New HCV Treatments
Yesterday the FDA approved Simeprevir with what appears to be a broad indication: "It is to be used as a component of a combination antiviral treatment regimen." The PDUFA date was November 28 so it appears to be 6 days early.
The Sofosbuvir pdufa date, last day for expected approval unless the FDA delays it which it can, is December 8 and a similarly broad indication is expected.
There are several new treatment possibilities in the near future, over the next several months until 2014 when both Abbvie & Gilead are expected to submit in the 1st half of 2014 their applications to the FDA for their interferon-free regimens - which have in phase 2/3 studies so far reported 96-100% SVR rates in patients never before treated & prior Peg/Rbv null responders. FDA approval is expected soon after these submissions in 2014.
Sofosbuvir+Ribavirin for 12 or 24 weeks
Sofosbuvir+Peg/Rbv for 12 weeks
Simeprevir+Sofosbuvir (COSMOS Study)
Daclatasvir+Sofosbuvir (European agency issued recommendation on Nov 22 for a compassionate access program for these 2 drugs in combination (email sent out by NATAP a few minutes ago with this announcement)
Boehringer-Ingelheim is expected to submit an application to the FDA soon for their protease inhibitor Faldaprevir+Peg/Rbv.
AASLD: Boehringer Ingelheim - (11/18/13)
Merck presented good & promising results in a phase 2 study of their interferon-free therapy at AASLD last week with MK5172 a 2nd generation protease & MK8742 a 2nd generation NS5A:
AASLD: Merck at AASLD - (11/18/13)
AASLD: Janssen at AASLD - (11/18/13)
AASLD: Gilead at AASLD: Sofosbuvir for GT 3, 2 and 1 - (11/18/13)
AASLD: BMS at AASLD - (11/18/13)
AASLD: Abbvie at AASLD - (11/18/13)
EASL: Sustained Virologic Response With Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) in Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) or Boceprevir (BOC) - (04/27/13)
High Rate of Sustained Virologic Response With the All-Oral Combination of Daclatasvir (NS5A Inhibitor) Plus Sofosbuvir (Nucleotide NS5B Inhibitor), With or Without Ribavirin, in Treatment-Naive Patients Chronically Infected With HCV GT 1, 2, or 3 - (11/13/12)
EASL: SAFETY AND EFFICACY OF INTERFERON-FREE REGIMENS OF ABT-450/r, ABT-267, ABT-333 +/- RIBAVIRIN IN PATIENTS WITH CHRONIC HCV GT1 INFECTION: RESULTS FROM THE AVIATOR STUDY - (04/25/13)
Yesterday the EMA issued a recommendation that Daclatasvir+Sofosbuvir be made available in a compassionate access program: "intended for adult patients at a high risk of their liver being no longer able to function normally (decompensation) or death within 12 months if left untreated, and who have a genotype 1 infection. Further, it is recognised that the potential benefit of such combination therapy may extend to patients infected with other HCV genotypes"
Here are the 2 press releases from yesterday from the FDA & from Janssen. As well below is the European regulatory agency EMA's recommendation that Sofosbuvir should be approved with a similarly broad indication: 'in combination with other medicinal products for the treatment of chronic (long-term) hepatitis C in adults'. The EMA also issued 'advise' on Sofosbuvir compassionate use:
European Medicines Agency advises on compassionate use of sofosbuvir - (10/28/13)
FDA NEWS RELEASE
For Immediate Release: Nov. 22, 2013
FDA approves new treatment for hepatitis C virus
The U.S. Food and Drug Administration today approved Olysio (simeprevir), a new therapy to treat chronic hepatitis C virus infection.
Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with the hepatitis C virus have no symptoms of the disease until liver damage becomes apparent, which may take several years. Most of these people then go on to develop chronic hepatitis C. Some will also develop scarring and poor liver function (cirrhosis) over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections or liver cancer. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with the hepatitis C virus.
Olysio is a protease inhibitor that blocks a specific protein needed by the hepatitis C virus to replicate. It is to be used as a component of a combination antiviral treatment regimen. In clinical studies, Olysio was evaluated in combination with peginterferon-alfa and ribavirin, two drugs also used to treat hepatitis C virus infection. Olysio is intended for adults with compensated liver disease (a diseased liver that is still functioning), including cirrhosis, who have not received treatment for their infection (treatment naïve) or for whom previous treatment has not been effective (treatment experienced).
"Olysio is the third FDA-approved protease inhibitor to treat chronic hepatitis C virus infection, and provides health professionals and patients with a new, effective treatment for this serious disease," said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research.
In 2011, the FDA approved Victrelis (boceprevir) and Incivek (telaprevir) for the treatment of hepatitis C. Olysio was reviewed under the FDA's priority review program, which provides for an expedited review of drugs that, if approved, would provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to available therapies.
The safety and effectiveness of Olysio were evaluated in five clinical studies of 2,026 treatment-naive and treatment-experienced participants randomly assigned to receive Olysio plus peginterferon-alfa and ribavirin or placebo plus peginterferon-alfa and ribavirin. The studies were designed to measure whether a participant's hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response), suggesting a participant's infection had been cured.
