Showing posts with label Simeprevir now Olysio. Show all posts
Showing posts with label Simeprevir now Olysio. Show all posts

Saturday, March 21, 2015

FDA Update - Important safety information: Harvoni , and Sovaldi‏

Related Update: April 16
FDA approved changes to the Olysio (simeprevir) package insert to include two new Warnings and Precautions;
--serious symptomatic bradycardia when co-administered with sofosbuvir and amiodarone
--hepatic decompensation and hepatic failure.
March 24
FDA - Safety Announcement
Facts about Harvoni and Sovaldi
More Info for Patients
More Info for Health Care Professionals
Data Summary

March 21:
FDA update and Gilead Sciences issued letter to Healthcare Providers;

FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi‏
Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of amiodarone with either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or with Sovaldi® (sofosbuvir) in combination with another direct acting antiviral.

Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......

On March 20, 2015, FDA approved changes to the Harvoni (ledipasvir/sofosbuvir fixed dose combination) and Sovaldi (sofosbuvir) labels to update the WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and DRUG INTERATIONS sections of the labeling and the patient package insert with information on post-marketing cases of symptomatic bradycardia when co-administered with amiodarone. Additionally, Gilead Sciences has issued a Dear Healthcare Provider letter (see below).

The specific changes to the each label are summarized below.

Harvoni label changes:

5 WARNINGS AND PRECAUTIONS

5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone

Postmarketing cases of symptomatic bradycardia, including fatal cardiac arrest and cases requiring pacemaker intervention, have been reported when amiodarone is coadministered with HARVONI. Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.

Coadministration of amiodarone with HARVONI is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered HARVONI:

• Counsel patients about the risk of serious symptomatic bradycardia

• Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking HARVONI who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting HARVONI should also undergo similar cardiac monitoring as outlined above.

Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately.

6 ADVERSE REACTIONS

6.2 Postmarketing Experience

Because postmarketing 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. The following adverse reactions have been identified during post approval use of HARVONI.

7 DRUG INTERACTIONS

Added amiodarone information to Table 3, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.
Concomitant Drug Class: Drug Name
Effect on Concentration
Clinical Comment
Antiarrhythmics:
amiodarone
Effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown
Coadministration of HARVONI with amiodarone may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with HARVONI is not recommended; if coadministration is required, cardiac monitoring is recommended [see Warnings and Precautions (5.1)]

Sovaldi Label Changes:

5 WARNINGS AND PRECAUTIONS

5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral

Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with SOVALDI in combination with an investigational agent (NS5A inhibitor) or simeprevir. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (HARVONI (ledipasvir/sofosbuvir)). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.

Coadministration of amiodarone with SOVALDI in combination with another direct acting antiviral (DAA) is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered SOVALDI and another DAA:

• Counsel patients about the risk of serious symptomatic bradycardia

• Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking SOVALDI in combination with another DAA who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting SOVALDI in combination with a DAA should also undergo similar cardiac monitoring as outlined above.

Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems [See Adverse Reactions (6.2), Drug Interactions (7.2)].

6 ADVERSE REACTIONS

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of SOVALDI. Because postmarketing 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.

Cardiac Disorders

Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiate treatment with SOVALDI in combination with another HCV direct acting antiviral [See Warnings and Precautions (5.1), Drug Interactions (7.2)].

7 DRUG INTERACTIONS

Added amiodarone information to Table 5, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.

Concomitant Drug Class: Drug Name
Effect on Concentration
Clinical Comment
Antiarrhythmics:
amiodarone
Effect on amiodarone and sofosbuvir concentrations unknown
Coadministration of amiodarone with SOVALDI in combination with another DAA may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with SOVALDI in combination with another DAA is not recommended; if coadministration is required, cardiac monitoring is recommended [See Warnings and Precautions (5.1), Adverse Reactions (6.2)].
Updated labeling will be posted soon at DailyMed

Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......

Harvoni and Sovaldi are products of Gilead Sciences.

Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Steve Morin
Office of Special Health Issues
Food and Drug Administration

Gilead Sciences issued letter to Healthcare Providers 

FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi

IMPORTANT DRUG WARNING

Subject: Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of Amiodarone With Either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or With Sovaldi® (sofosbuvir) in Combination with Another Direct Acting Antiviral.

Dear Health Care Provider,
The purpose of this letter is to inform you of new important safety information for Harvoni and Sovaldi

· Harvoni is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults.
· Sovaldi is indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.

Serious Risk of Symptomatic Bradycardia With Co-Use of Amiodarone with Either Harvoni or With Sovaldi in Combination with Another Direct Acting Antiviral (DAA)

· Postmarketing cases of symptomatic bradycardia, as well as one fatal cardiac arrest and cases requiring pacemaker insertion, have been reported in patients taking amiodarone and Harvoni, or amiodarone and Sovaldi in combination with another DAA.
· Bradycardia was observed within hours to days of starting Harvoni, or Sovaldi in combination with another DAA, but cases have been observed up to 2 weeks after initiating HCV treatment.
· Risk factors for the development of symptomatic bradycardia in patients receiving amiodarone may include coadministration of a beta blocker, or those with underlying cardiac comorbidities and/or advanced liver disease.
· Similar cases have not been reported in patients receiving Sovaldi with ribavirin or with pegylated interferon and ribavirin.

Warning and Precaution
Coadministration of amiodarone with either Harvoni or with Sovaldi in combination with another DAA is not recommended.

Further Information

Nine cases of symptomatic bradycardia have been reported during postmarketing in patients receiving amiodarone with either Harvoni, or Sovaldi in combination with another DAA (daclatasvir, an investigational DAA, or Olysio (simeprevir)). Seven patients were also receiving a beta blocker.

