Gilead avoids billions in U.S. taxes on its $1,000-a-pill drug

Gilead avoids billions in U.S. taxes on its $1,000-a-pill drug
By Richard Rubin, 

Bloomberg NewsBloomberg

WASHINGTON — Gilead Sciences Inc., whose $1,000-a-pill hepatitis C treatment is one of the world's most expensive drugs, is avoiding billions of dollars in U.S. taxes by booking profits overseas.

The company reported foreign income before taxes of $8.2 billion for 2014, earning more in non-U.S. profits than it recorded in non-U.S. sales. The data released in a securities filing Wednesday suggest that Gilead is taking advantage of U.S. rules that let companies shift valuable intellectual property to low-tax countries, said Robert Willens, an independent tax consultant based in New York.

"Whenever you have huge, very high profit margins and a lot of income as well, it almost always results from the exploitation of intangibles," Willens said in a telephone interview. "It's quite a dramatic increase from one year to the other. That's something you don't see very often."

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Bristol hep C drug helps cure 97 pct of HIV coinfected patients-study

Bristol hep C drug helps cure 97 pct of HIV coinfected patients-study

BY BILL BERKROT

Fri Feb 27, 2015 1:45am IST
Feb 26 (Reuters) - Ninety-seven percent of hepatitis C patients also infected with HIV were cured of the liver-destroying virus after 12 weeks of treatment with Bristol-Myers Squibb's daclatasvir and Gilead Sciences' Sovaldi, according to data from a study presented on Thursday.

The results could help put Bristol's hepatitis C program back on track in the United States, following a setback last year.

In the Ally-2 study, including new patients and those not helped by prior treatment, 149 of 153 were deemed cured of hepatitis C regardless of what other anti-viral regimens they were on for HIV, the virus that causes AIDS.

"The results of Ally-2 signaled that nearly all HIV-HCV coinfected patients in the study could be cured of hepatitis C with a 12-week regimen on daclatasvir and sofosbuvir," Dr. David Wyles, the study's lead investigator, said in a statement, using the chemical name for Sovaldi.

There were no reported serious side effects related to the hepatitis drugs, and patients did not require any alteration of HIV medications over potential drug-drug interactions.

"This is a paramount consideration for clinicians treating this patient population," added Wyles, who presented the data at the Conference on Retroviruses and Opportunistic Infections (CROI) meeting in Seattle.

About 300,000 Americans with HIV also suffer from hepatitis C, according to the Centers for Disease Control and Prevention, making them prone to more rapid progression to liver damage.

Daclatasvir is approved in Europe, Brazil and Japan as part of combination therapy, but has fallen behind rivals in the world's most lucrative market. In November, the U.S. Food and Drug Administration declined to approve daclatasvir in combination with other antiviral drugs.

The company had sought FDA permission to market daclatasvir in combination with another Bristol drug, asunaprevir. But Bristol abandoned its U.S. marketing application for asunaprevir due to potential competition from more potent drugs, leaving the FDA without data to gauge the effectiveness of daclatasvir as part of a combination regimen.

The FDA asked for new data on daclatasvir with other drugs, which the Ally results could help satisfy.

Sovaldi is part of Gilead's market-leading hepatitis C franchise and half of its own one-pill-per-day combination treatment Harvoni.

All 26 patients in the Ally-2 study with the less common genotypes 2, 3 and 4 of the virus were cured by the combination. A shorter eight-week regimen tested among 50 patients led to a 75 percent cure rate. (Reporting by Bill Berkrot; Editing by James Dalgleish)

Reuters

Gilead Announces SVR12 Rates From Phase 3 Study Evaluating Harvoni® for the Treatment of Chronic Hepatitis C in Patients Co-Infected With HIV‏

Title: Gilead Announces SVR12 Rates From Phase 3 Study Evaluating Harvoni® for the Treatment of Chronic Hepatitis C in Patients Co-Infected With HIV

Date(s): 26-Feb-2015 3:15 PM

- 96 Percent SVR12 Rate for Hepatitis C Genotypes 1 and 4 Among HIV-infected Patients on Antiretroviral Therapy -

SEATTLE--(BUSINESS WIRE)--Feb. 26, 2015-- Gilead Sciences, Inc. (NASDAQ:GILD) today announced results from a Phase 3 study, ION-4, evaluating the once-daily single tablet regimen Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) for the treatment of genotypes 1 or 4 chronic hepatitis C virus (HCV) infection among patients co-infected with HIV. In the trial, 96 percent (n=321/335) of HCV patients achieved a sustained virologic response 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV infection. These data were presented in a late-breaker oral session (Session 152LB) at the 22nd Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

"This trial provides strong evidence that people who are co-infected with HIV can achieve very high rates of hepatitis C cure with a combination direct-acting antiviral regimen," said Susanna Naggie, MD, MHS, Director of Infectious Diseases Research at Duke Clinical Research Institute and Principal Investigator for the ION-4 study. "These high cure rates were observed in most of the historically difficult-to-treat sub-populations, including those who failed previous treatment and those with cirrhosis. We are greatly encouraged by these findings."

