB025 will be submitted or approved for sale in any market. Nor can there be any guarantee that DEB025 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding DEB025 could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 119,000 full-time-equivalent associates (including 16,700 Alcon associates) and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com/ .
 Flisiak R, Pawlotsky JM, Crabbe R, Kryczka W, Haüssinger D, Mazella G, Romero-Gomez M, Purcea D, Vuagniaux G, Bao W, Zeuzem S. Once-daily alisporivir (DEB025) plus pegifnalfa2a/ribavirin results in superior sustained virologic response (SVR24) in chronic hepatitis C genotype 1 treatment naïve patients. Presented at European Association for Study of the Liver Congress, Berlin, March 2011.
 Hoofnagle JH. A step forward in therapy for hepatitis C. N Engl J Med. 2009; 360 (18):1899-901.
 Flisiak R, et al. The cyclophilin inhibitor Debio 025 combined with peg IFNa2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology. 2009; 49:1460-68.
 Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001; 345 (1):41-52.
 World Hepatitis Alliance, http://www.worldhepatitisalliance.org/ , Last accessed March 2011
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Clinical Trial MBL-HCV1: New treatment for the prevention of re-infection of the hepatitis c virus in liver transplant patients
Hope for liver patients at UMass
UMass tests drug to prevent re-infection after transplants
At the University of Massachusetts Medical School researchers are performing trials for a new hepatitis C antibody.
The University and five hospitals in Boston, NY and Connecticut are in the second phase of the clinical trial which will help patients with HCV who undergo a liver transplant. The new treatment is for the prevention of re-infection of the hepatitis c virus in liver transplant patients. The antibody thus far is known as MBL-HCV1, ten patients are currently in the trial, with the study looking at a total of 16 to be enrolled.
"Dr. Ambrosino, who is also a professor of pediatrics at the medical school, said results will likely be available in the summer. If the virus is not found in patients 42 days after transplantation, it will be deemed a success. If the virus is found, a trial with a higher dose of antibody will begin.You can read the full story here.
The antibody — or the placebo — is administered to patients by infusion, in phases.
The first dose is given a few hours before transplant surgery, and another is given during surgery between when the diseased liver is removed and the donor liver is implanted. A third infusion is given just after surgery, followed by daily infusions during the first week of recovery. A final infusion is given on the 14th day after surgery."
Results From Phase 3 REALIZE Study Showed Telaprevir-Based Therapy Improved SVR Rates in People Whose Prior Treatment For Hepatitis C Was Unsuccessful
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced final
results from its pivotal Phase 3 REALIZE study that evaluated people
with genotype 1 chronic hepatitis C whose prior treatment with
pegylated-interferon and ribavirin was unsuccessful either because they
relapsed, had a partial response or had a null response. Data from the
study showed that people in each of these subgroups who were treated
with telaprevir-based combination therapy achieved statistically
significant rates of sustained viral response (SVR) compared to those
treated with pegylated-interferon and ribavirin alone.
delaying the start of telaprevir by four weeks, during which time
patients received four weeks of pegylated-interferon and ribavirin alone
(lead-in), compared to a simultaneous start. The data showed no clinical
benefit to a lead-in for people treated with telaprevir-based
combination therapy. Safety and tolerability results were consistent
with results from the prior Phase 3 studies of telaprevir. These data
were presented today at The International Liver Congress™ 2011, 46th
annual meeting of the European Association for the Study of the Liver
(EASL) in Berlin, Germany. REALIZE was conducted by Vertex’s
collaborator, Tibotec BVBA.