· Six cases occurred within the first 24 hours and the remaining 3 cases occurred within the first 2-12 days following HCV treatment initiation.
· One case was a fatal cardiac arrest and 3 cases required pacemaker intervention.
· In 3 cases, rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia.
· In one case discontinuation of amiodarone followed by rechallenge of HCV treatment after 8 weeks did not result in recurrent bradycardia.
· Three of the 9 cases were in patients receiving Harvoni, 5 cases were in patients receiving Sovaldi plus an investigational agent (daclatasvir) and 1 case was in a patient receiving Sovaldi with Olysio (simeprevir).

The mechanism of the potential interaction between amiodarone and Harvoni, or Sovaldi in combination with another DAA is unknown.

Because the number of patients taking amiodarone who have been exposed to Harvoni or Sovaldi in combination with another DAA is unknown, it is not possible to estimate the incidence of occurrence of these events.

Prescriber Action
For patients taking amiodarone who have no other alternative, viable treatment options and who will be co-administered Harvoni, or Sovaldi in combination with another DAA:
· Counsel patients about the risk of serious symptomatic bradycardia
· Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking Harvoni or Sovaldi in combination with another DAA who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting Harvoni or Sovaldi in combination with a DAA should also undergo similar cardiac monitoring as outlined above.

Tell your patients if they develop signs or symptoms that might suggest symptomatic bradycardia they should seek medical evaluation immediately. Symptoms may include:

· Near-fainting or fainting
· Excessive tiredness
· Dizziness or lightheadedness
· Shortness of breath
· Malaise
· Chest pains
· Weakness
· Confusion or memory problems

Patients should not stop taking any of their medicines without talking to their healthcare provider.
This information is based on currently available data and recommendations may change. Additionally, the product labeling will be updated.

Reporting Adverse Events

Please report all adverse events, following or coincident with the use of Harvoni or Sovaldi, to Gilead Global Drug Safety at 1-800-GILEAD-5, option 3; or to FDA's MedWatch program by telephone at 1-800-332-1088; by fax at 1-800-332-0178; via www.FDA.gov/medwatch; or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857 (use postage-paid FDA Form 3500).

Please refer to the accompanying full prescribing information and approved patient information for a complete description of the risk profile for Harvoni or Sovaldi.
Contact Gilead Medical Information at 1-800-GILEAD-5, option 2 if you have additional questions.

This information is being sent in agreement with the FDA.

Sincerely,
John McHutchison, MD
Executive Vice President, Clinical Research
Gilead Sciences, Inc.
Download - SVD HVN - DHCP Letter 20March15 - FINAL.DOCX

Wednesday, February 25, 2015

NICE guidance recommends sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen) for treating hepatitis C


Updated: Mar 3
Gilead's Harvoni gains NICE yes - but won't face funding delay - genotype 1, 4 , but not genotype 3
unlike the company's Sovaldi, which won’t be paid for until the summer
Gilead's next generation hepatitis C pill Harvoni is set to be backed by NICE - and this time NHS England won't be delaying its funding as it has done with the firm's other hep C drug Sovaldi.

Pharmalot, Pharmalittle: We’re Reading About Gilead, Hepatitis C Drug Prices and More!!
A 30-member panel of doctors and health experts will, for the first time, address the cost effectiveness of hepatitis C drugs in updated guidelines that may change prescribing and coverage for the medicines, Bloomberg News reports....

Two new drug treatments for hepatitis C have been approved for NHS use by the National Institute for Health and Care Excellence.25 February, 2015 | By Steve Ford

NICE has recommended sofosbuvir (Sovaldi) and simeprevir (Olysio) as treatment options for some people with chronic hepatitis C.

Sofosbuvir and simeprevir are both oral antiviral drugs used to prevent hepatitis C viral replication in infected cells.

The NICE guidance on sofosbuvir recommends its use in combination with ribavirin, with or without peginterferon alfa, as an option for some people with genotypes 1-6 chronic hepatitis C.

However, there will be a delay before NHS providers must comply with the guidance on sofosbuvir, after a request from NHS England. It will not have to comply with the recommendations until 31 July.

Sofosbuvir, manufactured by Gilead Sciences, is given as one 400mg tablet daily. The duration of treatment is 12 or 24 weeks depending on hepatitis C virus genotype and history of prior treatment with interferon. It costs £11,660.98 per 28-tablet pack of 400mg tablets (excluding VAT).

In contrast, the guidance on simeprevir is not subject to any delay. It recommends the drug’s use, in combination with peginterferon alfa and ribavirin, as an option for treating both genotypes 1 and 4 chronic hepatitis C in adults.

Simeprevir, manufactured by Janssen, is a protease inhibitor that inhibits the NS3/4A enzyme, which the hepatitis C virus depends on to replicate. It costs £1,866.50 per pack of 7x150mg tablets (excluding VAT).

“This is good news, not just for people with chronic hepatitis C, but also because having more effectivetreatments for the condition could reduce the spread of the virus”

Carole Longson

Meanwhile, NICE noted that more data on the use of simeprevir in combination with sofosbuvir to treat chronic hepatitis C in people who cannot tolerate or are not eligible for treatment with interferon is due to become available soon.

As a result, it said recommendations on that treatment combination would be developed in separate guidance.

Professor Carole Longson, director of the NICE Centre for Health Technology Evaluation, said: “New treatments, like sofosbuvir and simeprevir, can shorten the length of interferon-based therapy and in some situations don’t need to be taken with interferon at all.

