Newly approved all-oral Hepatitis C combination drug found more effective in a head-to-head comparison
April 14, 2016
Press Releases
Head-to-head study: once daily oral combination of elbasvir and grazoprevir versus sofosbuvir and pegylated interferon alpha 2b + ribavirin
April 14, 2016, Barcelona, Spain: Findings presented today from a Phase 3 head-to-head study that compared two direct-acting antiviral treatment regimens, demonstrated that the all-oral, once daily combination of elbasvir and grazoprevir was more effective and safer than the combination of sofosbuvir and pegylated interferon with ribavirin, in certain patients with Hepatitis C (HCV). The results were shared at The International Liver Congress™ 2016 in Barcelona, Spain. The combination of elbasvir and grazoprevir – recently approved by the US Food and Drug Administration and Health Canada in January 2016 – is an all-oral once a day treatment that is taken over a 12 to 16 week course.1,2
The combination of sofosbuvir and pegylated interferon with ribavirin was previously recommended by treatment guidelines, however the guidelines have since been updated and no longer recommend this treatment combination. In the United States, genotype 1 HCV is the most common infection, accounting for approximately 70 to 75% of all HCV infections.3 HCV genotype 4 is less prevalent in the United States, however there is a high frequency of this strain in Egypt and Africa.4
“We have recently seen a great increase in the overall number of studies investigating different direct-acting antiviral treatment regimens for Hepatitis C, but direct comparative studies are lacking,” said study lead author Dr Jan Sperl, from the Institute for Clinical and Experimental Medicine, Prague, Czech Republic. “The combination of elbasvir and grazoprevir has shown to be more effective than previously recommended treatment options, giving physicians another treatment option against this damaging infection.”
The C-EDGE head-to-head study was a randomised, parallel-group trial that enrolled patients with HCV genotypes 1 and 4 who either had never received treatment or had prior unsuccessful treatment with pegylated interferon and ribavirin. Patients were randomised 1:1 to receive either 12 weeks of the combination of elbasvir/grazoprevir, or the sofosbuvir, pegylated interferon and ribavirin regimen. The primary efficacy endpoint of the study was achievement of a sustained virologic response (negative virus in the blood) at 12 weeks after the end of therapy (SVR12).
Results show that the elbasvir/grazoprevir combination was effective in HCV genotypes 1 and 4 with fewer overall side effects than the sofosbuvir, pegylated interferon combination and ribavirin combination.
The combination of elbasvir and grazoprevir resulted in an SVR12 of 99.2% (128/129) compared to 90.5% (114/126) in the sofosbuvir/pegylated interferon/ribavirin group. Elbasvir and grazoprevir demonstrated superior efficacy especially in subgroups of patients considered as hard-to-treat in the past (in cirrhotics, patients with high initial vireamia and in previous null-responders to pegylated interferon and ribavirin). Furthermore, elbasvir and grazoprevir demonstrated a superior safety profile compared to sofosbuvir/pegylated interferon/ribavirin. This is primarily due to the absence of adverse effects commonly associated with pegylated interferon and/or ribavirin, including low red blood cell count, low white blood cell count, flu-like illness, and pyrexia.
“A great wealth of data now exists on treatment approaches in HCV and these findings give the medical community another effective option in the treatment of this harmful disease,” said Professor Laurent Castera, EASL Secretary General.
Showing posts with label grazoprevir/elbasvir (MK-5172/MK-8742). Show all posts
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Thursday, April 14, 2016
Thursday, January 28, 2016
Merck Receives FDA Approval of ZEPATIER™ (elbasvir and grazoprevir) for the Treatment of Chronic Hepatitis C Virus Genotype 1 or 4 Infection in Adults Following Priority Review
ZEPATIER - Recommended Dosage and Durations, Drug Interactions, Side Effects, Clinical Studies
Prescribing Information for ZEPATIER
Prescribing Information for ZEPATIER
Patient Information for ZEPATIER
FDA approves Merck's new hepatitis C pill
BY DEENA BEASLEY
U.S. regulators on Thursday approved a new once-daily pill for the liver-destroying hepatitis C virus made by Merck & Co Inc, which said it will sell the drug at a lower list price than its competitors.
The list price for Zepatier will be $54,600 for a 12-week regimen, which Merck said it expects "to be in the range of net prices" for comparable treatments.
Gilead Sciences Inc, which secured an early lead in the lucrative market for oral hepatitis C drugs with the $1,000-per-pill Sovaldi, currently sells an enhanced version of that drug as a single-tablet regimen called Harvoni at a list price of $94,500. AbbVie Inc followed in late 2014 with a multi-pill regimen. Nevertheless, AbbVie secured exclusive contracts with payers such as pharmacy benefit manager Express Scripts Holding Co, forcing Gilead to discount its own contract prices.
Gilead has continued to dominate the market with hepatitis C drug sales of more than $14 billion in the first nine months of 2015.
The Food and Drug Administration approved Zepatier, with or without the older antiviral drug ribavirin, for patients infected with the most common form of hepatitis C, genotype 1, as well as the less common genotype 4.
The new drug's FDA label says liver-related blood tests should be performed prior to starting therapy and at certain times during treatment.
Clinical trials found that 12 or 16 weeks of treatment with Merck's Zepatier reduced the virus to undetectable levels, which is considered a cure, in more than 94 percent of patients, the FDA said in a statement.
Hepatitis C infects an estimated 3.2 million Americans.
(Reporting by Deena Beasley; Editing by Leslie Adler, Bernard Orr)
FDA approves Merck's new hepatitis C pill
BY DEENA BEASLEY
U.S. regulators on Thursday approved a new once-daily pill for the liver-destroying hepatitis C virus made by Merck & Co Inc, which said it will sell the drug at a lower list price than its competitors.
The list price for Zepatier will be $54,600 for a 12-week regimen, which Merck said it expects "to be in the range of net prices" for comparable treatments.
Gilead Sciences Inc, which secured an early lead in the lucrative market for oral hepatitis C drugs with the $1,000-per-pill Sovaldi, currently sells an enhanced version of that drug as a single-tablet regimen called Harvoni at a list price of $94,500. AbbVie Inc followed in late 2014 with a multi-pill regimen. Nevertheless, AbbVie secured exclusive contracts with payers such as pharmacy benefit manager Express Scripts Holding Co, forcing Gilead to discount its own contract prices.
Gilead has continued to dominate the market with hepatitis C drug sales of more than $14 billion in the first nine months of 2015.
The Food and Drug Administration approved Zepatier, with or without the older antiviral drug ribavirin, for patients infected with the most common form of hepatitis C, genotype 1, as well as the less common genotype 4.
The new drug's FDA label says liver-related blood tests should be performed prior to starting therapy and at certain times during treatment.
Clinical trials found that 12 or 16 weeks of treatment with Merck's Zepatier reduced the virus to undetectable levels, which is considered a cure, in more than 94 percent of patients, the FDA said in a statement.
Hepatitis C infects an estimated 3.2 million Americans.
(Reporting by Deena Beasley; Editing by Leslie Adler, Bernard Orr)
http://www.reuters.com/article/us-merck-co-hepatitis-fda-idUSKCN0V631S
FDA approves Zepatier for HCV genotypes 1, 4
January 29, 2016
Merck announced the FDA has approved Zepatier for the treatment of adult patients with chronic hepatitis C virus genotype 1 and 4 infection, with or without ribavirin.
Continue reading...
Press Release:
Merck Receives FDA Approval of ZEPATIER™ (elbasvir and grazoprevir) for the Treatment of Chronic Hepatitis C Virus Genotype 1 or 4 Infection in Adults Following Priority Review
TE, treatment-experienced; TN, treatment-naïve.
a Failed prior IFN or PegIFN +/- RBV.
b Failed prior PegIFN + RBV.
cFailed prior PegIFN + RBV + HCV NS3/4A protease inhibitor (PI): boceprevir, simeprevir or telaprevir.
d C-EDGE TE treatment outcomes for ZEPATIER with RBV for 12 weeks (n=104) or without RBV for 16 weeks (n=101) not shown because these regimens are not recommended in PegIFN + RBV-experienced GT1 patients.
Selected Safety Information about ZEPATIER (elbasvir and grazoprevir)
Elevations of alanine transaminase (ALT) to greater than 5 times the upper limit of normal (ULN) occurred in 1% of subjects, generally at or after treatment week 8. These late ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy. Healthcare professionals should perform hepatic lab testing on patients prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.
Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces. Healthcare providers should consider discontinuing ZEPATIER if ALT levels remain persistently greater than 10 times ULN. ZEPATIER should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalized ratio.
Recommended Dosage Regimens and Durations for ZEPATIER (elbasvir and grazoprevir)
The dosing regimens and durations for treatment with once-daily ZEPATIER for chronic HCV GT1 or GT4 infection in patients with or without cirrhosis, HIV-1 co-infection or renal impairment are as follows:
*Patients who have failed treatment with PegIFN + RBV.
†NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31 or 93.