“These data showed higher sustained viral response rates for patients
treated with a telaprevir-based regimen compared to re-treatment with
currently available medicines,” said Stefan Zeuzem, M.D., Professor of
Medicine and Chief of the Department of Medicine at the JW Goethe
University Hospital, Frankfurt, Germany and principal investigator for
Among those in the simultaneous start arm of REALIZE, 83 percent
(121/145) of prior relapsers, 59 percent (29/49) of prior partial
responders and 29 percent (21/72) of null responders achieved SVR
compared to 24 percent (16/68), 15 percent (4/27) and 5 percent (2/37),
respectively, who received pegylated-interferon and ribavirin. The SVR
rates among those in the lead-in arm were 88 percent (124/141) among
prior relapsers, 54 percent (26/48) among prior partial responders and
33 percent (25/75) among prior null responders. In a combined endpoint
analysis of the two telaprevir-based treatment arms, 86 percent
(245/286) of prior relapsers, 57 percent (55/97) of prior partial
responders and 31 percent (46/147) of prior null responders achieved SVR.
“Rates of sustained viral response among those treated with
telaprevir-based regimens were similar between the simultaneous and
delayed start arms of the study,” said Robert Kauffman, M.D., Ph.D.,
Senior Vice President and Chief Medical Officer for Vertex.
In this study, 48 percent (316/662) of patients overall had advanced
liver fibrosis or cirrhosis (scarring of the liver) and 89 percent
(586/662) of patients overall had high amounts of hepatitis C virus
(high viral load; HCV RNA ≥ 800,000 IU/mL) upon study entry.
Summary of REALIZE Results
In this study, patients were randomized 2:2:1 to two telaprevir-based
treatment arms (simultaneous or lead-in) or a control arm of 48 weeks of
pegylated-interferon and ribavirin alone. Patients in the telaprevir
treatment arms received a total of 12 weeks of telaprevir-based
combination therapy. In the lead-in arm, patients received four weeks of
pegylated-interferon and ribavirin followed by telaprevir in combination
with pegylated-interferon and ribavirin for 12 weeks followed by 32
weeks of pegylated-interferon and ribavirin alone. For those in the
simultaneous start arm, the telaprevir-based combination was followed by
an additional 36 weeks of pegylated-interferon and ribavirin alone. The
primary endpoint of the REALIZE study was SVR in each of the two
telaprevir treatment arms compared to the control arm and for the three
groups of people included in the study. The total treatment time for all
patients in REALIZE was 48 weeks.
|SVR Results % (n)||Prior Relapsers |
|Prior Partial Responders|
|Prior Null Responders|
Simultaneous Start Arm+
*The SVR rates observed were statistically significant when
compared with the control arm (p <0.001).
+Simultaneous start: 12 weeks of telaprevir (750 mg,
q8h), Pegasys® (PEG, pegylated-interferon alfa-2a) &
Copegus® (RBV, ribavirin), followed by 36 weeks of PEG
& RBV alone.
++Lead-in: 4 weeks of PEG & RBV alone followed by 12
weeks of telaprevir (750 mg, q8h), PEG & RBV, followed by 32 weeks
of PEG & RBV alone. There was no clinical benefit with the use of
a four-week lead in with no significant improvement in SVR rates
and no significant reduction in virologic failure and relapse
rates in the lead-in start arm compared to the simultaneous start
+++Control: 12 weeks of placebo, PEG & RBV, followed by
36 weeks of Peg & RBV alone.
Prior Relapser: Defined as a person
whose hepatitis C virus was undetectable at the completion of at
least 42 weeks of a prior course of therapy but whose virus became
detectable during the follow-up period.
Prior Partial Responder: Defined as a
person who achieved at least a 2 log in10 reduction in
HCV RNA at week 12, but whose hepatitis C virus never became
undetectable by week 24 of a prior course of therapy.
Prior Null Responder: Defined as a
person who achieved a less than 2 log10 reduction in
HCV RNA at week 12 of a prior course of therapy.
The safety and tolerability results of the telaprevir-based combination
regimens were consistent across the Phase 3 studies. The most common
adverse events were fatigue, pruritus, nausea, headache, rash, anemia,
flu-like symptoms, insomnia and diarrhea with the majority being mild to
moderate. Rash and anemia occurred more frequently in the
telaprevir-based treatment arms compared to the control group.