“Both drugs can also be given to people who have previously been treated but did not clear the virus, in people whose condition has relapsed, or in people who have become re-infected after treatment,” she said.

“Sofosbuvir and simeprevir could therefore be valuable treatment options for people with chronic hepatitis C. This is good news, not just for people with chronic hepatitis C, but also because having more effective treatments for the condition could reduce the spread of the virus,” she added.

There are six major genotypes and several subtypes of the hepatitis C virus, the prevalence of each vary geographically.

Genotypes 1 and 3 account for the majority of chronic hepatitis C cases in England (46% and 43%, respectively).

People with genotype 2 hepatitis C generally respond to treatment better than those with genotype 1, 3, 4, 5 or 6.
Source

Press Release
25 February 2015

NICE guidance recommends sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen) for treating hepatitis C


Healthcare guidance body NICE has today published final guidance recommending sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen) as treatment options for some people with chronic hepatitis C.


Hepatitis C is a virus that infects the liver. It is spread by contact with infected blood, for instance by using contaminated needles for injecting drugs or sharing razors or toothbrushes. The virus can cause inflammation of, and damage to, the liver, preventing it from working properly.

About a third of people infected with the hepatitis C virus will eventually develop liver cirrhosis, where normal liver tissue is replaced by scar tissue. A small number of people with chronic hepatitis C and cirrhosis also go on to develop liver cancer.

The aims of treatment are to clear the virus from the blood to prevent progression of liver disease, and to prevent the transmission of the hepatitis C virus. Sofosbuvir and simeprevir are oral antiviral drugs used to prevent hepatitis C viral replication in infected cells.

Sofosbuvir has a marketing authorisation in the UK for use in combination with other medicinal products for treating chronic hepatitis C in adults. The guidance on sofosbuvir recommends its use in combination with ribavirin, with or without peginterferon alfa, as an option for some people with genotypes 1- 6 chronic hepatitis C.[1]

Simprevir has a marketing authorisation in the UK for use in combination with other medicinal products for treating adults with genotype 1 or 4 chronic hepatitis C. The guidance on simeprevir recommends its use, in combination with peginterferon alfa and ribavirin, as an option for treating both genotypes 1 and 4 chronic hepatitis C in adults.

More data on the use of simeprevir in combination with sofosbuvir to treat chronic hepatitis C in people who can’t tolerate or aren’t eligible for treatment with interferon is due to become available soon. Therefore recommendations on this treatment combination will now be developed in separate guidance.

Commenting on today’s guidance Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation, said: “Poor diagnosis rates - estimates suggest around 50% of people with the condition in England remain undiagnosed - combined with a high number of new infections annually make hepatitis C a major public health challenge. But even when people are diagnosed, the long duration and potentially unpleasant side-effects of current interferon-based treatments can discourage people with the disease from completing the full course, or even from seeking treatment in the first place.

“New treatments, like sofosbuvir and simeprevir, can shorten the length of interferon-based therapy and in some situations don’t need to be taken with interferon at all. Both drugs can also be given to people who have previously been treated but did not clear the virus, in people whose condition has relapsed, or in people who have become re-infected after treatment.

“Sofosbuvir and simeprevir could therefore be valuable treatment options for people with chronic hepatitis C. This is good news, not just for people with chronic hepatitis C, but also because having more effective treatments for the condition could reduce the spread of the virus.”

Following a request from NHS England and consultation with stakeholders, the period during which NHS England has to comply with the recommendations for sofosbuvir is extended to 31 July 2015. The period during which NHS England has to comply with the recommendations for simeprevir has not been extended.

Ends

For further information, please contact the NICE press office on 0300 323 0142 /pressoffice@nice.org.uk or out of hours on 07775 583 813.

Notes to Editors

About the guidance on sofosbuvir
The guidance on sofosbuvir is available from the NICE website (from 00:01 on 25 February 2015).
The guidance states that:

1.1 Sofosbuvir is recommended as an option for treating chronic hepatitis C in adults, as specified in table 1.

1.2 People currently receiving treatment initiated within the NHS with sofosbuvir that is not recommended for them by NICE in this guidance should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Table 1 Sofosbuvir for treating adults with chronic hepatitis C


Sofosbuvir in combination with peginterferon alfa and ribavirin
Sofosbuvir in combination with ribavirin
Genotype
Treatment history
Recommendation
Treatment history
Recommendation
Adults with genotype 1 HCV
All
Recommended
All
Not recommended
Adults with genotype 2 HCV
All
Not licensed for this population
Treatment- naive
Only recommended for people who are intolerant to or ineligible for interferon
Treatment- experienced
Recommended
Adults with genotype 3 HCV
Treatment-naive
Only recommended for people with cirrhosis
Treatment-naive
Only recommended for people with cirrhosis who are intolerant to or ineligible for interferon
Treatment-experienced
Recommended
Treatment-experienced
Only recommended for people with cirrhosis who are intolerant to or ineligible for interferon
Adults with genotype 4, 5, or 6 HCV
All
Only recommended for people with cirrhosis
All
Not recommended
HCV – hepatitis C virus
Treatment-naive – the person has not had treatment for chronic hepatitis C
Treatment-experienced – the person’s hepatitis C has not adequately responded to interferon-based treatment


About sofosbuvir
Sofosbuvir (Sovaldi, Gilead Sciences) is an antiviral drug used to prevent hepatitis C viral replication in infected cells. It is administered orally.
Sofosbuvir has a UK marketing authorisation for use ‘in combination with other medicinal products for treating chronic hepatitis C in adults’. The recommended dose is one 400mg tablet daily. The summary of product characteristics for sofosbuvir states that peginterferon alfa and ribavirin, or ribavirin only, are the recommended co-administered medicinal products for use with sofosbuvir.
The duration of treatment is 12 or 24 weeks depending on the patient’s hepatitis C virus genotype and history of prior treatment with interferon.

