November 7, 2014

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

-- Studies focused on patients where there is a high unmet need today or anticipated in the near future --

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

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

The Janssen HCV clinical development program includes studies that investigate the use of simeprevir in several interferon-free regimens using selected combinations of direct-acting antivirals with different mechanisms of action targeting diverse patient populations. These studies are focused on potentially offering alternative and more immediate treatment options for physicians and patients where there is a high unmet need today or anticipated in the near future. Ongoing clinical studies include:

  • Phase 3 OPTIMIST studies examining the safety and efficacy of simeprevir and the nucleotide analog NS5B polymerase inhibitor sofosbuvir without interferon or ribavirin for the treatment of chronic HCV infection for treatment-naïve and treatment-experienced patients with and without cirrhosis.
  • Phase 2 IMPACT study evaluating the efficacy, safety and pharmacokinetics of simeprevir administered once daily in combination with sofosbuvir and the NS5A replication complex inhibitor daclatasvir in treatment-naïve and treatment-experienced patients with HCV genotype 1 and 4 infection and decompensated liver disease.

With the closing of the acquisition of Alios Biopharma, Inc. earlier today, Janssen now holds a platform of nucleotide analog polymerase inhibitors, the early-clinical stage compounds AL-335 and AL-516. 

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

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

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

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about OLYSIO®?

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

What should I tell my healthcare provider before taking OLYSIO®?

Before taking OLYSIO®, tell your healthcare provider if you:

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

What are the possible side effects of OLYSIO®?

  • The most common side effects in combination with Peg-IFN-alfa and RBV are skin rash, itching and nausea.
  • The most common side effects in combination with sofosbuvir are tiredness, headache and nausea.
  • Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of OLYSIO®. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.

When taking OLYSIO® in combination with Peg-IFN-alfa and RBV, you should also read those Medication Guides. When taking OLYSIO® in combination with sofosbuvir, you should also read its Patient Information leaflet.

Please see full Prescribing Information and Patient Information for more details.  

MEDIA CONTACTS:

Daniel de Schryver
+49 173 76 89 149
ddschryv@its.jnj.com

Ronan Collins
+47 488 425 00
Rcollin5@its.jnj.com

INVESTOR RELATIONS:
Stan Panasewicz
+1 732 524 2524

Louise Mehrotra
+1 732 524 6491

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SOURCE Janssen R&D Ireland

RELATED LINKS
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Baylor College of Medicine News

Glenna Picton
713-798-4710
Houston, TX - Nov 7, 2014

The largest ever study of the genomes of liver tumors identified a mutation signature that contributes more to cases of the disease in Japanese males that in men of European ancestry, said an international consortium of researchers in a report online in the journal Nature Genetics.

“The novelty of this study involves associating mutation patterns with different ethnic groups,” said Dr. David Wheeler, professor in the Baylor College of Medicine Human Genome Sequencing Center and a corresponding author of the report. Researchers from the University of Tokyo, The National Cancer Center Research Institute and the National Cancer Center Hospital in Tokyo, Japan, were also colleagues on this work.

“Patients are subject to different environmental factors or they are genetically different,” said Wheeler, also a member of the NCI-designated Dan L. Duncan Cancer Center at Baylor. The profiles of the tumors were not associated with hepatitis B, hepatitis C or cirrhosis, which are known environmental factors associated with hepatocellular carcinoma (liver) cancers.

“Liver cancer occurs in males at two to five times the frequency of females,” he said.

Data from 503 liver cancer genomes derived from different populations identified 30 candidates as genes that drive the cancer and 11 cancer pathways. In addition, the collaboration of two large-scale genome projects analyzed the changes found in 608 liver cancer cases and in doing so, identified the mutational pattern associated in the disease in Japanese men, said Wheeler.

The study found more extensive mutation in the mTOR pathways than had been realized before, suggesting that drugs that inhibit that pathway might be useful. One such drug is everolimus, an anti-cancer drug used in treating kidney as well as some types of pancreatic, breast and brain cancers, might also be effective in liver cancer, said Wheeler. (The mTOR pathway is an intracellular pathway important in programmed cell death and, thus, cancer.)’

