Rules restricting access to hepatitis C drugs leave patients waiting

INDIANAPOLIS (WISH) — Indiana’s HIV outbreak has generated more concern about another potentially deadly infection – hepatitis C.

But an I-Team 8 investigation has found Indiana’s poorest patients are being denied access to hepatitis C drugs that could potentially cure them.

State Medicaid programs have restricted access to the drugs like Sovaldi, Harvoni and Viekira. Instead of distributing the medications to all those infected, states have set up restrictions that require patients to have certain symptoms – including a fatty liver or liver scarring – before they can get treatment.

It’s not just Indiana – 31 other states require patients to show signs of liver scarring and have a specialty doctor prescribe the medication, according to a June article in the Annals of Internal Medicine.

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Snapshots, by Alan Franciscus, Editor-in-Chief

Originally Published July 15, 2015

Article: Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens—Vespasiani-Gentilucci U, et al.
  Source: World Journal of Gastroenterology, 07/06/2015

Results and Conclusions:  In this article the authors discuss some important issues regarding the treatment of elderly patients with interferon-free therapies.  Elderly patients have additional health concerns that affect treatment decisions including:

• A generally faster disease progression to cirrhosis and liver cancer than those who are younger
• More extrahepatic conditions such as fatigue, cognitive issues
• A potential decrease in quality of life
• Possible drug-drug interactions with medications taken by the elderly (diabetes, heart, blood-pressure medications)

The authors recommend that the best case scenario is to treat every elderly patient because of the risk of accelerated disease progression.  If this is not realistic, we should be treating those who need treatment first who are in danger of disease progression.   The patients who are not in immediate need of treatment should be monitored on a regular basis.  As with current recommendations, those who have only a short-term survival are excluded from HCV antiviral treatment.  

The Bottom Line:  In general, the elderly population faces many health complications.  The elderly also face discrimination from healthcare professionals.  It is important that everyone with hepatitis C have an advocate—a family member or friend to help them through the intricacies of monitoring HCV and accessing HCV treatment.  

Editorial Comments:  We now have medications that have fewer side effects and have been found to be safe in people with mild to moderate kidney impairment.  It is important that the newly approved drugs and the investigational drugs be tested with the many medications that are commonly prescribed to the elderly.

Everyone deserves the right to be cured of hepatitis C including the elderly with hepatitis C.  More importantly, don’t we have an obligation to make sure that our elderly population with hepatitis C be treated and cured?  This way they can live their lives in relative health and know that they no longer have to deal with the potential physical and emotional consequences of living with hepatitis C.  

Article:  Hepatitis B Virus Reactivation During Successful Treatment of Hepatitis C Virus with Sofosbuvir and Simeprevir—J. M. Collins et. Al
  Source:  Clinical Infectious Diseases Advance Access

Results and Conclusions: This was a case report of two individuals with hepatitis C. 

The first case was a 55 yo man who was coinfected with hepatitis B and hepatitis C genotype 1a.  He had been previously treated with pegylated interferon plus ribavirin but did not achieve a cure.  He was started on sofosbuvir and simeprevir.  After week 4 he was HCV undetectable, but at week 7 he started to have severe liver symptoms (AST of 1792 IU/L, ALT of 1495 IU/L, total bilirubin of 12.2 mg/dl and INR of 1.96) and his hepatitis B viral load rose to 22 million.  His other tests (antinuclear antibody, ferritin, a-fetoprotein, etc.) were also abnormal.

The HCV treatment was discontinued, and hepatitis B treatment (tenofovir/emtricitabine) was started and the hepatitis B viral load subsequently decreased to less than 20 IU/mL.  The hepatitis B treatment was continued for ongoing hepatitis B suppression.