The cost of sofosbuvir is £11,660.98 per 28-tablet pack of 400 mg tablets (excluding VAT, ‘British national formulary’ [BNF] May 2014). The cost of a 12-week course of treatment is £34,982.94 and a 24-week course is £69,965.88 (both excluding VAT), not including the cost for ribavirin and peginterferon alfa. Costs may vary in different settings because of negotiated procurement discounts.

Summary of Appraisal Committee’s key conclusions on cost effectiveness

Genotype 1

The ICER for treatment with sofosbuvir plus peginterferon and ribavirin compared with peginterferon and ribavirin was £17,500 per QALY gained in treatment naïve patients.
The Committee also considered sofosbuvir plus peginterferon and ribavirin to be cost effective compared with boceprevir plus peginterferon and ribavirin, and telaprevir in combination with peginterferon and ribavirin (ICERS of approximately £10,300 and £15,400 per QALY gained respectively).

The Committee considered sofosbuvir plus peginterferon and ribavirin to be cost effective in treatment experienced patients compared with peginterferon and ribavirin, boceprevir plus peginterferon and ribavirin, and telaprevir plus peginterferon and ribavirin with ICERs of approximately £12,600, £700 and £8200 per QALY gained respectively.

Sofosbuvir plus ribavirin was not recommended in people for whom interferon was unsuitable (regardless of previous treatment) because of the higher ICER compared with standard care (no treatment) which was in excess of £47,500 per QALY gained in the combined population of people with and without cirrhosis .

Genotype 2

The ICER for sofosbuvir plus ribavirin compared with peginterferon and ribavirin in people who were treatment experienced was £12,500 per QALY gained. However, in the treatment naïve group the treatment was not recommended because of the high ICER of £46,300 per QALY gained.
The Committee considered sofosbuvir plus ribavirin to be clinically effective and cost effective compared with no treatment in people for whom treatment with interferon was unsuitable regardless of treatment experience (with ICERs of approximately £8200 and £8600 per QALY gained respectively).

Genotype 3

The Committee considered the extended treatment duration (24 weeks) of sofosbuvir plus with ribavirin to be clinically effective compared with peginterferon alfa and ribavirin. The Committee considered sofosbuvir plus peginterferon alfa and ribavirin to be cost effective in people with treatment-naive HCV with cirrhosis (with an ICER of approximately £6600 per QALY gained) but not in people with treatment-naive HCV without cirrhosis (with a high ICER of approximately £40,600 per QALY gained). Treatment was recommended in people with treatment-experienced HCV regardless or cirrhosis status with ICERs of below approximately £19,000 per QALY gained
The Committee considered the cost effectiveness of sofosbuvir plus ribavirin to be acceptable in people with cirrhosis who were not eligible for peginterferon alfa regardless of previous treatment with ICERs of approximately £10,500 per QALY gained for treatment-naive HCV and £19,200 per QALY gained for treatment-experienced HCV. The Committee did not consider sofosbuvir in combination with ribavirin to be cost effective in people without cirrhosis with ICERs of approximately £28,000 and £31,400 per QALY gained in treatment-naive and experienced HCV respectively.

Genotypes 4, 5 and 6

The Committee considered sofosbuvir in combination with ribavirin with or without peginterferon alpha to be clinically effective compared with peginterferon and ribavirin in people with treatment naïve and experienced HCV genotypes 4, 5 and 6.
The Committee noted that the ICER for sofosbuvir plus peginterferon alfa and ribavirin compared with peginterferon and ribavirin in the combined cohort of people with treatment naive genotype 4, 5 and 6 HCV was £39,100 per QALY gained. The Committee did not consider sofosbuvir plus peginterferon alfa and ribavirin to be cost effective in people with genotype 4, 5 or 6 HCV without cirrhosis. The Committee considered that ICERs in the population with cirrhosis are consistently lower than in people without cirrhosis and that considering the high unmet need in the population of people with genotype 4, 5 and 6 with cirrhosis, the Committee could consider sofosbuvir plus peginterferon alpha and ribavirin to be cost effective in the treatment naive or experienced populations with ICERs that could be between £20,000 and £30,000 per QALY gained. In addition the Committee did not consider sofosbuvir plus ribavirin in people who were not eligible for interferon to be cost effective.

About the guidance on simeprevir
The guidance on simeprevir is available from the NICE website (from 00:01 on 25 February 2015).

The guidance states that:

1.1 Simeprevir, in combination with peginterferon alfa and ribavirin, is recommended within its marketing authorisation as an option for treating genotype 1 and 4 chronic hepatitis C in adults.

As part of this appraisal the Committee originally considered the effectiveness of simeprevir in combination with sofosbuvir. In the appraisal consultation document the Committee concluded that the true magnitude of the effect of simeprevir in combination with sofosbuvir could not be robustly estimated in people who cannot tolerate or are not eligible to have interferon treatment. At its second meeting, the Committee heard that mature observational data for simeprevir in combination with sofosbuvir would become available in the near future, and that this would include data on people who cannot tolerate or are not eligible to have interferon treatment. The Committee considered that it would be more appropriate to postpone making a decision on this combination until the more mature data become available. To avoid postponing the recommendations for the combination of simeprevir with peginterferon alfa and ribavirin for treating genotype 1 and 4 hepatitis C, the Committee recommended that this appraisal be split. Therefore, this appraisal no longer includes a recommendation for simeprevir in combination with sofosbuvir with or without ribavirin for treating people with genotype 1 and 4 HCV who are intolerant or ineligible for treatment with interferon.