The study’s first authors include Yasushi Totoki of the Division of Cancer Genomics at the National Cancer Center Research Institute in Tokyo, Kenji Tatsuno of the Genome Science Division of the Research Center for Advanced Science and Technology at the University of Tokyo and Kyle R. Covington of the Human Genome Sequencing Center at Baylor College of Medicine. Research also took place at the National Cancer Center Hospital in Tokyo and Nihon University School of Medicine in Tokyo.

Corresponding authors include Wheeler, Dr. Hiroyuki Aburatani of the Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo and Dr. Tatsuhiro Shibata of the Division of Cancer Genomics, National Cancer Center Research Institute in Tokyo, Japan.

Funding came from Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan for the third-term Comprehensive 10-Year Strategy for Cancer Control, grants from the U.S. National Human Genome Research Institute ( 5U54HG003273) and National Cancer Institute (HHSN261201000053C), the Program for Promotion of Fundamental Studies in Health Sciences from the National Institute of Biomedical Innovation (NIBIO) and the National Cancer Center Research and Development Funds (23-A-8). The National Cancer Center Biobank is supported by the National Cancer Center Research and Development Fund, Japan. The supercomputing resource SHIROKANE was provided by the Human Genome Center at the University of Tokyo.

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New Hepatitis C Vaccine May Overcome Previous Barriers

Medscape Medical News

Lara C. Pullen, PhD

November 06, 2014

A prophylactic hepatitis C virus (HCV) vaccine produces a long-lasting, sustained T-cell response that is characteristic of the T-cell response associated with a controlled HCV infection. Researchers have evaluated the vaccine in humans, and it is now ready for phase 2 efficacy studies.

Leo Swadling, a graduate student in the Nuffield Department of Medicine at the University of Oxford in the United Kingdom, and colleagues published the results from the phase 1 trial published online November 5 in Science Translational Medicine. They described their heterologous T-cell vaccine, which combines replication-defective chimpanzee adenovirus (ChAd3) and modified vaccinia Ankara (MVA) vectors, both encoding the HCV nonstructural (NS) proteins. The vaccine is referred to as ChAd3/MVA.

T-cell immunity appears to be critical in protection against natural infection from HCV. In particular, CD4+ T cells generate the CD8+ T-cell immunity that is associated with HCV viral control in both natural infection in humans and chimpanzee challenge studies. Thus, vaccinologists anticipate that an effective HCV vaccine will generate a robust T-cell response.

The ChAd3/MVA vaccine induced a large HCV-specific T-cell response in humans. In most individuals, vaccination induced T-cell responses against all six NS antigenic pools. Vaccination also increased CD8+ T-cell polyfunctionality. The investigators found no signs that the vaccine induced regulatory T cells that might suppress an anti-HCV immune response.

Vaccinated individuals possessed antigen-experienced T cells that were on a continuum from naive to memory populations. Vaccinated individuals also generated CD8+ memory T cells. All told, the phenotype of T cells after vaccination with ChAd3/MVA resembled T-cell populations after vaccination with the highly efficacious yellow fever and smallpox vaccines.

The ChAd3/MVA vaccine appeared to be significantly better than the previously tested ChAd3/Ad6 vaccine. It elicited a higher magnitude of T-cell response immediately, as well as long term after boost immunization.

The diversity of the HCV genome represents an additional barrier to the development of protective HCV vaccine. ChAd3/MVA appears to overcome this barrier though generation of cross-reactive T-cell responses between heterologous viral genotypes.

"I am impressed by the ability of this combination of ChAd3 prime/MVA boost with the NSmut HCV sequence to recapitulate the natural human immune response to HCV infection, to sustain a strong response, and to impart some cross-reactive response to other HCV genotypes. On a public health note, development of a vaccine against HCV has traditionally been challenging and the disease burden remains significant in the US. In particular, the disease is generally asymptomatic initially but has a high probability to become chronic, leading to bad outcomes," Litjen Tan, PhD, from the Immunization Action Coalition in St. Paul, Minnesota, told Medscape Medical News.

Several authors of the study are named inventors for patent applications covering the vaccine. Dr Tan has received honoraria from Baxter, Pfizer, Novartis, Temptime Corp, TruMedSystems, and Sanofi Pasteur for service as a scientific consultant.

Sci Transl Med. Published online November 5, 2014. Abstract

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New drug for common liver disease improves liver health

For Immediate Release: Friday, November 7, 2014

An experimental drug aimed at treating a common liver disease showed promising results and potential problems in a multicenter clinical trial funded by the National Institutes of Health. The FLINT study found that people with nonalcoholic steatohepatitis (NASH) who took obeticholic acid (OCA) had improved liver health during that period, including decreased inflammation and fat in the liver and decreased body weight versus people receiving a placebo. OCA was also associated with increases in itching and total cholesterol.

“NASH is a common and potentially serious disease that currently has no approved treatment.”

—Averell Sherker, M.D.
NIDDK program official for the NASH Clinical Research Network (NASH CRN)

The findings of FLINT, or the Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment Trial, were published online Nov. 6 in The Lancet. FLINT was sponsored by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases.

“NASH is a common and potentially serious disease that currently has no approved treatment. Management typically includes weight loss through diet and exercise,” said Averell Sherker, M.D., NIDDK program official for the NASH Clinical Research Network (NASH CRN), which performed the FLINT study.

Liver health improved in 45 percent of people on OCA versus 21 percent of the placebo group. “Although obeticholic acid did not eliminate liver disease in FLINT participants, it demonstrated a promising effect. Larger studies will be required to determine the drug’s safety and efficacy,” Sherker said.

FLINT enrolled 283 people at eight centers across the country. At the study’s start, participants were 18 and older and had been diagnosed with definite or borderline NASH. They were randomly assigned to one of two groups: one took 25 milligrams of OCA daily and one received a placebo that resembled the OCA pill. The study was double-blinded, so neither participants nor investigators knew which person was in which group.

Trial investigators intended for the groups to receive the drug or placebo for 72 weeks, with an additional 24 weeks of follow-up off treatment. However, planned interim analysis for safety and efficacy showed that OCA had significant beneficial effects on NASH-related liver health.

The analysis also found unanticipated increases in total cholesterol in the OCA group. They had increased LDL cholesterol (“bad” cholesterol) and decreased HDL cholesterol (“good” cholesterol) – notable because NASH patients are already at higher risk for cardiovascular diseases. As cholesterol treatment was not standardized as part of the study, further research is needed to fully understand the potential effect of OCA on cholesterol.

Because of both factors, and with the concurrence of the Data Safety and Monitoring Board, NIDDK decided to stop treatment but continue the study, move all patients into the follow-up phase, and perform no additional liver biopsies – which carry their own risks. Adverse cholesterol increases were not sustained after stopping OCA.

“The FLINT trial represents an important advance in the search for treatments of NASH. The causes of NASH are not fully understood, and causes and treatments may be different among patients,” said the study’s lead author, Brent Neuschwander-Tetri, M.D., a professor at St. Louis University. “We need to study the changes in cholesterol levels more to know if the increases caused by obeticholic acid increase the risk of hardening of the arteries. We found that the improvement in liver enzymes with obeticholic acid were not sustained after treatment was stopped, so we would expect that treatment would need to be indefinite, much like the medications for diabetes and hypertension.”

The major feature of NASH is fat in the liver, along with inflammation and damage.  Over time, these may lead to loss of liver function, the need for liver transplantation and death. NASH may have no symptoms and can only be diagnosed with a liver biopsy. Beyond maintaining a healthy weight, people with NASH are advised to avoid alcohol and unnecessary medications. New cases of NASH have grown alongside the obesity epidemic. NASH is the third leading diagnosis requiring U.S. liver transplantation.

The FLINT trial (Clinical Trials No. NCT01265498) was supported by the NIDDK, National Cancer Institute and National Center for Advancing Translational Sciences, all part of NIH. Intercept Pharmaceuticals, Inc. provided partial funding and supplies.

The NIDDK, a component of the NIH, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans. For more information about the NIDDK and its programs, see http://www.niddk.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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