§Patients who have failed treatment with PegIFN/RBV + HCV NS3/4A PI: boceprevir, simeprevir or telaprevir. For
GT1a-infected PegIFN/RBV/PI-experienced patients with one or more baseline NS5A resistance-associated
polymorphisms (positions 28, 30, 31 or 93), the optimal ZEPATIER-based treatment regimen and duration of therapy
has not been established.
In patients with GT1a infection, some hepatitis C viruses may contain mutations that can confer resistance to treatment. These are called resistance-associated polymorphisms, also referred to as resistance-associated variants (RAVs). GT1a infection accounts for 46 percent of U.S. HCV cases. To help as many patients as possible to achieve SVR12, testing for NS5A resistance-associated polymorphisms (positions 28, 30, 31 or 93) is recommended for GT1a-infected patients prior to starting treatment with ZEPATIER to determine the optimal dosage regimen and duration. In clinical trials of ZEPATIER, 12 percent (37/309) of GT1a-infected U.S. study participants had these NS5A resistance-associated polymorphisms at baseline. A 16-week regimen of ZEPATIER with RBV is recommended for GT1a-infected patients with these baseline NS5A polymorphisms as described in the above table.
“This approval provides patients and physicians with an additional treatment option that has the potential to cure many patients with chronic hepatitis C in the United States,” said Dr. Ira Jacobson, site chair, department of medicine, Mount Sinai Beth Israel, New York. “ZEPATIER is a once-daily, single-tablet direct-acting antiviral that has demonstrated high cure rates in genotype 1 and in genotype 4, including treatment-naïve and treatment-experienced patients with or without compensated cirrhosis and those with chronic kidney disease.”
The company anticipates that ZEPATIER will be available for shipping to wholesalers within seven business days.
“Chronic hepatitis C is a potentially devastating illness that can cause serious long-term health consequences for patients, including reduced liver function, liver failure or liver cancer,” said Michael Ninburg, executive director, Hepatitis Education Project, Seattle. "Today, chronic hepatitis C is a curable condition for many patients, and we are fortunate to have multiple therapeutic tools that can mitigate its impact.”
Selected Safety Information about ZEPATIER (elbasvir and grazoprevir) (continued)
The concomitant use of ZEPATIER with certain drugs may lead to possible clinically significant adverse reactions from greater exposure to ZEPATIER or concomitant drugs. Coadministration of ZEPATIER is not recommended with certain strong CYP3A inhibitors (e.g., ketoconazole or the cobicistat-containing regimens of elvitegravir/cobicistat/emtricitabine/tenofovir [disoproxil fumarate or alafenamide]). Healthcare professionals should not exceed atorvastatin 20mg/daily or rosuvastatin 10mg/daily when given with ZEPATIER. If ZEPATIER is given with fluvastatin, lovastatin or simvastatin, healthcare professionals should give the lowest statin dose necessary and closely monitor for statin-associated adverse events. If ZEPATIER and tacrolimus are coadministered, frequent monitoring of tacrolimus whole blood concentrations, changes in renal function and tacrolimus-associated adverse events is recommended.
The concomitant use of ZEPATIER and certain drugs may cause significant decrease of elbasvir and grazoprevir plasma concentrations, which may lead to reduced therapeutic effect of ZEPATIER and possible development of resistance. Coadministration of ZEPATIER is not recommended with moderate CYP3A inducers (e.g., nafcillin, bosentan, etravirine, modafinil).
In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache and nausea. In subjects receiving ZEPATIER with RBV for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.
Pricing Designed to Enable Broad Patient Access to ZEPATIER (elbasvir and grazoprevir)
The latest innovations in chronic HCV treatment that have become available over the past three years, now including ZEPATIER, provide the U.S. with an unprecedented opportunity to significantly reduce the burden of HCV. The scientific community believes that control of HCV infection may be possible and is actively working to achieve that goal by 2030. A significant medical need remains: it is estimated that less than one in five patients with chronic HCV infection are currently treated, with thousands of new cases each year.
ZEPATIER, which received two Breakthrough Therapy designations (for GT1 patients with end stage renal disease on hemodialysis and for GT4 patients) and was thereafter approved by the FDA following priority review, offers a highly effective option for a broad range of adult patients with chronic HCV GT1 or GT4 infection. Public reports indicate that net prices for the most commonly used direct-acting antiviral regimens are substantially lower than the list prices. However, the majority of patients with chronic HCV have not yet been treated, in some cases due to cost constraints. After considering these factors, Merck has established a list price of $54,600 for a 12-week regimen, which the company believes to be in the range of net prices for other commonly used HCV direct-acting antiviral regimens at 12 weeks of therapy. Merck anticipates that this price, as well as our comprehensive access strategy to seek broad coverage across commercial and public segments, will help broaden and accelerate patient access to treatment and move us closer to our shared goal of reducing the burden of chronic HCV in the U.S.
“Merck’s decades-long commitment in chronic hepatitis C -- and infectious diseases overall -- has been to both scientific innovation and access,” said Robert McMahon, president, U.S. Market, Global Human Health, Merck. “We are embracing this opportunity to partner with payers and physicians to enable as many appropriate patients to be treated as possible, as quickly as possible.”
Financial Assistance Programs for Those Who Need Help With the Cost of Their Medicine
Merck also anticipates that the list price of ZEPATIER will result in lower out-of-pocket medication costs for some patients. Lower out-of-pocket costs alone do not necessarily reflect a cost advantage in the outcome of the condition treated, because there are other variables that affect relative costs. The direct out-of-pocket costs to patients will vary, depending on an individual’s insurance plan.
Privately insured patients who have difficulty affording the co-pay set by their insurance plan may be eligible for significant co-pay assistance and may pay as little as $5 for each prescription. Maximum savings are limited and terms and conditions apply. Information is available at www.merckaccessprogram-ZEPATIER.com. Merck anticipates that the website for ZEPATIER will be accessible within 24 hours of FDA approval.
Merck also offers assistance to patients who cannot afford ZEPATIER through Merck’s 50-year-old Patient Assistance Program. The Merck PAP provides certain Merck medicines free of charge to eligible patients. The Merck PAP for ZEPATIER is designed primarily for the uninsured who, without our assistance, could not afford their medication. Additionally, for those patients whose insurance plan covers ZEPATIER, but who still cannot afford their medication, a request for an exception may be made if they meet certain financial, medical, and/or insurance criteria. For more information about the Merck PAP, please visit www.merckhelps.comor call the Merck Patient Assistance Program at 1-800-405-5810.
Summary of Study Designs
Clinical Trials for GT1 HCV
C-EDGE TN was a randomized, double-blind, placebo-controlled trial in treatment-naïve patients with GT1 or GT4 infection with or without cirrhosis. Patients were randomized in a 3:1 ratio to: ZEPATIER for 12 weeks (immediate treatment group) (N=306) or placebo for 12 weeks followed by open-label treatment with ZEPATIER for 12 weeks (deferred treatment group) (N=102). Among patients with GT1 infection randomized to the immediate treatment group, the median age was 55 years (range: 20 to 78); 56% of the patients were male; 61% were white; 20% were black or African American; 8% were Hispanic or Latino; mean body mass index was 26 kg/m2; 72% had baseline HCV RNA levels greater than 800,000 IU per mL; 24% had cirrhosis; 67% had non-C/C IL28B alleles (CT or TT); and 55% had GT1a and 45% had GT1b chronic HCV infection.
C-EDGE COINFECTION (CO-INFXN) was an open-label, single-arm trial in treatment-naïve HIV-1/HCV co-infected patients with GT1 or GT4 infection with or without cirrhosis. Patients received ZEPATIER for 12 weeks (N=217). Among patients with GT1 infection, the median age was 50 years (range: 21 to 71); 85% of the patients were male; 75% were white; 19% were black or African American; 6% were Hispanic or Latino; mean body mass index was 25 kg per m2; 59% had baseline HCV RNA levels greater than 800,000 IU per mL; 16% had cirrhosis; 65% had non-C/C IL28B alleles (CT or TT); and 76% had GT1a, 23% had GT1b, and 1% had GT1-Other chronic HCV infection.
C-SURFER was a randomized, double-blind, placebo-controlled trial in patients with GT1 infection, with or without cirrhosis, with chronic kidney disease (CKD) Stage 4 (eGFR 15-29 mL/min/1.73 m2) or CKD Stage 5 (eGFR <15 mL/min/1.73 m2), including patients on hemodialysis, who were treatment-naïve or who had failed prior therapy with IFN or PegIFN ± RBV therapy. Patients were randomized in a 1:1 ratio to one of the following treatment groups: elbasvir 50 mg once daily + grazoprevir 100 mg once daily for 12 weeks (N=111) (immediate treatment group) or placebo for 12 weeks followed by open-label treatment with elbasvir + grazoprevir for 12 weeks (N=113) (deferred treatment group). In addition, 11 patients received open-label elbasvir + grazoprevir for 12 weeks (intensive pharmacokinetic [PK] group). Patients randomized to the immediate treatment group and intensive PK group had a median age of 58 years (range: 31 to 76); 75% of the patients were male; 50% were white; 45% were black or African American; 11% were Hispanic or Latino; 57% had baseline HCV RNA levels greater than 800,000 IU/mL; 6% had cirrhosis; and 72% had non-C/C IL28B alleles (CT or TT).
