The Dark Side of Letting Insurance Payers Dictate Hepatitis C Treatment

Imagine that you have a disease and you have two choices of treatment. Both treatments are highly effective at treating your condition. Medication A has mild side effects. Medication B has lots of side effects including, fatigue, nausea, itching, insomnia, and weakness. Pretty much everyone who takes medication B has side effects. Medication A is a pill a day; medication B uses two pills in the morning and one at night, and sometimes additional pills are prescribed that must be taken twice daily. Medication B has the potential to interact with more drugs than medication A does. Which would you pick? I assume you'd pick medication A.

Your doctor would likely recommend medication A. Drug regimens with many side effects means that you are more likely to need assistance from your health care team, perhaps needing additional laboratory tests to monitor your safety. If your doctor has more patients on medication B, then your doctor's schedule will use appointment slots for side effect management, rather than for seeing other patients who also need to be treated.

So, it seems like medication A is the obvious choice. Unfortunately, for many people with hepatitis C, it isn't. In this case, medication A represents Gilead Sciences' Harvoni; medication B represents AbbVie's Viekira Pak or Technivie. Harvoni is not covered under all insurance plans, such as those using Express Scripts. In short, your doctor may want to treat you with Harvoni, but your insurance may not carry it on its drug formulary. Your hep C treatment may be limited to medication B.

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Q&A with AbbVie's Barry Bernstein, MD: Are More FDA Warnings in the Works ?

Note:  In addition to the label change and warning about their currently approved medications Dr. Bernstein gives an estimate on a possible approval of AbbVie's new pan-genotypic combination.  Alan


The effectiveness of the new arsenal of hepatitis C antivirals has elated physicians and patients and been a triumph—and lucrative development--for pharmaceutical companies.

The announcement on Oct. 22 that AbbVie, manufacturer of two such drug products was changing labeling to include new warnings dampened the euphoria. Post-marketing reports alerted the company and the US Food and Drug Administration (FDA) of patient deaths and severe liver damage sometimes requiring transplantation in some patients who received AbbVie’s treatments.

The company, in consultation with the FDA changed its package inserts and labeling for Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and Technivie (ombitasvir, paritaprevir, and ritonavir tablets.

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FDA Warns of Serious Liver Injury Risk with AbbVie's (ABBV) Viekira Pak

FDA warns of serious liver injury risk with Viekira Pak, according to Bloomberg headlines. The FDA will require Abbvie (NYSE: ABBV) to add new safety risk to its labels.

UPDATE - The FDA issued the following safety announcement on Thursday:

The U.S. Food and Drug Administration (FDA) is warning that hepatitis C treatments Viekira Pak and Technivie can cause serious liver injury mostly in patients with underlying advanced liver disease. As a result, we are requiring the manufacturer to add new information about this safety risk to the drug labels.

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FDA UPDATE - VIEKIRA PAK & TECHNIVIE SAFETY WARNING & LABEL CHANGE

Information about FDA Hepatitis product approvals, safety warnings, medical product labeling changes, notices of upcoming public meetings, and notices about proposed regulatory guidances.