ION-4 is a Phase 3, multicenter, open-label study investigating the efficacy, safety and tolerability of Harvoni treatment for 12 weeks in 335 patients with HCV genotype 1a (75 percent), 1b (23 percent) or 4 (2 percent) and HIV-1 co-infection. The study included HCV treatment-naïve (45 percent) and treatment-experienced (55 percent) patients, including patients with compensated cirrhosis (20 percent), whose HIV was suppressed using one of three HIV antiretroviral (ARV) regimens: tenofovir and emtricitabine with efavirenz (Atripla®), raltegravir or rilpivirine (Complera®).

SVR12 rates did not differ significantly by prior HCV treatment status, presence or absence of cirrhosis, or ARV regimen. No patients discontinued Harvoni due to an adverse event (AE). Of the 14 patients that did not achieve SVR12, two patients experienced virologic failure during treatment (likely due to non-compliance per physician reporting), 10 experienced virologic relapse post-treatment, one was lost to follow up and one died due to causes unrelated to study drug. The most common AEs reported were headache (25 percent), fatigue (21 percent) and diarrhea (11 percent).

Harvoni received regulatory approval for the treatment of chronic HCV genotype 1 infection in adults in the United States in October 2014. Based on the ION-4 trial results, Gilead plans to file a supplemental New Drug Application with the U.S. Food and Drug Administration for Harvoni to include the results from this study in the U.S. label. Harvoni received marketing authorization in Europe in November 2014, where data from a small study in HIV-HCV co-infected patients (ERADICATE) are included in the prescribing information.

Important Safety Information for Harvoni

Warnings and Precautions
Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi®).

Adverse Reactions

Most common (=10%, all grades) adverse reactions were fatigue and headache.

Drug Interactions
In addition to rifampin and St. John's wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.
Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Additionally, patients taking Harvoni concomitantly with the combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate should be monitored for tenofovir-associated adverse events.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that the supplemental New Drug Application may not be approved. In addition, physicians and patients may not see advantages of Harvoni over other therapies and physicians may therefore be reluctant to prescribe the product and private and public payers may be reluctant to provide coverage or reimbursement for the product. Further, additional studies of Harvoni may produce unfavorable results. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Harvoni and U.S. full Prescribing Information, including BOXED WARNING, for Atripla and Complera are available at www.gilead.com.

Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.

Complera and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O'Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)

Herbal products and adverse effects on the liver

Herbal products and adverse effects on the liver

The most recent issue of the Gastroenterology reviews adverse effects and mechanisms.

Herbal products have been used for centuries among indigenous people to treat symptoms and illnesses.

Recently, their use in Western countries has grown significantly, rivaling that of prescription medications.


Dr Leonard Seeff and colleagues from Pennsylvania, USA report that herbal products are used mainly for weight loss, and bodybuilding purposes but also to improve well-being and symptoms of chronic diseases.
Many people believe that because they are natural, they must be effective and safe.

However, these beliefs are erroneous.

Highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant

Gastroenterology

The researchers noted that few herbal products have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary.

The research team found that current highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant.

The team observed that herbal products are no safer than conventional drugs, and have caused liver injury severe enough to require transplantation or cause death.

Furthermore, their efficacy, safety, and claims are not assessed by regulatory agencies, and there is uncertainty about their reported and unreported contents.

Dr Seeff's team concludes, "We review the history of commonly used herbal products, as well as their purported efficacies and mechanisms and their adverse effects."

Gastroenterol 2015(148): 3: 517–532.e3
26 February 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.

Daclatasvir for hepatitis C: Hint of added benefit in genotype 4

Daclatasvir for hepatitis C: Hint of added benefit in genotype 4

Daclatasvir (trade name Daklinza) has been approved since August 2014 for the treatment of adults with chronic hepatitis C (CHC) infection. According to the dossier assessment conducted by the German Institute for Quality and Efficiency in Health Care (IQWiG) in December 2014, no added benefit could be derived for daclatasvir.

In an addendum, the Institute now examined information subsequently submitted by the drug manufacturer in the commenting procedure: According to the findings, there is a hint of an added benefit for treatment-naive patients with genotype 4. The extent is non-quantifiable, however. The study for patients infected with hepatitis C virus (HCV) of genotype 3, which was presented for the first time, is unsuitable to derive an added benefit.

Genotype 4: Additional analyses reinforce advantage of daclatasvir

In the dossier, the manufacturer had analysed one study (AI444042) for treatment-naive HCV genotype 4 patients. Since many patients had discontinued treatment, however, numerous values were missing in the analysis. These missing values had not been considered adequately in the analysis of the study data. The manufacturer dossier last year therefore provided no robust results for the valid surrogate outcome "sustained virologic response (SVR)".

The manufacturer presented further information on the SVR in its comment on IQWiG's dossier assessment. According to the assessment of these data and supplementary analyses by IQWiG, the results on the outcome "SVR" in favour of daclatasvir were shown to be robust: On completion of the treatment, virus particles (HCV RNA) were detectable in more patients in the control arm than in the daclatasvir arm. Overall however, the study results were so uncertain that no more than a hint of an added benefit can be derived from them.