C-EDGE TE was a randomized, open-label comparative trial in patients with GT1 or GT4 infection, with or without cirrhosis, with or without HCV/HIV-1 co-infection, who had failed prior therapy with PegIFN + RBV therapy. Patients were randomized in a 1:1:1:1 ratio to one of the following treatment groups: ZEPATIER for 12 weeks (N=105), ZEPATIER + RBV for 12 weeks (N=104), ZEPATIER for 16 weeks (N=101), or ZEPATIER + RBV for 16 weeks (N=104). Among patients with GT1 infection, the median age was 57 years (range: 19 to 77); 64% of the patients were male; 67% were white; 18% were black or African American; 9% were Hispanic or Latino; mean body mass index was 28 kg/m2; 78% had baseline HCV RNA levels greater than 800,000 IU/mL; 34% had cirrhosis; 79% had non-C/C IL28B alleles (CT or TT); and 60% had GT1a, 39% had GT1b, and 1% had GT1-Other chronic HCV infection.
C-SALVAGE was an open-label single-arm trial in patients with GT1 infection, with or without cirrhosis, who had failed prior treatment with boceprevir, simeprevir, or telaprevir in combination with PegIFN + RBV. Patients received elbasvir 50 mg once daily + grazoprevir 100 mg once daily + RBV for 12 weeks (N=79). Patients had a median age of 55 years (range: 23 to 75); 58% of the patients were male; 97% were white; 3% were black or African American; 15% were Hispanic or Latino; mean body mass index was 28 kg/m2; 63% had baseline HCV RNA levels greater than 800,000 IU/mL; 43% had cirrhosis; and 97% had non-C/C IL28B alleles (CT or TT); 46% had baseline NS3 resistance-associated substitutions.
Clinical Trials for GT4 HCV
The efficacy of ZEPATIER in patients with GT4 chronic HCV infection was demonstrated in C-EDGE TN, C-EDGE CO-INFXN, C-EDGE TE, and C-SCAPE. C-SCAPE was a randomized, open-label trial which included treatment-naïve patients with GT4 infection without cirrhosis. Patients were randomized in a 1:1 ratio to elbasvir 50 mg once daily + grazoprevir 100 mg once daily for 12 weeks (N=10) or elbasvir 50 mg once daily + grazoprevir 100 mg once daily + RBV for 12 weeks (N=10). In these combined studies in patients with GT4 infection, 64% were treatment-naïve; 66% of the patients were male; 87% were white; 10% were black or African American; 22% had cirrhosis; and 30% had HIV-1/HCV co-infection.
About Merck
Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visitwww.merck.com and connect with us onTwitter,Facebook,YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co. Inc., Kenilworth, NJ, USA
This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for ZEPATIER (elbasvir and grazoprevir) at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdfand the Patient Information for ZEPATIER at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_ppi.pdf
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FDA approves Zepatier for HCV genotypes 1, 4
January 29, 2016
Merck announced the FDA has approved Zepatier for the treatment of adult patients with chronic hepatitis C virus genotype 1 and 4 infection, with or without ribavirin.
Continue reading...
Press Release:
Merck Receives FDA Approval of ZEPATIER™ (elbasvir and grazoprevir) for the Treatment of Chronic Hepatitis C Virus Genotype 1 or 4 Infection in Adults Following Priority Review
ZEPATIER Achieves High Cure Rates (SVR12) in Broad Range of Patients with Chronic Hepatitis C Infection, Including Those with Compensated Cirrhosis, Renal Impairment of Any Degree and HIV-1/HCV Co-infection
Thursday, January 28, 2016 6:59 pm EST
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KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved ZEPATIER™ (elbasvir and grazoprevir) for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype (GT) 1 or GT4 infection, with or without ribavirin (RBV), following priority review by the FDA. ZEPATIER (pronounced ZEP-ah-teer) is a once-daily, fixed-dose combination tablet containing the NS5A inhibitor elbasvir (50 mg) and the NS3/4A protease inhibitor grazoprevir (100 mg). The FDA previously granted two Breakthrough Therapy designations to ZEPATIER, for the treatment of chronic HCV GT1 infection in patients with end stage renal disease on hemodialysis, and for the treatment of patients with chronic HCV GT4 infection. Breakthrough Therapy designation is given to investigational medicines for serious or life-threatening conditions that may offer substantial improvement over existing therapies. Across multiple clinical studies, ZEPATIER achieved high rates of sustained virologic response ranging from 94 to 97 percent in GT1-infected patients, and 97 to 100 percent in GT4-infected patients. Sustained virologic response is defined as HCV RNA levels measuring less than the lower limit of quantification at 12 weeks after the cessation of treatment (SVR12), indicating that a patient’s HCV infection has been cured.
ZEPATIER is not for use in patients with moderate or severe hepatic impairment (Child-Pugh B or C). ZEPATIER also is not for use with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s Wort), and efavirenz. If ZEPATIER is administered with RBV, healthcare professionals should refer to the prescribing information for RBV as the contraindications, warnings and precautions, adverse reactions and dosing for RBV also apply to this combination regimen.
“Continued innovation is needed to help address the worldwide epidemic of chronic hepatitis C virus infection,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Our clinical program was designed to study a broad range of patients infected with the hepatitis C virus, including difficult-to-treat patients such as those with stage 4 or 5 chronic kidney disease. The approval of ZEPATIER is a testament to Merck’s unwavering commitment to improving therapy for patients with hepatitis C virus infection, and we are eager to bring this innovation to patients and physicians in the United States.”
ZEPATIER was approved with a treatment duration of 12 or 16 weeks, depending on HCV genotype, prior treatment history and, for patients with GT1a infection, the presence of certain baseline NS5A polymorphisms. A 12-week, once-daily regimen is recommended for the vast majority of patients for whom ZEPATIER is indicated.
Merck’s broad clinical trial program supporting the efficacy of ZEPATIER included six studies in 1,373 patients with chronic HCV GT1 or GT4 infection. These studies assessed the rate of sustained virologic response 12 weeks after the completion of treatment with ZEPATIER (SVR12). The clinical development program for ZEPATIER enrolled diverse groups of HCV GT1- and GT4-infected patients, including treatment-naïve patients and those who had failed prior therapy with peginterferon alfa (PegIFN) and RBV, as well as patients suffering with meaningful co-morbidities and health complications, such as compensated cirrhosis and HIV-1 co-infection. GT1-infected patients with severe renal impairment on hemodialysis and those who previously failed therapy with PegIFN and RBV in combination with an HCV NS3/4A protease inhibitor (boceprevir, simeprevir or telaprevir) also were studied.
The following table provides a summary of clinical data that contributed to the efficacy assessment of ZEPATIER. The primary endpoint in each study was SVR12. Please see section entitled Summary of Study Designs below for additional study design information, including treatment arms and baseline characteristics.
Thursday, January 28, 2016 6:59 pm EST
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KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved ZEPATIER™ (elbasvir and grazoprevir) for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype (GT) 1 or GT4 infection, with or without ribavirin (RBV), following priority review by the FDA. ZEPATIER (pronounced ZEP-ah-teer) is a once-daily, fixed-dose combination tablet containing the NS5A inhibitor elbasvir (50 mg) and the NS3/4A protease inhibitor grazoprevir (100 mg). The FDA previously granted two Breakthrough Therapy designations to ZEPATIER, for the treatment of chronic HCV GT1 infection in patients with end stage renal disease on hemodialysis, and for the treatment of patients with chronic HCV GT4 infection. Breakthrough Therapy designation is given to investigational medicines for serious or life-threatening conditions that may offer substantial improvement over existing therapies. Across multiple clinical studies, ZEPATIER achieved high rates of sustained virologic response ranging from 94 to 97 percent in GT1-infected patients, and 97 to 100 percent in GT4-infected patients. Sustained virologic response is defined as HCV RNA levels measuring less than the lower limit of quantification at 12 weeks after the cessation of treatment (SVR12), indicating that a patient’s HCV infection has been cured.
ZEPATIER is not for use in patients with moderate or severe hepatic impairment (Child-Pugh B or C). ZEPATIER also is not for use with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s Wort), and efavirenz. If ZEPATIER is administered with RBV, healthcare professionals should refer to the prescribing information for RBV as the contraindications, warnings and precautions, adverse reactions and dosing for RBV also apply to this combination regimen.
“Continued innovation is needed to help address the worldwide epidemic of chronic hepatitis C virus infection,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Our clinical program was designed to study a broad range of patients infected with the hepatitis C virus, including difficult-to-treat patients such as those with stage 4 or 5 chronic kidney disease. The approval of ZEPATIER is a testament to Merck’s unwavering commitment to improving therapy for patients with hepatitis C virus infection, and we are eager to bring this innovation to patients and physicians in the United States.”