Rash was primarily characterized as eczema-like, manageable and resolved
upon stopping telaprevir. More than 90 percent of rash was mild to
moderate and primarily managed with the use of topical corticosteroids
and/or antihistamines. Anemia was primarily managed by reducing the dose
Sequential discontinuation of the medicines was recommended as a
strategy to manage certain adverse events. This strategy allowed
patients to continue on pegylated-interferon and ribavirin after
stopping telaprevir. Discontinuation of all medicines due to either rash
or anemia during the telaprevir/placebo treatment phase was 1 percent to
3 percent in the telaprevir treatment arms.
About the Study
REALIZE was a pivotal Phase 3, randomized, double-blind,
placebo-controlled global study. The majority of clinical trial sites
were in Europe. The study was designed to evaluate the efficacy, safety
and tolerability of telaprevir-based combination regimens in people
infected with genotype 1 chronic hepatitis C who did not achieve SVR
after at least one course of prior treatment with interferon-based
Status of Telaprevir Regulatory Applications
The safety and efficacy of telaprevir for the treatment of chronic
hepatitis C is still under investigation. Authorization to market
telaprevir has not yet been obtained.
The regulatory applications for the approval of telaprevir have been
granted Priority Review by the U.S. Food and Drug Administration (FDA)
and Health Canada and accelerated assessment by the European Medicines
Agency for the treatment of people with genotype 1 chronic hepatitis C.
The FDA has scheduled its Antiviral Drugs Advisory Committee to discuss
the New Drug Application for telaprevir on April 28, 2011. A target
response date of May 23, 2011 is set under the Prescription Drug User
Fee Act (PDUFA). The applications include data from three registration
studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in
combination with pegylated-interferon and ribavirin in people with
hepatitis C who were new to treatment as well as those who did not
achieve SVR after treatment with currently available medicines. For
complete information on the telaprevir clinical trials or a fact sheet
on the trial designs visit: www.vrtx.com/press.cfm.
About the Telaprevir Development Program
Telaprevir is an investigational, oral inhibitor that acts directly on
the HCV protease, an enzyme essential for viral replication. 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 chronic hepatitis C who had not been treated for their
disease previously as well as people who had been treated before but did
not achieve SVR.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and
Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir
in North America. Through its affiliate, Janssen, 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 serious liver disease caused by the hepatitis C virus,
which is spread through direct contact with the blood of infected people
and ultimately affects the liver.1 Chronic hepatitis C can
lead to serious and life-threatening liver problems, including liver
damage, cirrhosis, liver failure or liver cancer.1 Though
many people with hepatitis C may not experience symptoms, others may
have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Approximately 60 percent of people who undergo treatment with an initial
48-week regimen of pegylated-interferon and ribavirin, the currently
approved medicines for genotype 1 hepatitis C, do not achieve SVR.2,3,4 If treatment is not successful and a person does not achieve SVR,
they remain at an increased risk for progressive liver disease.5,6
Approximately 250,000 people in Canada have chronic hepatitis C and more
than a third of them do not know they are infected.7 Three
provinces account for 80 percent of hepatitis C infections in Canada:
Ontario (42 percent), British Columbia (22 percent) and Quebec (16
percent).8 Each year up to 5,000 people are newly infected
with hepatitis C, and in 2007 alone, nearly 8,000 people were infected.7,8 In 2010, the annual cost of hepatitis C due to medical treatment
and lost productivity in Canada was estimated to reach $1 billion.9 By
2022, the number of hepatitis C-related deaths is expected to increase
PEGASYS® and COPEGUS® are registered trademarks of
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including statements
regarding (i) the date of the scheduled meeting of the FDA’s Antivirial
Advisory Committee and (ii) the FDA's target review date for the
telaprevir NDA. 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 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; that future scientific,
clinical, competitive or other market factors may adversely affect the
potential for telaprevir-based 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://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.vrtx.com&esheet=6666721&lan=en-US&anchor=www.vrtx.com&index=2&md5=d53c1c8d6041bf3eaecb178f6ea93eb7.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.