The extent of this added benefit is non-quantifiable, also because it cannot be derived from the results on SVR how many cases of liver cancer can actually be prevented.

HCV genotype 3: uncontrolled study provided no comparator data

In the commenting procedure on the dossier assessment, the manufacturer presented data from a study (ALLY 3) on HCV genotype 3 patients for the first time. This study is unsuitable for conclusions on the added benefit, however: The presentation of study characteristics and results was incomplete, and the analyses were not comprehensible. In addition, the study participants were treated differently than recommended by the Summary of Product Characteristics. Due to the uncontrolled design, the study additionally provided no results on the comparison with the appropriate comparator therapy so that no added benefit can be derived.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the manufacturer's dossier and the IQWiG dossier assessment, the manufacturer submitted additional information in the commenting procedure. The G-BA subsequently commissioned IQWiG to assess the data subsequently submitted. IQWiG now presents this assessment in the form of an addendum. The G-BA conclusively decides on the extent of added benefit.

Explore further: Daclatasvir for hepatitis C: Added benefit not proven

Provided by Institute for Quality and Efficiency in Health Care

Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3

Frontline Gastroenterology
Interferon-free Treatment for Genotypes 2 and 3 Patients With Hepatitis C

Nowlan Selvapatt, Philip Hendy

Medscape

Zeuzem S, Dusheiko G, Salupere R, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014;370:21.

Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in Patients without Treatment Options. N Engl J Med 2013;368:1867–77.

This paper reviews the outcomes of the VALENCE study which evaluated an interferon-free treatment regime for patients with genotypes 2 and 3 hepatitis C virus (HCV).1 While demonstrating promising efficacy in the treatment of genotype 2 infected patients and certain subtypes of patients with genotype 3 infection, it also provides a timely reminder that careful patient selection is required.

Sofosbuvir (trade name Sovaldi) is an oral direct acting antiviral agent (NS5B polymerase inhibitor) licensed in the UK for the treatment of hepatitis C. It is currently under review at the National Institute for Health and Care Excellence. The study was designed as a phase III blinded placebo controlled trial of treatment of genotype 2 and 3 HCV infected patients. Both treatment-naive patients and those with previous interferon treatment were included, and presence of cirrhosis was not an exclusion criterion. It was originally designed for all patients to receive 12 weeks of treatment with either sofosbuvir plus ribavirin or with matching placebo. The dose of sofosbuvir was 400 mg once daily given orally and ribavirin was given orally in a split dose, dose dependent on weight (1000 mg daily in patients with a body weight of <75 kg and 1200 mg daily in patients with a body weight of ≥75 kg). However, after initiation of the VALENCE study, published results from the FUSION study demonstrated significant benefit in extending treatment of genotype 3 HCV infection beyond 12 weeks.2 The study was therefore altered from hypothesis generating to descriptive. The genotype 2 HCV treatment arm remained unchanged with 12 weeks of treatment, while the genotype 3 HCV treatment arm was made open label and extended to 24 weeks. The primary end point was sustained virological response at 12 weeks after completion of therapy (SVR12) and HCV RNA below the limit of quantification (25 IU/mL).

A total of 475 patients were screened for enrolment and 421 underwent randomisation with 419 starting treatment. Enrolment was in a 4:1 ratio of genotype 3 to genotype 2. Overall 60% were men, 21% had cirrhosis and 58% had received previous interferon treatment, of whom 30% were primary non-responders. Overall, 99% of patients receiving sofosbuvir and ribavirin had undetectable HCV RNA by week 4. Of the 73 genotype 2 infected patients, 93% of patients achieved SVR12.

There was greater variation in virological response in patients with genotype 3 infection. Among treatment naïve patients, SVR12 was 95% in non-cirrhotics and 92% in cirrhotics. However, for those with past exposure to interferon, SVR12 was 87% in non-cirrhotics and 62% in cirrhotics. Treatment was well tolerated with only 1% discontinuation. There were 10 serious adverse events out of 250 treated patients in the 24-week treatment arm but nil adverse events in either of the 12-week treatment groups. In common with previous published data, no resistance to sofosbuvir was demonstrated on viral resistance testing.

Using multivariate regression analysis, the study investigators demonstrated four possible predictors of sustained viral response among genotype 3 infected patients: absence of cirrhosis; low viral load at baseline; female sex; and younger age. This requires further validation before utilisation as a pretreatment predictor score.

The authors acknowledge the limitations of this study. First, the trial was altered from a hypothesis generating exercise to a descriptive study without any formal hypothesis or statistical comparisons. Second, very few pretreatment biopsies were available meaning that questions regarding levels of fibrosis and steatosis and links to treatment response could not be adequately addressed. Overall, the study is well powered to deliver definitive conclusions regarding the drug efficacy for both genotype 2 and 3 HCV, but it is not sufficiently powered to make definitive conclusions regarding the subgroup of genotype 2 patients who exhibit pretreatment characteristics associated with a lower response rate.