ZEPATIER was approved with a treatment duration of 12 or 16 weeks, depending on HCV genotype, prior treatment history and, for patients with GT1a infection, the presence of certain baseline NS5A polymorphisms. A 12-week, once-daily regimen is recommended for the vast majority of patients for whom ZEPATIER is indicated.
Merck’s broad clinical trial program supporting the efficacy of ZEPATIER included six studies in 1,373 patients with chronic HCV GT1 or GT4 infection. These studies assessed the rate of sustained virologic response 12 weeks after the completion of treatment with ZEPATIER (SVR12). The clinical development program for ZEPATIER enrolled diverse groups of HCV GT1- and GT4-infected patients, including treatment-naïve patients and those who had failed prior therapy with peginterferon alfa (PegIFN) and RBV, as well as patients suffering with meaningful co-morbidities and health complications, such as compensated cirrhosis and HIV-1 co-infection. GT1-infected patients with severe renal impairment on hemodialysis and those who previously failed therapy with PegIFN and RBV in combination with an HCV NS3/4A protease inhibitor (boceprevir, simeprevir or telaprevir) also were studied.
The following table provides a summary of clinical data that contributed to the efficacy assessment of ZEPATIER. The primary endpoint in each study was SVR12. Please see section entitled Summary of Study Designs below for additional study design information, including treatment arms and baseline characteristics.
Clinical Studies Supporting Efficacy of ZEPATIER (elbasvir and grazoprevir):
| |||||||||
| Clinical Trial(s) | Population | SVR12 (n/N) |
Treatment
Regimen and
Duration
| ||||||
| GT1 | |||||||||
C-EDGE TN
(double blind, placebo controlled) | TN +/- cirrhosis | 95% (273/288) | ZEPATIER
12 weeks
| ||||||
| C-EDGE CO-INFXN (open-label, single arm) |
TN +/- cirrhosis + HIV-1
co-infection | 95% (179/189) | |||||||
C-SURFER
(double blind, placebo controlled) |
TN/TEa +/- cirrhosis +
severe renal impairment | 94% (115/122) | |||||||
| C-EDGE TEd (open-label, comparative) |
TEb +/- cirrhosis +/- HIV-
1 co-infection | 94% (90/96)
97% (93/96)
| ZEPATIER
12 weeks
ZEPATIER
+ RBV
16 weeks
| ||||||
| C-SALVAGE (open-label, single arm) | TEc +/- cirrhosis | 96% (76/79) | ZEPATIER
+ RBV
12 weeks | ||||||
| GT4 | |||||||||
| C-SCAPE (open-label)
C-EDGE TN
C-EDGE CO-INFXN
|
TN without cirrhosis
TN +/- cirrhosis TN +/- cirrhosis + HIV-1 co-infection | 97% (64/66) | ZEPATIER
12 weeks
| ||||||
| C-EDGE TE | TEb +/- cirrhosis | 100% (8/8) | ZEPATIER
+ RBV
16 weeks
| ||||||
a Failed prior IFN or PegIFN +/- RBV.
b Failed prior PegIFN + RBV.
cFailed prior PegIFN + RBV + HCV NS3/4A protease inhibitor (PI): boceprevir, simeprevir or telaprevir.
d C-EDGE TE treatment outcomes for ZEPATIER with RBV for 12 weeks (n=104) or without RBV for 16 weeks (n=101) not shown because these regimens are not recommended in PegIFN + RBV-experienced GT1 patients.
Selected Safety Information about ZEPATIER (elbasvir and grazoprevir)
Elevations of alanine transaminase (ALT) to greater than 5 times the upper limit of normal (ULN) occurred in 1% of subjects, generally at or after treatment week 8. These late ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy. Healthcare professionals should perform hepatic lab testing on patients prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.
Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces. Healthcare providers should consider discontinuing ZEPATIER if ALT levels remain persistently greater than 10 times ULN. ZEPATIER should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalized ratio.
Recommended Dosage Regimens and Durations for ZEPATIER (elbasvir and grazoprevir)
The dosing regimens and durations for treatment with once-daily ZEPATIER for chronic HCV GT1 or GT4 infection in patients with or without cirrhosis, HIV-1 co-infection or renal impairment are as follows:
| Patient Population | Treatment | Duration | ||||
GT1a:
Treatment-naïve or PegIFN/RBV-experienced*
without baseline NS5A polymorphisms† | ZEPATIER | 12 weeks | ||||
GT1a:
Treatment-naïve or PegIFN/RBV-experienced*
with baseline NS5A polymorphisms† | ZEPATIER with RBV | 16 weeks | ||||
| GT1b:
Treatment-naïve or PegIFN/RBV-experienced*
| ZEPATIER | 12 weeks | ||||
| GT1a or GT1b:
PegIFN/RBV/PI-experienced§
| ZEPATIER with RBV | 12 weeks | ||||
| GT4:
Treatment-naïve
| ZEPATIER | 12 weeks | ||||
| GT4:
PegIFN/RBV-experienced*
| ZEPATIER with RBV | 16 weeks |
†NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31 or 93.
§Patients who have failed treatment with PegIFN/RBV + HCV NS3/4A PI: boceprevir, simeprevir or telaprevir. For
GT1a-infected PegIFN/RBV/PI-experienced patients with one or more baseline NS5A resistance-associated
polymorphisms (positions 28, 30, 31 or 93), the optimal ZEPATIER-based treatment regimen and duration of therapy
has not been established.
In patients with GT1a infection, some hepatitis C viruses may contain mutations that can confer resistance to treatment. These are called resistance-associated polymorphisms, also referred to as resistance-associated variants (RAVs). GT1a infection accounts for 46 percent of U.S. HCV cases. To help as many patients as possible to achieve SVR12, testing for NS5A resistance-associated polymorphisms (positions 28, 30, 31 or 93) is recommended for GT1a-infected patients prior to starting treatment with ZEPATIER to determine the optimal dosage regimen and duration. In clinical trials of ZEPATIER, 12 percent (37/309) of GT1a-infected U.S. study participants had these NS5A resistance-associated polymorphisms at baseline. A 16-week regimen of ZEPATIER with RBV is recommended for GT1a-infected patients with these baseline NS5A polymorphisms as described in the above table.
“This approval provides patients and physicians with an additional treatment option that has the potential to cure many patients with chronic hepatitis C in the United States,” said Dr. Ira Jacobson, site chair, department of medicine, Mount Sinai Beth Israel, New York. “ZEPATIER is a once-daily, single-tablet direct-acting antiviral that has demonstrated high cure rates in genotype 1 and in genotype 4, including treatment-naïve and treatment-experienced patients with or without compensated cirrhosis and those with chronic kidney disease.”
The company anticipates that ZEPATIER will be available for shipping to wholesalers within seven business days.
“Chronic hepatitis C is a potentially devastating illness that can cause serious long-term health consequences for patients, including reduced liver function, liver failure or liver cancer,” said Michael Ninburg, executive director, Hepatitis Education Project, Seattle. "Today, chronic hepatitis C is a curable condition for many patients, and we are fortunate to have multiple therapeutic tools that can mitigate its impact.”
Selected Safety Information about ZEPATIER (elbasvir and grazoprevir) (continued)
The concomitant use of ZEPATIER with certain drugs may lead to possible clinically significant adverse reactions from greater exposure to ZEPATIER or concomitant drugs. Coadministration of ZEPATIER is not recommended with certain strong CYP3A inhibitors (e.g., ketoconazole or the cobicistat-containing regimens of elvitegravir/cobicistat/emtricitabine/tenofovir [disoproxil fumarate or alafenamide]). Healthcare professionals should not exceed atorvastatin 20mg/daily or rosuvastatin 10mg/daily when given with ZEPATIER. If ZEPATIER is given with fluvastatin, lovastatin or simvastatin, healthcare professionals should give the lowest statin dose necessary and closely monitor for statin-associated adverse events. If ZEPATIER and tacrolimus are coadministered, frequent monitoring of tacrolimus whole blood concentrations, changes in renal function and tacrolimus-associated adverse events is recommended.
The concomitant use of ZEPATIER and certain drugs may cause significant decrease of elbasvir and grazoprevir plasma concentrations, which may lead to reduced therapeutic effect of ZEPATIER and possible development of resistance. Coadministration of ZEPATIER is not recommended with moderate CYP3A inducers (e.g., nafcillin, bosentan, etravirine, modafinil).
In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache and nausea. In subjects receiving ZEPATIER with RBV for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.
Pricing Designed to Enable Broad Patient Access to ZEPATIER (elbasvir and grazoprevir)
The latest innovations in chronic HCV treatment that have become available over the past three years, now including ZEPATIER, provide the U.S. with an unprecedented opportunity to significantly reduce the burden of HCV. The scientific community believes that control of HCV infection may be possible and is actively working to achieve that goal by 2030. A significant medical need remains: it is estimated that less than one in five patients with chronic HCV infection are currently treated, with thousands of new cases each year.
