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

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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.

Media Contact: Craig Stoltz
Mobile: +1 (215) 325-3612

Media Contact: Daniel De Schryver
Mobile: +49 173 76 89 149

Investor Contact: Stan Panasewicz
Office: +1 (732) 524-2524

Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment

 Medscape Gastroenterology

The Next Wave of Agents for Treatment of Hepatitis C

William F. Balistreri, MD
November 21, 2013

For several years, the recommended standard of care for patients with chronic hepatitis C virus (HCV) infection consisted of a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). On the basis of understanding of the biology of the virus and identification of proteins involved in HCV replication came the development of agents that inhibited the HCV protease and polymerase enzymes.

A few years ago, the US Food and Drug Administration (FDA) approved 2 direct-acting antiviral agents for the treatment of HCV genotype 1: the NS3 protease inhibitors telaprevir and boceprevir. The American Association for the Study of Liver Diseases guidelines[1] were updated to recommend triple therapy consisting of one of these protease inhibitors given in combination with PEG-IFN and RBV. This recommendation was based on results of clinical trials of this combination, which showed significantly improved sustained virologic response (SVR) rates. Although this triple therapy is generally well tolerated, troublesome side effects occur in many patients. The good news is that the guidelines may once again be revised thanks to the emergence of the next wave of direct-acting antivirals.

Simeprevir and Sofosbuvir

Simeprevir is a potent, once-daily oral investigational NS3/4A protease inhibitor that was shown to be effective when coadministered with standard therapy (PEG-IFN and RBV) for treatment of HCV genotype 1 infection both in treatment-naive patients and in patients who did not respond to standard therapy.[2-10]

Primary efficacy and safety data from clinical trials of simeprevir in patients with genotype 1 chronic HCV infection were in part responsible for the recommended FDA approval of this agent on October 24, 2013. The FDA's Antiviral Drugs Advisory Committee recommendation was unanimous, commenting that the available data overwhelmingly supported approval of the simeprevir, PEG-IFN, and RBV combination for HCV genotype 1 infection in treatment-naive patients and in those who had relapse after previous therapy. The committee reviewed safety and efficacy data from a series of double-blind, placebo-controlled trials -- phase 3 studies of treatment-naive patients and patients with previous relapse, and a phase 2b study involving patients with previous relapse and nonresponders.

For example, simeprevir (TMC435) administered once daily in combination with PEG-IFN and RBV was associated with SVR 12 weeks after the end of treatment (SVR12) in approximately 80% of treatment-experienced (relapsed) genotype 1 chronic hepatitis C patients. The SVR12 rate was less than 40% in patients receiving placebo plus PEG-IFN and RBV. Treatment failure rates and relapse rates were lower in simeprevir recipients than placebo recipients.

Simeprevir was shown to be generally safe and well tolerated, even among patients with advanced liver fibrosis. The most common adverse events were fatigue, headache, and influenza-like illness.

The FDA Advisory Committee did, however, further recommend that patients be screened for the commonly occurring Q80K mutation because simeprevir was found to be less effective in the presence of this mutation. They also recommended that the label should indicate that sunburn is a common side effect. More information about the simeprevir clinical trials can be found at ClinicalTrials.gov.

Soon to follow was the recommended FDA approval of sofosbuvir, a nucleotide analog that inhibits NS5B-directed HCV replication; this agent has also been shown to be highly effective. Sofosbuvir in combination with standard therapy was associated with SVR12 rates of 90% compared with 58% in placebo-treated patients.[11,12]                        

Both agents will be indicated for treatment of patients with HCV genotype 1, but only in combination with PEG-IFN and RBV. These drugs represent an advance in management -- they promise to be capable of inducing high SVR rates with 1 pill per day, shorter duration of therapy, better tolerability, and no resistance development. The 1-pill-daily regimen simplifies the treatment strategy; however, the cost and side effects are likely to remain high.

A Glimpse of the Future in HCV Treatment

There is an even higher degree of optimism, however, because recent studies may usher in the next wave of treatment strategies for HCV infection. In my opinion, the goal for treatment in terms of efficacy, safety, and tolerability is an IFN-free regimen. Simeprevir is being studied in phase 2 IFN-free trials with and without RBV and in combination with a host of other agents that act synergistically to inhibit HCV replication, and which include all oral regimens. For example, studies in progress suggest that high SVRs can be achieved in patients treated with simeprevir and sofosbuvir together, with and without RBV.

I will end by offering a glimpse of the future. Currently under evaluation in clinical studies are second-generation protease inhibitors and small-molecule drugs that inhibit other viral enzymes. Drug cocktails that target multiple HCV enzymes simultaneously may ultimately become the standard of treatment, as in the current strategy for the management of infection with HIV.

The bottom line is that these exciting advances in antiviral therapy will lead to significant improvements in response rates with reduced adverse effects. These advantages may lower the threshold for HCV treatment for both patients and physicians.

It is important to note, though, that at present only a minority of HCV-infected patients may benefit because of multiple barriers that have been identified and that impede delivery of therapy. A major issue is inadequate case-finding, an obstacle that could be overcome by widespread screening. The Centers for Disease Control and Prevention recently advised enhanced testing; their guidelines state that many persons who test positive for hepatitis C do not receive the necessary follow-up to determine whether they require medical care. Therefore, enhanced efforts to improve awareness, education, and specialist availability are needed.

The high prevalence of HCV infection worldwide should also stimulate expanded efforts in primary prevention, including vaccine development. Perhaps we can soon wave good-bye to HCV!

http://www.medscape.com/viewarticle/814701_3

Simeprevir SVR in Treatment-Naïve and Treatment-Experienced Geno 1 Chronic Hepatitis C Patients

Simeprevir Administered Once Daily Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Patients

Beerse, Belgium (Nov. 11, 2013) Janssen R&D Ireland (Janssen) today announced the presentation of new data for the new generation protease inhibitor simeprevir (TMC435) in the treatment of genotype 1 chronic hepatitis C (HCV) in treatment-naïve and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, the efficacy of simeprevir was observed in HCV patients considered difficult to treat, including patients with the IL28B TT genotype and METAVIR scores of F4.

