FDA addresses concerns on approval of drugs to treat chronic hepatitis C

Public Release:1-Jun-2015 

Wiley 

Treatment options for chronic hepatitis C, a serious and life-threatening infection, have improved substantially and several new regimens with shorter durations and improved efficacy and safety profiles are now available.

Groups have raised concerns about the evidence used to support the approval of some newer drugs, however, and the issue has been used to cast doubt on their efficacy and even to question treatment or deny reimbursement.

To address these concerns, the US Food and Drug Administration's Division of Antiviral Products in the Center for Drug Evaluation and Research (CDER) has published a paper that highlights the agency's scientific approaches and regulatory processes that support the development and approval of promising drugs to treat hepatitis C.

"FDA's approach to evaluation of recent hepatitis C drugs underscores the Agency's flexibility in considering innovative or alternative trial designs for drugs that have demonstrated highly promising outcomes in early phase development," said Dr. Poonam Mishra, deputy director for Safety, Division of Antiviral Products/Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research and lead author of the Hepatology paper. "Expedited approaches can be used without compromising efficacy standards for drugs that demonstrate breakthrough therapy potential."

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Source: http://www.eurekalert.org/pub_releases/2015-06/w-fac060115.php

Hep C drug tourism has begun as patients seek Harvoni, Sovaldi overseas

When Gilead Sciences ($GILD) struck its hepatitis C supply deal with Indian generics makers, the terms were tight, with provisions designed to keep the knockoff pills in countries where Gilead allows cut-rate pricing. Some state health systems overseas require patients to show IDs to get their meds and present empty pill bottles for refills.

And this is why.

As Bloomberg reports, everyone from individual patients on up to pharmacy benefits managers has been scheming about how to get Gilead's Harvoni and Sovaldi at the lower prices available in other countries--as low as 1% of the U.S. sticker price, the news service notes.

Read more..

Almost three quarters of HIV/HCV group may have DDA-ARV interactions

Among 125 HIV/HCV-coinfected people taking antiretrovirals in a Denver group, 70% could have moderate or severe interactions with one of four common direct-acting antiviral (DAA) regimens for HCV [1]. Researchers calculated that 20% of patients who needed to switch antiretrovirals because of certain DAA interactions could not switch because of antiretroviral resistance.
 
This retrospective study involved 125 HIV/HCV-coinfected adults with antiretrovirals prescribed within the last year. All participants were in care at an academic medical center in Denver. Researchers assessed potential interactions between each person's antiretroviral regimen and four possible DAA combinations: simeprevir and sofosbuvir (SIM/SOF), sofosbuvir and ledipasvir (SOF/LDV), sofosbuvir and daclatasvir (SOF/DCV), and ritonavir-boosted paritaprevir plus dasabuvir and ombitasvir (3D). The analysis did not explore potential interactions between non-HIV drugs and DAAs.

Read  more...

HealthWise: Hepatitis C and Pain—Part 1, by Lucinda K. Porter, RN

Hepatitis C or no hepatitis C, everyone experiences pain from time to time. However, if you have chronic hepatitis C virus (HCV) infection, you are likely to have pain. The Institute of Medicine (IOM) estimates that around 100 million Americans have pain. Compare this to the 3 million Americans living with HCV, how do you know if HCV or something else is causing your pain? This two-part series will explore hepatitis C and pain.

Hepatitis C is called the “silent killer,” because the liver is a non-complaining organ. Liver cells don’t have nerves, so there can be serious tissue damage, but no pain. However, lack of nerve cells doesn’t mean there can’t be liver pain (hepatalgia or hepatodynia). Located in the right upper part of the abdomen, hepatalgia is usually caused by stretching of the capsule surrounding the liver, as well as by complaints from nearby organs. Liver pain does not mean that hepatitis C is worsening. The discomfort may be dull, sharp, mild, severe, constant or intermittent. For me it felt like my liver was fluttering. The only way I can describe it was it felt like when I was pregnant and the baby moved.

Even if there isn’t discomfort in the area of the liver, HCV may cause pain in other parts of the body. These are known as extrahepatic manifestations, and the complaints most associated with pain other than hepatalgia are:

• Musculoskeletal (myalgia)
• Joint pain (arthralgia)
• Stomach pain 

Since pain is a common symptom of many medical conditions, the first order of business is to get a medical diagnosis to determine the cause of your discomfort. Is HCV the cause, or is there something else? It doesn’t have to be either/or, as some people have more than one cause of pain. If HCV is the cause, the next order of business is to find out if the pain is a direct result of the virus, or has HCV caused a secondary problem, such as cryoglobulinemia or an autoimmune disorder.

In the case of cryoglobulinemia, hepatitis C causes the body to produce proteins called cryoglobulins. Cryoglobulins clump together in the blood when they are cold; this causes joint pain. Various studies have shown that successful HCV treatment also improves cryoglobulinemia. The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) HCV Guidelines highly recommend HCV treatment for people with cryoglobulinemia.