ZEPATIER, which received two Breakthrough Therapy designations (for GT1 patients with end stage renal disease on hemodialysis and for GT4 patients) and was thereafter approved by the FDA following priority review, offers a highly effective option for a broad range of adult patients with chronic HCV GT1 or GT4 infection. Public reports indicate that net prices for the most commonly used direct-acting antiviral regimens are substantially lower than the list prices. However, the majority of patients with chronic HCV have not yet been treated, in some cases due to cost constraints. After considering these factors, Merck has established a list price of $54,600 for a 12-week regimen, which the company believes to be in the range of net prices for other commonly used HCV direct-acting antiviral regimens at 12 weeks of therapy. Merck anticipates that this price, as well as our comprehensive access strategy to seek broad coverage across commercial and public segments, will help broaden and accelerate patient access to treatment and move us closer to our shared goal of reducing the burden of chronic HCV in the U.S.
“Merck’s decades-long commitment in chronic hepatitis C -- and infectious diseases overall -- has been to both scientific innovation and access,” said Robert McMahon, president, U.S. Market, Global Human Health, Merck. “We are embracing this opportunity to partner with payers and physicians to enable as many appropriate patients to be treated as possible, as quickly as possible.”
Financial Assistance Programs for Those Who Need Help With the Cost of Their Medicine
Merck also anticipates that the list price of ZEPATIER will result in lower out-of-pocket medication costs for some patients. Lower out-of-pocket costs alone do not necessarily reflect a cost advantage in the outcome of the condition treated, because there are other variables that affect relative costs. The direct out-of-pocket costs to patients will vary, depending on an individual’s insurance plan.
Privately insured patients who have difficulty affording the co-pay set by their insurance plan may be eligible for significant co-pay assistance and may pay as little as $5 for each prescription. Maximum savings are limited and terms and conditions apply. Information is available at www.merckaccessprogram-ZEPATIER.com. Merck anticipates that the website for ZEPATIER will be accessible within 24 hours of FDA approval.
Merck also offers assistance to patients who cannot afford ZEPATIER through Merck’s 50-year-old Patient Assistance Program. The Merck PAP provides certain Merck medicines free of charge to eligible patients. The Merck PAP for ZEPATIER is designed primarily for the uninsured who, without our assistance, could not afford their medication. Additionally, for those patients whose insurance plan covers ZEPATIER, but who still cannot afford their medication, a request for an exception may be made if they meet certain financial, medical, and/or insurance criteria. For more information about the Merck PAP, please visit www.merckhelps.comor call the Merck Patient Assistance Program at 1-800-405-5810.
Summary of Study Designs
Clinical Trials for GT1 HCV
C-EDGE TN was a randomized, double-blind, placebo-controlled trial in treatment-naïve patients with GT1 or GT4 infection with or without cirrhosis. Patients were randomized in a 3:1 ratio to: ZEPATIER for 12 weeks (immediate treatment group) (N=306) or placebo for 12 weeks followed by open-label treatment with ZEPATIER for 12 weeks (deferred treatment group) (N=102). Among patients with GT1 infection randomized to the immediate treatment group, the median age was 55 years (range: 20 to 78); 56% of the patients were male; 61% were white; 20% were black or African American; 8% were Hispanic or Latino; mean body mass index was 26 kg/m2; 72% had baseline HCV RNA levels greater than 800,000 IU per mL; 24% had cirrhosis; 67% had non-C/C IL28B alleles (CT or TT); and 55% had GT1a and 45% had GT1b chronic HCV infection.
C-EDGE COINFECTION (CO-INFXN) was an open-label, single-arm trial in treatment-naïve HIV-1/HCV co-infected patients with GT1 or GT4 infection with or without cirrhosis. Patients received ZEPATIER for 12 weeks (N=217). Among patients with GT1 infection, the median age was 50 years (range: 21 to 71); 85% of the patients were male; 75% were white; 19% were black or African American; 6% were Hispanic or Latino; mean body mass index was 25 kg per m2; 59% had baseline HCV RNA levels greater than 800,000 IU per mL; 16% had cirrhosis; 65% had non-C/C IL28B alleles (CT or TT); and 76% had GT1a, 23% had GT1b, and 1% had GT1-Other chronic HCV infection.
C-SURFER was a randomized, double-blind, placebo-controlled trial in patients with GT1 infection, with or without cirrhosis, with chronic kidney disease (CKD) Stage 4 (eGFR 15-29 mL/min/1.73 m2) or CKD Stage 5 (eGFR <15 mL/min/1.73 m2), including patients on hemodialysis, who were treatment-naïve or who had failed prior therapy with IFN or PegIFN ± RBV therapy. Patients were randomized in a 1:1 ratio to one of the following treatment groups: elbasvir 50 mg once daily + grazoprevir 100 mg once daily for 12 weeks (N=111) (immediate treatment group) or placebo for 12 weeks followed by open-label treatment with elbasvir + grazoprevir for 12 weeks (N=113) (deferred treatment group). In addition, 11 patients received open-label elbasvir + grazoprevir for 12 weeks (intensive pharmacokinetic [PK] group). Patients randomized to the immediate treatment group and intensive PK group had a median age of 58 years (range: 31 to 76); 75% of the patients were male; 50% were white; 45% were black or African American; 11% were Hispanic or Latino; 57% had baseline HCV RNA levels greater than 800,000 IU/mL; 6% had cirrhosis; and 72% had non-C/C IL28B alleles (CT or TT).
C-EDGE TE was a randomized, open-label comparative trial in patients with GT1 or GT4 infection, with or without cirrhosis, with or without HCV/HIV-1 co-infection, who had failed prior therapy with PegIFN + RBV therapy. Patients were randomized in a 1:1:1:1 ratio to one of the following treatment groups: ZEPATIER for 12 weeks (N=105), ZEPATIER + RBV for 12 weeks (N=104), ZEPATIER for 16 weeks (N=101), or ZEPATIER + RBV for 16 weeks (N=104). Among patients with GT1 infection, the median age was 57 years (range: 19 to 77); 64% of the patients were male; 67% were white; 18% were black or African American; 9% were Hispanic or Latino; mean body mass index was 28 kg/m2; 78% had baseline HCV RNA levels greater than 800,000 IU/mL; 34% had cirrhosis; 79% had non-C/C IL28B alleles (CT or TT); and 60% had GT1a, 39% had GT1b, and 1% had GT1-Other chronic HCV infection.
C-SALVAGE was an open-label single-arm trial in patients with GT1 infection, with or without cirrhosis, who had failed prior treatment with boceprevir, simeprevir, or telaprevir in combination with PegIFN + RBV. Patients received elbasvir 50 mg once daily + grazoprevir 100 mg once daily + RBV for 12 weeks (N=79). Patients had a median age of 55 years (range: 23 to 75); 58% of the patients were male; 97% were white; 3% were black or African American; 15% were Hispanic or Latino; mean body mass index was 28 kg/m2; 63% had baseline HCV RNA levels greater than 800,000 IU/mL; 43% had cirrhosis; and 97% had non-C/C IL28B alleles (CT or TT); 46% had baseline NS3 resistance-associated substitutions.
Clinical Trials for GT4 HCV
The efficacy of ZEPATIER in patients with GT4 chronic HCV infection was demonstrated in C-EDGE TN, C-EDGE CO-INFXN, C-EDGE TE, and C-SCAPE. C-SCAPE was a randomized, open-label trial which included treatment-naïve patients with GT4 infection without cirrhosis. Patients were randomized in a 1:1 ratio to elbasvir 50 mg once daily + grazoprevir 100 mg once daily for 12 weeks (N=10) or elbasvir 50 mg once daily + grazoprevir 100 mg once daily + RBV for 12 weeks (N=10). In these combined studies in patients with GT4 infection, 64% were treatment-naïve; 66% of the patients were male; 87% were white; 10% were black or African American; 22% had cirrhosis; and 30% had HIV-1/HCV co-infection.
About Merck
Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visitwww.merck.com and connect with us onTwitter,Facebook,YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co. Inc., Kenilworth, NJ, USA
This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for ZEPATIER (elbasvir and grazoprevir) at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdfand the Patient Information for ZEPATIER at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_ppi.pdf
RELATED MATERIALS
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Tuesday, November 10, 2015
Grazoprevir, Elbasvir Combination Effective for Patients With Hepatitis C, Kidney Disease: Presented at Kidney Week
Grazoprevir, Elbasvir Combination Effective for Patients With Hepatitis C, Kidney Disease: Presented at Kidney Week
By Nancy A. Melville
By Nancy A. Melville
Source
SAN DIEGO -- November 10, 2015 -- The combination of grazoprevir (GZR) and elbasvir (EBR), in a single tablet, shows strong efficacy in the treatment of hepatitis C virus (HCV) in patients with stage 4 or 5 chronic kidney disease (CKD), researchers reported here at Kidney Week 2015, the Annual Meeting of the American Society of Nephrology (ASN).