Results showed 80 percent of treatment-naive participants given Olysio plus peginterferon-alfa and ribavirin achieved sustained virologic response, compared to 50 percent of participants receiving peginterferon-alfa and ribavirin alone. In one of the studies with treatment-experienced participants whose infection returned (prior relapsers), 79 percent receiving Olysio plus peginterferon-alfa and ribavirin achieved sustained virologic response compared to 37 percent of participants receiving peginterferon-alfa and ribavirin alone.
Another study examined Olysio's safety and effectiveness in treatment-experienced participants, including prior relapsers, those who partially responded to prior therapy (partial responders) and those who did not respond to prior therapy (null responders). Adding Olysio improved response rates in each of these subgroups compared to peginterferon-alfa and ribavirin alone.
A reduction in Olysio's effectiveness was observed in participants infected with the genotype 1a hepatitis C virus with an NS3 Q80K polymorphism, a strain of the hepatitis C virus commonly found in the United States. Olysio's drug label includes a recommendation to screen for the presence of the strain prior to beginning therapy and to consider alternative therapy if the strain is detected.
The most common side effects reported in clinical study participants treated with Olysio in combination with peginterferon-alfa and ribavirin were rash (including photosensitivity), itching (pruritis) and nausea. Serious photosensitivity reactions resulting in hospitalization were reported. Patients will be advised to limit sun exposure and to use sun protective measures during treatment with Olysio in combination with peginterferon alfa and ribavirin. Olysio should not be used alone to treat chronic hepatitis C infection.
Olysio is marketed by Janssen Pharmaceuticals, based in Raritan, N.J. Victrelis is marketed by Whitehouse Station, N.J.-based Merck, and Incivek is marketed by Cambridge, Mass.-based Vertex Pharmaceuticals.
OLYSIOTM (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 patientscompared 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 visitOLYSIO.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.
Please see full Prescribing Information for more details.
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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NOTE: Janssen Therapeutics, Division of Janssen Products, LP, provides support to the Hepatitis C Association for initiatives benefitting individuals living with hepatitis C.
European Medicines Agency recommends approval of sofosbuvir for the treatment of chronic hepatitis C
First-in-class medicine provides the first interferon-free treatment option
The European Medicines Agency's Committee for Medicinal Products for Human use(CHMP) has recommended granting a marketing authorisation for Sovaldi (sofosbuvir), for use 'in combination with other medicinal products for the treatment of chronic (long-term) hepatitis C in adults'.
Hepatitis C virus (HCV) infection is a major European public-health challenge. It occurs in between 0.4% and 3.5% of the population in different European Union (EU) Member States.
The current standard of care includes a combination of the medicines pegylated interferon and ribavirin, with or without an inhibitor of the viral NS3/4A protease enzyme. However, interferon-based therapies are associated with potentially serious side effects, which are sometimes difficult to manage and also make a considerable proportion of HCV patients ineligible for therapy. This includes patients with very advanced liver disease, as well as patients with psychiatric diseases, autoimmune disorders, etc. For these patients, there is a very clear unmet medical need for new HCV treatment regimens.
The treatment of hepatitis C is a rapidly moving therapeutic area, with several new classes of direct-acting antivirals now in advanced stages of development. The European Medicines Agency is actively supporting the development of these new treatment options for patients through provision of scientific advice and drafting of guidance to developers of these medicines.
Sovaldi is the first representative of a new class of antivirals that act as inhibitors of an essential enzyme of HCV, the NS5B ribonucleic acid polymerase. This medicine provides the first interferon-free treatment option for chronic hepatitis C.
In clinical trials where sofosbuvir was used in combination with ribavirin alone, it has convincingly shown efficacy with a good safety profile. A high proportion of patients had no detectable virus in their blood 12 to 24 weeks after the end of the treatment and could therefore be considered to be cured of their hepatitis C virus infection.
Furthermore, when Sovaldi is used in combination with pegylated interferon as well as ribavirin, shortened treatment duration down to 12 weeks (compared to 24-48 weeks with the current standard of care) is possible and provides high efficacy. This is of value considering the side-effect profile of interferon.
New treatment option for HCV patients undergoing liver transplantation
HCV infection is the most common single cause of liver transplantation in the EU. However, patients who do undergo liver transplantation due to hepatitis C have a worse prognosis than patients who do so for other reasons, because recurrence of the virus in the graft is near-universal and often aggressive. For many of these patients, there are currently no approved treatment options that are likely to be effective.
In clinical trials, Sovaldi in combination with ribavirin has shown its capacity to prevent reinfection of the graft, and thus provides a treatment option for patients with HCV infection who are on the waiting list for liver transplantation.
Advice on compassionate use of sofosbuvir
During its October 2013 meeting, the CHMP gave an opinion on the conditions under which early access to sofosbuvir, in combination with other medicines, could be given in compassionate-use programmes, for patients with chronic hepatitis C infection before or after liver transplantation.
Such programmes, set up at the national level, are intended to give patients with a life-threatening, long-lasting or seriously disabling disease who have no available treatment options access to treatments that are still under development and that have not yet been authorised.
During its November meeting, the CHMP also provided an opinion on the use of a combination of sofosbuvir with the antiviral daclatasvir in certain patients with chronic hepatitis C virus (HCV) infection, in a compassionate-use programme.