HCV is a major problem in the EMEA region, where an estimated 15 million people are living with the disease.1 Many patients living with chronic HCV are in need of treatment and the genotype of the virus often determines how efficacious treatment will be.2

"Patients with certain baseline characteristics can be more likely to fail or relapse after prior treatment," said Ira Jacobson, M.D., simeprevir clinical trial investigator, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center, United States. "The breadth of simeprevir data presented at The Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) reinforce the potential of simeprevir as an effective treatment option in multiple patient populations, including patients who are considered difficult to treat, and will offer important guidance to physicians once simeprevir is approved."

On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend simeprevir 150mg capsules administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic HCV in adult patients with compensated liver disease. A Marketing Authorisation Application was submitted to the European Medicines Agency seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic HCV in April 2013. Simeprevir was approved in September 2013 in Japan, for the treatment of genotype 1 HCV. Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. UK/HCV/1113/0021

Pooled Analysis from QUEST-1 and QUEST-2 Confirms Clinical Benefit of Simeprevir in Sub-Populations of Patients (Abstract 1122)

In the Phase 3 QUEST-1 and QUEST-2 studies, 80% of treatment-naïve patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 50% of patients treated with placebo plus pegylated interferon and ribavirin. The analysis, which included patients considered difficult to treat, found that 61% of patients with the IL28B TT genotype, 60% of patients with a METAVIR score of F4 and 75% of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 21%, 34% and 47% of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 58% of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 52% of patients treated with placebo in combination with pegylated interferon and ribavirin, but the difference was not statistically significant. 3% of patients treated with simeprevir discontinued treatment early due to an adverse event, compared to 2% of patients treated with placebo.

Analysis from PROMISE Reinforces Efficacy of Simeprevir in Sub-Populations of Patients (Abstract 1092)

In the pivotal Phase 3 PROMISE study, 79% of treatment-experienced HCV patients treated with simeprevir in combination with pegylated interferon and ribavirin who previously experienced a relapse after prior treatment with pegylated interferon-based therapy achieved the primary endpoint of SVR12 compared to 37% of patients treated with placebo plus pegylated interferon and ribavirin. In this sub-analysis, among patients considered difficult to treat, 65% of patients with the IL28B TT genotype, 74% of patients with a METAVIR score of F4 and 70% of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 19%, 26% and 28% of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 47% of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 30% of patients treated with placebo in combination with pegylated interferon and ribavirin. The most common adverse events in patients treated with simeprevir combined with pegylated interferon and ribavirin in the first 12 weeks were fatigue, headache and influenza-like illness.

"The data presented at AASLD offers further evidence of simeprevir’s efficacy in difficult to treat patient types," said Dr Maria Beumont, medical lead for simeprevir, Janssen. "Following the recent positive vote from the FDA’s Antiviral Drugs Advisory Committee to recommend approval of simeprevir, we look forward to making simeprevir available to patients living with chronic HCV in need of treatment in the near future, while we continue to evaluate the role of simeprevir as part of different HCV treatment combinations."

About Simeprevir

Simeprevir (TMC435) is a new generation NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, currently in Phase III development. Simeprevir works by blocking the viral protease enzyme that enables HCV to replicate in host cells. To date, more than 3,700 patients have been treated with simeprevir in clinical trials. UK/HCV/1113/0021 Page 3

Janssen Therapeutics EMEA, a division of Janssen Pharmaceutica NV has the commercialisation rights of simeprevir in Europe, Middle East & Africa. Medivir AB will commercialise the product in the Nordic countries.

In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate Phase 2 studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company’s non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.

For additional information about simeprevir clinical studies, please visit: https://www.clinicaltrialsregister.eu or www.clinicaltrials.gov.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver that affects approximately 150 million people worldwide, and causes 350,000 deaths annually.2 In the European region alone the incidence rate is 8.7 per 100,000 and leads to 86,000 deaths annually.1

When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure. It is the leading cause of primary liver cancers in Europe.3

About Janssen R&D Ireland

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world.

Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

Janssen Therapeutics EMEA is fully dedicated to HCV and simeprevir. Janssen-Cilag International NV is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit www.janssen-emea.com and www.janssentherapeutics-emea.com for more information. UK/HCV/1113/0021 Page 4

References

1. World Health Organisation Regional Office for Europe. Hepatitis data and statistics. http://www.euro.who.int/en/health-topics/communicable-diseases/hepatitis/data-and-statistics . Last accessed October 2013.

2. World Health Organisation Media Centre: Hepatitis C Fact Sheet No. 164; July 2013.

http://www.who.int/mediacentre/factsheets/fs164/en/ . Last accessed October 2013.

3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 2011;55:245–264.

AASLD - COSMOS study with Simeprevir and Sofosbuvir in cirrhotic and non-cirrhotic HCV genotype 1 patients

Results from the COSMOS study with Simeprevir and Sofosbuvir in cirrhotic and non-cirrhotic HCV genotype 1 patients presented at AASLD

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced data from the interferon-free COSMOS study demonstrating safety and efficacy of the investigational protease inhibitor simeprevir (TMC435) in combination with the investigational nucleotide inhibitor sofosbuvir (GS-7977), with and without ribavirin, in genotype 1 chronic hepatitis C adult patients with compensated liver disease was presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C. during the late-breaking oral session on Monday, November 4.

“The high sustained virologic response (SVR) rates seen in genotype 1 patients with prior null response and in treatment-naïve and prior null response patients with advanced liver disease, in the COSMOS study, are highly encouraging. These difficult-to-cure patient groups are in urgent need of efficacious treatment options which today are lacking” says Charlotte Edenius, EVP Development, Medivir.

COSMOS - Study Design
COSMOS is a phase IIa, randomized, open-label study investigating the safety and efficacy of simeprevir in combination with sofosbuvir, with and without ribavirin, for either 12 or 24 weeks. The study enrolled HCV genotype 1 patients who were prior null responders to treatment with interferon and ribavirin with METAVIR F0-F2 scores (cohort 1, n=80), or treatment-naïve patients and prior null responders with METAVIR F3-F4 scores (cohort 2, n=87).

Final sustained virologic response 12 weeks after the end of treatment (SVR12) data from cohort 1 in previous null responder patients with METAVIR scores F0-F2 were presented, along with sustained virologic response 4 weeks after the end of treatment (SVR4) data from the 12 week arms of cohort 2 in treatment-naïve and previous null-responder patients with METAVIR scores F3-F4. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver. Liver fibrosis is scored on a four-point scale.

