2 New Easy C Treatment Fact Sheets

Be sure to check out these 2 new Easy C Facts fact sheets on treatment for Genotype 3 and Genotype 4

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Bristol-Myers wins approval for 1st hepatitis C type 3 drug

TRENTON, N.J. (AP) - An experimental drug for one of the hardest-to-treat types of hepatitis C has been approved by the Food and Drug Administration, adding to the surge of new options - all much more effective but extremely costly - for patients with the liver-destroying virus.

Daklinza, developed by New York-based Bristol-Myers Squibb Co., is the first drug approved to treat genotype 3, the second-most-common form. About 10 percent of Americans with hepatitis C have genotype 3.

Because genotype 3 is so hard to cure and damages the liver more quickly than other types, Daklinza is to be taken with Sovaldi, one of two blockbuster hepatitis C drugs sold by market leader Gilead Sciences Inc., along with Harvoni.

Meanwhile, the FDA on Friday also approved Technivie, a combination drug made by AbbVie Inc. for one of the least common forms of hepatitis C, genotype 4. Technivie also must be taken with a second drug, a much-older, generic pill called ribavirin.

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FDA approves Technivie for treatment of chronic hepatitis C genotype 4

For Immediate Release

July 24, 2015

The U.S. Food and Drug Administration today approved Technivie (ombitasvir, paritaprevir and ritonavir) for use in combination with ribavirin for the treatment of hepatitis C virus (HCV) genotype 4 infections in patients without scarring and poor liver function (cirrhosis).

Technivie in combination with ribavirin is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for co-administration of interferon, an FDA-approved drug also used to treat HCV infection.

“Today’s approval provides the first treatment option for patients with genotype 4 HCV infections without requiring use of interferon,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take several years. Some people with chronic HCV infection develop cirrhosis over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections or liver cancer. According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV, of which genotype 4 is one of the least common.

The safety and efficacy of Technivie with ribavirin were evaluated in a clinical trial of 135 participants with chronic HCV genotype 4 infections without cirrhosis. Ninety-one participants received Technivie with ribavirin once daily for 12 weeks. Forty-four participants received Technivie once daily without ribavirin for 12 weeks. The studies were designed to measure whether a participant’s hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured.

Results showed that 100 percent of the participants who received Technivie with ribavirin achieved a sustained virologic response. Of those who received Technivie without ribavirin, 91 percent achieved sustained virologic response.

Safety information was available for 316 participants with HCV treated with the recommended dose of Technivie in combination with other anti-HCV drugs in clinical trials. The three drugs included in Technivie are also included in Viekira Pak, previously approved for the treatment of HCV genotype 1 infection. Additional safety information for those drugs was available from the Viekira Pak trials. The most common side effects of Technivie with ribavirin were fatigue, weakness (asthenia), nausea, insomnia, itching (pruritus) and other skin reactions.

Technivie carries a warning alerting patients and health care providers that elevations of liver enzymes to greater than five times the upper limit of normal occurred in approximately 1 percent of clinical trial participants. The elevations occurred more frequently in females taking contraceptives containing ethinyl estradiol. Contraceptives containing ethinyl estradiol must be discontinued prior to starting Technivie. Hepatic laboratory testing should be performed during the first four weeks of starting treatment, and as clinically indicated thereafter.

Technivie and Viekira Park are marketed by AbbVie Inc. based in North Chicago, Illinois.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Press Release Source:  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455857.htm

EASL 2015: Part 2 —Alan Franciscus, Editor-in-Chief

In part 2 of our European Association for the Study of the Liver (EASL) coverage I will wrap up with a brief overview of some of the remaining data. 

AbbVie:  Ombitasvir/Paritaprevir/Ritonavir for Treatment of HCV Genotype 1b In Japanese Patients with or without Cirrhosis: Results from Gift-I –K Chayama et al

In this current study, Japanese patients were treated with AbbVie’s 2D (paritaprevir/ritonavir plus ombitasvir) given once-a-day for 12 weeks.  This is different from the 3D regime given in the United States and elsewhere because Japanese patients metabolize AbbVie’s drugs differently.  With the 2D combinations Japanese patients reach high enough levels even without ribavirin or dasabuvir.    

In the study there were 215 HCV genotype 1b patients who received the study drugs, 42% were cirrhotic, and 35% were treatment experienced.  The overall cure rate was 95%.  The cure rates among those who had never been treated, as well as those who were treated previously (cirrhotic and non-cirrhotic) were all similar.  The most common side effects were headache, edema and sore throat. 