Comment

This study reaffirms the potential for shortened duration of treatment when compared with interferon based regimes, particularly for genotype 2 HCV. It also demonstrates the efficacy of this treatment regime for those numerous patients unable to take an interferon based regimen due to contraindications or intolerance. Importantly, it also provides a timely reminder that there are limitations to this therapy, with SVR₁₂ lower in certain difficult to treat groups (especially patients with cirrhosis and previous exposure to interferon therapy). Future work should evaluate the addition of interferon and/or other direct acting agents, as well as longer treatment durations, for those patients with pretreatment characteristics associated with decreased treatment response. This study also highlights our lack of understanding of the basis for differences in response to sofosbuvir between genotype 2 and 3 patients, especially given the similarities in viral kinetics between these two groups

Medscape

Canada - With hep C, no province is an island

With hep C, no province is an island
André Picard 

The Globe and Mail
Published Tuesday, Feb. 24 2015, 3:00 AM EST

So far, PEI has committed to spend $1.6-million a year for three years to purchase a drug combo called Holkira Pak, a product of AbbVie Canada with a list price of $55,860.

About 400 Islanders are infected with HCV, including 60 in the advanced stages of the disease, which suggests that PEI is getting the drug at a deep discount – about $25,000.

This will put intense pressure on the other main producer of the new generation HCV drugs, Gilead Sciences Inc., to discount its product, known as Harvoni. Its list price is roughly $67,000.

Continue reading.. 

AbbVie study results from VIEKIRA PAK in chronic hepatitis C patients

AbbVie announces results from study of VIEKIRA PAK in chronic hepatitis C patients

North Chicago, Illinois

Tuesday, February 24, 2015, 18:00 Hrs [IST]

AbbVie 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 recently 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 per cent (n=29/31) and 91 per cent (n=29/32), respectively. The SVR12 rates were 91 per cent (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," says Michael Severino, MD, 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 per cent), insomnia (19 per cent), nausea (17 per cent), headache (16 per cent), itching (13 per cent), cough (11 per cent), irritability (10 per cent), and yellowing of the eyes (10 per cent). 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

TURQUOISE-I is an ongoing phase 2/3, multi-center, randomised, 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+ per cent =14 per cent). 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 anaemia or reduced haemoglobin occurred in 10 per cent of patients (n=6/63); all six patients achieved SVR12.

VIEKIRA PAK (ombitasvir, paritaprevir, ritonavir tablets; dasabuvir tablets) has been studied in a broad range of genotype 1 (GT1) patients with chronic hepatitis C virus (HCV) infection, ranging from treatment-naïve to some of the most difficult to treat, such as patients with compensated (mild, Child-Pugh A) cirrhosis of the liver, HCV/HIV-1 co-infection, liver transplant recipients with normal hepatic function and mild fibrosis, and those who have failed previous treatment with pegylated interferon (pegIFN) and ribavirin (RBV). VIEKIRA PAK is not recommended in patients with moderate hepatic impairment (Child-Pugh B), and is contraindicated in patients with severe hepatic impairment (Child-Pugh C). VIEKIRA PAK consists of the fixed-dose combination of ombitasvir 25mg (an NS5A inhibitor), paritaprevir 150mg (an NS3/4A protease inhibitor), and ritonavir 100mg (an inhibitor of an enzyme that breaks down paritaprevir), dosed once daily with a meal, and dasabuvir 250mg (a non-nucleoside NS5B palm polymerase inhibitor), dosed twice daily with a meal. VIEKIRA PAK is taken for 12 weeks, except in GT1a patients with cirrhosis, who should take it for 24 weeks. Ribavirin should be co-administered in GT1a patients, and in all patients who have cirrhosis or who have received a liver transplant.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir is being investigated by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

VIEKIRA PAK was granted priority review and designated as a Breakthrough Therapy by the US FDA, a status given to medicines or regimens that may offer substantial improvement over available therapies.

Mylan Signs Exclusive Agreement with Gilead Sciences to Distribute Sovaldi® and Harvoni® in India

Mylan Signs Exclusive Agreement with Gilead Sciences to Distribute Sovaldi® and Harvoni® in India

PITTSBURGH and HYDERABAD, India, Feb. 23, 2015 /PRNewswire/ -- Mylan Inc. (Nasdaq: MYL) today announced that its Indian subsidiary, Mylan Pharmaceuticals Private Limited, has entered into an agreement with Gilead Sciences, under which Mylan has been appointed as the exclusive distributor of Sovaldi® (sofosbuvir 400mg tablets) and Harvoni®(ledipasvir 90mg/sofosbuvir 400 mg tablets) for the treatment of chronic hepatitis C, in India. As Gilead's exclusive branded medicine distribution partner, Mylan expects to begin distribution of Sovaldi in India in Q2 2015. Sovaldi received regulatory approval in India in January 2015 – the first country in Asia to approve the medicine.

Mylan President Rajiv Malik said, "Hepatitis C is a growing public health concern, particularly in developing countries such as India where access to high quality, effective and affordable treatment remains a challenge. Mylan is proud to partner with Gilead to expand access to Sovaldi and Harvoni, life-saving medications that offer an improvement in the standard of care for the 12 million hepatitis C patients in India."