The second case was a 57 yo man with HCV genotype 1a.  He had been treated for HCV with pegylated interferon plus ribavirin but had not been cured. He was positive for the hepatitis B virus, but the hepatitis B viral load was below the level of detection (20 IU/mL).  He was started on HCV treatment—sofosbuvir and simeprevir and his HCV and hepatitis B viral loads were monitored every two weeks.  After two weeks, his HCV viral load was undetectable and his hepatitis B viral load increased to 353 IU/mL.  After four weeks of HCV treatment, HCV was still undetectable, but the hepatitis B viral load increased to 11,255 IU/mL.  The liver function tests were normal, and there were no other signs of liver disease.  The patient remained on sofosbuvir/simeprevir treatment.  Tenofovir was added to the HCV treatment regime to treat hepatitis B. 

The Bottom Line:  The reactivation of HBV in people who were coinfected with HBV and HCV was rare in the days of pegylated interferon based therapies.  This was most likely because PEG works against HBV whereas the new HCV direct acting antivirals do not have antiviral properties that will suppress hepatitis B while treating HCV.   

Editorial Comment:  A couple of important points:

• Everyone with hepatitis C should be tested for hepatitis B (and A), and if not previously infected should be vaccinated.
• People who are chronically infected with HBV and HCV who are being treated with the direct-acting antiviral medications (Harvoni or Viekira Pak) should be monitored very closely—every two weeks as listed in the second study—for HBV flares and treated for HBV as needed. 

http://hcvadvocate.org/news/newsLetter/2015/advocate0715_mid.html#4

Disability and Benefits:Medicare at Age 65, by Jacques Chambers, CLU

Originally Published July 15, 2015

This column has written about Medicare fairly regularly, however, eligibility for Medicare has usually been focused on those who get it after collecting Social Security Disability benefits for 24 months.

Perhaps it would be appropriate now, with improved treatments and a cure for HCV, to look at the process of enrolling in Medicare when turning age 65. Unlike those on SSD who are enrolled automatically in Parts A & B of Medicare, people turning age 65 must actively choose whether or not to enroll in Medicare in addition to deciding which parts are appropriate for them.

This is especially important because if you don’t enroll in Medicare at the appropriate times penalty surcharges can be added to the premiums and they will last as long as you are on Medicare.

For people who are already on Medicare due to disability, you are entitled to the same enrollment opportunities at age 65 as those just joining Medicare. It is your chance to make changes.

Here is a summary of the various parts and choices of Medicare:

• Part A Hospital – This covers hospital-related charges as well as Skilled Nursing Facilities and hospice care. Most people have paid sufficiently through MedFICA payroll taxes so there is no charge for Part A. For those that have not, there is a premium charge based on how many “work credits” you accumulated while working.
• Part B Medical – This covers other Medical charges, such as doctors, lab tests, X-rays and other tests, durable medical equipment, and some injection medications. The premium in 2015 is $104.90 per month, although high income persons pay a higher premium.
• Part C Medicare Advantage – These are Managed Care Plans from insurance companies, HMOs, PPOs, etc. Persons who are enrolled in Parts A and B of Medicare can “trade” that coverage for one of these plans. Most of them also cover prescription medications, and many do not charge a separate premium over the Part B premium; which must still be paid.
• Part D Prescription Drug Coverage – This coverage for prescription drugs is offered by private insurance companies, although all plans must meet the federal law’s requirements for such plans. Premiums vary by plan. To find the best Part D plan for you, go to www.medicare.gov; click on Find Health and Drug Plans. You can enter your medications to find the plan that covers them for the least out-of-pocket expense to you.
• Medicare Supplement (Medigap) Plans – These plans are offered by private insurance companies and are designed to accompany Parts A and B and cover portions of medical charges not covered by Parts A and B. There are ten different levels of coverage, and premiums vary by plan and insurance company. Since these plans are private insurance plans, if you do not enroll during the Initial Enrollment Period, you will be required to go through medical underwriting to purchase a plan later.

Initial Enrollment Period. If you are newly eligible for Medicare because of turning age 65, you can enroll in Medicare Parts A, B, and D or a Medicare Advantage Plan (Part C) during the initial 7 month enrollment period. The Initial Enrollment Period begins three months before the month you turn 65, includes the month you turn 65, and ends three months after the month you turn 65. The coverage will be effective on either the first of the month you turn 65 or the first of the month following your enrollment, whichever comes later.

