FDA Approved Simeprevir: Welcomed, but not the proverbial “home-run”

New Hepatitis C Drug Approved: Janssen’s Hepatitis C Drug Simeprevir Now Available

by Dr. Joe Galati on 11/29/2013

This past week, the FDA gave approval to Janssen’s new drug to treat hepatitis C. Simeprevir, commercially know as OLYSIO, is the first new hepatitis C drug since the release of telapravir (Incevik) and boceprevir (Victrelis) in 2011. Simeprevir is a NS3/4A protease inhibitor, used in combination with interferon and ribavirin.

The release of simeprevir marks the beginning of a new wave of direct acting antiviral agents against the hepatitis C virus. Additional drugs are set for FDA approval, including the Gilead drug sofosbuvir in early December 2013.

Most of the new hepatitis C drugs will have a number of features in common.

These include:
Very high cure rate, in the 80-90% range – lower in null and non-responders

Less side effects
Shorter duration of treatment
Less pills to take each day
Cirrhosis reduces response rates
Less drug-drug interactions
Genotype 1 subtype differences exist

Looking at the dosing of simeprevir, I have attached the official product insert that describes how the drug will be doses. Several points to consider:

This is an interferon/ribavirin based therapy

Patients with genotype 1 need additional screening for the NS3 Q80K polymorphism

Those with this variant have a decreased response rate to the therapy, and should be considered for an alternative therapy

The initial dosing is 12 weeks of simeprevir with interferon and ribavirin, followed by an additional 12 or 36 weeks of interferon and ribavirin combination therapy.

There are drug-drug interaction which have to be monitored closely

FDA approval is for genotype 1 patients only

While the release of simeprevir is welcomed, it has not provided the proverbial “home-run” we have been looking for in our quest to cure hepatitis C. In well selected patients, achieving a better than 80% cure rate is available. The concerns I have relate to the Q80K polymorphism noted above. This will be an additional step required in screening our patients. Additionally, in patients with prior non-response or null responders, as well as those with cirrhosis, these patients will still require a full 48 week of interferon and ribavirin. One of the goals of the next generation of hepatitis C therapies is reduced interferon exposure, or complete elimination. Simeprevir does not fully meet this goal.

In the days to come, I will post additional information on sofosbuvir. For now, these are the highlights to consider (refer to this FDA document for additional details):

Sofosbuvir will likely receive FDA approval for Genotype 1,2,3, and 4 patients with hepatitis C
Interferon-free treatment in genotype 2 and 3 for 12 weeks

Sofosbuvir combined with interferon and ribavirin in genotype 1 and 4 for 12 to 16 weeks

This treatment strategy is far different than the simeprevir treatment noted above.

Looking further, we will eventually have all interferon-free protocols. It is anticipated that as additional new drugs are approved, they will be combined (example sofosbuvir and simeprevir), allowing us to treat a wide range of patients, safely, and with a cure rate many of us may have never envisioned 20 years ago.

For a consultation to see if you are a candidate for these new drugs, contact Lexa at our office at 713-794-0700 and visit our webpage for additional information.

 Source - http://blog.texasliver.com/#sthash.ju2JBHrL.dpuf

Related:
OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment

Hepatitis C-A third agent that acts directly against the virus has been approved

New HCV Drug Approved

Published: Nov 25, 2013

By Michael Smith, North American Correspondent, MedPage Today

 

A third agent that acts directly against hepatitis C (HCV) has been approved, according to the company that makes the drug.

But simeprevir (Olysio) -- an NS3/4A protease inhibitor intended to be used in combination with two standard HCV medications, pegylated interferon, and ribavirin -- is the first such agent that can be taken once a day, Janssen Therapeutics said in a release.

The other two protease inhibitors to win approval -- telaprevir (Incivek) and boceprevir (Victrelis) -- got the nod in 2011.