This agreement is in addition to the licensing and technology transfer agreement that Mylan entered into with Gilead, which grants Mylan the non-exclusive rights to manufacture and distribute generic sofosbuvir, ledipasvir/sofosbuvir and, upon approval, the investigational NS5A inhibitor GS-5816 and single tablet regimen of sofosbuvir/GS-5816 in 91 developing countries. Mylan also partners with Gilead on expanding access to high quality, affordable antiretrovirals for the treatment of HIV/AIDS in India and other developing countries.

Sovaldi is the latest addition to Mylan India's new gastrointestinal segment called Hepato Care. The company also offers four additional unique and innovative segments – Critical Care, HIV Care, Women's Care and Oncology.

About Sovaldi
Sovaldi was approved by the U.S. Food and Drug Administration (FDA) in December 2013 based on clinical studies that showed, in combination with other agents, the drug achieved very high cure rates with a course of treatment as short as 12 weeks depending on viral genotype. Sovaldi also was approved by the European Commission in January 2014 and is a recommended treatment option in the World Health Organization's first hepatitis C treatment guidelines (released inApril 2014).

About Harvoni
Harvoni was approved by the US FDA in October 2014 as a once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults.

Private Securities Litigation Reform Act of 1995 — A Caution Concerning Forward-Looking Statements

This press release includes statements that constitute "forward-looking statements," including with regard to sales of products, product approvals and the company's strategy, future growth and performance. These statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Because such statements inherently involve risks and uncertainties, actual future results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: the impacts of competition; changes in economic and financial conditions of the company's business; strategies by competitors or other third parties to delay or prevent product introductions; risks inherent in legal and regulatory processes; risks associated with international operations; uncertainties and matters beyond the control of management; and the other risks detailed in the company's filings with the Securities and Exchange Commission. The company undertakes no obligation to update these statements for revisions or changes after the date of this release.

Mylan is a global pharmaceutical company committed to setting new standards in health care. Working together around the world to provide 7 billion people access to high quality medicine, we innovate to satisfy unmet needs; make reliability and service excellence a habit; do what's right, not what's easy; and impact the future through passionate global leadership. We offer a growing portfolio of more than 1,300 generic pharmaceuticals and several brand medications. In addition, we offer a wide range of antiretroviral therapies, upon which approximately 40% of HIV/AIDS patients in developing countries depend. We also operate one of the largest active pharmaceutical ingredient manufacturers and currently market products in approximately 140 countries and territories. Our workforce of more than 25,000 people is dedicated to improving the customer experience and increasing pharmaceutical access to consumers around the world. 

Learn more at mylan.com

1. World Health Organization. Hepatitis C Surveillance and Control. 

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index4.html. Accessed on Jan. 15, 2015.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/mylan-signs-exclusive-agreement-with-gilead-sciences-to-distribute-sovaldi-and-harvoni-in-india-300039439.html

SOURCE Mylan Inc.

Risk Factors of HCC Development in Non-cirrhotic Patients with Sustained Virologic Response for Chronic HCV Infection

Risk Factors of HCC Development in Non-cirrhotic Patients with Sustained Virologic Response for Chronic HCV Infection


Hidenori Toyoda*, Takashi Kumada, Toshifumi Tada, Seiki Kiriyama, Makoto Tanikawa, Yasuhiro Hisanaga, Akira Kanamori, Shusuke Kitabatake and Takanori Ito
DOI: 10.1111/jgh.12915


Abstract
Background and Aim

Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, i.e., eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV-infected patients who achieved SVR.


Methods

The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon-based antiviral therapy for HCV. Patients maintained regular follow-up every 6 months for HCC surveillance. The FIB-4 index and aspartate aminotransferase to platelet count ratio index calculated based on laboratory data at the time that SVR was documented (SVR24).


Results

Patients continued follow-up visits for 1.0 to 22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at five years and 4.3% at ten years. Use of peginterferon or ribavirin for treatment and a history of antiviral therapy prior to the course when SVR was achieved were not associated with the incidence of HCC after SVR. Presence of diabetes mellitus (risk ratio 2.08; p=0.0451) and FIB-4 index calculated at the time of SVR24 (risk ratio 1.73; p=0.0198) were associated with a higher likelihood of HCC after SVR by multivariate analysis.


Conclusions

Patients with diabetes mellitus and patients with the elevation of FIB-4 index at SVR24 are at higher risk of HCC after SVR. Surveillance for HCC should be continued in this patient subpopulation.


Accepted manuscript online: 13 FEB 2015 04:58AM EST | DOI: 10.1111/jgh.12915

• Abstract
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Gilead Faces Challenge For Hepatitis C Drug Patent

Gilead Faces Challenge For Hepatitis C Drug Patent
By sonali raj February 15 2015 10:26 PM

Gilead is facing a challenge to its hepatitis C drug in Europe. A medical aid is challenging its patent for the popular drug Sovaldi on claims that Gilead is abusing its patent by charging an exorbitant price for the drug, making it inaccessible to many patients.