Vertex creates new possibilities in medicine. Our team aims to discover,
develop and commercialize innovative therapies so people with serious
diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to
cure or significantly advance the treatment of hepatitis C, cystic
fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing
worldwide research programs and sites in the U.S., U.K. and Canada.
For more information and to view Vertex's press releases, please visit
1 Centers for Disease Control and Prevention. Hepatitis C
Fact Sheet: CDC Viral Hepatitis. Available at: http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.cdc.gov%2Fhepatitis%2FHCV%2FPDFs%2FHepCGeneralFactSheet.pdf&esheet=6666721&lan=en-US&anchor=http%3A%2F%2Fwww.cdc.gov%2Fhepatitis%2FHCV%2FPDFs%2FHepCGeneralFactSheet.pdf&index=4&md5=dc3c8b2fe5bf684b55a8ceb8470468a3.
Accessed March 21, 2011.
2 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.
3 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.
4 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.
5 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).
6 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.
7 Public Health Agency of Canada. Hepatitis C: Get the facts.
You could have it and not know it.
Updated September 21, 2010. Accessed January 18, 2011.
8 Public Health Agency of Canada. Modeling the incidence of
prevalence of hepatitis C infection and its sequelae in Canada, 2007.
Updated October 20, 2010. Accessed January 18, 2011.
9 Public Health Agency of Canada. A renewed public health
response to address hepatitis C: A summary report of the
priority-setting process and strategic framework to action.
Updated June 2009. Accessed January 2011.
10 Sherman M, Sharfran S, Burak K, et al. Management of
chronic hepatitis C consensus guidelines. Can J Gastroenterol.
2007;21 (Suppl C):25C-34C.
617-444-6992 or email@example.com
Lora Pike, 617-444-6755
Friday 1st April 2011
Telaprevir-based regimens are significantly better than standard care for treatment-experienced hepatitis C patients, research suggests.
Tibotec Virco-Virology BVBA has announced that a significantly greater proportion of patients who have previously failed treatment for chronic genotype 1 hepatitis C virus (HCV) achieved a sustained viral response (SVR) with 12 week telaprevir combination regimens than with the current standard of care, pegylated-interferon and ribavirin, alone.
Telaprevir is an investigational DAA (Direct Acting Antiviral) being co-developed by Tibotec and Vertex Pharmaceuticals.
Final data from the REALIZE trial were presented today at the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin.
SVR, which means the virus remains undetectable in patients' blood six months after completion of treatment, is the goal of HCV treatment and is considered a cure.
An estimated 170 million people globally suffer from chronic HCV and approximately 10-20 percent of these people will develop cirrhosis and liver failure.
Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and HCV is the most common cause of liver transplant in Europe.
"These groundbreaking data show that a telaprevir combination regimen significantly improves cure rates for patients with genotype 1 HCV, the most common form of the virus, who have failed previous treatment," said lead investigator Professor Stefan Zeuzem, Chief of the Department of Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany.
"Significant advancements in treatment such as this will make a real difference in reducing the burden of HCV."
CareLine will provide help to patients across the country to resolve healthcare access and insurance issues, at no charge to the patient.
Reducing the cost of new hepatitis C drugs
Daclatasvir, Harvoni (ledipasvir/sofosbuvir)/Sovaldi/Viekira Pak.
An index of articles pointing the reader to the current controversy over the high price of Sovaldi, Harvoni (ledipasvir/sofosbuvir) and AbbVie Viekira Pak.
Class Action Lawsuit Challenges the Exorbitant Pricing of Gilead's Hepatitis-C Drug Sovaldi - The situation has Medicaid plans and insurers nationwide groping for the right balance. Worldwide patients are unable to afford treatment, while others wait in the wings on coverage.
Lucinda K. Porter, RN, the author of "Free from Hepatitis C" has graced the HCV community with a second book "Hepatitis C Treatment One Step at a Time" available now on Amazon.
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