Simeprevir is approved for genotype 1 infected adults with compensated liver disease, including cirrhosis, the company release said. The move was expected, after an advisory board in October voted unanimously in favor of approval. The FDA usually follows such advice, although it is not obliged to do so.

The three protease inhibitors are the leading edge of a wave of so-called direct-acting agents, or DAAs, that target aspects of HCV replication. In contrast, ribavirin is a general anti-viral agent and interferon works by boosting the immune system.

Simeprevir, combined with interferon and ribavirin, yielded solid results in various patient groups, where cure was defined as undetectable virus 12 or 24 weeks after the end of therapy (SVR₁₂ or SVR₂₄):

• Among treatment-naive patients, 80% of those getting simeprevir, along with interferon and ribavirin, achieved SVR12, compared with 50% of those getting interferon and ribavirin plus a placebo.
• Among those who had relapsed after previous treatment with interferon and ribavirin, SVR₁₂ rates were 79% in the simeprevir group and 37% in the placebo group.
• Among patients who had only partly responded to previous therapy with interferon and ribavirin, simeprevir-based treatment led to undetectable virus 24 weeks after the end of treatment (SVR₂₄) in 65%, compared with 9% in the placebo group.
• And among patients who had not responded at all to previous treatment with interferon and ribavirin, 53% reached SVR₂₄ on simeprevir-based therapy, compared with 19% in the placebo group.

For both treatment-naive patients and those who had relapsed, the drug is recommended to be used for 12 weeks, combined with 24 weeks of interferon and ribavirin.

For those whose previous response was partial or null, a treatment regimen of 12 weeks, combined with 48 weeks of interferon and ribavirin, is recommended.

The efficacy of the drug is "greatly decreased" in patients whose virus has the so-called Q80K polymorphism in the protease gene, the company noted, urging that patients discuss the issue of testing for the variant with their doctors and choose a different therapy if Q80K is present.

Despite that limitation, the approval is "an important milestone," according to Douglas Dieterich, MD, of Mount Sinai School of Medicine in New York City, who was involved in the simeprevir clinical trials.

"It means that patients have a new treatment option with the potential to cure this challenging disease," he said in the release.

http://www.medpagetoday.com/Gastroenterology/Hepatitis/43101
 

 

New Video: Hepatitis C Drug OLYSIO™ (simeprevir)

New Video: Hepatitis C Drug OLYSIO™ (simeprevir)

Related
OLYSIO™ (simeprevir) Receives FDA Approval
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment

New Video: Hepatitis C Drug OLYSIO™ (simeprevir)

*Audio begins after introduction

HCV Drug Olysio (simeprevir) - The New Kid On The Block

HCV Drug Olysio (simeprevir) - The New Kid On The Block

Hello everyone,
It sure is another cold weekend here in Michigan, hope it's warmer in your part of the world.

Today, as I sat cuddled in my warm chair, gazing out the window, I found myself watching the birds on our backyard feeder. One seed at a time, slowly they ate their afternoon meal. This arduous task ensures their survival, and will continue day in and day out, season after season.

The same can be said of hepatitis C patients, waiting day after day, year after year for new therapies to be approved. In some cases, the drugs are needed for patients to remain healthy, and yes, for others, they are needed for survival.

The HCV standard-of-care treatment in 2001 was the combination of pegylated interferon and ribavirin. Unfortunately this treatment only cured around 50% of individuals with genotype 1, which is the most prevalent HCV genotype in the US and Europe.  The HCV community waited ten years before a new drug was available, finally, in 2011 the first direct-acting antivirals (DAAs) boceprevir and telaprevir received FDA approval.

Two years later, and some 48 hours ago, the FDA approved Olysio (simeprevir), a new drug to treat HCV.

On this special occasion, and for the newly diagnosed, I thought a few links for reference purposes and a bit of information on simeprevir may be helpful.