Treatment may also help HCV-positive people with autoimmune disorders such as lupus and rheumatoid arthritis. If the pain is primarily from HCV, then eradicating the virus usually eliminates the aches and pains that are caused by the virus.

Pain Medication
Acute pain, meaning that it is short-lived, is the easiest to manage. There is a wide selection of pain medications or analgesics, ranging from over-the-counter (OTC) aspirin to prescription narcotics. These drugs generally work well for acute pain because patients don’t take them for long periods of time, since the problem that caused the pain usually heals. 

That is not to say that there aren’t risks and downsides to taking painkillers—there are, especially from a liver standpoint. This risk increases if the liver is severely damaged by HCV. However, if someone with hepatitis C has a well-functioning liver, most physicians are comfortable prescribing a short-course of narcotics for conditions that warrant it, such as injuries or surgery. The risk to the liver is low, and it’s inhumane and medically unwise to withhold pain relief.

A much bigger problem is chronic pain, or pain that lasts for more than three months (some experts say six months). Chronic pain affects body, mind, and spirit, and it can change your life. The more severe the pain, the greater the transformation. Not the good transformation, like from a caterpillar to a butterfly; more like from a butterfly to an ogre.  

People with hepatitis C who are in pain, are confronted with the issue of finding pain relief that doesn’t further damage the liver. Fortunately, there is a wide selection of medications and pain management tools. Let’s explore pain medication this month; next month I’ll delve into medication-free pain management.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Acetaminophen (Tylenol) is one of the most commonly used non-prescription analgesics. Known as paracetamol in Europe, acetaminophen is great for headaches, fever and mild pain. Technically, acetaminophen is an NSAID, but it’s anti-inflammatory effects are not as good as drugs such as ibuprofen.

cetaminophen is one of the safest drugs there is, even if you have liver disease. It is harmless at low doses. However, acetaminophen can cause acute liver injury and death from acute liver failure at amounts just twice the maximum recommended dose of acetaminophen. The big problem with acetaminophen is that it is added to many medications. Remedies for colds, headaches, pain, sleep, sinus problems, cough and PMS often contain acetaminophen. Lose track of this fact, and you may take toxic amounts. For more information, read Acetaminophen: Safe or Harmless?(HCV Advocate,February 2014)

In the U.S., approximately 50 million people take acetaminophen every week, and more than 25 billion doses are sold yearly. Slightly more than 300 people die annually from it. Nearly all of these are from overdose; half are from intentional overdose (suicide attempts). Acetaminophen hepatotoxicity most commonly arises after a suicide attempt using more than 7.5 grams, but more often at more than 15 grams as a single overdose.

Aspirin is perhaps the most commonly used analgesic and fever-reducing medication in the world. At low daily doses (81 mg), aspirin is used to decrease the risk of stroke, and may prevent a second heart attack. Daily aspirin is no longer recommended to prevent heart disease unless there is a pre-existing condition.

At high doses, aspirin can injure the liver. However, this damage is not from toxicity, such as what may occur with high doses of acetaminophen. The biggest risk with aspirin is a gastrointestinal (GI) bleed. Far more people are injured every year from aspirin use than from acetaminophen. Mortality and morbidity studies are scant, but it appears that there are 10 times more deaths and hospitalizations from NSAID use than from acetaminophen. Complications may occur even at low doses, and the risk increases with age.

Rounding out OTC NSAIDs are drugs such as ibuprofen (Advil, Motrin) and naproxen (Alleve). These drugs are used for mild-to-moderate pain and inflammation. Around 30 million Americans take NSAIDs every year. These drugs rarely cause liver problems, but have other risks, such as injury to the kidneys and GI tract. In addition to OTC NSAIDs, there are many prescription NSAIDs.

Opioids
Opioids are medications related in structure to the natural plant alkaloids found in opium. There are natural and synthetic opioids, and many medications in this category. The most commonly prescribed opioids for pain are codeine, hydrocodone (Vicodin), and oxycodone (Oxycontin). Unlike NSAIDs, opioids have a high potential for dependency and abuse.

According to the CDC, more than 16,000 people in the United States die every year from overdose of prescription painkillers. This is approximately 44 people every day. On their own, opioids rarely injury the liver. However, opioids are sometimes formulated with acetaminophen, and excessive amounts can injure the liver. The FDA has recommended that physicians not use opioid combinations in which the dose of acetaminophen is greater than 325 mg per dose.

Opioid use is making the news these days. Hepatitis C infections rates are increasing at alarming rates in young people, most notably in Kentucky, Tennessee, Virginia and West Virginia. Sharing needles through opioid abuse is fueling this rise.

Another reason that opioids are making the news has to do with how it is prescribed. In some cases, opioids are over-prescribed. Just as bad, is that in some cases opioids are under-prescribed, leaving patients in misery. I am not going to dive in to this debate, but for those looking for well-written information on this, I highly recommend Judy Foreman’s book, “A Nation in Pain.”