In cohort 1, 77 percent of the patients had genotype 1a (GT1a) subtype with 50 percent of those having baseline Q80K polymorphism. Seventy percent had IL28B CT genotype, 24 percent had IL28B TT genotype and 59 percent had METAVIR score F2.

In cohort 2, 78 percent of patients had GT1a subtype with 40 percent of those having baseline Q80K polymorphism. Fifty-six percent had IL28B CT genotype, 23 percent had IL28B TT genotype, 47 percent had METAVIR score F4 (cirrhosis) and 54 percent were prior null responders.

COSMOS – Efficacy Summary
In cohort 1, the SVR12 rate was 93 percent in genotype 1 null-responder patients with METAVIR scores of F0-F2 treated with simeprevir and sofosbuvir for either 12 or 24 weeks.

In an interim analysis of cohort 2, the SVR4 rate was 100 percent in both genotype 1 treatment-naive patients and prior null-responder patients with METAVIR scores of F3-F4 treated with simeprevir and sofosbuvir for 12 weeks.

In a pooled analysis of the 12-week treatment arms in cohorts 1 and 2, SVR4 was achieved among patients treated with simeprevir and sofosbuvir with or without ribavirin, in 96 percent of patients with IL28B non-CC genotype, 91 and 100 percent of patients with a METAVIR score of F4, respectively, and 95 percent of prior null responders.

All patients who completed treatment were HCV RNA undetectable at end of treatment and there were no viral breakthroughs in either cohort 1 or 2. The COSMOS study interim results show no benefit from adding ribavirin to simeprevir and sofosbuvir in this difficult to treat groups of hepatitis C patients and that 12 week treatment may confer similar clinical benefit to 24 week treatment.

Efficacy results with 150 mg simeprevir (SMV) and 400 mg sofosbuvir (SOF) once daily with or without ribavirin (RBV). Intent-to-treat (ITT) population.

 

**SVR4 data was only available for 12-week arms at time of interim analysis cut-off

COSMOS - Summary Safety
The most common adverse events in both treatment arms were fatigue, headache, nausea and insomnia. Rash, itching, anemia and bilirubin increases occurred mainly in the ribavirin-containing arms of treatment. Four percent of patients (2/54) treated with simeprevir and sofosbuvir with ribavirin and 7 percent of patients (2/31) treated with simeprevir and sofosbuvir without ribavirin, respectively, discontinued treatment due to an adverse event in the 24 week arms, while no patients (0/82) in the 12 week arms discontinued treatment due to an adverse event at the time of this analysis.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292.

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 4.30 p.m. EST on 4 November 2013.

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide – including approximately 3.2 million people in the United States – and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Simeprevir
Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and its affiliated companies and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the viral protease enzyme that enables the hepatitis C virus to replicate in host cells.

Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except for the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these Nordic countries under the marketing authorization held by Janssen-Cilag International NV.

On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend approval of the new drug application filed by Janssen Research & Development, LLC for simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C virus (HCV) in adult patients with compensated liver disease. Simeprevir was approved on September 27, 2013 in Japan for the treatment of genotype 1 hepatitis C. A Marketing Authorisation Application was submitted in April to the European Medicines Agency (EMA) by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C.

Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. To date, more than 43,700 patients have been treated with simeprevir in clinical trials.

In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in phase II development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate phase II studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company’s non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.

About Sofosbuvir
Sofosbuvir (formerly referred to as GS-7977) is a once-daily nucleotide analog polymerase inhibitor for the treatment of HCV infection being developed by Gilead Sciences, Inc. Sofosbuvir is being evaluated as part of multiple therapeutic regimens, including programs with RBV alone and in combination with peg-IFN and RBV.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Related:

Simeprevir + sofosbuvir produces high sustained response rates for hard-to-treat patients in COSMOS trial

By Liz Highleyman

Produced in collaboration with hivandhepatitis.com

Published: 05 November 2013

 

A 12-week all-oral combination of simeprevir plus sofosbuvir led to sustained virological response in 93% of genotype 1 prior null responders with mild-to-moderate liver fibrosis, working as well as a longer course of treatment or triple therapy including ribavirin, according to late-breaking findings from the COSMOS trial presented yesterday at 'The Liver Meeting 2013', the 64th annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC.

The study also showed that 100% of treatment-naive patients and null responders with advanced fibrosis or cirrhosis achieved early sustained response at 4 weeks post-treatment using the same dual regimen.

Continue Reading @ NAM

AASLD-Janssen Will Present New Data For Simeprevir In Genotype 1 Hepatitis C Patients W-compensated Liver Disease

Simeprevir Administered Once Daily as Part of Combination Therapy Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patients 

Janssen announced today the presentation of new data for simeprevir in genotype 1 chronic hepatitis C patients with compensated liver disease at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC. These data include analyses of simeprevir in the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, including patients with the IL28B TT genotype and METAVIR scores of F4. This follows last week's unanimous vote by the FDA's Antiviral Drugs Advisory Committee to recommend approval of simeprevir.
 
Data from the Phase 2a COSMOS study of simeprevir administered once daily with Gilead's investigational nucleotide inhibitor sofosbuvir, with and without ribavirin, in genotype 1 chronic hepatitis C adult patients with compensated liver disease will also be presented during a late-breaking oral session on Monday, November 4.
 
Simeprevir Administered Once Daily as Part of Combination Therapy Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patients
 
WASHINGTON (Nov. 2, 2013) -- Janssen R&D Ireland (Janssen) today announced the presentation of new data at The Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC for the investigational protease inhibitor simeprevir (TMC435) in the treatment of genotype 1 chronic hepatitis C in treatment-naïve and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, the efficacy of simeprevir was observed in hepatitis C patients, including patients with the IL28BTT genotype and METAVIR scores of F4.
 
"Patients with certain baseline characteristics can be more likely to fail or relapse after prior treatment," said Ira Jacobson, M.D., simeprevir clinical trial investigator, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center. "The breadth of simeprevir data presented at AASLD reinforce its potential as a treatment option for patients and will offer important guidance to physicians once simeprevir is approved."
 
On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend approval of the new drug application filed by Janssen Research & Development, LLC for simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C virus (HCV) in adult patients with compensated liver disease.
 