NOTE: You can enroll in Medicare on line at www.ssa.gov, by phone at 800-772-1213, or at your local Social Security office. During this period you also may enroll in a Medigap policy regardless of your medical history or condition; you will need to do that directly with the insurance company or through an insurance agent. 

Late Enrollment. If you do not enroll in Medicare during this Initial Enrollment Period, and you do not qualify for a Special Enrollment Period, described below, then you must wait to enroll in Medicare during the annual General Enrollment Period.

Late Enrollment Penalty. If you do not enroll in Medicare during the Initial Enrollment Period and you do not later qualify for a Special Enrollment Period, the premiums you pay will have a penalty surcharge. The surcharge varies slightly by which part of Medicare is late in being enrolled; however, it is about 10 – 12% additional for each year you could have enrolled in Medicare but chose not to. This surcharge will be added to the regular premium during the entire time you remain on Medicare.

General Enrollment Period. General enrollment is from January 1 through March 31 of each year, with coverage effective the following July 1.

Choices When Enrolling in Medicare. Enrolling in Medicare requires making choices. Before enrolling in a plan you should do some research to make sure you are getting into a plan that meets your needs.

First you will need to enroll in both Part A (hospital) and Part B (Medical); see Special Enrollment Period below for exceptions.

Your primary choices for coverage are:

• Remain with Parts A & B, and add a stand-alone Prescription Drug Plan, Part D. You may also want to add a Medicare Supplement Plan (Medigap) to cover deductibles and co-insurance that Part A and B do not pay.
• Trade your Parts A & B coverage for a Medicare Advantage (Part C) PPO or HMO. You will still have to continue paying the Part B premium. Most Medicare Advantage Plans include Part D Prescription Drug coverage in their plan. For those that do not, you will need to purchase a stand-alone Drug plan to go with it. If you consider this option, make sure the medical providers you wish to continue seeing are contracting or preferred providers with the plan you choose.

As you might imagine, to find the right combination of coverage for you, you will need to do some research and perhaps speak with an insurance agent that specializes in health coverage for people age 65 or over.

Special Enrollment Periods
Not everyone who turns 65 needs or wants to switch their health insurance to Medicare. For those with a valid reason for not joining Medicare at age 65, provisions are made to allow enrollment at a later date without being subject to Late Enrollment Penalties.

Many people who already have health insurance when reaching age 65 want to continue their coverage. That is not always a good idea:

• If you have individual health insurance, and it is not from the Affordable Care Act, you may keep it, but chances are you will have better coverage for a lower premium if you enroll in Medicare A, B and D plus purchase one of the broad Medigap plans.
• If you have individual health insurance that is from the Affordable Care Act, the same would apply as the premium subsidies are no longer available after age 65.
• If you have insurance through an employer due to current employment by you or your spouse, you may wish to postpone signing up for Medicare. You can sign up for Medicare anytime while covered. Also, when your employer-based coverage stops, you have an 8-month Special Enrollment Period to sign up for Medicare.
• NOTE: COBRA Continuation Coverage is NOT considered to be from active employment so the 8-month enrollment period begins when your “active employment” coverage stops.
• To enroll in a Part D Prescription Drug Plan during this period you will need to provide a letter from your employer’s health insurance carrier, called a “Certificate of Creditable Coverage” that states the drug coverage they offered was as good or better than Medicare Part D coverage. Most group plans meet this requirement.
• If you are covered under TRICARE (coverage for active-duty military or retirees and their families), you will be required to enroll in Medicare Part B once you retire.

There are other times when you may take advantage of a Special Enrollment Period:

• You move to an area that is not in your Medicare Advantage Plan’s service area;
• You move to an area that is still in your Medicare Advantage Plan’s service area but which now has options available in your new location; and,
• You move back to the United States after living outside the country.