What’s Ahead
When it comes to managing pain, there are more choices than just prescription and OTC medications. Next month, I will present information on effective alternatives, such as medical marijuana and drug-free pain management techniques including an effective technique that may surprise you. 

Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of Free from Hepatitis C and Hepatitis C One Step at a Time. Her blog is www.LucindaPorterRN.com

Resources

• LiverTox: Clinical and Research Information on Drug-Induced Liver Injury
• U.S. Veterans Administration’s: Viral Hepatitis and Managing Pain

http://hcvadvocate.org/news/newsLetter/2015/advocate0615.html#2

Ireland: Hepatitis C patients to finally start life-saving treatment

Nearly all 250 sufferers expected to recover after treatment costing up to €55,000 each 

Some 250 seriously ill patients with hepatitis C are to begin receiving a life-saving new treatment after a six-month delay caused by bureaucratic red tape.

The first group of patients with advanced liver disease who have been approved will be treated at one of 10 centres across the State in the coming weeks. Virtually all are expected to be “cured” of the disease following a 12-week programme, which is costing between €45,000 and €55,000 per patient.

Last month, doctors warned that patients were dying because of the failure of the Government to roll out a national treatment programme, even after negotiations with drug companies had ended. Other patients were paying privately for the treatment because of the absence of State support.

Read more...

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

AIDS LifeCycle Rider Loses Mom to Hep C, Uses Mic to Talk About Treatment and HIV-Hep C Co- infections

By David Heitz

What happened to Nenna Joiner’s mother is getting to be a really, really old story for people living with Hepatitis C.

Joiner’s mother died Nov. 22, 2014, because she could not get access to lifesaving Hepatitis C treatment.

Joiner, 40, of Oakland, Calif., is riding in AIDS LifeCycle this year to raise awareness about this all too common story. She did not even know her mother had Hepatitis C for many years, even though her mom knew she had it.

Serving as one of several spokespeople for the ride, Joiner is using her platform not only to raise Hepatitis C awareness, but also to highlight the reality of HIV-Hepatitis C co-infections. Such co- infections tend to be more common among intravenous drug users and men who have sex with men.
Joiner also is dedicating the ride to all women of color.

“When I heard about (the Hepatitis C), it pierced me, and I had to learn more about it, because I was caretaking for mom at my home,” Joiner said. “She had known for a while. I went to a doctors’ appointment with her and asked (healthcare providers), ‘What are you testing for?’ They just want to give you paperwork and fliers, you know.”

Joiner said her mother had battled alcoholism many years, and had been in the hospital many times. Her mother also is a Baby Boomer. Baby Boomers have been identified as a high risk group for Hepatitis C by the U.S. Centers for Disease Control and Prevention (CDC). In fact, every Baby Boomer in America needs to get tested for Hepatitis C, according to the CDC.

“I asked her, ‘Well what is this?’” Joiner recalled. “And she said, ‘Oh, don’t worry about it.’ Well I need to worry about it. I need to know about it. So I took the paperwork and began reading it myself, and I  began to tell people to get vaccinated for Hepatitis A and B.”

Last year, just as Joiner had competed AIDS LifeCycle, she got a call from a friend. Her mom had ended up in the emergency room. She was in Los Angeles and could not be there.

Joiner said her mother was getting help from Oasis Clinic in Oakland. But her mom was unable to win approval for either the new, expensive medications that cure Hepatitis C or a liver transplant.
Oasis is a small clinic that fights for access to Hepatitis C for the most marginalized of the marginalized, including uninsured or underinsured alcoholics and/or drug addicts.

“The whole insurance thing…I was being a good advocate, but with not really knowing anything, I would go with her to the doctor and they would say, ‘Come back in a couple of months, insurance will approve it,” Joiner said. She did not know the ins and outs of working pharmaceutical patient assistance programs or the rest of the red tape that often comes along with winning approval for drugs such as Sovaldi and Harvoni. Often, it takes being a self-advocate to get the medications on top of getting help from a doctor of advocacy group.

“It was a stalemate,” Joiner said. “They would forget things, paperwork was getting lost….I just don’t think (insurers) are doing exactly what’s necessary.”

Joiner said what was even worse was that her mother became afraid to get too close to her daughter, Joiner said, fearing she could be contagious. Hepatitis C is a bloodborne disease and cannot be spread  through casual contact such as kissing and hugging.

“I never stopped kissing her or holding her hand,” Joiner said.

Joiner’s messages are: Get tested for Hepatitis C. You may be infected for many years, not know it, and be passing the disease along to others. Hepatitis C can be in your bloodstream for decades before you ever show any symptoms.

Also, if a loved one has the disease, educate yourself about it, and help them seek treatment.
Joiner says she’s get some flak from others for speaking out about Hepatitis C because she owns an adult book store. They insinuate that she thinks she’s changing the world by passing out free condoms.

“People would say, ‘Oh, you own a sex shop, and you’re going to save the world,’” Joiner said. “It’s not the condoms that are saving lives. It’s the information.”