Following a request from NHS England to extend the period during which funding must be made available, NICE consulted on a proposal to grant an extension to the deferred funding period until 31 July 2015. Following consideration of comments received during the consultation on a decision to amend the deferred funding, the NICE Guidance Executive decided that no extension to the normal period was required for simeprevir in combination with peginterferon alpha and ribavirin. This is because simeprevir will be used in the same way as boceprevir and telaprevir. Both these interventions have been funded by the NHS since the publication of NICE appraisal guidance in early 2012. The resources and arrangements for safe delivery of treatment are already in place as a result of the availability of telaprevir and boceprevir. Therefore, additional resources or training are not required to support the implementation of simeprevir. In addition, simeprevir treatment is less complex to administer than telaprevir and boceprevir, and the additional small patient population with genotype 4, for whom simeprevir is licensed is not expected to constitute a substantial challenge to the implementation. Consequently, section 5 of the FAD states that clinical commissioning groups, NHS England and, with respect to their public health functions, local authorities are required to comply with the recommendations in this appraisal within 3 months of its date of publication.

About simeprevir
Simeprevir (Olysio, Janssen) is a protease inhibitor; it inhibits the NS3/4A enzyme that the hepatitis C virus (HCV) depends on to replicate. Simeprevir is administered orally.
Simeprevir has a UK marketing authorisation in the UK for use in combination with peginterferon alfa and ribavirin or in combination with sofosbuvir (with or without ribavirin) for treating adults with genotype 1 or 4 chronic hepatitis C, including people with or without cirrhosis, and people with HIV.

For people who have not had previous treatment or whose disease has responded to previous treatment but subsequently relapsed, simeprevir in combination with peginterferon alfa and ribavirin is indicated for 12 weeks, followed by 12 weeks of peginterferon alfa and ribavirin alone.
For other people, the course of simeprevir is the same, but the course of pegylated interferon and ribavirin is longer than 24 weeks; specifically, for people whose disease did not respond to previous treatment, and for people with HIV who also have cirrhosis, simeprevir in combination with peginterferon alfa and ribavirin is indicated for 12 weeks, followed by 36 weeks of peginterferon alfa and ribavirin alone.
Simeprevir costs £1866.50 per pack of 7x150 mg tablets (excluding VAT, MIMS online, accessed July 2014). A course of simeprevir (for 12 weeks) plus peginterferon alfa and ribavirin (both for 24 weeks) costs £27,220. A course of simeprevir (for 12 weeks) plus peginterferon alfa and ribavirin (both for 48 weeks) costs £32,155.
For treating genotype 1 HCV, the ICERs for simeprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone was between £14,200 and £9800 per QALY. Simeprevir dominated both telaprevir and boceprevir (both with peginterferon alfa and ribavirin), that is simeprevir was less expensive and provided more QALYs.

The Committee noted that, in all scenarios for genotype 4 HCV, the ICERs for simeprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin remained below £20,000 per QALY gained.

About chronic hepatitis C
15 to 20% of people infected with the hepatitis C virus naturally clear their infections within 6 months, the remainder develop chronic hepatitis which can be life-long.
Figures from 2012 suggest that around 160,000 people are chronically infected with the hepatitis C virus in England. More than half of people with chronic hepatitis C do not know they are infected because they only have mild symptoms or no symptoms at all for a long period of time.
About 1 in 3 people infected with the hepatitis C virus will eventually develop liver cirrhosis, where normal liver tissue is replaced by scar tissue.
A small percentage of people with chronic hepatitis C and cirrhosis also develop liver cancer.

For people with mild disease, a ‘watchful waiting’ approach may be agreed, on an individual basis, between the patient and clinician.

Current NICE guidance (NICE technology appraisal 75 and NICE technology appraisal 106) recommends that standard treatment for the majority of people with chronic hepatitis C is peginterferon alfa and ribavirin combination therapy. Monotherapy with peginterferon alfa-2a or peginterferon alfa-2b is recommended for patients who are unable to tolerate ribavirin or for whom ribavirin is contraindicated.
Other NICE guidance on hepatitis C (NICE technology appraisal 200) also recommends that people who have been previously treated with peginterferon alfa and ribavirin or with peginterferon alfa monotherapy have an option to receive further courses of peginterferon alfa and ribavirin.
Shortened courses of peginterferon alfa and ribavirin are also recommended as an option for certain patient subgroups (NICE technology appraisal 200).
For people with genotype 1 chronic hepatitis C, who have not been previously treated or who have been previously treated, NICE guidance also recommends telaprevir in combination with peginterferon alfa and ribavirin (NICE technology appraisal 252) or boceprevir in combination with peginterferon alfa and ribavirin (NICE technology appraisal 253).

[1] There are 6 major genotypes and several subtypes of the hepatitis C virus, the prevalence of each vary geographically. Genotypes 1 and 3 account for the majority of chronic hepatitis C cases in England (46% and 43% respectively). People with genotype 2 hepatitis C generally respond to treatment better than those with genotype 1, 3, 4, 5 or 6.

National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.

Our aim is to help practitioners deliver the best possible care and give people the most effective treatments, which are based on the most up-to-date evidence and provide value for money, in order to reduce inequalities and variation.

Our products and resources are produced for the NHS, local authorities, care providers, charities, and anyone who has a responsibility for commissioning or providing healthcare, public health or social care services.

To find out more about what we do, visit our website:www.nice.org.uk and follow us on Twitter: @NICEComms.