Comments:  Japan has a long history of hepatitis C.  AbbVie’s 2D combination will be a welcome addition to the drugs in Japan to treat Japanese patients.  For more information about HCV in Japan check out our HCV in Japan—HCV Around the World series.

 

NHANES:  Advanced Fibrosis is Common in Individuals whose Hepatitis C Has Not Been Diagnosed: Results from the National Health and Nutrition Examination Survey 2001-2012—P Udompap et al

This study has been reported at previous conferences, but it is worth discussing again.  The National Health and Nutrition Examination Survey (NHANES) used data from a group of 62,000 American adults of whom 45,000 were tested for hepatitis C antibodies—591 tested antibody positive and of those 420 were HCV RNA or viral load positive. 

Of the 420 who had chronic hepatitis C, 1 in 10 had cirrhosis and 1 in 5 had advanced fibrosis.  Approximately 50% did not know that they had hepatitis C. 

Comments:  This validates the recommendation for “Baby Boomer” testing.  This should WAKE UP the complacency among physicians and associations and start testing baby boomers NOW.  We want to test, monitor, treat, cure and save lives.

 

Gilead:  Ledipasvir/sofosbuvir treatment results in high SVR rates in patients with chronic genotype 4 and 5 HCV infection— A Abergel et al

A total of 44 HCV genotype 4 patients and 41 HCV genotype 5 patients were treated with the combination of sofosbuvir and ledipasvir for 12 weeks.  In both of the groups the patients were evenly divided between treatment experienced (TE) and those who had never been treated (TN) and those with and without cirrhosis (C & w/o C).  The cure rates in the HCV genotype 4 patients was TN =96% (21 of 22 pts); TE = 91% (20 of 22 pts); C= 100% (10 of 10 pts); w/o C = 91% (31 of 34 pts).  The most common side effects were fatigue and headache.

 

Comments:  These are very good cure rates with few side effects.  While the population of genotype 4 and 5 in the United States is very low—genotype 4 is very high in Egypt and other parts of the world (see HCV in Egypt in our HCV Around the World series).  Genotype 5 is primarily seen in South Africa and parts of Europe.  I will be writing an article on Genotype 5 for the June Mid-Monthly edition so stay-tuned.

 

Merck: The Phase 3 C-Edge Treatment-Naive (TN) Study of a 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) in Patients with Chronic HCV Genotype (Gt) 1, 4, or 6 Infection—S Zeuzem et al

This was a phase 3 study of a one pill, once-a-day grazoprevir and elbasvir pill taken for 12 weeks.  The study included treatment naïve (TN). The trial included a total of 421 infected HCV genotype 1, 4 or 6.  Most of the trial participants were male sex, and White.  Ninety-one percent were genotype 1.   Approximately 22% had cirrhosis. 

The overall cure rate was 95%: 92% for genotype 1a and 99% for genotype 1b; 100% (36 of 36 pts) of the genotype 4 patients were cured; 80% (5 of 6 pts) of genotype 6 patients were cured.  The most common side effects were headache, fatigue, nausea and joint pain.

 
Comments:  These are high cure rates with a low side effect profile and it will make a good addition to the treatment landscape of HCV in 2016.  In people with the genotype 1a NS5A resistance-associated variants (RAVs) it shows greater than a 5-fold loss in sensitivity to elbasvir (a protease inhibitor).  What this means in clinical practice in unknown at this time.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615.html#1

Merck’s Pivotal Phase 3 C-EDGE Program Evaluating Grazoprevir/Elbasvir Shows High Sustained Virologic Responses Across Broad Range of Patients with Chronic Hepatitis C Virus Infection

• Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection
• Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015

 VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentations of data from the company’s ongoing C-EDGE pivotal Phase 3 clinical trial program evaluating the investigational once-daily tablet grazoprevir/elbasvir (100mg/50mg) in patients with or without cirrhosis who are infected with chronic hepatitis C virus (HCV) genotypes 1, 4 or 6 (GT1, 4 or 6).1 Patients in both the HCV infected, treatment-naïve (C-EDGE TN), and HIV/HCV co-infected, treatment-naïve (C-EDGE CO-INFXN) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95 percent (299/316 and 207/218, respectively). In addition, HCV infected, treatment-experienced patients (C-EDGE TE) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94 percent (98/104) and 92 percent (97/105), respectively, and those treated for 16 weeks achieved SVR12 rates of 97 percent (103/106) and 92 percent (97/105), respectively. These data were presented at The International Liver CongressTM 2015 – the 50th annual congress of the European Association for the Study of the Liver (Abstract #G07, E-Poster P0886 and E-Poster P0887). A paper detailing the findings of C-EDGE TN was published online in the Annals of Internal Medicine today.

“Patients with co-morbidities and varying treatment experiences represent important segments of the chronic hepatitis C population in need of additional innovative treatment options,” said Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute and clinical professor of medicine, The University of Texas Health Science Center, San Antonio. “These findings are important because they demonstrate that a single pill of grazoprevir/elbasvir taken once-daily achieved consistently high rates of SVR12 in the patient populations studied.”

Summary of SVR12 findings: C-EDGE TN, C-EDGE CO-INFXN, C-EDGE TE

C-EDGE TN

C-EDGE CO-INFXN

C-EDGE TE

Without RBV (n=316)

Without RBV (n=218)

Without RBV (n=105)

With RBV (n=104)

Without RBV (n=105)

With RBV (n=106)

Duration

12 weeks

12 weeks

12 weeks

12 weeks

16 weeks

16 weeks

All Patients:

95%

95%

92%

94%

92%

97%

SVR12

(299/316)

(207/218)

(97/105)

(98/104)

(97/105)

(103/106)

Cirrhotic

97%

100%

89%

89%

92%

100%

(68/70)

(35/35)

(33/37)

(31/35)

(35/38)

(37/37)

Non-cirrhotic

94%

94%

94%

97%

93%

96%

(231/246)

(172/183)

(64/68)

(67/69)

(62/67)

(66/69)

Genotype 1a

92%

94%

90%

93%

94%

95%

(144/157)

(136/144)

(55/61)

(56/60)

(45/48)

(55/58)

Genotype 1b or

other Genotype

99%

96%

100%

97%

96%

100%

1

(129/131)

(43/45)

(35/35)

(28/29)

(46/48)

(38/38)

Genotype 4

100%

96%

78%

93%

60%

100%

(18/18)

(27/28)

(7/9)

(14/15)

(3/5)

(8/8)

Genotype 6

80%

100%

75%

100%

(8/10)

(1/1)

N/A

N/A

(3/4)

(2/2)

“At Merck, we continue to build upon our clinical experience using grazoprevir/elbasvir across diverse populations of patients infected with chronic hepatitis C virus,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We remain on track to submit a New Drug Application with the U.S. Food and Drug Administration in the first half of 2015.”

C-EDGE TN Overview and Additional Findings
C-EDGE TN is a randomized, blinded, placebo-controlled trial evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks. Patients were randomized to an immediate treatment group that received grazoprevir/elbasvir for 12 weeks or to a deferred treatment group that received placebo for 12 weeks, were followed for an additional four weeks, and then received open label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included those patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of the 316 patients who received immediate treatment with grazoprevir/elbasvir, 50 percent were infected with GT1a, 42 percent with GT1b, six percent with GT4 and three percent with GT6. Overall, 22 percent of patients had liver cirrhosis.

In this study, virologic failure occurred in 13 patients (4%) in the immediate treatment group, including one virologic breakthrough and 12 virologic relapses. Serious adverse events occurred in nine (3%) and three (3%) patients in the immediate treatment and corresponding placebo arms, respectively; none were considered drug-related. The most common adverse events reported (greater than 5% incidence) in the immediate treatment and corresponding placebo groups, were headache (17%, 18%), fatigue (16%, 17%), nausea (9%, 8%) and arthralgia (6%, 6%), respectively.

C-EDGE CO-INFXN Overview and Additional Findings
C-EDGE CO-INFXN is an open label, single-arm study evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 and HIV who received therapy for 12 weeks. Of the 218 patients enrolled in the trial, 66 percent were infected with HCV GT1a, 21 percent with GT1b or other GT1, 13 percent with GT4, and one percent with GT6. Overall, 16 percent of patients had liver cirrhosis.
In this study, virologic failure occurred in seven patients (3%), including six virologic relapses and one reinfection. There were no reported drug-related serious adverse events. The most common (greater than 5% incidence) adverse events reported were fatigue (13%), headache (12%) and nausea (9%).

C-EDGE TE Overview and Additional Findings
C-EDGE TE is a randomized study evaluating the efficacy and safety of once-daily grazoprevir/elbasvir with or without twice-daily RBV in treatment-experienced (prior null response, partial response or relapse with peg-interferon/RBV) patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks or 16 weeks.

12 week arms
 Of the 209 patients randomized to the 12 week arms, 105 patients received grazoprevir/elbasvir only and 104 patients received grazoprevir/elbasvir plus RBV. Patients in the grazoprevir/elbasvir only arm comprised 58 percent GT1a, 33 percent GT1b or other GT1 and nine percent GT4. Overall, 35 percent had liver cirrhosis. Among the 104 patients receiving grazoprevir/elbasvir plus RBV, 58 percent were infected with chronic HCV GT1a, 28 percent GT1b or other GT1, and 14 percent GT4. Overall, 34 percent had liver cirrhosis.

In the grazoprevir/elbasvir only and grazoprevir/elbasvir plus RBV arms, six patients in each arm (6%) were reported to have virologic relapse. No patients were reported to have virologic breakthrough or rebound. Serious adverse events were reported in four patients in the grazoprevir/elbasvir only arm (4%) and three patients in the grazoprevir/elbasvir plus RBV arm (3%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (19%, 27%), headache (21%, 20%) and nausea (9%, 14%).

16 week arms
Of the 211 patients enrolled in the 16 week arms, 105 patients received grazoprevir/elbasvir only and 106 patients received grazoprevir/elbasvir plus RBV. In the grazoprevir/elbasvir only arm, 46 percent were infected with chronic HCV GT1a, 46 percent with GT1b or other GT1, five percent with GT4 and four percent with GT6. Overall, 36 percent of patients had liver cirrhosis. Among those in the grazoprevir/elbasvir plus RBV arm, 55 percent were infected with chronic HCV GT1a, 36 percent with GT1b or other GT1, eight percent with GT4, and two percent with GT6. Overall, 35 percent had liver cirrhosis.

Among the patients receiving grazoprevir/elbasvir only, three patients (3%) were reported to have virologic breakthrough or rebound and four patients (4%) were reported to have virologic relapse. No virologic failures occurred in patients receiving grazoprevir/elbasvir plus RBV. Serious adverse events were reported in three patients in the grazoprevir/elbasvir only arm (3%) and four patients in the grazoprevir/elbasvir plus RBV arm (4%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (16%, 30%), headache (19%, 19%) and nausea (4%,17%).

About the C-EDGE Program
C-EDGE is the Phase 3 clinical development program for Merck’s investigational HCV treatment grazoprevir/elbasvir comprising five studies with more than 1,700 patients across more than 25 countries. These studies are evaluating grazoprevir/elbasvir in multiple genotypes (GT1, 4 and 6) and diverse patient populations, including difficult-to-treat patients such as: treatment-experienced, patients with cirrhosis, HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and those receiving opiate substitution therapies.

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Merck oral hepatitis C regimen shows 95 pct cure rate

(Reuters) - Merck and Co Inc presented trial results on Friday showing that a once-daily combination of two experimental pills cured 95 percent of previously untreated hepatitis C patients after 12 weeks.

The trial included patients infected with the most common form of the liver-destroying virus, genotype 1, along with less common genotypes 4 and 6. It also involved patients with and without liver cirrhosis.

Cure rates, defined as sustained virologic response 12 weeks after treatment, were 92 percent for patients with genotype 1a; 99 percent for genotype 1b; 100 percent for genotype 4; and 80 percent for genotype 6. Cures were achieved in 97 percent of cirrhotic patients and 94 percent of non-cirrhotic patients.

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MTP pattern predicted SVR in Egyptian patients with HCV genotype 4

Microsomal triglyceride transfer protein, or MTP, could be used as a predictor for measuring sustained virologic response from antiviral therapy in Egyptian patients with hepatitis C virus genotype 4 infection, according to study data.

“Till now, (there has been) no sufficient data about correlation of MTP variants with response to therapy in HCV,” the researchers wrote. “To justify this issue, the current study aimed to determine the pattern of MTP gene polymorphisms in naive HCV genotype 4 patients to then identify the impact of MTP polymorphism on the response to combined pegylated interferon-ribavirin therapy in chronic HCV genotype 4.”

One hundred treatment-naive patients with HCV genotype 4 were recruited to receive antiviral therapy with 180 mcg of PEG-IFN alfa-2a per week and weight-based ribavirin for 48 weeks. Forty controls also were included in the study, and all 140 patients underwent DNA and laboratory testing to determine any impact of MTP polymorphism. 

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