Pooled Analysis from QUEST-1 and QUEST-2 Confirms Clinical Benefit of Simeprevir in Sub-Populations of Patients (Abstract 1122)
In a pooled analysis of the Phase 3 QUEST-1 and QUEST-2 studies, 80 percent of treatment-naïve patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 50 percent of patients treated with placebo plus pegylated interferon and ribavirin. The pooled analysis found that 61 percent of patients with the IL28B TT genotype, 60 percent of patients with a METAVIR score of F4 and 75 percent of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 21 percent, 34 percent and 47 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 58 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 52 percent of patients treated with placebo in combination with pegylated interferon and ribavirin, but the difference was not statistically significant.
 
Eight percent and 10 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin experienced on-treatment failure and relapse, respectively, compared to 33 percent and 15 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively. Three percent of patients treated with simeprevir discontinued treatment early due to an adverse event compared to two percent of patients treated with placebo.
 
Analysis from PROMISE Reinforces Efficacy of Simeprevir in Sub-Populations of Patients (Abstract 1092)
In the pivotal Phase 3 PROMISE study, 79 percent of treatment-experienced hepatitis C patients treated with simeprevir in combination with pegylated interferon and ribavirin who previously experienced a relapse after prior treatment with pegylated interferon-based therapy achieved the primary endpoint of SVR12 compared to 37 percent of patients treated with placebo plus pegylated interferon and ribavirin. In this sub-analysis, 65 percent of patients with the IL28B TT genotype, 74 percent of patients with a METAVIR score of F4 and 70 percent of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 19 percent, 26 percent and 28 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively.Among patients with the genotype 1a Q80K polymorphism at baseline, 47 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 30 percent of patients treated with placebo in combination with pegylated interferon and ribavirin.
 
The most common adverse events in patients treated with simeprevir combined with pegylated interferon and ribavirin in the first 12 weeks were fatigue, headache and influenza-like illness. Three percent and 18 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin experienced on-treatment failure and relapse, respectively, compared to 27 percent and 34 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively.
 
"We are very proud of the depth and breadth of our clinical trial program," said Gaston Picchio, Disease Area Leader Hepatitis, Janssen Research & Development. "Following last week's positive vote from the FDA's Antiviral Drugs Advisory Committee to recommend approval of simeprevir, we look forward to making simeprevir available to patients living with chronic HCV."
 
About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide - including approximately 3.2 million people in the United States - and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.
 
About Simeprevir
Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and its affiliated companies and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the viral protease enzyme that enables the hepatitis C virus to replicate in host cells.
 
Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except for the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these Nordic countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved on September 27, 2013 in Japan for the treatment of genotype 1 hepatitis C and a Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C.
 
Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.
 
In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate Phase 2 studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company's non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.
 
For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.
 
About Janssen R&D Ireland
 
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information. #
 
###
Craig Stoltz
Director, Product Communication
Global Pharmaceuticals Communication & Public Affairs
 
Janssen Global Services, LLC
Phone 609-730-2823
Fax 609-730-3770
Mobile 215-779-9396
cstoltz@its.jnj.com

Cocktails of new oral antiviral drugs to fight hepatitis C have aced clinical trials

Improved treatments offer hope for eradication of viral liver infection

Sara Reardon           

30 October 2013

For decades, people with hepatitis C virus (HCV) have had to endure gruelling treatment regimens that include injections of the drug interferon, which can cause severe nausea and depression. But with the imminent approval of several highly effective oral antiviral drugs, and more on the way, researchers say that eradicating the infection worldwide is now a realistic goal.

Unlike previous HCV treatments, which sought to enhance the immune system with interferon and other drugs, the latest group of oral medications interferes with the virus's ability to replicate and make proteins. A US Food and Drug Administration (FDA) board recommended two such drugs - simeprevir, made by Johnson & Johnson in New Brunswick, New Jersey,  and sofosbuvir from Gilead Sciences in Foster City, California - for approval last week. When each is taken in combination with a drug called ribavirin, the treatment eliminates hepatitis C in around 80% of people.

"This is the first time in the history of humankind that we have a cure for a viral disease," says pharmacologist Raymond Schinazi of Emory University in Atlanta, Georgia.

Findings from trials of different drug combinations are set to be released this week. A phase II study called COSMOS tested a combination of sofosbuvir and simeprevir in 197 people with HCV who had either not responded to interferon or who had advanced liver fibrosis caused by the virus. After 12 weeks of treatment, the drugs completely cleared the virus in more than 90% of participants.

Another study, led by physician Kazuaki Chayama at Hiroshima University in Japan, treated 220 people with a combination of daclatasvir and asunaprevir, two new drugs from Bristol-Myers Squibb in New York. The cocktail cured 85% of participants. Eric Hughes, lead global medical researcher at the company, says that it plans to submit the drugs for FDA approval in 2014.
 

Stopped short
Despite such encouraging results, larger studies of drug combinations involving multiple drug companies seem to be unlikely. Charlotte Edenius, vice-president of development at Medivir, a drug company in Stockholm that collaborated with Johnson & Johnson on the COSMOS study, says that Gilead and Johnson & Johnson do not plan to work together for a phase III trial. Similarly, a Bristol-Myers Squibb spokesperson says the company has no plans to collaborate with Gilead on larger trials of a combined sofosbuvir daclatasvir therapy, despite a phase II trial completed earlier this year in which the drug pairing cured all 41 participants.

Even without phase III trials or FDA approval for this approach, David Thomas, a hepatitis C researcher at Johns Hopkins University in Baltimore, Maryland, expects that some physicians will begin prescribing such combinations 'off-label' for difficult-to-treat cases.

And, he says, the impressive cure rates achieved in clinical trials suggest that potent drug combinations could eradicate HCV worldwide - at least in theory. The virus does not have an animal reservoir, meaning that it is not harboured by other animals, and it is not easily spread between people, except through blood. Improved screening of blood supplies used for transfusions and better patient-screening techniques have already greatly cut transmission rates over the last 15 years. Emergence of drug-resistant virus strains could be a hurdle, adds Thomas, but they might be rare because the latest antiviral drugs are so potent in combination.