Saturday, November 8, 2014

JANSSEN HIGHLIGHTS ITS HEPATITIS C CLINICAL DEVELOPMENT IN ADVANCE OF AASLD

Related - FDA approves simeprevir-sofosbuvir combo for hepatitis C
November 5, 2014 - Janssen Therapeutics, Division of Janssen Products, LP (Janssen) announced the U.S. Food and Drug Administration (FDA) has approved OLYSIO® (simeprevir), a hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination with sofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C (CHC) infection in adult patients as part of a combination antiviral treatment regimen. Sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

Janssen Highlights its Hepatitis C Clinical Development Program in Advance of 2014 American Association for the Study of Liver Diseases (AASLD) Annual Meeting

BOSTON, Nov. 7, 2014 /PRNewswire/ -- Janssen R&D Ireland (Janssen) highlights its hepatitis C (HCV) clinical development program in advance of The Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held November 7-11, 2014 in Boston, Massachusetts.

Given the size, complexity and diversity of the HCV patient population, physicians will continue to need multiple treatment options and combinations in order to offer patients an opportunity for cure into the next decade.

The Janssen HCV clinical development program includes studies that investigate the use of simeprevir in several interferon-free regimens using selected combinations of direct-acting antivirals with different mechanisms of action targeting diverse patient populations. These studies are focused on potentially offering alternative and more immediate treatment options for physicians and patients where there is a high unmet need today or anticipated in the near future. Ongoing clinical studies include:
  • Phase 3 OPTIMIST studies examining the safety and efficacy of simeprevir and the nucleotide analog NS5B polymerase inhibitor sofosbuvir without interferon or ribavirin for the treatment of chronic HCV infection for treatment-naïve and treatment-experienced patients with and without cirrhosis.
  • Phase 2 IMPACT study evaluating the efficacy, safety and pharmacokinetics of simeprevir administered once daily in combination with sofosbuvir and the NS5A replication complex inhibitor daclatasvir in treatment-naïve and treatment-experienced patients with HCV genotype 1 and 4 infection and decompensated liver disease.
With the closing of the acquisition of Alios Biopharma, Inc. earlier today, Janssen now holds a platform of nucleotide analog polymerase inhibitors, the early-clinical stage compounds AL-335 and AL-516.

"Janssen is committed to combating hepatitis C by exploring the potential to bring forth, in a timely manner, an in-house interferon-free combination regimen to make a difference in patients' lives," said Gaston Picchio, Ph.D., Hepatitis disease area leader, Janssen.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is a major global public health concern. Approximately 170 million people are infected with hepatitis C worldwide and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about OLYSIO®?
  • If you are pregnant, or plan to become pregnant, talk with your healthcare provider before taking OLYSIO®. It is not known if OLYSIO® will harm your unborn baby. Also read the Medication Guides for peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) if your healthcare provider prescribes these medications for you in combination with OLYSIO®.
    • Females must use an effective form of birth control during treatment with OLYSIO®. Talk with your healthcare provider about birth control methods that you may use during treatment with OLYSIO®.
  • OLYSIO® combination treatment may cause rashes and skin reactions to sunlight. These rashes and skin reactions to sunlight can be severe and you may need to be treated in a hospital. Rashes and skin reactions to sunlight are most common during the first 4 weeks of treatment, but can happen at any time during combination treatment with OLYSIO®.
    • Use sunscreen, and wear a hat, sunglasses, and protective clothing when you will be exposed to sunlight during treatment with OLYSIO®.
    • Limit sunlight exposure during treatment with OLYSIO®.
    • Avoid use of tanning beds, sunlamps, or other types of light therapy during treatment with OLYSIO®.
    • Call your healthcare provider right away if you get any of the following symptoms:
      • burning, redness, swelling or blisters on your skin
      • mouth sores or ulcers
      • red or inflamed eyes, like "pink eye" (conjunctivitis)
  • You should not take OLYSIO® alone. OLYSIO® should be used together with other medicines to treat chronic hepatitis C infection.
What should I tell my healthcare provider before taking OLYSIO®?