The once-daily therapy combines a NS3/4A protease inhibitor and an NS5A replication complex inhibitor and is being investigated for a variety of HCV genotypes and in conditions ranging from HIV/HCV co-infection to opiate substitution therapy and liver cirrhosis.
The C-SURFER trial included 224 patients with stage 4 or 5 CKD who were on haemodialysis and had concomitant HCV genotype 1. Patients were randomised to either immediate treatment with GZR/EBR 100 mg/50 mg (n = 111) or deferred treatment, which consisted of placebo for 12 weeks followed by GZR/EBR 100 mg/50 mg.
The sustained virologic response (SVR) rate 12 weeks post-therapy in the GZR/EBR group was 94.6%, compared with 95% in placebo-treated patients after receiving deferred treatment.
The overall SVR rate after 12 weeks was 98.6%, excluding patients who had discontinued for reasons not related to the study drug.
Among 12 patients who failed to achieve SVR at 12 weeks, 3 had a virologic relapse, 1 discontinued due to an adverse event and 8 had administrative reasons.
Serious adverse events were reported in 16 (14%) patients in the GZR/EBR group and in 17 (15%) patients in the placebo group prior to their deferred treatment. The rate of discontinuation due to an adverse event in GZR/EBR-treated patients was 0% versus 4% in placebo-treated patients.
“Once-daily GZR/EBR for 12 weeks was highly effective with a low rate of adverse events in patients with advanced kidney disease and HCV genotype 1 infection,” wrote David Roth, MD, University of Miami, Miami, Florida, and colleagues in their presentation.
Funding for this study was provided by Merck.
[Presentation title: Grazoprevir (GZR)/Elbasvir (EBR) Treatment of Hepatitis C Virus (HCV) Infection in Patients With Chronic Kidney Disease Stage 4/5: Final Results of the C-SURFER Phase 3 Study]
To read more Conference Dispatch articles, click here.
SAN DIEGO -- November 10, 2015 -- The combination of grazoprevir (GZR) and elbasvir (EBR), in a single tablet, shows strong efficacy in the treatment of hepatitis C virus (HCV) in patients with stage 4 or 5 chronic kidney disease (CKD), researchers reported here at Kidney Week 2015, the Annual Meeting of the American Society of Nephrology (ASN).
The once-daily therapy combines a NS3/4A protease inhibitor and an NS5A replication complex inhibitor and is being investigated for a variety of HCV genotypes and in conditions ranging from HIV/HCV co-infection to opiate substitution therapy and liver cirrhosis.
The C-SURFER trial included 224 patients with stage 4 or 5 CKD who were on haemodialysis and had concomitant HCV genotype 1. Patients were randomised to either immediate treatment with GZR/EBR 100 mg/50 mg (n = 111) or deferred treatment, which consisted of placebo for 12 weeks followed by GZR/EBR 100 mg/50 mg.
The sustained virologic response (SVR) rate 12 weeks post-therapy in the GZR/EBR group was 94.6%, compared with 95% in placebo-treated patients after receiving deferred treatment.
The overall SVR rate after 12 weeks was 98.6%, excluding patients who had discontinued for reasons not related to the study drug.
Among 12 patients who failed to achieve SVR at 12 weeks, 3 had a virologic relapse, 1 discontinued due to an adverse event and 8 had administrative reasons.
Serious adverse events were reported in 16 (14%) patients in the GZR/EBR group and in 17 (15%) patients in the placebo group prior to their deferred treatment. The rate of discontinuation due to an adverse event in GZR/EBR-treated patients was 0% versus 4% in placebo-treated patients.
“Once-daily GZR/EBR for 12 weeks was highly effective with a low rate of adverse events in patients with advanced kidney disease and HCV genotype 1 infection,” wrote David Roth, MD, University of Miami, Miami, Florida, and colleagues in their presentation.
Funding for this study was provided by Merck.
[Presentation title: Grazoprevir (GZR)/Elbasvir (EBR) Treatment of Hepatitis C Virus (HCV) Infection in Patients With Chronic Kidney Disease Stage 4/5: Final Results of the C-SURFER Phase 3 Study]
To read more Conference Dispatch articles, click here.
Tuesday, October 20, 2015
Merck to Present New Data on HCV Treatment Elbasvir/Grazoprevir at The Liver Meeting® 2015
Merck to Present New Data on Investigational Chronic Hepatitis C Treatment Elbasvir/Grazoprevir at The Liver Meeting® 2015, Including Phase 3 Results in Selected Difficult-to-Treat Populations
New Data Will Also be Presented from Phase 2a C-CREST Trials of Merck’s Investigational Triple-Combination Chronic Hepatitis C Therapies
KENILWORTH, N.J., Oct 20, 2015 (BUSINESS WIRE) -- Merck MRK, -1.56% known as MSD outside the United States and Canada, today announced that new data from clinical trials of its investigational treatment portfolio for chronic hepatitis C virus (HCV) are scheduled to be presented at The Liver Meeting [®] 2015 (the 66 [th] annual scientific congress of the American Association for the Study of Liver Diseases) in San Francisco, from Nov. 13-17, 2015. Merck’s late-stage investigational portfolio includes elbasvir/grazoprevir [1] , MK-3682 [2] and MK-8408 [3] .
A range of data will be presented from more than 20 accepted abstracts. Among these are two late-breaking abstracts from the C-CREST and C-SWIFT clinical trial programs.
“Recent innovations in the treatment of chronic hepatitis C are enabling health systems and physicians to address the burden of this disease. Continued innovation is essential, particularly for patients for whom current therapies may not be suitable,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Merck is committed to evaluating our chronic hepatitis C investigational medicines in a broad range of patients and treatment durations to help address the global unmet needs that still exist.”
Elbasvir/grazoprevir is currently under Priority Review with the U.S. Food and Drug Administration, with a Prescription Drug User Fee Act (PDUFA) action date of Jan. 28, 2016.
Key Presentations of Interest
Oral Presentations for Elbasvir/Grazoprevir
Sunday, Nov. 15:
C-EDGE CO-STAR: Efficacy of Grazoprevir and Elbasvir in Persons Who Inject Drugs (PWID) Receiving Opioid Agonist Therapy (Abstract #40, 3:45 – 4:00 p.m. PST)
An Integrated Analysis of 402 Compensated Cirrhotic Patients With HCV Genotype (GT) 1, 4 or 6 Infection Treated With Grazoprevir/Elbasvir (Abstract #42, 4:15 – 4:30 p.m. PST)
Tuesday, Nov. 17:
High Efficacy of Grazoprevir/Elbasvir (GZR/EBR) in HCV Genotype 1, 4, and 6-Infected Patients With HIV Coinfection: SVR24 Data From the Phase 3 C-EDGECoinfection Study (Abstract #210, 9:15 – 9:30 a.m. PST)
High Efficacy of Grazoprevir and Elbasvir With or Without Ribavirin in 103 Treatment-Naive and Experienced Patients With HCV Genotype 4 Infection: A Pooled Analysis (Abstract #251, 12:15 – 12:30 p.m. PST)
Late-Breaking Presentations
Monday, Nov. 16:
Poster: Prevalence and Impact of Baseline NSA Resistance Associated Variants (RAVs) on the Efficacy of Elbasvir/Grazoprevir (EBR/GZR) against GT1a Infection (Abstract #LB-22)
Poster: Phase 2, Randomized, Open-Label Clinical Trials of the Efficacy and Safety of Grazoprevir and MK-3682 (NS5B Polymerase Inhibitor) with Either Elbasvir or MK-8408 (NS5A Inhibitor) in Patients with Chronic HCV GT1, 2 or 3 Infection (Part A of C-CREST-1 & 2) (Abstract #LB-15)
Poster:C-SWIFT Retreatment (Part B): 12 weeks of Elbasvir/Grazoprevir with Sofosbuvir and Ribavirin Successfully Treated GT1-infected Subjects who Failed Short-Duration All-Oral Therapy (Abstract #LB-12)
Select Poster Presentations for Elbasvir/Grazoprevir
Saturday, Nov. 14:
Projected Long-Term Impact of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) in Treatment-Naive and Treatment-Experienced Patients with Hepatitis C Virus Genotype 1 Infection and Chronic Kidney Disease (Abstract #727)
C-EDGE Co-Infection: Impact of 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) on Patient-Reported Outcomes (PROs) in Treatment-Naïve Patients with HCV/HIV Co-infection (Abstract #729)
C-EDGE TN: Impact of 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) on Patient-Reported Outcomes (PROs) in Treatment-Naïve Patients with Chronic Hepatitis C Virus (HCV) Genotype (GT) 1, 4, or 6 Infection (Abstract #717)
High Efficacy of the Combination HCV Regimen Grazoprevir and Elbasvir for 8 or 12 Weeks With or Without Ribavirin in Treatment-Naive, Noncirrhotic HCV GT1b–Infected Patients: An Integrated Analysis (Abstract #701)
Predictors of Response to Grazoprevir/Elbasvir Among HCV Genotype 1 (GT1)–Infected Patients: Integrated Analysis of Phase 2-3 Trials (Abstract #700)
Safety and Tolerability of Grazoprevir/Elbasvir in Patients With Chronic Hepatitis C (HCV) Infection: Integrated Analysis of Phase 2-3 Trials (Abstract #712)
The Combination of Grazoprevir and Elbasvir ± RBV is Highly Effective for the Treatment of GT1a-Infected Patients (Abstract #703)
Efficacy, Safety And Pharmacokinetics Of Grazoprevir (MK-5172) And Elbasvir (MK-8742) In Hepatitis C Genotype 1 Infected Non-Cirrhotic Japanese Patients (Phase 2 Portion In Phase 2/3 Combined Study) (Abstract #707)
For more information, including a complete list of abstract titles, please visit:http://www.aasld.org.