Medicins du Monde, the charity that has challenged the drug patent, says that the nearly $50,000 cost is out of reach for most patients in Europe. Between 7.3 and 8.8 million people are believed to be infected with hepatitis C in Europe. The director of Medicins du Monde said that even in a wealthy country like France, with an annual medicines budget of $30 billion, the cost is not easy to meet.

Continue reading...

ABBVIE SUBMITS NEW DRUG APPLICATION IN JAPAN FOR ITS INVESTIGATIONAL, ALL-ORAL, TREATMENT FOR CHRONIC HEPATITIS C

Related - UPDATED: With hep C approval app, AbbVie eyes franchise growth in Japan

Press Release;

ABBVIE SUBMITS NEW DRUG APPLICATION IN JAPAN FOR ITS INVESTIGATIONAL, ALL-ORAL, TREATMENT FOR CHRONIC HEPATITIS C

- SUBMISSION BASED ON PHASE 3 GIFT-I STUDY IN PATIENTS WITH GENOTYPE 1B CHRONIC HEPATITIS C VIRUS INFECTION

- GIFT-I MET ITS PRIMARY ENDPOINT, ACHIEVING 95 PERCENT SUSTAINED VIROLOGIC RESPONSE RATE AT 12 WEEKS POST-TREATMENT; TWO PATIENTS (0.9 PERCENT) DISCONTINUED TREATMENT DUE TO ADVERSE EVENTS

- ABBVIE'S TREATMENT FOR JAPANESE HEPATITIS C PATIENTS CONSISTS OF A 12-WEEK, TWO DIRECT-ACTING ANTIVIRAL, FIXED-DOSE COMBINATION OF PARITAPREVIR/RITONAVIR WITH OMBITASVIR, DOSED ONCE DAILY

Feb 11, 2015

NORTH CHICAGO, Ill., Feb. 11, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) submitted a New Drug Application (NDA) to the Japanese Ministry of Health, Labour and Welfare (MHLW) seeking approval for the company's investigational, all-oral, ribavirin (RBV) and interferon (IFN)-free, 12-week, two direct-acting antiviral treatment of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r), dosed once daily. The submission is for the treatment of patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection.

The NDA is supported by the Phase 3 GIFT-I study, which met its primary endpoint, achieving a 95 percent (n=106/112) sustained virologic response rate at 12 weeks post-treatment (SVR₁₂) in the sub-group of previously untreated, non-cirrhotic, adult genotype 1b (GT1b)-infected Japanese patients who were eligible for therapy with IFN and had a high viral load (≥ 100,000 IU/mL). Additionally, two patients without cirrhosis (0.9 percent) discontinued treatment due to adverse events. GIFT-I included a placebo-controlled arm and studied patients with and without compensated cirrhosis, who were new to therapy or treatment-experienced (with IFN and with or without RBV).

"We are pleased to announce the regulatory submission of our two direct-acting hepatitis C antiviral treatment in Japan, which follows on quickly from recent approvals of our three direct-acting antiviral treatment in the U.S., Canada and the European Union," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "This submission is based on a large Phase 3 study in multiple patient types and brings us closer to offering the possibility of cure for patients with chronic genotype 1b hepatitis C infection, the most common form of the disease in the country."

AbbVie studied a two direct-acting antiviral regimen without RBV in Japan due to patient and viral characteristics specific to the Japanese population, including high prevalence of GT1b. In Japan, approximately 1.5 to 2 million people are living with HCV.¹ Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the GT1b sub-type.²

About the GIFT-I Study GIFT-I (M13-004) is a Phase 3, multi-center study designed to evaluate the efficacy and safety of 12 weeks of treatment with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in adult Japanese patients (n=363) with chronic genotype 1b hepatitis C virus infection. Patients included those without cirrhosis and with compensated cirrhosis, who were new to therapy (treatment-naïve) or had failed previous treatment with interferon with or without ribavirin (treatment-experienced).

The study consists of two sub-studies. Sub-study one included patients without cirrhosis randomized to OBV/PTV/r or placebo. Sub-study two included patients with compensated cirrhosis, who received open-label treatment with OBV/PTV/r.

Within the primary efficacy patient population, there were no on-treatment virologic failures and 2.8 percent of patients (n=3/109) experienced relapse.

In patients without cirrhosis, the most commonly reported adverse events in the treatment arm were nasopharyngitis (16.7 percent OBV/PTV/r vs. 13.2 percent placebo), headache (8.8 percent OBV/PTV/r vs. 9.4 percent placebo), and oedema peripheral (5.1 percent OBV/PTV/r vs. 0 percent placebo).

Additional information about AbbVie's GIFT-I study can be found on www.clinicaltrials.gov.

About AbbVie's Investigational Two Direct-Acting Antiviral HCV TreatmentFor the treatment of genotype 1 chronic hepatitis C virus (HCV) infection in Japan, AbbVie's investigational two direct-acting antiviral treatment consists of the fixed-dose combination of paritaprevir/ritonavir (150/100 mg) with ombitasvir (25 mg), dosed once daily.

AbbVie's chronic HCV treatment combines two direct-acting antivirals, each with a distinct mechanism of action that targets and inhibits specific HCV proteins of the viral replication process.

