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

Disability and Benefits:Who Is Disabled? —Jacques Chambers, CLU

Originally Published June 15, 2015

The term “disability” or “disabled” is heard frequently, especially when discussing a medical condition such as Hepatitis B or C, which tend to be progressive in their symptoms and can lead to an inability to work.

The word is used in so many contexts, however, that it has become virtually generic to mean any type of limitation. It really has no special meaning other than describing a condition of some sort that prevents a person from doing something.

• Is lack of height a disability? It is if you stand 5’ 6” and you are trying out for the NBA.
• Does an infected hangnail constitute a disability? Probably not. Then again, if you are a surgeon, it could be “disabling” – preventing him or her from performing surgery.
• Missing an arm or leg certainly seems to be a disability, but many people can perform their jobs perfectly well in that situation.

Clearly, then, when the term “disability” or “disabled” is used for a specific purpose, for example, to pay benefits to someone who is “disabled,” a clear definition of the term must be established. Social Security, disability insurance policies, and other programs for people with “disabilities” must define the term, and each seems to put their own slight twist on how they define it. That is why your doctor’s letter stating that you are disabled will not automatically get you disability benefits. Each party trying to determine your disability status must see that you meet their own definition of disability through the medical record and, occasionally, through physical examination.

Totally Disabled/Total Disability
First, be aware that in this context, “disabled” and “disability” are really shorthand for what Insurance companies and the Social Security Administration actually refer to as “Total Disability” and “Totally Disabled.” All apply specific definitions to the term and it is important to know the specific definition as that is the yardstick with which a claimant’s medical condition is measured to see if they qualify for benefits.

Social Security defines “totally disabled” as:

• “You have a serious, DOCUMENTED, physical or mental health condition;
• Which prevents you from being able to earn Substantial Gainful Activity ($1,090/month in 2015); and,
• That condition is expected to last at least twelve months or result in death.”

This is a very detailed definition, yet it can be one of the most difficult to meet. Notice that Social Security immediately eliminates coverage for brief periods of disability by including the “12 month” limitation. The disability does not have to have lasted 12 months, only that it is expected to last that long. Also an exception is made for those with an illness that is terminal and can lead to death within twelve months.

Under Social Security rules, you are not necessarily disabled just because you can’t perform the occupation you used to have. Instead, if you can’t do your prior job, they will look to see if there is another occupation for which you might qualify either by past experience or training or education. Unfortunately, they will not find you that job; they will just list some occupations they feel you could perform.

For example, they may expect a 35 year old with a college degree, who can no longer perform his prior job, to be able to move to another job that he is able to do, both physically and mentally. In another case, a 55 year old who has only a high school diploma and spent his entire career in one, relatively unskilled job may be eligible for benefits just because he can no longer perform the only job he is qualified through education or experience to perform.

Private Disability Insurance
Benefits paid under either employer provided disability plans or individually purchased disability policies are all paid according to the terms of the disability plan document or the insurance contract.  Each policy will define “totally disabled/totally disability” in the contract so anyone contemplating leaving work due to disability should know how the particular plan defines it.

Although each plan’s definition may vary, there are some basic provisions that are usually included in the definition in one form or another:

• Inability to work – Most definitions include a phrase such as: “due to medical condition, the claimant is unable to perform the material and substantial duties of an “occupation.”  This provision has some variants:
• “His regular occupation” – If this is used in the definition, then a person is disabled only if he is unable to do the job he was doing when he became disabled; or
• “Any occupation for which he is suited based on education, training, or experience.” This is somewhat similar to Social Security in that they are looking for any job the claimant might be able to do based on the claimant’s background.
• Most employer-provided disability plans use both of the above definitions of inability to work.  They look only at the “regular occupation” during the first two or three years of the claim and then shift to “any suitable occupation” for the remainder of the claim.  This is one reason many claimants are dropped from benefits after the first couple of years.

• Loss of income – Some plans define disability as “due to a medical condition, the claimant has lost at least twenty percent of his prior earnings.”  Such plans will only pay full benefits if the claimant has lost 80% or more of his income.  If the income loss is between 20% and 80% of prior earnings, then only a proportionate benefit is paid.  Some plans use this provision without an “inability to work” provision; most, however, will use a combination of the two effectively requiring inability to work AND a loss of income.
• Under medical care – Many definitions also include a requirement that the claimant be under the ongoing care of a physician, although some contracts will waive that requirement if there is nothing medically to be done by further treatment.

The way insurance companies define “Totally Disabled” has a profound effect on who will get benefits, and knowing what definition a claimant has to meet should help him or her and his or her physician clearly document the medical record to reflect the claimant’s condition in the light of the definition used. Some older contracts written by professionals such as doctors and dentists defined disability so narrowly that they were obligated to pay full benefits even though the claimant was able to do other types of full-time employment.  The days when those policies were written are long gone.

Partially Disabled
Sometimes called Residual Disability, is not defined or used by Social Security. Their disability programs, both Social Security Disability (SSD) and Supplemental Security Income (SSI) have programs for persons “working while disabled” that effectively provide coverage for a partial disability.  Note that the rules for working while disabled vary dramatically between SSD and SSI.

Partially Disabled is also used in disability insurance plans, both individual Disability Income and group Long Term Disability.  Usually, they provide a proportionate benefit to the claimant based on the amount of wages they are able to earn compared with what they earned prior to disability, adjusted for inflation.  For example a person who can do some work and earn 40% of their prior earnings would be eligible to get 60% of the total disability benefit.  At least that is a “typical” partial disability provision.  The contract should be checked as the provision can vary.

Permanently disabled
This is really a non-term when referring to disability benefits.  Other than Social Security’s requirement of lasting at least one year, benefit plans are more concerned with how total the disability is not how long it will last. All plans require that the person remain disabled and may terminate benefits if a medical review shows the disability has ended.

However, the term “permanently disabled” is occasionally used in some pension plans as the grounds for a disability retirement designation.  To be honest, to say someone is permanently disabled is simply a prediction that may or may not be true. No disability plan makes you promise never to work again.

You Can Help
Now that you know what yardstick a program uses to measure whether or not you are disabled, you can see why they will not accept your physician’s opinion of your condition. You also can see why it is important that you discuss the disability definition of your plan with your doctor before, well before if possible, filing a disability claim.

While you and your physician usually focus on finding the diagnosis of your condition and methods of treatment, the disability carrier wants to know what symptoms your conditions cause that prevent you from doing whatever occupation the definition calls for. Unfortunately, in today’s healthcare that limits time spent with doctors – instead there are computerized records that just require checking boxes and filling in blanks; there is little opportunity for a detailed description of your symptoms, much less details of their severity and frequency, and how they limit your ability to function.

Therefore, it is extremely important for people who may someday have to file for disability to provide such details to your physician regularly, and insist that they be included in the medical record. Take a written summary with you each time you see the doctor. List what symptoms you experienced and how they affected your ability to perform tasks at home and at work.

Check These Out! HCV Benefits and Disability Issues

• A Guide to Hepatitis and Disability
• American with Disabilities Act: What It Does and Doesn't Do
• Completing Social Security and Insurance Questionnaires
• Getting Disability Benefits under Social Security

http://hcvadvocate.org/news/newsLetter/2015/advocate0615_mid.html#3