Check back often, as new updates are available links and information will be provided below;

December 5-3 Updates
Simeprevir (Olysio): J & J Patient Access Programs

Video - Dr. Joseph Galati talks about HCV drug OLYSIO (simeprevir)

Olysio (simeprevir) - Resistant Variant (Q80K) 
Although, simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, and easier to take, there are some drawbacks. Before starting simeprevir patients with HCV genotype 1a need to be screened for a genetic mutation called Q80K polymorphism.

November 26th updates: An article written by Marc Iskowitz on the cost of OLYSIO and an educational video from Janssen

OLYSIO (Simeprevir) Cost?
Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. That's roughly $66,360 for a three-month course.
Read more here...

Video
Hepatitis C Drug OLYSIO™ (simeprevir)

The Basics

OLYSIO (Simeprevir) - The New Kid On The Block

Simeprevir is used to treat HCV genotype 1 infected subjects with compensated liver disease (including cirrhosis) in combination with peginterferon and ribavirin. Simeprevir has yet to be studied in patients who have previously failed therapy with a treatment regimen that includes other HCV protease inhibitors.

Before starting simeprevir patients with HCV genotype 1a should be screened for a genetic mutation called Q80K polymorphism. Alternative therapy should be considered for people with the mutation according to Prescribing Information.

Like Simeprevir, both boceprevir and telaprevir are protease inhibitors approved to treat HCV genotype 1 patients in combination with peginterferon and ribavirin.

Simeprevir and telaprevir are used for 12 weeks, boceprevir is used from 24 to 44 weeks.

Peginterferon and ribavirin are used with these drugs, from 24 to 48 weeks.

Simeprevir Duration of Treatment

The recommended duration of treatment with OLYSIO is 12 weeks in combination with peginterferon alfa and ribavirin. In all patients, treatment with OLYSIO should be initiated in combination with peginterferon alfa and ribavirin and should be administered for 12 weeks.

All treatment - naïve and prior relapser patients , including those with cirrhosis , should receive an additional 12 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO , peginterferon alfa and ribavirin (total treatment duration of 24 weeks)

All prior non - responder patients (including partial and null - responder s), including those with cirrhosis, should receive an additional 36 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 48 weeks)

The good news? Simeprevir is taken only once daily (capsule of 150 mg taken orally) with food.

*The type of food does not affect exposure to simeprevir. The capsule should be swallowed as a whole. 

Boceprevir and telaprevir are both taken three times a day with a meal or snack, telaprevir should be taken with a snack that contains protein (cheese, peanut butter, eggs). Although, in some patients telaprevir can be taken twice daily.

Lesson Learned

Telaprevir and boceprevir have significantly increased the ability to cure HCV, but both PIs have their own side effects, including those from interferon.

An important lesson we learned from these drugs may serve as a reminder for future DDAs, that is, once telaprevir and boceprevir were used in larger groups of patients, or in "real-life" settings - outside clinical trials, new response rates and adverse effects began to emerge.

For instance  Dr. Arpita Sheth presented a poster at the Interscience Conference which found 30% of veterans taking direct-acting antivirals boceprevir and telaprevir in "real-life" settings, discontinued treatment by week 24, despite high rates of early response. The study included a greater proportion of cirrhotic patients, then compared to clinical trials. Anemia was  increased by 15%  - over what has been reported elsewhere. The study appears in the 2013 August issue of Clinical Gastroenterology and Hepatology

Food For Thought

In an editorial, in which both simeprevir and sofosbuvir were the topic, researchers wrote; Time will tell if these first second wave DAA agents will prove to be safe and effective when used in large numbers of real life chronic HCV infected patients. The article was published in the November, December issue of Annals Of Hepatology.

Simeprevir Side Effects

Common side effects reported in clinical trials were rash, itching, and nausea, some patients experienced serious photosensitivity reactions which required a trip to the hospital.

The FDA’s advisory panel determined simeprevir was much easier to take than the first generation protease inhibitors (PIs) telaprevir and boceprevir. With SVR rates of 79%-80% in phase III studies and an impressive risk profile the drug was unanimously supported by the panel and approved by the FDA.

In the above mentioned editorial researchers agreed, both simeprevir and sofosbuvir, had a better safety profile and comparable, if not higher, efficacy then telaprevir and boceprevir. However,

In an article written by Elizabeth Mechcatie, the side effects reported in the simeprevir phase III trials included;

In phase III studies fatigue, headache, and influenza like illness, associated with PR, were the most common adverse events. The only deaths reported were in three patients treated with simeprevir after they stopped taking the drug, but were not considered related to the drug. During the first 12 weeks of treatment, dyspnea was also higher among those on simeprevir (12% vs. 8%), but so far, the cause has not been determined, according to the FDA reviewer. Hyperbilirubinemia was also higher among those on simeprevir (49% vs. 26%), mostly grade 1 and 2 abnormalities.

In the first 12 weeks in the phase III studies, rashes (including photosensitivity) were reported in 28% of those on simeprevir, vs. 20% of those on PR only. Pruritus was also more common among those on simeprevir (22% vs. 15%); 1% of patients discontinued treatment because of a rash.

Download the FDA review package for simeprevir and Johnson & Johnson document released Oct 23.

Drug-drug interactions

The complexity of managing drug–drug interactions is another similarity shared by the PIs. A study in the December 2013 issue of Alimentary Pharmacology & Therapeutics, investigating drug–drug interactions in patients using telaprevir and boceprevir reported;  Drug–drug interactions between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients.

Other medications used while treating with telaprevir and boceprevir can interfere with the way DDAs are metabolized. The drug–drug interactions can either increase drug concentrations which may cause toxicity and lead to side effects, or decrease drug concentrations leading to a loss of efficacy, and, if the PIs are affected, this may lead to treatment failure due to emergence of viral resistance and subsequently a virological breakthrough.

An excerpt from the study;

The next wave of DAAs including the protease inhibitors faldaprevir and simeprevir as well as the NS5B nucleotide inhibitor sofosbuvir may be available in early 2014 and more will follow in the upcoming years. 

Risk for DDIs differ between the various future DAA classes. The nucleotide NS5B inhibitor sofosbuvir does not seem to be involved in significant DDIs.[24, 25] In contrast, DDIs have to be considered for several nonnucleotide NS5B inhibitors.[15] DDIs may also play a role for some NS5A inhibitors. Daclatasvir is substrate and inhibitor of P-glycoprotein and substrate of CYP3A4. However, pharmacokinetic data suggest that risk for significant DDIs is far lower compared with using protease inhibitors.[15]  

Soon-available PIs faldaprevir and simeprevir are also both inhibitors and substrates of CYP3A4 and it has already been shown that drug levels are altered in the presence of other strong inhibitors or inducers of CYP3A4.[15] Taken together, it can be assumed that the challenge of DDIs will certainly accompany HCV therapy in upcoming years, in particular, as combination treatments with several DAAs will most likely be necessary to finally achieve an efficient interferon-free anti-viral treatment.[6, 26]

Continue to the full text @ Alimentary Pharmacology & Therapeutics

Simeprevir has a list of medications that can cause drug–drug interactions as well, those medications along with patient and prescribing information, can be found online at http://www.olysio.com/intro/.

Let this be an important reminder folks, to ensure a safe, successful treatment plan, provide a complete health history to your healthcare provider and include a list of all medications, vitamins, or herbs you are taking before and during HCV therapy. Going forward, treating with new agents, the importance of preparing for treatment can not be underestimated, communicating with your physician or treatment nurse is key to a promising outcome.

Simeprevir 

Sustained Virologic Response - SVR 

The results from three phase III studies used to determine the FDA approval of simeprevir were QUEST-1 and QUEST-2, made up of treatment-naïve patients. In PROMISE patients relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients.