$5M Hepatitis C strategy announced by P.E.I. government

P.E.I. is first province to offer newly-approved treatments with cure rates of 95% to 100%
CBC News

Posted: Feb 12, 2015 11:56 AM AT Last Updated: Feb 12, 2015 11:56 AM AT

A new $5-million hepatitis C management strategy unique to P.E.I. was announced by the province's Health and Wellness Minister Thursday morning.

Health Canada recently approved new treatments that can cure the HCV Hepatitis C genotype 1, which is carried by 70 to 75 per cent of Islanders with the contagious liver disease.

It is also the most difficult genotype to treat.

The new treatments have a cure rate of 95 to 100 per cent, few or no side effects, and a much shorter treatment cycle.

Current medications have a cure rate of up to 70 per cent but they have serious side effects.

"These are lifesaving and life-changing therapies… and I am very pleased that Prince Edward Island will be the first province in Canada to make them available," Health and Wellness Minister Doug Currie said in a news release.
$1.6M invested in each of next 3 years

Currie said the province's small size offers advantages in implementing this type of strategy.

"As a small province, we can closely monitor and assess HCV cases and mobilize and coordinate our provincial health care resources."

The province will work with the Quebec-based pharmaceutical company AbbVie to offer services including referral of patients, assessments, treatment support, education and followup.

Patients will be screened from emergency rooms, addiction services, primary care centres, methadone clinics and corrections facilities.

"This strategy will provide the best treatment available to many Islanders with hepatitis C and prevent further spread and serious complications among those with the disease," said P.E.I. physician and former chief public health officer Dr. Lamont Sweet.

The province will invest $1.6 million in the program in each of the next three years.

Hepatitis C is spread through contact with infected blood.

The P.E.I. government says about 400 Islanders are known to have been infected with the hepatitis C virus and at least 60 are in the advanced stages of the disease.

Dr. Morris Sherman, chairman of the Canadian Liver Foundation, said the province has "stepped up as a role model" and he hopes that "other provinces will soon follow their lead."

Read more....

Gilead agrees 41,000 eur hep-C drug price for 12 week treatment

Gilead agrees 41,000 eur hep-C drug price for 12 week treatment
FRANKFURT Thu Feb 12, 2015 8:54am EST

Feb 12 (Reuters) - Drugmaker Gilead has agreed on a price for its hepatitis C drug Sovaldi of 41,000 euros ($46,625) for a 12-week treatment for Germany's statutory medical insurers, the GKV association of Germany's statutory medical insurers said.

GKV, who provides coverage for about nine out of 10 Germans, said the U.S. biotechnology company had agreed on a price of 43,562.52 euros, which is subject to a 5.88 percent discount for statutory insurers.

The drug had initially been offered in Germany for a list price of 60,000 euros, or about 56,500 euros including the discount. ($1 = 0.8794 euros) (Reporting by Ludwig Burger; Editing by Christoph Steitz)

Related
Gilead Sciences, Inc. Offers Sovaldi For €41,000 In Germany

Patient-reported outcomes in chronic hepatitis C - the impact of liver disease and new treatment regimens

Alimentary Pharmacology & Therapeutics
Volume 41, Issue 6, pages 497–520, March 2015

Patient-reported outcomes in chronic hepatitis C
Source - GastroHep.com
 March's Alimentary Pharmacology & Therapeutics investigates patient-reported outcomes in chronic hepatitis C, the impact of liver disease, and new treatment regimens.

Treatment for chronic hepatitis C is rapidly changing and moving away from an interferon and ribavirin-based therapy to interferon-free ribavirin-free all oral regimens.

These regimens are simpler and shorter to administer with very high efficacy rates and better side effect profiles.

As advances in the treatment of chronic hepatitis C occur, it is imperative to capture both clinical outcomes as well as patient-reported outcomes.

In fact, patient-reported outcome assesses and quantifies the impact of these regimens on patient experience.

PROs assess patients' health-related quality of life (HRQOL) especially in the realms of fatigue and neuropsychiatric issues such as depression which can affect treatment adherence and work productivity.

Drs Younossi and Henry from France reviewed the literature related to patient-reported outcomes in HCV patients, and summarized the impact of chronic hepatitis C, and its treatment on patient-reported outcomes.

Databases Ovid MEDLINE and PubMed were searched from 1990 to 2014 using a combination of MEsh, thesaurus terms and relevant text words.

The text words included hepatitis C, chronic hepatitis C, treatment, quality of life, health-related quality of life, fatigue, work productivity, adherence, patient-reported outcomes, direct acting anti-viral agents and second generation direct acting anti-viral agents.

Each manuscript was assessed for pertinence to the issue of patient-reported outcomes in chronic hepatitis C as well as the quality of study design and publications.

The researchers found that chronic hepatitis C patients have baseline patient-reported outcome impairment.

Furthermore, treatment with interferon with or without ribavirin and first generation DAAs causes additional patient-reported outcome burden which can negatively impact treatment adherence and indirectly, treatment efficacy and work productivity.