These are the major periods when you can enroll in the parts of Medicare, but not all of them. If you are approaching age 65, you should get more detailed information by downloading the Tip Sheet, “Understanding Medicare Enrollment Periods” at: www.medicaresupplementplans.com/
publications/ Understanding_Medicare_Enrollment _Periods.pdf

http://hcvadvocate.org/news/newsLetter/2015/advocate0715_mid.html#3

The Five: The Next HCV Drugs, by Alan Franciscus, Editor-in-Chief

Originally Published July 15, 2015

The current standard of care for treating HCV is currently Harvoni and Viekira PAK for genotype 1, Sovaldi plus ribavirin to treat genotype 2 and 3, and Sovaldi plus pegylated interferon/ribavirin to treat genotype 4.  There are a couple of combinations of drugs submitted to, and likely to be approved by, the Food and Drug Administration (FDA) by the end of this year or early next year.  Additionally, many more drugs are being developed that are in early to mid-stage development.  These medications hold the promise to cure even more people with HCV genotypes 1 through 6.   This month’s “The Five” will discuss the most promising drugs in development.

1. Merck: Grazoprevir/Elbasvir (one pill/once-a-day) in treatment-naïve and treatment-experienced patients infected with HCV genotype 1, 4 or 6 and treated for 12 weeks.  The cure rates were up to 100%.  There were issues with NS5A resistance, but Merck is conducting more clinical trials with NS5A inhibitors to overcome this problem.  Merck has filed a New Drug Application earlier this year.  Merck was awarded Breakthrough Therapy Designation by the FDA for genotype 4 and to treat those with severe kidney disease—the studies above included patients with genotype 4 and severe kidney problems.  FDA approval is expected by year end.
   
   
2. Bristol-Myers Squibb (BMS): BMS has two drug combinations that are being tested to treat hepatitis C.

Ally-1:  Daclatasvir plus sofosbuvir has been awarded Breakthrough Therapy Designation for patients with advanced cirrhosis and those with HCV genotype 1 with HCV post-liver transplant.  In the Ally-1 study, the cure rates of the patients with advanced cirrhosis were 82% for genotypes 1 and 94% for the post-patients with genotype 1.

Ally-3:  BMS has completed their phase 3 clinical trials of daclatasvir plus sofosbuvir and submitted their data to the FDA for approval.  In the trials treatment naïve people treated for 12 weeks with the combination of daclatasvir/sofosbuvir achieved cure rates of 90%, and 86% in people who are treatment experienced.  In people who did not have cirrhosis, the cure rates were 96%. These are very high cure rates. 

BMS also has a fixed-dose single-pill regime (daclatasvir, asunaprevir, beclabuvir) to treat HCV genotype 1a and 1b that is taken twice daily for 12 weeks.  There were two separate studies that included treatment naïve and treatment experienced patients with and without cirrhosis.  The studies also included arms with and without ribavirin.  The overall cure rates were up to 98% with ribavirin and 93% without ribavirin.  Breaking it down by subtype—genotype 1b had approximately 10% higher cure rates than genotype 1a.  The cure rates observed in the ribavirin groups were not statistically higher. 

The second single-pill combination listed above hasn’t been submitted to the FDA but it is expected to be submitted soon, and approval is expected mid-2016.

3. Gilead:  Sofosbuvir plus GS-5816 with and without ribavirin.  In a phase 2 study of 104 genotype 3 patients treated for eight weeks the cure rates were up to 100%.  GS-5816 is active against genotypes 1-6 (pangenotypic).  It is listed in www.clinicaltrials.gov as a phase 3 trial that is active but not recruiting.  The phase 3 study will be a fixed dose of one pill with both drugs given once a day to treat genotypes 1 through 6.  The treatment duration will be either 8 or 12 weeks. 


4. Janssen: Olysio made a big splash last year as a combination with sofosbuvir with major prescriptions and high cure rates.  They have acquired Vertex’s HCV drugs in development (ALS-2200).  This year Janssen signed an agreement to codevelop and commercialize Achillion’s inhibitors (ACH-3102, ACH-3422 and sovaprevir).  Although no data is available, it should make for a very interesting 2015-2016.  If I can steal a common term, they seem to have a very robust pipeline.  As listed above, Janssen many opportunities to develop and commercialize HCV drugs for the short term and long term.  Keep on eye on Janssen.