About Elbasvir/Grazoprevir
Elbasvir/grazoprevir is Merck’s investigational, once-daily, fixed-dose combination therapy containing elbasvir (HCV NS5A replication complex inhibitor) and grazoprevir (HCV NS3/4A protease inhibitor). Merck’s broad clinical trials program includes evaluations of elbasvir/grazoprevir with or without ribavirin for multiple HCV genotypes, together with patients with difficult-to-treat conditions such as cirrhosis, advanced chronic kidney disease, HIV/HCV co-infection, inherited blood disorders and those on opiate substitution therapy. In July 2015, the U.S. Food and Drug Administration (FDA) granted Priority Review for the New Drug Application for elbasvir/grazoprevir, with a Prescription Drug User Fee Act (PDUFA) action date of Jan. 28, 2016.
In April 2015, the FDA granted Breakthrough Therapy designation for elbasvir/grazoprevir for the treatment of patients with chronic HCV GT1 infection with end stage renal disease on hemodialysis, and Breakthrough Therapy designation for elbasvir/grazoprevir for the treatment of patients with chronic HCV GT4 infection. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Merck’s Commitment to HCV
For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.
About Merck
Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook andYouTube.
Forward-Looking Statement of Merck & Co. Inc., Kenilworth, NJ, USA
This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
[1] Elbasvir is an HCV NS5A replication complex inhibitor and grazoprevir is an HCV NS3/4A protease inhibitor
[2] MK-3682 is an oral prodrug HCV nucleotide analogue NS5B polymerase inhibitor
[3] MK-8408 is an HCV NS5A replication complex inhibitor
http://www.businesswire.com/news/home/20151020006240/en/
New Data Will Also be Presented from Phase 2a C-CREST Trials of Merck’s Investigational Triple-Combination Chronic Hepatitis C Therapies
KENILWORTH, N.J., Oct 20, 2015 (BUSINESS WIRE) -- Merck MRK, -1.56% known as MSD outside the United States and Canada, today announced that new data from clinical trials of its investigational treatment portfolio for chronic hepatitis C virus (HCV) are scheduled to be presented at The Liver Meeting [®] 2015 (the 66 [th] annual scientific congress of the American Association for the Study of Liver Diseases) in San Francisco, from Nov. 13-17, 2015. Merck’s late-stage investigational portfolio includes elbasvir/grazoprevir [1] , MK-3682 [2] and MK-8408 [3] .
A range of data will be presented from more than 20 accepted abstracts. Among these are two late-breaking abstracts from the C-CREST and C-SWIFT clinical trial programs.
“Recent innovations in the treatment of chronic hepatitis C are enabling health systems and physicians to address the burden of this disease. Continued innovation is essential, particularly for patients for whom current therapies may not be suitable,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Merck is committed to evaluating our chronic hepatitis C investigational medicines in a broad range of patients and treatment durations to help address the global unmet needs that still exist.”
Elbasvir/grazoprevir is currently under Priority Review with the U.S. Food and Drug Administration, with a Prescription Drug User Fee Act (PDUFA) action date of Jan. 28, 2016.
Key Presentations of Interest
Oral Presentations for Elbasvir/Grazoprevir
Sunday, Nov. 15:
C-EDGE CO-STAR: Efficacy of Grazoprevir and Elbasvir in Persons Who Inject Drugs (PWID) Receiving Opioid Agonist Therapy (Abstract #40, 3:45 – 4:00 p.m. PST)
An Integrated Analysis of 402 Compensated Cirrhotic Patients With HCV Genotype (GT) 1, 4 or 6 Infection Treated With Grazoprevir/Elbasvir (Abstract #42, 4:15 – 4:30 p.m. PST)
Tuesday, Nov. 17:
High Efficacy of Grazoprevir/Elbasvir (GZR/EBR) in HCV Genotype 1, 4, and 6-Infected Patients With HIV Coinfection: SVR24 Data From the Phase 3 C-EDGECoinfection Study (Abstract #210, 9:15 – 9:30 a.m. PST)
High Efficacy of Grazoprevir and Elbasvir With or Without Ribavirin in 103 Treatment-Naive and Experienced Patients With HCV Genotype 4 Infection: A Pooled Analysis (Abstract #251, 12:15 – 12:30 p.m. PST)
Late-Breaking Presentations
Monday, Nov. 16:
Poster: Prevalence and Impact of Baseline NSA Resistance Associated Variants (RAVs) on the Efficacy of Elbasvir/Grazoprevir (EBR/GZR) against GT1a Infection (Abstract #LB-22)
Poster: Phase 2, Randomized, Open-Label Clinical Trials of the Efficacy and Safety of Grazoprevir and MK-3682 (NS5B Polymerase Inhibitor) with Either Elbasvir or MK-8408 (NS5A Inhibitor) in Patients with Chronic HCV GT1, 2 or 3 Infection (Part A of C-CREST-1 & 2) (Abstract #LB-15)
Poster:C-SWIFT Retreatment (Part B): 12 weeks of Elbasvir/Grazoprevir with Sofosbuvir and Ribavirin Successfully Treated GT1-infected Subjects who Failed Short-Duration All-Oral Therapy (Abstract #LB-12)
Select Poster Presentations for Elbasvir/Grazoprevir
Saturday, Nov. 14:
Projected Long-Term Impact of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) in Treatment-Naive and Treatment-Experienced Patients with Hepatitis C Virus Genotype 1 Infection and Chronic Kidney Disease (Abstract #727)
C-EDGE Co-Infection: Impact of 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) on Patient-Reported Outcomes (PROs) in Treatment-Naïve Patients with HCV/HIV Co-infection (Abstract #729)
C-EDGE TN: Impact of 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) on Patient-Reported Outcomes (PROs) in Treatment-Naïve Patients with Chronic Hepatitis C Virus (HCV) Genotype (GT) 1, 4, or 6 Infection (Abstract #717)
High Efficacy of the Combination HCV Regimen Grazoprevir and Elbasvir for 8 or 12 Weeks With or Without Ribavirin in Treatment-Naive, Noncirrhotic HCV GT1b–Infected Patients: An Integrated Analysis (Abstract #701)
Predictors of Response to Grazoprevir/Elbasvir Among HCV Genotype 1 (GT1)–Infected Patients: Integrated Analysis of Phase 2-3 Trials (Abstract #700)
Safety and Tolerability of Grazoprevir/Elbasvir in Patients With Chronic Hepatitis C (HCV) Infection: Integrated Analysis of Phase 2-3 Trials (Abstract #712)
The Combination of Grazoprevir and Elbasvir ± RBV is Highly Effective for the Treatment of GT1a-Infected Patients (Abstract #703)
Efficacy, Safety And Pharmacokinetics Of Grazoprevir (MK-5172) And Elbasvir (MK-8742) In Hepatitis C Genotype 1 Infected Non-Cirrhotic Japanese Patients (Phase 2 Portion In Phase 2/3 Combined Study) (Abstract #707)
For more information, including a complete list of abstract titles, please visit:http://www.aasld.org.
About Elbasvir/Grazoprevir
Elbasvir/grazoprevir is Merck’s investigational, once-daily, fixed-dose combination therapy containing elbasvir (HCV NS5A replication complex inhibitor) and grazoprevir (HCV NS3/4A protease inhibitor). Merck’s broad clinical trials program includes evaluations of elbasvir/grazoprevir with or without ribavirin for multiple HCV genotypes, together with patients with difficult-to-treat conditions such as cirrhosis, advanced chronic kidney disease, HIV/HCV co-infection, inherited blood disorders and those on opiate substitution therapy. In July 2015, the U.S. Food and Drug Administration (FDA) granted Priority Review for the New Drug Application for elbasvir/grazoprevir, with a Prescription Drug User Fee Act (PDUFA) action date of Jan. 28, 2016.
In April 2015, the FDA granted Breakthrough Therapy designation for elbasvir/grazoprevir for the treatment of patients with chronic HCV GT1 infection with end stage renal disease on hemodialysis, and Breakthrough Therapy designation for elbasvir/grazoprevir for the treatment of patients with chronic HCV GT4 infection. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Merck’s Commitment to HCV
For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.
About Merck
Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook andYouTube.