The team noted that new treatment regimens with interferon- and ribavirin-free regimens not only have very high efficacy, but also result in the improvement of patient-reported outcome scores as early as 2 weeks into treatment as well as possibly better adherence to treatment regimens.

Dr Younossi and colleague commented, "Chronic hepatitis C and its treatment have been associated with patient-reported outcome impairment."

"The new IF-free and RBV-free regimens are associated with high efficacy and substantial improvement of patient-reported outcomes in clinical trial setting."

"Although very encouraging, more data are needed to assess patient-reported outcomes, adherence and work productivity of chronic hepatitis C patients in the real world setting of clinical practice.

Full text available @ Alimentary Pharmacology & Therapeutics: Systematic review: patient-reported outcomes in chronic hepatitis C - the impact of liver disease and new treatment regimens

New@CCO - HCV Special Populations And Genotype 3: Still Difficult to Treat?

HCV Special Populations
Good day folks, CCO launched a new learning activity which offers an overview of key clinical trial data relevant to the management of HCV in patients with advanced liver disease.

Easy Reading
Each presentation is followed up by expert analysis, making it easy for patients to follow.

Genotype 3 HCV: Still Difficult to Treat?
In addition future treatment options for treating HCV genotype 3 is highlighted in an article written by Jordan J. Feld, MD, MPH, including the NS5A inhibitor GS-5816 combined with sofosbuvir, here is an excerpt; Genotype 3 HCV: Still Difficult to Treat?

In genotype 3 treatment-experienced cirrhotics, 96% achieved SVR with 12 weeks of GS-5816 plus sofosbuvir and ribavirin. The fixed-dose combination of sofosbuvir/GS-5816 with and without ribavirin is now being evaluated in phase III trials. If the results hold up, genotype 3 may soon become the “easy-to-cure” genotype it once was.... 

I Would Rather.....
Checking out this CME may not be on your agenda today, so lets inspire you a bit with a little sample of the activity; HCV Special Populations and Other Highlights.

TRIO Real-World Outcomes: 12-Week Simeprevir- and Sofosbuvir-Based Regimens in Cirrhotic Patients
Stefan Zeuzem, MD:
Flamm and colleagues^[1] presented results of an efficacy analysis of sofosbuvir-based regimens in the TRIO network, a collaboration of academic medical centers, community physicians, and specialty pharmacies that manages more than 6000 patients with HCV infection....

Overall, I found the results from this analysis to be somewhat disappointing because some of these SVR12 outcomes are lower than what was seen in the pivotal clinical trials.^[2-5] For example, the overall SVR was 93% among cirrhotic patients treated with simeprevir plus sofosbuvir with or without ribavirin in the COSMOS trial vs 75% in the TRIO group. In the FISSION trial, 83% of treatment-naive patients with genotype 2 HCV achieved SVR with sofosbuvir and ribavirin vs only 65% in this real-world cohort. Why might this be?....

Jordan J. Feld, MD, MPH:I agree that overall, the SVR12 rates were lower than expected, particularly for patients infected with genotype 2 HCV. This group achieved....

Paul Y. Kwo, MD:I agree. In addition, I believe it would be useful to obtain more granularity regarding the findings from this study. For example, I was surprised to see that among patients with genotype 2 HCV.....
Continue learning....

Links:
HCV Special Populations and Other Highlights

In this expert analysis, Jordan J. Feld, MD, MPH; Paul Y. Kwo, MD; and Stefan Zeuzem, MD, discuss the most clinically relevant data on the management of hepatitis C infection in patients with advanced liver disease, cirrhosis, liver transplantation, and HIV coinfection, as well as new advances in the treatment of hepatitis D infection.
Source: Official Conference Coverage
2014 Annual Meeting of the American Association for the Study of Liver Diseases
Faculty: Jordan J. Feld MD, MPH, Paul Y. Kwo MD, Stefan Zeuzem MD
Released: 2/10/2015

Genotype 3 HCV: Still Difficult to Treat?

Jordan J. Feld, MD, MPH - 2/10/2015  More from this author

The current influx of newly approved all-oral therapies for HCV has meant that every day in clinic, I am able to start treatment for patients who for years have had no treatment options. For patients with genotype 1 HCV infection, who still comprise the majority in the United States, the options are plentiful and highly effective, and access is the only barrier remaining. However, for patients with genotype 3 HCV infection, the details matter. For treatment-naive patients, even if they have advanced fibrosis or compensated cirrhosis, sofosbuvir with ribavirin for 24 weeks is an excellent option with high cure rates and generally very good tolerability. Unfortunately, many of the patients I see with genotype 3 HCV have failed previous therapy, often more than once, and have clear evidence of cirrhosis. Most were originally told that they were fortunate to have an “easy-to-cure” genotype and could expect a ≥ 80% response rate with peginterferon and ribavirin. What they were often not told was that genotype 3 HCV infection causes more rapidly progressive liver disease than other genotypes and that the SVR rate with peginterferon and ribavirin was closer to 50% in those with cirrhosis. These patients are now very disappointed to learn that the new generation of highly effective drugs are less effective for treatment-experienced patients with genotype 3 HCV infection and cirrhosis.
Continue reading....

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