Before taking OLYSIO®, tell your healthcare provider if you:
  • have liver problems other than hepatitis C virus infection
  • have ever taken any medicine to treat hepatitis C virus infection
  • had a liver transplant
  • are receiving phototherapy
  • have any other medical condition
  • are of East Asian descent
  • are breastfeeding. It is not known if OLYSIO® passes into your breast milk. You and your healthcare provider should decide if you will take OLYSIO® or breastfeed. You should not do both.
  • Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
  • OLYSIO® and other medicines may affect each other. This can cause you to have too much or not enough OLYSIO® or other medicines in your body, which may affect the way OLYSIO® or your other medicines work, or may cause side effects. Do not start taking a new medicine without telling your healthcare provider or pharmacist.
  • Especially tell your healthcare provider if you take any of the following medicines (when taken by mouth or given by injection, where applicable): amiodarone (Cordarone®, Pacerone®), amlodipine (Norvasc®), atazanavir (Reyataz®), atorvastatin (Lipitor®, Caduet®), carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®), cisapride (Propulsid®, Propulsid Quicksolv®), clarithromycin (Biaxin®, Prevpac®), cobicistat-containing medicine (Stribild®), cyclosporine (Gengraf®, Neoral®, Sandimmune®), darunavir (Prezista®), delavirdine mesylate (Rescriptor®), dexamethasone, digoxin (Lanoxin®), diltiazem (Cardizem®, Dilacor XR®, Tiazac®), disopyramide (Norpace®), efavirenz (Sustiva®, Atripla®), erythromycin (E.E.S.®, Eryc®, Ery‑Tab®, Erythrocin®, Erythrocin Stearate®), etravirine (Intelence®), felodipine (Plendil®), flecainide (Tambocor®), fluconazole (Diflucan®), fosamprenavir (Lexiva®), indinavir (Crixivan®), itraconazole (Sporanox®, Onmel®), ketoconazole (Nizoral®), lopinavir (Kaletra®), lovastatin (Advicor®, Altoprev®, Mevacor®), mexiletine (Mexitil®), midazolam, milk thistle (Silybum marianum) or products containing milk thistle, nelfinavir (Viracept®), nevirapine (Viramune®, Viramune XR®), nicardipine (Cardene®), nifedipine (Adalat CC®, Afeditab CR®, Procardia®), nisoldipine (Sular®), oxcarbazepine (Oxtellar XRTM,Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Phenytek®), pitavastatin (Livalo®), posaconazole (Noxafil®), pravastatin (Pravachol®), propafenone (Rythmol SR®), quinidine (Nuedexta®, Duraquin®, Quinaglute®), rifabutin (Mycobutin®), rifampin (Rifadin®, Rifamate®, Rifater®, Rimactane®), rifapentine (Priftin®), ritonavir (Norvir®), rosuvastatin (Crestor®), saquinavir mesylate (Invirase®), sildenafil (Revatio®, Viagra®), simvastatin (Zocor®, Vytorin®, Simcor®), sirolimus (Rapamune®), St. John's wort (Hypericum perforatum) or products containing St. John's wort, tadalafil (Adcirca®, Cialis®), telithromycin (Ketek®), tipranavir (Aptivus®), triazolam (Halcion®), verapamil (Calan®, Covera‑HS®, Isoptin®, Tarka®), voriconazole (Vfend®).
  • This is not a complete list of medicines that could interact with OLYSIO®. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above.
  • Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
What are the possible side effects of OLYSIO®?
  • The most common side effects in combination with Peg-IFN-alfa and RBV are skin rash, itching and nausea.
  • The most common side effects in combination with sofosbuvir are tiredness, headache and nausea.
  • Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of OLYSIO®. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.
When taking OLYSIO® in combination with Peg-IFN-alfa and RBV, you should also read those Medication Guides. When taking OLYSIO® in combination with sofosbuvir, you should also read its Patient Information leaflet.

Wednesday, November 5, 2014

FDA Hepatitis Update: Changes to Olysio (simeprevir) label‏

FDA Hepatitis Update: Changes to Olysio (simeprevir) label‏

On November 5, 2014, FDA approved changes to the Olysio (simeprevir) label to include use of Olysio in combination with sofosbuvir for the treatment of patients with chronic hepatitis C virus genotype 1 infection.

Highlights of the label changes are summarized below.

INDICATIONS AND USAGE

OLYSIO® is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection as a component of a combination antiviral treatment regimen.

Limitations of Use:
OLYSIO monotherapy is not recommended.
OLYSIO efficacy in combination with peginterferon alfa (Peg IFN alfa) and ribavirin (RBV) is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients infected with hepatitis C virus (HCV) genotype 1a without the Q80K polymorphism. Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism.
OLYSIO is not recommended in patients with severe hepatic impairment (Child Pugh Class C) due to substantial increases in simeprevir exposures, which have been associated with increased frequency of adverse reactions.

OLYSIO is not recommended in patients who have previously failed therapy with a treatment regimen that included OLYSIO or other HCV protease inhibitors.

DOSAGE AND ADMINISTRATION

2.1 OLYSIO Combination Treatment

Administer OLYSIO in combination with other antiviral drugs for the treatment of CHC infection. For specific dosing recommendations for the antiviral drugs used in combination with OLYSIO, refer to their respective prescribing information. OLYSIO monotherapy is not recommended. Administer OLYSIO in combination with either:
Peg‑IFN‑alfa and RBV: Table 1 displays the recommended dosage regimen and treatment duration of OLYSIO in combination with Peg‑IFN‑alfa and RBV. Refer to Table 3 for treatment stopping rules for OLYSIO combination therapy with Peg‑IFN‑alfa and RBV; or
Sofosbuvir: Table 2 displays the recommended dosage regimen and treatment duration of OLYSIO in combination with sofosbuvir.

The recommended dosage of OLYSIO is one capsule taken orally once daily with food. The capsule should be swallowed as a whole.

Table 1



‡ Recommended duration of treatment if patient does not meet stopping rules (see Table 3).

# Prior partial responder: prior on-treatment ≥ 2 log10 IU/mL reduction in HCV RNA from baseline at Week 12 and HCV RNA detected at end of prior IFN‑based therapy [see Clinical Studies (14)].

§ Prior null responder: prior on‑treatment < 2 log10 reduction in HCV RNA from baseline at Week 12 during prior IFN‑based therapy [see Clinical Studies (14)]

Table 2



2.2 Testing Prior to Initiation of OLYSIO in HCV Genotype 1a‑Infected Patients

Prior to initiation of treatment with OLYSIO with Peg‑IFN‑alfa and RBV, screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism is strongly recommended and alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism. Prior to initiation of treatment with OLYSIO with sofosbuvir, screening patients infected with HCV genotype 1a for the presence of virus with the NS3 Q80K polymorphism is not strongly recommended but may be considered. [See Indications and Usage (1)].

2.3 Discontinuation of Dosing

Use with Peg‑IFN‑Alfa and RBV

During treatment, HCV RNA levels should be monitored as clinically indicated using a sensitive assay with a lower limit of quantification of at least 25 IU/mL.