5. AbbVie:  In cooperation with Enanta, AbbVie is testing ABT-493, plus ABT-530 with and without ribavirin to treat genotypes 1 through 6 for 8 to 12 weeks.  The drugs are in phase 2 studies. 

The Merck approval is expected soon. The BMS plus sofosbuvir is also expected to be approved soon.  The new Gilead drugs are likely to be approved by next year and will be followed by the second BMS combination, Janssen’s combinations, and AbbVie’s.  Hopefully, more agents will be discovered that will show even more promise, and we just may have a market that is flooded with excellent drugs that will work for everyone.

Be sure to keep an eye out for the return of the HCV Advocate Drug Pipeline in September!

http://hcvadvocate.org/news/newsLetter/2015/advocate0715_mid.html#2

Hepatitis C: The Problem with Numbers, by Alan Franciscus, Editor-in-Chief

Originally Published July 15, 2015

A recently released journal article estimated that the real number of acute hepatitis C cases are much higher than the figures published by the Centers for Disease Control and Prevention (CDC).  This is not a revelation to those who work in HCV.  In this article, I will discuss the published numbers of acute and chronic HCV and what some experts believe is a better estimate of the number of acute, chronic and annual deaths caused by hepatitis C.

Acute
The CDC estimated that there were 29,700 acute cases of HCV in 2013 (range 23,500 to 101,400).  In the article, “Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System: A Case Series and Chart Review,” by S Onofrey, MPH et. al., published in the Annals of Internal Medicine, the authors challenged the way the CDC defined an acute case and compared the actual diagnosed cases to the number of diagnosed cases that fit the CDC definition. 

Note:  There are many problems with diagnosing acute HCV—there are no viral markers to distinguish acute vs. chronic.  Another issue is that most people acutely infected have no symptoms.

The current study took place in Massachusetts from 2001 to 2011.  There were 183 patients diagnosed with acute HCV, but only 149 cases were reported to the Massachusetts Department of Public Health.  Of these, 130 were classified as potential acute infection.  But only ONE met the national case definition that was reported to the CDC.  

This means that only 1% of acute HCV cases were ever reported to the CDC.  We know that there have been outbreaks of acute HCV around the country including recent outbreaks in regions in or near the Appalachia area. 

Chronic Hepatitis C
The CDC estimated that in 2013 there were 2.7 to 3.9 million people who were chronically infected with hepatitis C.  However, the NHANES survey doses not count certain populations such as prisoners, homeless, nursing home residents, people in mental institutions, nor active duty military—many of these populations have a very high incidence of hepatitis C.  If the populations that were excluded from the NHANES survey were to be included the number of people with chronic hepatitis C could reach 5 million Americans. 

Also if you include the surge of the new acute infections that would turn chronic this would also increase the total chronic infections.  It is all connected. 

HCV Deaths
The CDC estimated that there were 19,368 deaths caused by HCV in 2013.  There was also a footnote that read “Current information indicates these represent a fraction of deaths attributable in whole or in part to chronic hepatitis C.” 

Another article, “Mortality among Persons in Care with Hepatitis C Virus Infection—The Chronic Hepatitis Cohort Study (CHeCS), 2006–2010,” by R Mahajan and colleagues, was published in Clin Infect Disease 2014 Jun; 59(12)1792.  The study estimated the number of deaths caused by hepatitis C

In the study, 2,143,369 patients (MCOD group—all patients) seen between 2006 – 2010 at the CHeCS clinics were included in the analysis.  There were 11,703 (0.5%) HCV patients.  A total of 1,590 (14%) died and had HCV listed as the cause of death.  The majority were born between 1945 and 1965 (75%), white (50%), and male (68%).  The mean age was 59 yo. 

To illustrate why HCV is under reported on death certificates the following was mentioned in the study:

“Among the 1590 CHeCS members who died, only 306 (19%) had HCV infection listed as an underlying cause on their death certificate. Among people who died of liver cancer, only 32% had HCV listed as an underlying cause. Death certificates did not list HCV for most deaths regardless of whether the deaths were liver-related or not. Among CHeCS members who died, medical records (ICD-9 codes) noted liver disease in 63%, and FIB-4 scores indicated liver disease in 76%.”

