PRINCETON, N.J., Nov. 23, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS), a clinical stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections, today reported financial results and operational highlights for the fiscal year ended September 30, 2010. At fiscal year end Pharmasset held $127.1 million in cash and cash equivalents.
Pipeline Update and 2010 highlights
RG7128
Phase 2b PROPEL and JUMP-C trials
During February 2010, dosing in the Phase 2b PROPEL study was completed. Four hundred and eight treatment-naïve, genotypes 1 or 4 hepatitis C virus (HCV)-infected patients (cirrhotic and non-cirrhotic) were enrolled. The trial is evaluating the dose and duration of treatment of RG7128 in combination with pegylated interferon and ribavirin (SOC).
In November 2010 at the AASLD meeting, Roche presented results from a 12 week interim analysis of the PROPEL study. The results presented included:
• RG7128 1000 mg BID in combination with SOC for 12 weeks achieved a high rate of complete Early Virologic Response (cEVR; <15 IU/mL) of 83% with no on-treatment viral breakthrough
• The safety and tolerability of RG7128 1000 mg BID with SOC were comparable to placebo/SOC with no renal or hematologic safety signals, and a discontinuation rate similar to placebo/SOC
• No drug resistance was observed in 367 patients treated with up to 12 weeks of RG7128
In early May 2010, Roche completed enrollment of 168 treatment naive, genotypes 1 or 4 HCV-infected patients in its JUMP-C trial.
An amendment to the PROPEL and JUMP-C trial has been implemented by Roche which allows patients who were initially randomized to the placebo/SOC arm and who are non-responders to receive open label RG7128 1000mg BID in combination with SOC for 24 weeks, followed by an additional 24 weeks of SOC.
In addition, Roche is planning to initiate a Phase 2b study of RG7128 in combination with SOC in patients with HCV genotypes 2 or 3 during the first half of 2011. Roche is also planning to initiate a Phase 3 program for RG7128 during 2011 and plans to submit a marketing application for RG7128 to one or more regulatory authorities in 2013.
PSI-7977
In January 2010, Pharmasset initiated a 28 day phase 2a dose-finding trial with PSI-7977 in combination with SOC. The trial enrolled 63 treatment-naïve, genotype 1 HCV infected patients who received either 100mg QD, 200mg QD, 400mg QD or placebo in combination with SOC for 28 days. In May 2010, we reported interim results from the trial which demonstrated that PSI-7977 was generally safe and well tolerated, as well as exhibiting potent antiviral activity (i.e. 94% RVR with 200 mg QD in combination with SOC). All patients receiving active PSI-7977 demonstrated continuous and substantial declines in HCV RNA with no viral breakthrough during the 28 days of therapy at any dose. Final results were reported in three posters at AASLD 2010 (Abstracts 815, 806, 1861).
In August 2010, we initiated a phase 2b dose-finding trial with PSI-7977 for 12 weeks in combination with SOC. The trial is expected to enroll approximately 125 treatment naïve, genotype 1 HCV-infected patients who will receive either 200mg QD, 400mg QD or placebo in combination with SOC for 12 weeks, followed by 12 weeks or 36 weeks of SOC alone. A fourth arm has completed enrollment of 25 treatment naïve, genotypes 2 or 3 HCV infected patients who will receive 400mg QD PSI-7977 in combination with SOC for 12 weeks only. We anticipate reporting preliminary safety results from this genotype 2/3 arm in the first quarter 2011 and SVR12 in the second quarter 2011.
In August 2010, Pharmasset received fast track designation from the US Food and Drug Administration (FDA) for PSI-7977 for the treatment of chronic hepatitis C (HCV) infection.
We are planning to initiate a Phase 2b study of PSI-7977 in combination with ribavirin administered with and without pegylated interferon in early December 2010. The study is expected to enroll approximately 40 treatment-naïve patients with HCV genotypes 2 or 3 and is designed to assess SVR with limited durations of pegylated interferon.