QUEST-1 and QUEST-2
In the two studies deemed QUEST-1 and QUEST-2, of 785 treatment-naive patients, 80 percent of those treated with simeprevir achieved sustained virologic response 12 weeks after the end of treatment, called SVR12, compared with 50 percent in the placebo groups.

PROMISE
In the third study called PROMISE of 393 prior-relapsers, 79 percent in the simeprevir group achieved SVR12 compared with 37 percent of patients in the placebo group.

ASPIRE
Results from ASPIRE led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 65 percent of prior partial-responder patients and 53 percent of prior-null responder patients compared with 9 percent and 19 percent of prior partial- and null-responder patients in the placebo groups, respectively.

Links
OLYSIO Website
Simeprevir (Olysio): J & J Patient Access Programs
Prescribing Information
Patient Information
Important Safety Information

With great anticipation we patiently await for the approval of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor. The FDA approval is expected to be announced in early December. Sofosbuvir will be used only with ribavirin, for treating adult HCV genotypes 2 and 3. However, in HCV genotype 1 and 4 treatment-naive patients, sofosbuvir will be used in combination with pegylated interferon and ribavirin. 

Off Label Use - Simeprevir and Sofosbuvir

Paul Sax, Editor-in-Chief at NEJM Journal Watch wrote an article this past summer; Both Simeprevir and Sofosbuvir Likely Approved by 2014 - Clinical/Ethical/Pharmacoeconomic Dilemmas Loom on the possibility of combining simeprevir and sofosbuvir with or without ribavirin, to create an off label interferon-free regimen;

The interim results of the COSMOS study, presented at CROI this year, showed a >90% cure rate in 80 prior null responders (no cirrhosis) who received simeprevir and sofosbuvir together for 12 or 24 weeks, with and without ribavirin. There was no interferon in this study. (The full slide set of the presentation is on NATAP.)

So if these two drugs are both approved as expected, one could easily make the case that the best treatment for HCV genotype 1 — in terms of efficacy, safety, tolerability, pretty much everything except drug-drug interactions and cost — will be the COSMOS regimen of simeprevir and sofosbuvir, with or without ribavirin. And emphatically without interferon.

And that, my dear friends, is off-label use.

Continue reading...

I hate to be redundant, but once again, in the editorial discussing simeprevir and sofosbuvir, I noticed the mention of off label use combining simeprevir and sofosbuvir;

THE FIRST ALL ORAL INTERFERON-FREE COMBINATION OUTSIDE CLINICAL TRIALS:OFF-LABEL USE OF SIMEPREVIR PLUS SOFOSBUVIR?

As soon as simeprevir and sofosbuvir become commercially available, it is possible that some people will entertain the possibility of combining both agents with our without RBV, to create an off label IFN free regimen. In this regard, it is important to review the results of the COSMOS study.23 This Phase 2 exploratory trial enrolled two cohorts of HCV genotype 1 null responders:one with fibrosis stage Metavir F0-F2 and the other with F3-F4. Both cohorts were randomized to receive simeprevir plus sofosbuvir with or without RBV for 12 vs. 24 weeks of fixed therapy duration.

Preliminary results are so far available only for the12 week arm of the first cohort, with less significant liver fibrosis. Among 27 patients that received simeprevir plus sofosbuvir with RBV, the rate of undetectable HCV RNA 8 weeks after the end of therapy (SVR-8) was 96%. Similarly, among 14patients treated with simeprevir plus sofosbuvir without RBV, SVR-8 was 93%. Overall, 24 patients already reached 12 weeks of follow-up after the end of therapy and all maintain undetectable HCV RNA(SVR-12). Eight patients reached week 24 follow up after the end of therapy and also remain HCV RNA undetectable (SVR-24). Only 2% of patients had to interrupt prematurely the trial for adverse events.These results are surely preliminary, however the message they send out is powerful: in some areas of the world we may start to see the first IFN free regimens already being used to treat chronic HCV patients in routine clinical practice as early as 2014. 

Continue reading...

Once sofosbuvir is FDA approved I assume we will be reading more on off label use, as is often the case, the patient is the last to know.

Other then simeprevir and sofosbuvir, there are many additional potent agents in the clinical pipeline. AbbVie reported this month an interferon-free combination of three drugs plus ribavirin achieved a sustained virologic response (SVR12) in 96 percent of previously untreated genotype 1 patients.

I am determined to remain optimistic that in the future, interferon-free regimens will provide safe and effective therapy in all different HCV infected patient populations.

Stay healthy and positive.

OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C

Related:
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment

U.S. FDA approves J&J hepatitis C pill

Reuters) - U.S. regulators on Friday approved the use of Johnson & Johnson's Olysio, also known as simeprevir, as a treatment for chronic infection with the liver-destroying hepatitis C virus.

Olysio, a protease inhibitor that blocks a specific protein needed by the virus to replicate, is to be used in combination with interferon, given by injection, and ribavirin, another pill.

Hepatitis C affects about 3.2 million Americans, killing more than 15,000 each year, mostly from illnesses such as cirrhosis and liver cancer.

The often-undiagnosed virus is transmitted through contaminated blood. Infection rates have dropped since the early 1990s, due in part to the introduction of blood and organ screening. Still, many older adults remain at risk, according to the Centers for Disease Control and Prevention, which has called for baby boomers to be routinely tested for the virus.

Olysio is a member of the same class of drugs as Merck & Co's Victrelis and Vertex Pharmaceuticals' Incivek. The FDA approved both those drugs in 2011.

Olysio was shown in clinical trials to cure patients with a shorter duration of treatment.

Drugmakers have been racing to develop more effective, easier-to-tolerate antivirals to treat hepatitis C. Wall Street analysts have forecast annual sales of billions of dollars for new drugs that would allow doctors to skip use of interferon, which can cause severe flu-like side effects.

The FDA is slated to decide by December 8 on Gilead Sciences' application for sofosbuvir, a member of a different class known as nucleotide analogue inhibitors, or "nukes," designed to block a different enzyme the virus needs to copy itself.

European regulators on Friday recommended approval of the Gilead drug, under the brand name Sovaldi.

Other companies working to develop new hepatitis C drugs include AbbVie and Bristol-Myers Squibb.
(Reporting By Deena Beasley)

Press Release

OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C

OLYSIOTM is the first once-daily protease inhibitor approved for the treatment of chronic hepatitis C in a combination antiviral regimen for adults with compensated liver disease

TITUSVILLE, N.J. (November 22, 2013) – Janssen Therapeutics, Division of Janssen Products, LP (Janssen), announced today the U.S. Food and Drug Administration (FDA) has approved OLYSIOTM (simeprevir), an NS3/4A protease inhibitor, for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis. OLYSIOTM may benefit patients with chronic hepatitis C, including those who are treatment naïve or who have failed prior interferon-based therapy.

Chronic hepatitis C is a blood-borne infectious disease of the liver that affects approximately 3.2 million people in the United States.

OLYSIOTM works by blocking the viral protease enzyme that enables the hepatitis C virus (HCV) to replicate in host cells. The goal of treatment for chronic hepatitis C is cure, also known as sustained virologic response (SVR), which is defined as undetectable levels of HCV in the patients’ blood 12 to 24 weeks after the end of treatment. For treatment-naïve and prior-relapser patients, a fixed treatment regimen of 12 weeks of OLYSIOTM combined with 24 weeks of pegylated interferon and ribavirin is recommended. For prior partial- and null-responder patients, a treatment regimen of 12 weeks of OLYSIOTM combined with 48 weeks of pegylated interferon and ribavirin is recommended.

“Given the complexity of the condition, OLYSIOTM was studied in a number of different patient populations, including individuals who have relapsed or failed to respond to previous treatments,” said Douglas Dieterich, M.D., Professor of Medicine in the Division of Liver Diseases, Mount Sinai School of Medicine, and OLYSIOTM clinical trial investigator. “The FDA approval of OLYSIOTM is an important milestone for people living with chronic hepatitis C as it means that patients have a new treatment option with the potential to cure this challenging disease.”

OLYSIOTM is a prescription medicine used with other antiviral medicines, pegylated interferon and ribavirin, to treat genotype 1 chronic hepatitis C in adults with stable liver problems. OLYSIOTM must not be taken alone. The efficacy of OLYSIOTM in combination with peginterferon and ribavirin is greatly decreased in patients who have genotype 1a Q80K. Please talk to your doctor about testing for genotype 1a Q80K and using a different therapy when genotype 1a Q80K is present. It is not known if OLYSIOTM is safe and effective in children under 18 years of age.

The New Drug Application (NDA) filed by Janssen Research & Development, LLC, for OLYSIOTM was based in part on efficacy and safety results from three pivotal Phase 3 studies – QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients. Each of the studies evaluated OLYSIOTM dosed once daily in combination with pegylated interferon and ribavirin versus treatment with placebo plus pegylated interferon and ribavirin.

Results from a pooled analysis of QUEST-1 and QUEST-2 demonstrated that 80 percent of treatment-naïve patients in the group receiving OLYSIOTM achieved sustained virologic response 12 weeks after the end of treatment (SVR12), compared with 50 percent of patients in the placebo groups. In PROMISE, 79 percent of prior-relapser patients in the simeprevir group of the study achieved SVR12 compared with 37 percent of patients in the placebo group. Results from ASPIRE demonstrated that use of OLYSIOTM led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 65 percent of prior partial-responder patients and 53 percent of prior-null responder patients compared with 9 percent and 19 percent of prior partial- and null-responder patients in the placebo groups, respectively.

In the QUEST-1 and QUEST-2 studies, among genotype 1a treatment-naïve patients receiving OLYSIOTM who had the Q80K polymorphism (a naturally occurring variation in the HCV NS3/4A protease enzyme), 58 percent achieved SVR12 versus 84 percent of patients without the Q80K polymorphism. In the placebo arm, 52 percent of patients with the Q80K polymorphism achieved SVR12. In the PROMISE study, among prior-relapser patients with the Q80K polymorphism who received OLYSIOTM, 47 percent achieved SVR12 versus 78 percent of patients without the polymorphism. In the placebo arm, 30 percent of patients with the Q80K polymorphism achieved SVR12.

“As an advocate working with the hepatitis C community, I’m pleased to know that Janssen has been working to make sure OLYSIOTM will be reasonably priced and available to the patients who need it,” said Sue Simon, President of the Hepatitis C Association. “It is notable that in addition to introducing a new treatment option for patients, Janssen is establishing comprehensive programs to support and assist patients in their treatment journey.”

Janssen has launched OLYSIOTM Support, a comprehensive support program designed in partnership with the HCV community to assist in the hepatitis C treatment journey so that patients and caregivers – and their healthcare providers – can focus on treatment. To register for OLYSIOTM Support or for additional information, please visit OLYSIO.com.

About OLYSIOTM (simeprevir)
OLYSIOTM (simeprevir) is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated in the U.S. for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 infected subjects with compensated liver disease, including cirrhosis.

Janssen is responsible for the global clinical development of OLYSIOTM and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for OLYSIOTM in these countries under the marketing authorization held by Janssen-Cilag International NV. The treatment was approved in September 2013 in Japan under the trade name SOVRIADTM and in November 2013 in Canada under the trade name GALEXOSTM for the treatment of genotype 1 hepatitis C. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of OLYSIOTM for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with OLYSIOTM in clinical trials.

For additional information about OLYSIOTM, please visit www.OLYSIO.com

Important Safety Information

What is OLYSIO?

• OLYSIOTM (simeprevir) is a prescription medicine used with other antiviral medicines, peginterferon alfa and ribavirin, to treat genotype 1 chronic (lasting a long time) hepatitis C in adults with stable liver problems.

• OLYSIO must not be taken alone. The efficacy of OLYSIO in combination with peginterferon and ribavirin is greatly decreased in patients who have genotype 1a Q80K. Please talk to your doctor about testing for genotype 1a Q80K and using a different therapy when genotype 1a Q80K is present.
It is not known if OLYSIO is safe and effective in children under 18 years of age.

Important Safety Information

What is the most important information I should know and who should not take OLYSIO?
OLYSIO, in combination with peginterferon alfa and ribavirin may cause birth defects or death of your unborn baby. If you are pregnant or your sexual partner is pregnant, or plans to become pregnant, do not take these medicines. You or your sexual partner should not become pregnant while taking OLYSIO with peginterferon alfa and ribavirin and for 6 months after treatment is over.
Females and males must use two effective forms of birth control during treatment and for 6 months after treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy. Talk to your healthcare provider about forms of birth control that may be used during this time.

Females must have a pregnancy test before starting treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy, every month while being treated, and every month for 6 months after your treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy is over.
If you or your female sexual partner becomes pregnant while taking OLYSIO, peginterferon alfa, and ribavirin combination therapy or within 6 months after you stop taking these medicines, tell your healthcare provider right away. You or your healthcare provider should contact the Ribavirin Pregnancy Registry by calling 1-800-593-2214. The Ribavirin Pregnancy Registry collects information about what happens to mothers and their babies if the mother takes ribavirin while she is pregnant.

OLYSIO in combination with peginterferon alfa and ribavirin 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 treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy.

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)
Do not take OLYSIO alone. OLYSIO should be used together with peginterferon alfa and ribavirin 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 taken the medicines telaprevir (Incivek®) or boceprevir (Victrelis®)
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: 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 (when administered by injection or when taken by mouth), 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 (when taken by mouth or when administered by injection) (Diflucan®), fosamprenavir (Lexiva®), indinavir (Crixivan®), itraconazole (when taken by mouth) (Sporanox®, Onmel®), ketoconazole (when taken by mouth) (Nizoral®), lopinavir (Kaletra®), lovastatin (Advicor®, Altoprev®, Mevacor®), mexiletine (Mexitil®), midazolam (when taken by mouth), 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 (Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Phenytek®), pitavastatin (Livalo®), posaconazole (when taken by mouth) (Noxafil®), pravastatin (Pravachol®), propafenone (Rythmol SR®), quinidine (Nuedexta®, Duraquin®, Quinaglute®), rifabutin (Mycobutin®), rifampin (Rifadin®, Rifamate®, Rifater®), 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, tacrolimus (Prograf®), tadalafil (Adcirca®, Cialis®), telithromycin (Ketek®), tipranavir (Aptivus®), triazolam (when taken by mouth) (Halcion®), verapamil (Calan®, Covera-HS®, Isoptin®, Tarka®), voriconazole (when taken by mouth or when administered by injection) (Vfend®), warfarin (Coumadin®)

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 most common side effects of OLYSIO?
The most common side effects of OLYSIO when used in combination with peginterferon alfa and ribavirin include skin rash, itching, 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.

About Janssen Therapeutics
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in hepatitis C, HIV and other infectious diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Headquartered in Titusville, New Jersey, Janssen Therapeutics, Division of Janssen Products, LP, is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Visit www.JanssenTherapeutics.com for more information and follow us on Twitter at @JanssenUS.

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(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Therapeutics, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; impact of business combinations; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2012. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

NOTE: Janssen Therapeutics, Division of Janssen Products, LP, provides support to the Hepatitis C Association for initiatives benefitting individuals living with hepatitis C.

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