The U.S. Food and Drug Administration (FDA) is warning that hepatitis C treatments Viekira Pak and Technivie can cause serious liver injury mostly in patients with underlying advanced liver disease. As a result, new information about this safety risk was added to the Viekira Pak and Technivie labels. Please refer to the FDA Drug Safety Communication for specific details [http://www.fda.gov/Drugs/DrugSafety/ucm468634.htm] In addition, FDA approved changes to the DOSAGE AND ADMINSTRATION, CONTRAINDICATIONS AND WARNINGS AND PRECAUTIONS sections of the Viekira Pak and Technivie labeling and to the respective patient package insert with information on postmarketing reports of hepatic decompensation and hepatic failure including liver transplantation or death among patients with cirrhosis. The specific changes to the each label are summarized below. Major revisions to the Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets), co-packaged for oral use label include: 2 DOSAGE AND ADMINISTRATION 2.1 Testing Prior to Initiation of VIEKIRA PAK Prior to initiation of VIEKIRA PAK, assess for laboratory and clinical evidence of hepatic decompensation 2.4 Hepatic Impairment VIEKIRA PAK is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) 4 CONTRAINDICATIONS VIEKIRA PAK is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity. Additionally, colchicine was added to the list of contraindicated drugs due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment. 5 WARNINGS AND PRECAUTIONS 5.1 Risk of Hepatic Decompensation and Hepatic Failure in Patients with Cirrhosis Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported postmarketing in patients treated with VIEKIRA PAK. Most patients with these severe outcomes had evidence of advanced cirrhosis prior to initiating therapy with VIEKIRA PAK. Reported cases typically occurred within one to four weeks of initiating therapy and were characterized by the acute onset of rising direct serum bilirubin levels without ALT elevations in association with clinical signs and symptoms of hepatic decompensation. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. VIEKIRA PAK is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C). For patients with cirrhosis: Monitor for clinical signs and symptoms of hepatic decompensation (such as ascites, hepatic encephalopathy, variceal hemorrhage). Hepatic laboratory testing including direct bilirubin levels should be performed at baseline and during the first 4 weeks of starting treatment and as clinically indicated. Discontinue VIEKIRA PAK in patients who develop evidence of hepatic decompensation. 6 ADVERSE REACTIONS 6.2 Post-Marketing Adverse Reactions The following adverse reactions have been identified during post approval use of VIEKIRA PAK. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hepatobiliary Disorders: Hepatic decompensation, hepatic failure 8 USE IN SPECIFIC POPULATIONS 8.6 Hepatic Impairment No dosage adjustment of VIEKIRA PAK is required in patients with mild hepatic impairment (Child-Pugh A). VIEKIRA PAK is contraindicated in patients with moderate to severe (Child-Pugh B and C) hepatic impairment Major revisions to the Technivie (ombitasvir, paritaprevir and ritonavir) tablet label include: The updated label will be available at drugs@fda or dailymed. Richard Klein Office of Health and Constituent Affairs Food and Drug Administration Steve Morin Office of Health and Constituent Affairs Food and Drug Administration For more information about the Hepatitis Liaison Program visit the FDA Patient Network

2 new hepatitis C drugs to be available in November in Egypt

CAIRO: Minister of Health Adel al-Adawy announced that two new hepatitis C drugs, Harvoni and Viekira, are to be available at the hepatitis treatment centers by next November, youm7 reported Wednesday.

There are 2.3 million hepatitis C patients in Egypt, while 996,642 patients applied on the website of the National Committee for the Control of Viral Hepatitis to be treated by Sovaldi until last June, according to Adawy.

He added that 85,536 patients were provided with the treatment until the end of June.

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Results from AbbVie's Study of VIEKIRA PAK™ (ombitasvir, paritaprevir, ritonavir tablets; dasabuvir tablets) in Chronic Hepatitis C Patients with HIV-1 Co-Infection (TURQUOISE-I) Published Online in JAMA; Sub-analyses to be Presented at the Annual Conference on Retroviruses and Opportunistic Infections (CROI)

- In adult patients co-infected with genotype 1 (GT1) hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1), TURQUOISE-I, using VIEKIRA PAK with ribavirin (RBV), demonstrated sustained virologic response rates 12 weeks post-treatment (SVR12) of 94 percent with 12 weeks of treatment and 91 percent with 24 weeks of treatment, respectively

 - TURQUOISE-I results published online today in The Journal of the American Medical Association (JAMA) - 

Additional sub-analyses of TURQUOISE-I data to be presented this week at the Annual Conference on Retroviruses and Opportunistic Infections (CROI)

NORTH CHICAGO, Ill., Feb. 23, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that results from part one of the Phase 2 portion of its Phase2/3 open-label study, TURQUOISE-I, in genotype 1 chronic hepatitis C patients with human immunodeficiency virus type 1 (HIV-1) co-infection were published online in The Journal of the American Medical Association (JAMA). Additional sub-analyses also will be presented in both oral and poster presentations on Feb. 26, at the Annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Wash.

As published today in JAMA, and originally presented at The Liver Meeting® 2014, the TURQUOISE-I study showed patients co-infected with genotype 1 (GT1) hepatitis C virus (HCV) and HIV-1 receiving VIEKIRA PAK™ and ribavirin (RBV) for 12 weeks or 24 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 94 percent (n=29/31) and 91 percent (n=29/32), respectively. The SVR₁₂ rates were 91 percent (n=51/56) for subjects with HCV GT1a infection and 100 percent (n=7/7) for those with HCV GT1b infection.