 

Price problem
Hepatologist Rajender Reddy at the University of Pennsylvania in Philadelphia sees a second stumbling block: getting such treatments to people who need them. Many of the roughly 170 million people worldwide who carry hepatitis C will not be able to afford the drugs, he says. There is also little incentive for drug companies to lower costs - unlike antiviral therapies for HIV, which must be taken for a patient's lifetime, HCV treatment is given for only 12 weeks. Identifying HCV carriers is also challenging, because most people do not know that they have the disease until they develop severe cirrhosis or liver cancer - sometimes decades after being infected.  Mandatory screening of at-risk populations such as the elderly and drug users would need to be a major part of an eradication effort, says virologist Charles Rice of Rockefeller University in New York. Crucial too is education to prevent people from contracting the disease in the first place. Even the most effective oral drugs do not raise a lasting immune response against the virus, and people can be reinfected. That is why the search for a preventative HCV vaccine continues, with the most promising ones currently in phase II clinical trials. "Even if we have all the drugs we need - which is still an open question - it will be decades, if not a century, before it's gone," says Rice.

 

http://www.nature.com/news/united-states-to-approve-potent-oral-drugs-for-hepatitis-c-1.14059

FDA panel unanimously backs Gilead's hepatitis C drug sofosbuvir

The FDA Antiviral Drugs Advisory Committee  reviewed  Gilead's Sofosbuvir on October 25 and Johnson & Johnson's Simeprevir on October 24.  Both drugs have won support from the committee for approval by U.S. health regulators. The FDA is scheduled to decide whether to approve sofosbuvir by Dec. 8, and simeprevir by Nov. 27.

Panel recommends FDA approve sofosbuvir for hepatitis C

Oct 25

The FDA’s Antiviral Drugs Advisory Committee today recommended approval of sofosbuvir, a first-in-class, once-daily oral nucleotide inhibitor from Gilead Sciences, for treatment of chronic hepatitis C virus genotypes 1, 2, 3 and 4.

The panel voted unanimously and enthusiastically in support of approving sofosbuvir in combination with ribavirin for treatment of HCV GT 2 and 3 in adult patients.

“This is a game-changer,” committee member Marc G. Ghany, MD, MHSc, staff physician with the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases, said.

The panel also voted 15-0 but offered more reservations in support of approving sofosbuvir in combination with pegylated interferon and ribavirin (PR) for treatment of HCV GT 1 and 4 in treatment-naive patients.

“I was hesitant to give approval for a one-arm study,” committee member Dean Follmann, PhD, chief, biostatistics research branch, National Institute of Allergy and Infectious Diseases, said. “The 90% success rate is what really made me comfortable with this.”

The votes followed a discussion on a series of phase 3 studies of a sofosbuvir-based regimen, generally of 12 to 16 weeks, that demonstrated similar or superior effectiveness to current treatment options at primary endpoint of sustained virologic response (SVR) at 12 weeks.

The committee also discussed, but did not vote, on whether evidence supported sofosbuvir in combination with PR for treatment of chronic hepatitis C in patients with GT 1 infection who are nonresponders to a prior course of PR.

Studies did not directly analyze this patient population, but the FDA presented extrapolated data that suggested about 75% of treatment-experienced patients might respond positively to the therapy.

Several committee members expressed concern over the lack of real data, while others suggested it was a risk worth taking.

Thomas P. Giordano, MD, MPH, associate professor of medicine at Baylor College of Medicine, questioned whether voicing approval was appropriate.

“Clinicians are going to do what they have to do to take care of their patients, but the agency’s responsibility is at a different level,” he said.

On the discussion of whether evidence supported use of sofosbuvir in combination with ribavirin in hepatocellular carcinoma patients meeting Milan criteria awaiting liver transplantation, panel Chairman Yoshihiko Murata, MD, PhD, division of infectious diseases, University of Rochester School of Medicine and Dentistry, said there was a consensus among the panel on the need to treat this population.

“It’s work in progress, but it’s work that has to be done,” Donald J. Alcendor, PhD, associate professor, department of microbiology and immunology at Meharry Medical College, said.
Source - Healio

FDA Advisory Committee Supports Approval of Gilead's Sofosbuvir for Chronic Hepatitis C Infection

Date(s): 25-Oct-2013 4:43 PM

- Final FDA Decision on Sofosbuvir Anticipated by December 8, 2013

FOSTER CITY, Calif.--(BUSINESS WIRE)--Oct. 25, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has voted unanimously (15-0) that the available data support approval of the once-daily nucleotide analogue sofosbuvir in combination with ribavirin for the treatment of chronic hepatitis C in adult patients with genotype 2 and 3 infection. Committee members also voted unanimously (15-0) that the available data support approval of sofosbuvir in combination with pegylated interferon and ribavirin for the treatment of chronic hepatitis C in treatment-naïve adult patients with genotype 1 and 4 infection.

   
The recommendations of the Advisory Committee are not binding, but will be considered by FDA as the agency completes its review of Gilead's New Drug Application (NDA) for sofosbuvir. Gilead submitted the NDA on April 8, 2013 and was granted a priority review. The FDA also granted sofosbuvir a Breakthrough Therapy designation. The FDA grants Breakthrough Therapy designation and priority review status to drug candidates that may offer major advances in treatment over existing options. A target review date of December 8, 2013 has been set under the Prescription Drug User Fee Act (PDUFA). Applications for marketing approval of sofosbuvir are also pending in the European Union, Australia, Canada, New Zealand, Switzerland and Turkey.
   
The sofosbuvir NDA is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, in which 12 or 16 weeks of sofosbuvir-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). During the review, data from an additional Phase 3 study, VALENCE, were filed to the NDA. In this study, patients with genotype 3 HCV infection were treated with sofosbuvir and ribavirin for 24 weeks. Patients who achieve SVR12 are considered cured of HCV.
   
About Sofosbuvir
Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sofosbuvir is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Sofosbuvir is an investigational product and its safety and efficacy have not been established.
   
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 worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.
   
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 FDA, EMA and other regulatory agencies may not approve sofosbuvir in the currently anticipated timelines or at all, and that any marketing approvals, if granted, may have significant limitations on their use. In addition, future studies of sofosbuvir, including in combination with other products, may not produce favorable results. Further, even if approved, Gilead may not be able to successfully commercialize sofosbuvir, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. 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 Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2013, 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.

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.
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FDA panel unanimously backs Gilead's hepatitis C drug sofosbuvir

By Toni Clarke

WASHINGTON Oct 25 (Reuters) - A federal advisory panel recommended on Friday that the U.S. Food and Drug Administration approve Gilead Sciences Inc's experimental hepatitis C drug sofosbuvir, paving the way for a treatment that is more effective than current therapies and takes less time.

The FDA advisory panel voted 15 to 0 in favor of approval of the drug in patients with two variants of the liver-damaging disease - genotype 2 and genotype 3 - in combination with an existing treatment, ribavirin.

If approved, it will be the first all-oral treatment for genotypes 2 and 3, obviating the need for the injectable drug interferon, which can cause debilitating side effects. Panelists called the vote "historic" and a "game-changer."

"Our patients have been waiting for this for a long time," said Dr. Curt Hagedorn, chief of medicine service at the Central Arkansas Veterans Healthcare Service.

The panel also voted unanimously to approve the drug in patients with genotype 1 and genotype 4 variants in combination with ribavirin and interferon in patients who have not received prior therapy.
Genotype 1 accounts for roughly 70 percent of hepatitis C cases. The FDA is not bound to follow the advice of its panels but typically does so.

"We'd already built in 100 percent chance of approval into our valuation for the company," said Karen Andersen, an analyst at Morningstar. "Gilead is still really in the prime position looking ahead in the hepatitis C market."

Panelists also appeared to support the use of sofosbuvir in patients who failed prior treatment, even though the company has little hard data to support such a claim.
"I did think there was a surprise upside result by the end of the panel," said Michael Yee, an analyst at RBC Capital Markets.

Bristol-Myers Squibb Co and Abbvie Inc have advanced all-oral clinical trial programs in late-stage development, using a variety of so-called direct acting antivirals, which directly interfere with the virus's ability to replicate. But Gilead is widely seen to be in the lead.

Chronic hepatitis C affects at least 3 million people in the United States, according to the U.S. Centers for Disease Control.

Analysts on average expect Gilead's drug to generate sales of $1.73 billion in 2014, according to Thomson Reuters data.

Current standard treatments for genotype 1 often include a protease inhibitor. These are oral drugs that include Merck & Co Inc's Victrelis and Vertex Inc's Incivek.
Gilead acquired sofosbuvir, known as a nucleotide analogue inhibitor, with its $11 billion purchase of Pharmasset Inc in 2012.

Panelists urged Gilead to make the drug available to other companies to study in combination with other oral regimens waiting in the wings.
Bristol-Myers is expected to present data from a late-stage clinical trial of its interferon-free treatment of genotype 1 patients at next month's meeting of the American Association for the Study of Liver Diseases in Washington, D.C.

The FDA is due to rule on whether to approve the drug by Dec. 8.
http://www.reuters.com/article/2013/10/25/gilead-hepatitisc-idUSL1N0IF1JN20131025

Hepatitis C: CHMP Backs 'Compassionate Use' of Sofosbuvir

Miriam E. Tucker

The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) has issued a "compassionate use" opinion for Gilead Sciences Inc's antiviral drug sofosbuvir in patients who have chronic hepatitis C virus (HCV) infection and who are awaiting a liver transplant or have already received one.

This is the third time the CHMP has used the compassionate use designation for a drug. Set up at the national level, compassionate use programs aim to give patients with life-threatening, chronic, or seriously disabling disease who do not have other treatment options access to drugs that are still under development or consideration and that have not yet been authorized for wider use.

Sofosbuvir, an NS5B polymerase inhibitor, is currently under evaluation by the EMA for wider use in patients with chronic HCV. In the meantime, Sweden had requested a CHMP opinion for use of the antiviral in combination with other agents specifically in patients before or after liver transplantation.

In the United States, sofosbuvir is being discussed today at a US Food and Drug Administration advisory committee hearing for the treatment of chronic HCV infection in combination with other agents in adult patients with genotypes 1 to 6 and/or adult patients awaiting liver transplantation.

HCV infection occurs in 0.4% to 3.5% of the population in different EU member states and is the most common single cause of liver transplantation in the European Union. There is currently no standard therapy for patients with chronic HCV who are awaiting transplantation or who have already received a liver transplant, and there are no approved treatments for most of these patients.

"Many patients with HCV infection in the pre- and post-transplant setting are therefore in urgent medical need of therapy to prevent graft reinfection or to treat recurrent HCV infection in the graft," the EMA said in a statement.

The CHMP opinion is intended to ensure a common approach for member states that are considering setting up a compassionate use program. It is not mandatory. An assessment report and conditions of use of sofosbuvir in this setting will be published shortly on the agency's Web site, the EMA says.
Medscape Medical News

FDA Panel Backs HCV Drugs

Published: Oct 25, 2013

By Michael Smith, North American Correspondent, MedPage Today

An FDA committee has unanimously supported approval of both simeprevir and sofosbuvir, drugs that act directly against hepatitis C (HCV).

The Antiviral Drugs Advisory Committee voted 19-0 to recommend approval of simeprevir, in combination with pegylated interferon and ribavirin, as suitable for treatment of patients with genotype 1 HCV.

The committee voted 15-0 to support approval of sofosbuvir in combination with ribavirin for treatment of patients with genotype 2 and 3 HCV.
And, by the same margin, the committee supported approval of the drug, in combination with pegylated interferon and ribavirin, for patients with genotype 1 and 4 infection.
If the agency agrees with the advice, simeprevir and sofosbuvir will be the first new HCV drugs approved since 2011.

The FDA is not bound to take the advisory committee's advice but usually does so.
The two drugs are the first in an anticipated wave of second-generation, direct-acting agents for the disease, which chronically afflicts about 3.2 million Americans.

For years, the standard therapy for hepatitis C was a combination of pegylated interferon-alfa and ribavirin, drugs that are regarded as both difficult and dangerous to take.
In 2011, the FDA approved the first agents that act directly against the virus itself -- the protease inhibitors boceprevir (Victrelis) and telaprevir (Incivek).

Simeprevir, another protease inhibitor, would be the third drug in the class, while sofosbuvir -- a nucleotide analog NS5B polymerase inhibitor -- would be the first in its class to get the nod.
The simeprevir application was based on efficacy results from three placebo-controlled phase III trials, two in treatment-naive patients and one in patients who had relapsed after interferon-based therapy.

In all three trials, the primary endpoint was the proportion of patients with undetectable virus 12 weeks after the end of therapy -- the so-called SVR₁₂.
Among treatment-naive patients, the SVR₁₂ rate was 80% among those getting all three drugs and 50% among those in the control group, who got placebo along with interferon and ribavirin.
Among relapsers, the SVR₁₂ rates were 79% in the simeprevir group and 36% among placebo patients.

In genotypes 2 and 3, regarded as relatively easy to treat, the sofosbuvir application was based on several studies of the drug in combination with ribavirin, a general anti-viral medication.
In some cases, the study evaluated efficacy over different treatment durations, while in others, the combination was compared with placebo or peginterferon and ribavirin.
An open-label trial evaluated the drug in patients with other genotypes, including the difficult-to-treat genotype 1, using sofosbuvir in combination with ribavirin and peginterferon, an immune system booster.

FDA reviewers, summarizing the data for genotypes 2 and 3 in briefing documents before the advisory committee meeting, said the combination of sofosbuvir and ribavirin was both efficacious and safe and would be the first all-oral, interferon-free treatment for HCV, if approved.

As well as efficacy, the combination offers a shorter treatment duration and improved safety profile compared with interferon-based regimens, the current standard of care, the reviewers concluded.
On the other hand, sofosbuvir appeared to offer better efficacy in patients with genotype 2 than in those with genotype 3, they noted.

It would also address an unmet need -- therapy for patients ineligible for, intolerant of, or unwilling to take interferon-based regimens.

Among those with HCV genotypes 1 and 4, the reviewers argued, sofosbuvir plus pegylated interferon and ribavirin would offer increased efficacy and shorter treatment than currently approved regimens.

But the available data were not sufficient to make definite dosing recommendations for patients with genotypes 5 or 6, the reviewers concluded.
Source

Related Links:

Download FDA Review Information For Sofosbuvir And Simeprevir.

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FDA Revised Draft Guidance on Hepatitis C Drug Development
The US Food and Drug Administration (FDA) released a new guidance document on 16 October 2013 detailing its preferred methods of developing applications in support of drugs to treat chronic infections caused by the hepatitis C virus.

Simeprevir - FDA Advisers Unanimously Back J&J Hepatitis C Drug

FDA Advisers Unanimously Back J&J Hepatitis C Drug


SILVER SPRING, Md. October 24, 2013 (AP)
By MATTHEW PERRONE AP Health Writer

An experimental hepatitis C drug from Johnson & Johnson has won unanimous support from government advisers who say the medication should be approved to treat patients infected with the liver-destroying virus.

All 19 members of the Food and Drug Administration's panel of virus experts voted in favor of approving J&J's simeprevir, a daily pill designed to eliminate the most common form of hepatitis C.

The FDA is not required to follow the group's recommendations, though it often does. A decision on the drug is expected next month.

Roughly 3.2 million people in the U.S. have hepatitis C, a blood-borne disease that causes liver damage and is blamed for 15,000 deaths a year. J&J is one of a half-dozen companies working to develop more effective treatments for the virus as it threatens to become a major health epidemic among baby boomers and middle-age Americans.

"We clearly need better drugs and the evidence is strong that this is a better drug," said panelist Dr. Curt Hagedorn of the Central Arkansas Veterans Healthcare Service.

New Brunswick, N.J.-based J&J is seeking approval to combine its pill with the long-established drug cocktail used to treat the most common form of the virus.

Despite the unanimous vote Thursday, the panel's endorsement came with a number of conditions.

The panelists stressed that the drug is less effective in patients with a common genetic mutation called Q80K, and that people with the abnormality should be screened out so they can receive other drugs. The group also said the drug's label should warn patients and doctors that sunburn is a common side effect. Finally, panelists said that the FDA should require J&J to conduct additional studies of the drug's effectiveness in minorities, especially African-Americans who are disproportionately infected.

"They shouldn't have any trouble finding these patients in the U.S.," said panelist Dr. Marc Ghany of the National Institutes of Health, noting that the company's research has overwhelmingly involved white patients.

The FDA meeting comes as federal health officials urge all baby boomers to get tested for the virus, which can go unnoticed for decades before causing symptoms. People born between 1945 and 1965 are five times more likely to have the virus than people of other age groups. Many of them contracted the virus by sharing needles or having sex with an infected person in their youth. The disease was also spread by blood transfusions before 1992, when blood banks began testing for the virus.

For the last 20 years, the standard treatment for hepatitis C has involved a grueling one-year regimen of pills and injections. These two antiviral drugs, known as ribavirin and interferon-alpha, cause flu-like side effects including nausea, diarrhea and muscle achiness. The introduction of new drugs from Merck and Vertex Pharmaceuticals in 2011 helped shorten the treatment period and boost cure rates as high as 75 percent.

J&J's simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of patients who had not previously been treated for the disease, according to studies submitted to the FDA. More significantly, the drug helped most patients cut the amount of time they had to take the traditional drug cocktail, with its unpleasant side effects, to six months rather than one year. Additionally, panelists said the drug's once-a-day dosage should be far more manageable for patients than the current drugs from Merck and Vertex, which require taking 12 pills or six pills a day, respectively.

"Reducing exposure to interferon and ribavirin is a wonderful thing, especially with a drug that is easier to take than the other options," said Dr. Demetre Daskalakis, associate professor at Mt. Sinai School of Medicine in New York.

On Friday the same panel of experts will review another experimental hepatitis C drug from Gilead Sciences Inc. Many analysts expect the drug, known as sofosbuvir, to become the leading treatment for the disease, based on research showing it cures 90 percent of patients with the most common form of hepatitis C in 12 weeks.

http://abcnews.go.com/Health/wireStory/fda-advisers-unanimously-back-jj-hepatitis-drug-20673544


FDA Advisory Committee recommends approval of Simeprevir for combination treatment of genotype 1 chronic hepatitis C in adult patients

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced that the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) voted 19 to 0 to recommend approval of the investigational protease inhibitor simeprevir (TMC435) 150 mg capsules administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis. The Advisory Committee recommended the approval of simeprevir based on analyses of data from clinical trials in patients who are treatment-naïve or who have failed previous interferon-based therapy.

”The recommendation from the Advisory Committee is indeed a very positive event for Medivir and we hope that it will lead to a rapid approval of simeprevir by the FDA”, said Maris Hartmanis, Medivir’s CEO.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292.

About Simeprevir
Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, for the treatment of genotype 1 and genotype 4 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells.

Janssen R&D Ireland, and its affiliated companies, are responsible for the global clinical development of simeprevir and have acquired exclusive, worldwide marketing rights, except for the Nordic countries where Medivir AB have retained the marketing rights under the marketing authorization held by Janssen-Cilag International NV.

Simeprevir was approved in Japan in September 2013 for the treatment of genotype 1 hepatitis C. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide – including approximately 3.2 million people in the United States – and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com
  
Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people’s health and quality of life.

Janssen’s Simeprevir: Hep C Patients Hope It Is Worth the Wait

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Specialty Pharmacy News

Janssen's Simeprevir: Hep C Patients Hope It Is Worth the Wait
Randi Hernandez, MS, Associate Editor/Online
Published Online: Monday, July 8, 2013

Recent actions by the FDA to accelerate simeprevir’s journey to market may be instrumental in helping close the treatment gap for genotype 1 hepatitis C patients in need.

The hepatitis C (HCV) patient population is incredibly complex and diverse. Patients with genotype 1 chronic HCV—especially patients who have relapsed after prior interferon-based treatment—can be particularly difficult to cure.

The current standard of care for genotype 1 chronic HCV involves treatment with pegylated interferon and ribavirin plus a protease inhibitor, but a number of new agents in the pipeline have been creating a great deal of buzz in the HCV community. In fact, many physicians are encouraging their HCV patients to defer treatment (a practice known as “warehousing”) until these new, potentially more effective drugs are approved by the FDA.

These investigational agents reportedly have fewer side effects than the interferon-based therapies and appear to produce significantly higher sustained virologic response (SVR) rates in clinical trials. In addition, most of the new therapies can be taken orally. Before 2011, all HCV treatments required weekly injections.

If these new interferon-free medications are approved, their impact could be widespread. Indeed, uptake of the new therapies is expected to quadruple spending on HCV over the next 3 years, according to a recent drug trend forecast from Express Scripts.

Simeprevir, a protease inhibitor developed by Janssen and Medivir, is 1 of the prospective agents that has been creating a stir in the HCV community The FDA recently granted the drug priority review, which may accelerate its journey to market and help close the treatment gap for patients in need. Janssen is seeking approval for simeprevir administered once daily along with pegylated interferon and ribavirin to treat adult patients with genotype 1 chronic HCV with compensated liver disease.

Janssen’s HCV clinical development program has investigated simeprevir’s potential use in a number of different treatment combinations and HCV patient populations. Specialty Pharmacy Times recently corresponded with Gaston Picchio, hepatitis disease area leader at Janssen, to learn more about the development of simeprevir.
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SPT: What is novel about simeprevir?

GP: Currently available protease inhibitors are administered 3 times daily in the United States and 2 or 3 times daily in the European Union. If simeprevir is approved by the FDA, it would offer the option of a protease inhibitor–based regimen that includes simeprevir taken once daily for 12 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin.

SPT: How does simeprevir compare with other protease inhibitors already on the market in terms of sustained virologic response?

GP: Simeprevir has not been investigated in a head-to-head study with other PIs already on the market.

In the QUEST-1 and QUEST-2 Phase 3 trials, the use of simeprevir led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 80% and 81%, respectively, of treatment-naïve genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin. In the PROMISE Phase 3 trial, the use of simeprevir led to SVR12 in 79% of treatment-experienced genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin.

SPT: What is the anticipated FDA approval date for simeprevir? Will the drug’s Priority Review status affect this date?

GP: On March 28, 2013, Janssen announced it had submitted a New Drug Application (NDA) to FDA seeking approval for simeprevir with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients. In May, the FDA granted Priority Review to the NDA for simeprevir.

Under the Prescription Drug User Fee Act, FDA review will begin approximately 60 days after receipt of the application and will aim to be complete within 6 months from when the review period begins, which for simeprevir is expected to be in late November.

SPT: Tell us something about the drug that may not have been included in the press releases from Janssen that you think is important to note.

GP: Simeprevir is being studied in combination with several direct-acting antiviral agents with different mechanisms of action, with and without ribavirin, as part of multiple interferon-free regimens. These include:

1. The Phase 2 COSMOS study of simeprevir and Gilead’s nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naïve and previous null-responder genotype 1 HCV patients, including patients with cirrhosis;
2. A Phase 2 study of simeprevir and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir in treatment-naïve and previous null-responder genotype 1 HCV patients; and
3. A Phase 2a trial of simeprevir and TMC647055, Janssen R&D Ireland’s non-nucleoside polymerase inhibitor, with and without ribavirin in treatment-naïve genotype 1a and 1b HCV patients.

SPT: Were pegylated interferon and ribavirin added to therapy in both of the QUEST trials and the PROMISE trial?

GP: In QUEST-1, QUEST-2, and PROMISE, patients were randomized to receive one 150 mg capsule of simeprevir or placebo once daily plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin alone for either 12 or 36 weeks based on response-guided therapy.

SPT: NDAs were submitted in both United States and Japan for simeprevir. What factors went into filing in these 2 areas in particular?

GP: In February, Janssen submitted a regulatory application to Japanese authorities for approval of simeprevir administered with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C patients who are treatment-naïve, prior non-responders, or relapsed following treatment with pegylated interferon with or without ribavirin. This was the first worldwide regulatory application for simeprevir.

In March, Janssen submitted a New Drug Application to the FDA seeking approval of simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of adult patients with genotype 1 chronic HCV with compensated liver disease.

Additionally, in April, Janssen submitted a Marketing Authorisation Application to the European Medicines Agency seeking approval for simeprevir administered as 1 capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 or genotype 4 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis), with or without HIV-1 co-infection, who are treatment-naïve or who have failed previous interferon-based therapy.

SPT: It has been said that simeprevir treatment will be part of an “interferon-free regimen.” Could you please explain what this means and the benefit of not using an interferon regimen to treat HCV?

GP: As a result of the complexity and diversity of the patient population, a proportion of patients with HCV do not tolerate interferon-containing regimens. Therefore, physicians need multiple treatment options, including interferon-free ones, in order to provide their patients the best possible chance at successful therapy - See more at: http://www.specialtypharmacytimes.com/news/Janssens-Simeprevir-Hep-C-Patients-Hope-It-Is-Worth-the-Wait#sthash.Mf8mjPeR.dpuf