Forward-Looking Statement of Merck & Co. Inc., Kenilworth, NJ, USA
This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
[1] Elbasvir is an HCV NS5A replication complex inhibitor and grazoprevir is an HCV NS3/4A protease inhibitor
[2] MK-3682 is an oral prodrug HCV nucleotide analogue NS5B polymerase inhibitor
[3] MK-8408 is an HCV NS5A replication complex inhibitor
http://www.businesswire.com/news/home/20151020006240/en/
Tuesday, September 29, 2015
Full Text: HCV targeting of patients with cirrhosis
October 2015
Volume 63, Issue 4, Pages 1015–1022
HCV targeting of patients with cirrhosis
Volume 63, Issue 4, Pages 1015–1022
HCV targeting of patients with cirrhosis
Peter Ferenci, Karin Kozbial
, Mattias Mandorfer
, Harald Hofer
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
Received: March 11, 2015; Received in revised form: June 9, 2015; Accepted: June 10, 2015; Published Online: June 19, 2015 Article has an altmetric score of 10
DOI: http://dx.doi.org/10.1016/j.jhep.2015.06.003
[Free review] @ Journal Of Hepatology
Summary
Interferon (IFN)-free treatments are now the treatment of choice for patients with chronic hepatitis C. Previously difficult to treat patients by IFN-containing treatments can now be treated safely by IFN-free therapies. More than 90% of hepatitis C genotype 1 and 4 patients with compensated cirrhosis or after orthotopic liver transplantation (OLT) can be cured by sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the paritaprevir/ritona-vir/ombitasvir/±dasabuvir (3D) combination. Addition of ribavirin confers to a minimal, if any, benefit to increase SVR. The need for ribavirin is controversial and remains to be studied. The optimal length of treatment is still unknown, and an individual approach may be needed. Most patients require only 12 weeks of therapy. The safety of these drugs is not fully explored in patients with decompensated cirrhosis (Child-Pugh C), who should not be treated with protease inhibitors. In cirrhosis hepatitis C virus eradication does not necessarily mean a cure of the disease and patients regularly require follow-up. Drug-drug interactions with immunosuppressant in patients after OLT are easier to manage but still require attention. Better drugs are needed for genotype 3 patients
Table 1
Received: March 11, 2015; Received in revised form: June 9, 2015; Accepted: June 10, 2015; Published Online: June 19, 2015 Article has an altmetric score of 10
DOI: http://dx.doi.org/10.1016/j.jhep.2015.06.003
[Free review] @ Journal Of Hepatology
- Read Online
- Download PDF (746 KB)
Summary
Interferon (IFN)-free treatments are now the treatment of choice for patients with chronic hepatitis C. Previously difficult to treat patients by IFN-containing treatments can now be treated safely by IFN-free therapies. More than 90% of hepatitis C genotype 1 and 4 patients with compensated cirrhosis or after orthotopic liver transplantation (OLT) can be cured by sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the paritaprevir/ritona-vir/ombitasvir/±dasabuvir (3D) combination. Addition of ribavirin confers to a minimal, if any, benefit to increase SVR. The need for ribavirin is controversial and remains to be studied. The optimal length of treatment is still unknown, and an individual approach may be needed. Most patients require only 12 weeks of therapy. The safety of these drugs is not fully explored in patients with decompensated cirrhosis (Child-Pugh C), who should not be treated with protease inhibitors. In cirrhosis hepatitis C virus eradication does not necessarily mean a cure of the disease and patients regularly require follow-up. Drug-drug interactions with immunosuppressant in patients after OLT are easier to manage but still require attention. Better drugs are needed for genotype 3 patients
Table 1
Impact of treatment duration and addition of ribavirin on the response to IFN-free treatments in patients with cirrhosis due to HCV-GT1 infection.
[Free review] @ Journal Of Hepatology
Click Image To Enlarge
[Free review] @ Journal Of Hepatology
- Read Online
- Download PDF (746 KB)
© 2015 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
Saturday, September 19, 2015
Hepatitis C-Salvage Study Grazoprevir and Elbasvir Plus Ribavirin: Final 24-week Follow-up Results
C-SALVAGE: Final 24-week Follow-up Results
Posted on September 17, 2015
Posted on September 17, 2015
Non-cross-resistant drugs are needed for salvage therapy of patients with chronic hepatitis C virus infection who do not achieve sustained virologic response on direct acting antiviral (DAA) regimens. The final follow-up week 24 results from the C-SALVAGE study (Hepatitis C-Salvage Study for Patients who Failed DAA/PR Therapy), have been published in the journal Clinical Infectious Diseases (Buti M, et al. Clin Infect Dis. 2015 Sep 14. [Epub ahead of print]).
In the C-SALVAGE study, an interferon free combination of grazoprevir (an NS3/4A protease inhibitor) and elbasvir (an NS5A inhibitor) with ribavirin was used to treat patients with chronic HCV genotype 1 infection who had previously failed triple therapy with pegylated interferon and ribavirin plus an earlier-generation protease inhibitor. Both SVR12 and SVR24 were achieved in all but 3 patients who had relapsed by or before follow-up week 8, yielding a durable response rate of 76 of 79 (96.2%), which likely reflects the cure rate.
The international, open-label, phase 2, C-SALVAGE study (Hepatitis C-Salvage Study for Patients who Failed DAA/PR Therapy) established that a non-cross-resistant protease inhibitor such as grazoprevir could be successfully used with a potent DAA of another class to treat patients harboring signature NS3 variants resistant to earlier protease inhibitors. The primary results were recently published in the Journal of Hepatology (Forns X, et al. J Hepatol. 2015;63:564–72).
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C-SALVAGE: Final 24-week Follow-up Results
HCV Drug Costs: A Treatment Access Barrier
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In the C-SALVAGE study, an interferon free combination of grazoprevir (an NS3/4A protease inhibitor) and elbasvir (an NS5A inhibitor) with ribavirin was used to treat patients with chronic HCV genotype 1 infection who had previously failed triple therapy with pegylated interferon and ribavirin plus an earlier-generation protease inhibitor. Both SVR12 and SVR24 were achieved in all but 3 patients who had relapsed by or before follow-up week 8, yielding a durable response rate of 76 of 79 (96.2%), which likely reflects the cure rate.
The international, open-label, phase 2, C-SALVAGE study (Hepatitis C-Salvage Study for Patients who Failed DAA/PR Therapy) established that a non-cross-resistant protease inhibitor such as grazoprevir could be successfully used with a potent DAA of another class to treat patients harboring signature NS3 variants resistant to earlier protease inhibitors. The primary results were recently published in the Journal of Hepatology (Forns X, et al. J Hepatol. 2015;63:564–72).
- 79 patients (including 30 patients with genotype 1a infections [38%] and 34 patients with cirrhosis [43%]) were retreated with grazoprevir 100 mg/day and elbasvir 50 mg/day plus ribavirin after having failed at least 4 weeks of combination therapy with pegylated interferon and ribavirin (PR) plus either boceprevir, telaprevir, or simeprevir
- A total of 66 (84%) patients had a history of virologic failure.
- Despite a high prevalence of NS3 variants at baseline, the overall SVR rate at 12 weeks (SVR12) was 96.2% (76/79) due to 3 patients relapsing during the initial 8 weeks of post-therapy follow-up coincident with the emergence of NS3 ± NS5A RAVs
- 78 patients (99%) completed their final scheduled visit at follow-up week 24. One patient who had completed the prescribed course of treatment dropped out of the study at follow-up week 6 after relapsing 4 weeks after cessation of therapy.
- SVR24 was attained in 76 of 79 patients (96.2% [95% CI, 89.3%–99.2%]) overall, in 28 of 30 (93.3%) patients with genotype 1a infection, 63 of 66 (95.5%) patients with prior virologic failure, 33 of 36 (91.7%) patients with baseline NS3 and/or NS5 RAVs, and 32 of 34 (94.1%) patients with cirrhosis. No further relapses occurred subsequent to follow-up week 8, and undetectable HCV RNA levels were maintained in these 76 patients throughout the full 24 weeks of follow up.
- After removal of 9 patients for serious protocol violations during the treatment period, 68 of the 70 (97.1%) patients remaining in the primary per-protocol population achieved SVR24
- 3 patients relapsed during the initial 8 weeks of post-therapy follow-up, coincident with the emergence of NS3 ± NS5A RAVs
- Every NS3 and NS5A variant detected at baseline reappeared at the time of relapse and persisted throughout the available follow up period, suggesting that virus persisted below the level of detection while on treatment
- NS3_A156T (conferring >5 times increase in grazoprevir EC50 in vitro) emerged in virus from each patient at relapse, but rapidly disappeared over the ensuing 2 weeks in 2 patients
- NS5A_Y93H (conferring a >5 times increase in elbasvir EC50 in vitro) emerged in virus from 2 patients at relapse and persisted for the entire follow-up period
Recent Posts
New HCV Peer-Reviewed PDFs For Free!
C-SALVAGE: Final 24-week Follow-up Results
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