The conclusion of the authors was that in 2010 listed deaths from hepatitis C only represent 1/5 of the 80,000 people with HCV who died that year—this figure includes 53,000 patients who had indications of chronic liver disease in their medical records. It’s important to remember that behind all these numbers are real people who have family, friends and loved ones.  As such they deserve to have medical care and treatment. And no one should die of hepatitis C!

http://hcvadvocate.org/news/newsLetter/2015/advocate0715_mid.html#1

'Sensational' HCV response rates in HIV coinfection trial

Researchers in the C-EDGE study found that a combination of a protease inhibitor and an NS5A inhibitor led to a sustained virologic response in patients infected with both HIV and hepatitis C virus (HCV).

Researchers in the C-EDGE study found that a combination of a protease inhibitor and an NS5A inhibitor led to a sustained virologic response in patients infected with both HIV and hepatitis C virus (HCV). Jurgen Rockstroh, MD, of the University of Bonn in Germany, reported that the sustained virologic response was 96.3% overall after stopping treatment for 12 weeks. The response rate for the 35 patients with cirrhosis at baseline was 100%. Of the study's 218 patients, two experienced a relapse after stopping therapy, but both had been reinfected with HCV. The Phase III study included patients infected with HCV genotypes 1, 4, or 6, and HIV. All patients received grazoprevir 100 mg and elbasvir 50 mg, which were coformulated by Merck into one tablet that was taken once daily for 12 weeks. No patients experienced any serious drug-related adverse events during the study. The results were presented at the International AIDS Society Conference in Vancouver.

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Urban ERs see high rates of hepatitis C infection

American College of Emergency Physicians

WASHINGTON --An urban emergency department that set up a hepatitis C testing protocol saw high rates of infection among intravenous drug users and Baby Boomers, with three-quarters of those testing positive unaware they were infected. The results of a screening and diagnostic testing program for hepatitis C were reported online Tuesday in Annals of Emergency Medicine ("Results of a Rapid Hepatitis C Virus Screening and Diagnostic Testing Program in an Urban Emergency Department").

"Given skyrocketing rates of injection heroin use around the country, we expect the already high rates of hepatitis C infection to explode," said lead study author Douglas White, MD, of Highland Hospital, Alameda Health System in Oakland, Calif. "Intervention by emergency departments, in the form of screening and referral for treatment, could help slow the spread of this potentially deadly, communicable disease."

Researchers tested 10 percent of emergency department patients for hepatitis C virus (HCV), mostly but not exclusively focusing testing on those considered high-risk, such as intravenous drug users, Baby Boomers and patients with unspecified liver disease. Of patients tested, 10.3 percent tested positive for HCV, with 70 percent of those confirmed as chronically infected. Only 24 percent of patients who tested positive for the virus had prior knowledge of HCV infection.

Hepatitis C virus is the most common chronic blood-borne infection in the U.S., affecting an estimated 3 million people and is a leading cause of end-stage liver disease, liver cancer and liver transplants. It is estimated that HCV prevalence in the United States among people born between 1945 and 1965 (the "Baby Boom") is as high as 4 percent. Baby Boomers account for 75 percent of people living with HCV infection and as many as 1.75 million of them do not know they are infected.

"In addition to the myriad public health functions they already perform, urban emergency departments may play an important role as safety net providers for HCV screening," said Dr. White. "We have a better than even chance of reaching many of the three million people who are infected since they tend to be heavy emergency department users already. It gives us a chance to connect these people to ongoing care at HCV clinics or elsewhere in the health care system."

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Annals of Emergency Medicine is the peer-reviewed scientific journal for the American College of Emergency Physicians, the national medical society representing emergency medicine. ACEP is committed to advancing emergency care through continuing education, research, and public education. Headquartered in Dallas, Texas, ACEP has 53 chapters representing each state, as well as Puerto Rico and the District of Columbia. A Government Services Chapter represents emergency physicians employed by military branches and other government agencies. For more information, visit http://www.acep.org.

Press Release Source:  http://www.eurekalert.org/pub_releases/2015-08/acoe-ues080615.php