"It is common for people to live with both GT1 chronic HCV and HIV, but data supporting treatment of chronic HCV in these co-infected patients have been limited," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "TURQUOISE-I is one of the few dedicated studies looking specifically at this historically difficult-to-treat population and we are proud to offer the HCV community an important new treatment option."

VIEKIRA PAK is contraindicated with efavirenz (Sustiva) because co-administration is poorly tolerated and results in liver enzyme elevations. The ritonavir component of VIEKIRA PAK is an HIV-1 protease inhibitor and can select for HIV-1 protease inhibitor resistance. To reduce this risk, HCV/HIV-1 co-infected patients should also be on a suppressive antiretroviral (ART) drug regimen. The most common adverse events occurring in at least 10 percent of patients in TURQUOISE-I were fatigue (48%), insomnia (19%), nausea (17%), headache (16%), itching (13%), cough (11%), irritability (10%), and yellowing of the eyes (10%).

Sub-analyses of these data will be presented later this week at CROI in oral and poster presentations:

• High SVR Regardless of Time to Suppression with Paritaprevir/r/Ombitasvir & Dasabuvir + RBV Oral Presentation #147
  February 26, 2015, 10:30-10:45 p.m. PST, Room 6AB 
  Analysis of time to HCV suppression in HCV/HIV co-infected patients in TURQUOISE-I
• Hematologic Analysis of Paritaprevir/r/Ombitasvir and Dasabuvir + RBV in TURQUOISE-I Poster #691
  February 26, 2015, 2:30-4 p.m. PST, Poster Hall 
  In this analysis of the TURQUOISE-I study, certain laboratory values in patients taking paritaprevir/r/ombitasvir and dasabuvir with RBV were examined, including hemoglobin, CD4+ T cells, and lymphocyte count

About TURQUOISE-I  TURQUOISE-I is an ongoing Phase 2/3, multi-center, randomized, open-label study evaluating the efficacy and safety of VIEKIRA PAK (ombitasvir, paritaprevir, ritonavir (25/150/100 mg once daily) and dasabuvir (250 mg twice daily) with RBV (weight based dosing of 1000 mg or 1200 mg per day divided twice daily) for 12 or 24 weeks in adult patients with chronic GT1 HCV infection with or without compensated liver cirrhosis who are also infected with HIV-1.

Study patients were either new to therapy (treatment-naïve) or had failed previous treatment with pegylated interferon and RBV (treatment-experienced), had a stable immune status (CD4+ counts of ≥200 cells/mm³ or CD4+ % ≥14%). Patients were on a stable HIV-1 ART regimen that included tenofovir disoproxil fumarate plus emtricitabine or lamivudine, administered with ritonavir-boosted atazanavir or raltegravir. Patients on atazanavir stopped the ritonavir component of their HIV-1 ART regimen upon initiating treatment with VIEKIRA PAK + RBV. Atazanavir was taken with the morning dose of VIEKIRA PAK. The ritonavir component of the HIV-1 ART regimen was restarted after completion of treatment with VIEKIRA PAK and RBV. Of the five patients who were non-responders, one experienced virologic failure, one discontinued treatment, one experienced relapse and two patients had evidence of HCV reinfection post-treatment. Based on the results of this study, prescribers should follow the same dosing recommendations for mono-infected patients as outlined in the VIEKIRA PAK prescribing information.

Elevations in total bilirubin were the most common laboratory abnormality, were mainly composed of indirect bilirubin, and were not associated with elevations in commonly measured liver enzymes. Reductions in RBV dose because of anemia or reduced hemoglobin occurred in 10 percent of patients (n=6/63); all six patients achieved SVR₁₂.

Read complete press release here...

Missouri to save $4.2 million by switching hepatitis C drug

JEFFERSON CITY, Mo. (AP) — State officials say Missouri’s Medicaid program will save an estimated $4.2 million in fiscal year 2016 by using a newer, cheaper drug to treat hepatitis C.

The state joined a group of 25 other states to receive rebates on Viekira from drug maker AbbVie. The state in most cases will provide that drug instead of Gilead Science’s Sovaldi in an agreement announced Monday.

The expensive treatment with Sovaldi, about $84,000 for a normal course, was cited as one driver of increased Medicaid costs for the state in 2015 by the state budget director.

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Genotype 1: VIEKIRA PAK Therapy

Be sure to check out our new HCSP fact sheet on Genotype 1: VIEKIRA PAK Therapy

Click here to download

HCV Drugs —Alan Franciscus, Editor-in-Chief

AbbVie's VIEKIRA PAK Approval & AASLD 2014

In this month’s HCV Drugs we have news on AbbVie’s drug approval of their HCV drugs, and, yes, more coverage from the American Association for the Study of Liver Diseases (AASLD).  In Lucinda’s Snapshots column this month, information on Janssen’s AASLD presentations is included.

AbbVie
On December 19, 2014 the Food and Drug Administration (FDA) approved AbbVie’s 3D combination—VIEKIRA PAK—to treat HCV genotype 1 patients.   On December 23, 2014, the 3D combination was approved by Health Canada as HOLKIRA PAK. AbbVie conducted phase 3 trials in about 2,300 patients and the cure rates were over 90%.  Included in the FDA label was information about HIV/HCV coinfection and liver transplantation treatment results.  For more information, visit our website for new VIEKIRA PAK fact sheets, FDA Approved Prescribing Information and detailed information from their phase 3 studies included in past issues of our HCV Advocate monthly and mid-monthly newsletters. 

        VIEKIRA PAK

Gilead
GS-5816 is a new investigational NS5A inhibitor being developed by Gilead.  It has activity across all genotypes (pan-genotypic).  In the current studies, it is being combined with sofosbuvir (polymerase inhibitor) with and without ribavirin.

Safety and Efficacy of Treatment with Sofosbuvir plus GS-5816 With and Without Ribavirin for 8 or 12 Weeks in Treatment-Naïve Patients with Genotype 1-6 HCV Infection—T Tran et al.

Summary:  The combination of sofosbuvir plus GS-5816 without ribavirin produced high cure rates in all genotypes. 

Gilead continues to study sofosbuvir in combination with other investigational compounds—in this case with GS-5816, an NS5A inhibitor. 

Part A of the current study comprised 8 arms—all arms received sofosbuvir plus GS-5816 at either 25 mg or 100 mg without ribavirin for 12 weeks. Included in the study were treatment-naïve patients without cirrhosis.  There were two parts (A and B) of the study.  Part A had six treatment arms that included genotypes 1 through 6.  Listed below are the number of patients and cure rates. 

• Genotype 1:  55 patients:  96% to 100%
• Genotype 2:  21 patients: 91% to 100%
• Genotype 3:  54 patients 93%
• Genotype 4:  14 patients 86% to 100%
• Genotype 5:  1 patient 100%
• Genotype 6:  9 patients 100%

Part B of the study included only genotype 1 and 2 patients.  There were also 8 arms in Part B, but the genotype 1 non-cirrhotic patients received only 8 weeks of treatment at the same doses.  Half of the patients in the study received ribavirin.   Genotype, number of patients and cure rates are listed below:

• Genotype 1:  59 patients no ribavirin 83% to 87%; 61 patients (81% - 83%) with ribavirin
• Genotype 2:  52 patients no ribavirin 87% to 90%; 51 patients (88%) with ribavirin

The combination of sofosbuvir and GS-5816 with and without ribavirin was safe and well-tolerated.  The most common side effects were fatigue, headache, and nausea.

The combination of sofosbuvir (400 mg) and GS-5816 (100 mg) has been co-formulated into one pill taken once daily.  It is currently in phase 3 clinical trials to be studied with and without ribavirin for the treatment of HCV genotype 1, 2, 3, 4, 5, and 6.  

Comments:  Sofosbuvir and GS-5816 has been co-formulated into 1 pill taken once-a-day and is in phase 3 clinical trials with and without ribavirin for a treatment duration of 12 weeks for genotype 1 through 6.  Another study being conducted in genotype 3 patients is comparing the treatment duration of 12 vs. 24 weeks.

AASLD/ IDSA/IAS-USA Recommendations
Check out the updated HCV Guidance from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America that include Harvoni and VIEKERA PAK. Seven sections of the HCV Guidance have been extensively revised based on newly available therapies and data: Initial, Retreatment, Monitoring, and Unique Populations (HIV/HCV Coinfection, Cirrhosis, Post-Liver Transplantation, and Renal Impairment).
www.hcvguidelines.org


http://hcvadvocate.org/news/newsLetter/2015/advocate0115.html#2