Because patients with an inadequate on‑treatment virologic response (i.e., HCV RNA ≥ 25 IU/mL) are not likely to achieve a sustained virologic response (SVR), discontinuation of treatment is recommended in these patients. Table 3 presents treatment stopping rules for patients who experience an inadequate on‑treatment virologic response at Weeks 4, 12, and 24.



No treatment stopping rules apply to the combination of OLYSIO with sofosbuvir [see Clinical Studies (14.)].

ADVERSE REACTIONS

Adverse Reactions when Used with Sofosbuvir

In the COSMOS trial, the most common (> 10%) adverse reactions reported during 12 weeks treatment with OLYSIO in combination with sofosbuvir without RBV were fatigue (25%), headache (21%), nausea (21%), insomnia (14%) and pruritus (11%). Rash and photosensitivity were reported in 11% and 7% of subjects, respectively. During 24 weeks treatment with OLYSIO in combination with sofosbuvir, dizziness (16%), and diarrhea (16%) were also commonly reported.

Microbiology

In the COSMOS trial in HCV genotype 1-infected subjects treated with OLYSIO in combination with sofosbuvir (without or with RBV), virus from 5 out of 6 (83%) subjects with relapse had emerging NS3 amino acid substitutions R155K or D168E. No emerging NS5B amino acid substitutions associated with sofosbuvir resistance were observed.

Failure to achieve SVR with simeprevir does not select virus that is cross‑resistant to sofosbuvir or vice versa.

CLINICAL STUDIES

OLYSIO in Combination with Sofosbuvir

Adult Subjects with HCV Genotype 1 Infection

The COSMOS trial was an open‑label, randomized Phase 2 trial to investigate the efficacy and safety of 12 or 24 weeks of OLYSIO (150 mg once daily) in combination with sofosbuvir (400 mg once daily) without or with RBV in HCV genotype 1‑infected prior null responders with METAVIR fibrosis score F0‑F2 (Cohort 1), or treatment‑naïve subjects and prior null responders with METAVIR fibrosis score F3‑F4 and compensated liver disease (Cohort 2).

The 80 enrolled subjects without advanced hepatic fibrosis in Cohort 1 had a median age of 56 years (range 27 to 70 years; with 8% above 65 years); 61% were male; 71% were White, 29% Black or African American, and 25% were Hispanic; 30% had a BMI greater than or equal to 30 kg/m2; 98% had HCV RNA levels greater than 800,000 IU/mL; 41% had METAVIR fibrosis score F0 or F1 and 59% had METAVIR fibrosis score F2; 78% had HCV genotype 1a, and the remaining patients had HCV genotype 1b; 39% of the overall population and 50% of the subjects with genotype 1a had the NS3 Q80K polymorphism at baseline; 6% had IL28B CC genotype, 70% IL28B CT genotype, and 24% IL28B TT genotype. All subjects were prior null responders to Peg‑IFN‑alfa and RBV.

The 87 enrolled subjects with advanced hepatic fibrosis in Cohort 2 had a median age of 58 years (range 28 to 70 years; with 3% above 65 years); 67% were male; 91% were White, 9% Black or African American, and 17% were Hispanic; 44% had a BMI greater than or equal to 30 kg/m2; 84% had HCV RNA levels greater than 800,000 IU/mL; 53% had METAVIR fibrosis score F3 and 47% had METAVIR fibrosis score F4 (cirrhosis); 78% had HCV genotype 1a, and 22% HCV genotype 1b; 31% of the overall population and 40% of the subjects with genotype 1a had the NS3 Q80K polymorphism at baseline; 21% had IL28B CC genotype, 56% IL28B CT genotype, and 23% IL28B TT genotype. Fifty-four percent of subjects were prior null responders to Peg‑IFN‑alfa and RBV and 46% were treatment‑naïve.

Table 16 shows the response rates by combining prior null responders in Cohort 1 and treatment‑naïve subjects and prior null responders in Cohort 2. When treatment arms with and without ribavirin were combined, the overall SVR12 rate was 95% (61/64) in subjects with METAVIR fibrosis score F0-F3 who received 12 weeks treatment of OLYSIO in combination with sofosbuvir with/without RBV when pooling both cohorts. The overall SVR12 rate was 96% (22/23) in subjects with METAVIR fibrosis score F4 who received 24 weeks treatment of OLYSIO in combination with sofosbuvir with/without RBV when pooling both cohorts. Addition of RBV did not increase response rates in comparison with OLYSIO in combination with sofosbuvir alone; and therefore these data are not shown in Table 16.

Table 16:   Treatment Response by METAVIR Fibrosis Score in Treatment‑Naïve Subjects or Prior Null Responders* with HCV Genotype 1 Infection Receiving 12 or 24 Weeks of OLYSIO with Sofosbuvir (Pooled Data for Cohort 1 and 2)

OLYSIO + Sofosbuvir
12 weeks
% (n/N)
OLYSIO + Sofosbuvir
24 weeks
% (n/N)
Overall SVR12
93 (26/28)
97 (30/31)
F0-3
95 (20/21)
95 (20/21)
F4
86 (6/7)
100 (10/10)
Viral Relapse
7 (2/28)
0 (0/30)
F0-3
5 (1/21)
0 (0/20)
F4
14 (1/7)
0 (0/10)
SVR12: sustained virologic response 12 weeks after planned EOT.
*    Null Responders to prior Peg‑IFN‑alfa and RBV therapy.
   Viral relapse rates are calculated with a denominator of subjects with HCV RNA not detected at EOT and with at  least one follow‑up HCV RNA assessment. No subjects experienced virologic on-treatment failure.
The complete product label will be available soon at DailyMed or at Drugs@FDA.
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration