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

MSD Announces European Medicines Agency Acceptance of Marketing Authorisation Application for Grazoprevir/Elbasvir, an Investigational Therapy for Treatment of Chronic Hepatitis C Infection

KENILWORTH N.J., Jul 23, 2015 (BUSINESS WIRE) -- MSD, known as Merck MRK, -0.10% in the United States and Canada, today announced the European Medicines Agency (EMA) has accepted for review a marketing authorisation application (MAA) for grazoprevir/elbasvir (100mg/50mg), an investigational, once-daily, single-tablet combination therapy, for the treatment of adult patients with chronic hepatitis C (HCV) genotypes (GT) 1, 3, 4 or 6 infection.1 The EMA will initiate review of the MAA under accelerated assessment timelines.

“Given the diversity of patient populations affected by chronic hepatitis C, including the estimated 15 million people living with the disease in Europe, it is important to provide patients and physicians with treatment options,” said Dr. Roy Baynes, senior vice president of clinical development, Merck Research Laboratories, a U.S.-based division of Merck & Co., Inc., Kenilworth, N.J., U.S.A. “We are pleased to be working with regulatory authorities as we advance grazoprevir/elbasvir for appropriate patients living with chronic hepatitis C around the world.”

The EMA’s accelerated assessment is available for products that respond to unmet medical needs or represent a significant improvement over current treatment options within a major public health interest, such as the treatment of chronic HCV infection. The Committee for Medicinal Products for Human Use (CHMP) will continue to evaluate the accelerated assessment status throughout the MAA evaluation process.

The MAA for grazoprevir/elbasvir (100mg/50mg) is based in part upon data from the pivotal C-EDGE clinical trials programme, as well as the C-SURFER, C-SALVAGE and C-SWIFT clinical trials, evaluating grazoprevir/elbasvir (100mg/50mg), with or without ribavirin, in patients with chronic HCV infection. Collectively, these trials evaluated treatment regimens in multiple genotypes (GT1, 3, 4 and 6), including patient populations who were previously treated, and those with cirrhosis or certain co-morbidities (i.e., HIV co-infection, chronic kidney disease stages 4 and 5).

The company submitted a New Drug Application for grazoprevir/elbasvir (100mg/50mg) to the U.S. Food and Drug Administration (FDA) in May 2015 for the treatment of chronic HCV GT 1, 4 or 6 infection, and is submitting additional license applications in other markets by the end of 2015. In April 2015, the U.S. FDA granted Breakthrough Therapy designation status for grazoprevir/elbasvir for the treatment of patients infected with chronic HCV GT1 with end stage renal disease on hemodialysis, and Breakthrough Therapy designation status for grazoprevir/elbasvir for the treatment of patients infected with chronic HCV GT4. 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.
 
About Grazoprevir/Elbasvir
Grazoprevir/elbasvir is MSD’s investigational, once-daily, single-tablet combination therapy consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of MSD’s broad clinical trials programme, grazoprevir/elbasvir is being evaluated in multiple HCV genotypes including patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and in those on opiate substitution therapy.
 
About MSD
Today's MSD is a global health care leader working to help the world be well. MSD is a tradename of Merck & Co., Inc., with headquarters in Kenilworth, N.J., U.S.A. 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, programmes and partnerships.

Read complete press release here..

Janssen Submits Supplemental New Drug Application to U.S. FDA for All-Oral, Once-Daily OLYSIO® (Simeprevir) in Combination with Sofosbuvir

Filing Supported by Data from the Phase 3 OPTIMIST-1 and -2 Clinical Trials Evaluating OLYSIO® Combination Therapy in Hepatitis C Patients with and without Cirrhosis

TITUSVILLE, N.J., July 23, 2015 /PRNewswire/ -- Janssen Therapeutics, Division of Janssen Products, LP (Janssen), today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) to update the label for once-daily, all-oral OLYSIO^® (simeprevir). OLYSIO^® is a hepatitis C virus (HCV) NS3/4A protease inhibitor, currently approved for use with sofosbuvir for adults with genotype 1 chronic hepatitis C (CHC) infection as a 12-week treatment for patients without cirrhosis or a 24-week treatment regimen for patients with cirrhosis. Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor marketed by Gilead Sciences, Inc.

OLYSIO^® was approved in November 2014 in combination with sofosbuvir based on the Phase 2 COSMOS clinical trial. This sNDA is based on results from the Phase 3 OPTIMIST-1 and OPTIMIST-2 trials, which evaluated 12 and eight weeks of therapy for treatment-naive and treatment-experienced genotype 1 CHC adult patients without cirrhosis, and 12 weeks of therapy for treatment-naive and treatment-experienced genotype 1 CHC adult patients with cirrhosis.

"OLYSIO^® has contributed significantly to the care of people living with hepatitis C. The availability of multiple treatment options is important to help offer an opportunity for cure, and we believe OLYSIO^® will continue to play a meaningful role going forward," said Richard Nettles, M.D., vice president, Medical Affairs, Janssen Therapeutics. "We're pleased to submit the data from the Phase 3 OPTIMIST trials, which adds to the body of clinical information about this combination in patients with and without cirrhosis."

Results from the OPTIMIST trials were presented in April 2015 at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) in Vienna.

About the OPTIMIST TrialsOPTIMIST-1 is a Phase 3, randomized, open-label trial to investigate the efficacy and safety of the all-oral regimen of simeprevir and sofosbuvir (SMV/SOF) among treatment-naive and treatment-experienced genotype 1 CHC patients without cirrhosis. The primary study endpoint is sustained virologic response (SVR) at 12 weeks after treatment (SVR12) with 12 and eight weeks of treatment with SMV/SOF versus a historical control (patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon and ribavirin).

• Ninety-seven (97) percent of patients treated with SMV/SOF for 12 weeks (n=150/155) achieved SVR12, which was superior to the SVR12 rate of 87 percent among the historical control.
  • SVR12 rates of 100 percent were seen among patients with IL28B CC genotype (n=43/43) and those with baseline NS5A and NS3 Q80K polymorphisms (n=9/9).
• Patients treated with eight weeks of SMV/SOF achieved an SVR12 rate of 83 percent (n=128/155), which was not superior to the SVR12 rate of 83 percent in the historical control.
  • High SVR12 rates were seen among patients with baseline HCV RNA < 4 million IU/mL (96 percent; n=46/48), IL28B CC genotype (93 percent; n=38/41), patients with genotype 1b CHC (92 percent; n=36/39) and patients without baseline NS5A and Q80K polymorphisms (89 percent; n=78/88).
• The most frequently reported adverse events in the 12- and eight-week treatment arms were headache (14 and 17 percent, respectively), fatigue (12 and 15 percent, respectively) and nausea (15 and 9 percent, respectively).

OPTIMIST-2 is a Phase 3, open-label, single-arm trial to investigate the efficacy and safety of SMV/SOF in treatment-naive and treatment-experienced genotype 1 CHC patients with cirrhosis. The primary endpoint is SVR12 with SMV/SOF versus a historical control.

• Twelve (12) weeks of treatment with SMV/SOF resulted in SVR12 rates of 84 percent (n=86/103), which was superior to the SVR12 rate of 70 percent in the historical control.
• Higher SVR12 rates were seen in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100 percent; n=13/13), patients with albumin ≥4 g/dL (94 percent; n=47/50) and treatment-naïve patients (88 percent; n=44/50).
• The most common adverse events were fatigue (20 percent), headache (20 percent) and nausea (11 percent).

Read complete press release here

World Hepatitis Day — July 28, 2015

Morbidity and Mortality Weekly Report (MMWR)

Weekly

July 24, 2015 / 64(28);753

July 28, 2015, marks the fifth annual World Hepatitis Day, established in 2010 by the World Health Organization to increase awareness and understanding of viral hepatitis. Millions of acute hepatitis infections occur each year, and approximately 400 million persons are living with chronic hepatitis B or hepatitis C (1). An estimated 1.4 million persons die each year from the various forms of viral hepatitis (1). The theme of this year's World Hepatitis Day is "Prevent Hepatitis. Act Now." Key messages will focus on risks, safe injection practices, vaccination, and testing and treatment.

This issue of MMWR includes a report describing the launch of a nationwide hepatitis C elimination program in Georgia, a country with a high burden of hepatitis C. The initial phase of the program is focused on increasing access to affordable diagnostics, free treatment of persons with severe liver disease who are at highest risk for hepatitis C–related morbidity and mortality with new curative regimens, and building capacity to achieve program goals of prevention of transmission and elimination of disease. Georgia's program might provide information and experience that can inform similar efforts in other parts of the world.

A second report summarizes viral hepatitis surveillance and outbreak data from a national surveillance system in India for epidemic-prone diseases. This report sheds light on the burden and epidemiology of acute viral hepatitis in India, particularly hepatitis A and E, and highlights the important role that routine hepatitis surveillance can play in guiding prevention efforts.
Additional information about World Hepatitis Day is available at http://worldhepatitisday.org. Resources for health professionals are available at http://www.cdc.gov/hepatitis.

Reference

1. World Health Organization. Hepatitis. Geneva, Switzerland: World Health Organization; 2015. Available at http://www.who.int/hiv/topics/hepatitis/hepatitisinfo/en.

Rural docs want looser rules for Hepatitis C treatment

INDIANAPOLIS – The only doctor at the center of an HIV outbreak in rural Indiana cannot prescribe the latest treatments for patients also infected with the deadly Hepatitis C virus.

Dr. William Cooke, a family practitioner in Scott County, is treating dozens of people with HIV, the AIDS-causing virus that exploded in numbers among intravenous drug users earlier this year.

But state Medicaid rules forbid him from prescribing new treatments to those same patients with Hepatitis C, the blood-borne disease that causes inflammation in the liver and now claims more lives than HIV in the United States.

Read more...

Genotype 5, by Alan Franciscus, Editor-in-Chief

Originally Published June 15, 2015

Of all the genotypes identified, Genotype 5 is the least studied, and the least prevalent.  However, it is possibly the most interesting in terms of where it is believed to have originated and where there are pockets of it found around the world. 

Epidemiology
In terms of the worldwide prevalence of genotype 5 it is estimated at 1.5 million. The highest incidence of genotype 5 is found in the northern part of the nation of South Africa.  Globally, there are an estimated 436,000 people in Eastern sub-Sahara, 47,000 people in North Africa, the Middle East, 80,000 people in South Asia, 26,000 people in Western Europe, Southern Latin America and 887,000 people Southern sub-Africa.  

The percentage of genotype 5 is found in the following countries:  South Africa-northern (39%); France-central (14%); Syria (10%); Saudi Arabia (1%); Canada-Montreal, Quebec ( 5%); Belgium (4%); Spain-southeast (10%). 

Origins and Spread
The exact origin of genotype 5 is unknown, but there have been studies that have been able to ‘predict’ where it originated and how it spread with a reasonable certainty.  However, like most facts in science, it needs more studies to confirm if it is a fact and until it is confirmed or disproved, it remains a theory.

What is on scientific ground is that the hepatitis C virus originated in Africa and most likely in Western or Central Africa.  Genotype 5 most likely originated in Central Africa possibly what is now the Democratic Republic of Congo more than 120 years ago based on the genetic testing of the viral makeup.  However, why is the highest prevalence of genotype 5 in the northern part of South Africa and only in small pockets in other regions of the world?  That question has been not fully answered, but there are some interesting theories.   There were trade routes from Central Africa to South Africa that could have spread genotype 5 from central Africa to South Africa.  The pockets of genotype 5 in Belgium, France, and the Netherlands can be explained by the European trade and colonization of Africa.    

Genotype 5 only has one subtype – 5a.  This means that the viral diversity remained intact because it was not widely transmitted like the other genotypes.  There have been studies in the other clusters of genotype subtype 5a but most of them have been isolated in ethnic communities in Belgium, the Netherlands, Luxembourg and rural France.   Many of those that have been studied have found that the infections had come from a single source of infection. 

Treatment
There have been only a handful of studies about treatment of genotype 5.  Pegylated interferon plus ribavirin for a treatment duration of 24 to 48 weeks achieved cure rates from 64% to 71%. 

In a study recently released at the EASL 2015 conference showed great promise with interferon-free and ribavirin-free therapy.  The study included 41 genotype 5 patients—21 treatment naïve/20 treatment experience patients treated with Harvoni (ledipasvir/sofosbuvir) for 12 weeks.  The cure rates were 95% (20 of 21 pts) of treatment naïve patients and 95% (19 of 20 pts) in the treatment experienced patients.  The treatment was safe and well tolerated.

These are very high cure rates.  Very good news for those with genotype 5.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615_mid.html#5

HCV Drugs —Alan Franciscus, Editor-in-Chief

Originally Published June 15, 2015

This month’s column discusses Merck’s New Drug Application (NDA) application to the Food and Drug Administration (FDA), BMS’s Breakthrough Designation, a pharmaceutical collaboration, and good news for patients who need help with co-payments for HCV medications. 

Merck
On May 28, 2015, Merck submitted a NDA to the FDA for their combination of one pill (grazoprevir/elbasvir) taken once-a-day to treat HCV genotypes 1, 4 and 6.  Merck’s combination was granted Breakthrough Therapy designation status for the combination by the FDA for people with genotype 1 with end state kidney disease on hemodialysis (to filter the kidneys) and for patients with genotype 4.  Breakthrough Therapy is given to a drug(s) to treat a serious or life-threatening disease or condition when a drug may demonstrate a substantial improvement over existing therapies.    There were many reports on Merck’s HCV medications from EASL 2015 that resulted in cure rates up to 95-99% in people with genotype 1; 100% in genotype 4 and 80% in genotype 6. 

Merck states that they will be notified within 60 days if the FDA will accept their application for review. Furthermore, Merck is expected to file additional licenses in the European Union and other markets by the end of 2015. This will be good news for paients—we may just have another choice of medications in the near future.

BMS
Bristol-Myers-Squibb announced that they have been granted Breakthrough Therapy Designation by the FDA for the combination of daclatasvir and sofosbuvir.   The cure rates of Daclatasvir, sofosbuvir and ribavirin performed well in liver transplant patients and in those who had advanced cirrhosis.  I reported on a study from EASL 2015 that in this population there was a cure rate of 76% to 100%. 

Achillion and J&J Deal
It was announced in May that Johnson and Johnson would collaborate with Achillion.  The deal would mean that J & J would invest in and help develop Achillion’s HCV 3 drug pipeline.  The three drugs are all in early development and could work on all HCV genotypes, i.e., be pan-genotypic.  J & J hopes to co-develop their drug pipeline with Achillion and achieve an effective 6-week HCV treatment cure. 

 
Co-Pay Assistance
The current medications to treat hepatitis C can have high co-payments.  Presented here is another co-pay assistant program for patients—HealthWell Foundation’s New Fund.  For more information visit their website at http://healthwellfoundation.org/ or contact:  Ginny Dunn 240-632-5309, email Ginny.Dunn@HealthWellFoundation.org

http://hcvadvocate.org/news/newsLetter/2015/advocate0615_mid.html#4