PSI-938
In April 2010, Pharmasset initiated a phase 1 single ascending dose trial with PSI-938, a purine nucleotide analog for HCV. In July 2010, we reported that single doses of PSI-938 ranging from 100mg to 800mg, and subsequently 1600mg, were generally safe and well tolerated and that a 7 day, multiple ascending dose trial had been initiated.
In October 2010, we reported positive preliminary antiviral data with PSI-938 demonstrating a median decline in HCV RNA of between 3.94 log10 to 4.64 log10 from baseline at all doses tested (100mg QD, 200mg QD, 300mg QD, 100mg BID). For the 16 subjects who received PSI-938 200mg QD or 300mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).
We are screening patients for Part 2 of a phase 1 study that includes the first combinations of a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for the treatment of HCV. The cohorts within Part 2 are expected to evaluate PSI-938 QD, in the absence of interferon, as monotherapy and in combination with PSI-7977 QD. The primary objective of Part 2 of this study is to assess the safety, tolerability and pharmacokinetics of PSI-938 alone and in combination with PSI-7977 in the clinically-relevant setting of combination therapy for 14 days. The secondary objective of Part 2 of this study is to evaluate the short-term change in HCV RNA. Preliminary results are expected in the first quarter of 2011. Approximately forty patients are expected to be randomized into the study.
PSI-661
In October 2009, we nominated PSI-661, a purine nucleotide analog, for preclinical development. Our current plan is to submit an IND application, or its foreign equivalent, during the first quarter of 2011. We also plan to initiate a Phase 1 SAD study to assess the safety, tolerability, and pharmacokinetics of PSI-661 during the second quarter of 2011.
Financial Results
For the fiscal year ended September 30, 2010 Pharmasset reported revenues of $1.0 million, compared with revenues of $13.3 million for fiscal year 2009. The receipt of a $10.0 million milestone from Roche for the initiation of the phase 2b study with RG7128 led to higher reported revenues in fiscal year 2009.
Total costs and expenses for the fiscal year ended September 30, 2010 were $64.7 million compared to $65.9 million for the same period in 2009. The decrease in operating expenses for the fiscal year ended September 30, 2010 was primarily the result of discontinuing our clevudine program in April 2009. This reduction was mostly offset by increases in development costs for PSI-7977, PSI-938 and PSI-661.
Pharmasset reported a net loss of $66.1 million, or $2.13 per share for the fiscal year ended September 30, 2010, as compared to a net loss of $55.6 million, or $2.10 per share for the same period in 2009.
"Pharmasset had a very productive year, advancing all of its HCV clinical programs," stated Schaefer Price, President and Chief Executive Officer. "During the year, we advanced PSI-7977 through a Phase 2a trial and into a Phase 2b study in genotype 1, 2 or 3 patients. At the same time, we also reported very exciting data with our first purine nucleotide, PSI-938, and look forward to advancing this candidate into a 'nuc-nuc' combination trial this month. In 2011, Roche plans to start a Phase 3 program with RG7128 and we are anticipating reporting data throughout the year from our PSI-7977 Phase 2b trial and our 'nuc-nuc' combination trial."
Calendar Year 2011 Anticipated Milestones:
• Roche expects to initiate a phase 3 program with RG7128 in 2011
• Pharmasset expects to report 12 week safety from its ongoing phase 2b trial with PSI-7977 in genotype 2/3 patients in the first quarter 2011; SVR 12 data in the second quarter 2011
• Pharmasset expects to report the 12 week interim analysis from its PSI-7977 Phase 2b genotype 1 arms in the second quarter 2011
• Pharmasset expects to initiate a 24 week Phase 2b trial with PSI-7977 in the second quarter 2011
• Pharmasset expects to initiate Part 2 of a phase 1 study with PSI-938 alone and in combination with PSI-7977 in the fourth quarter 2010; report preliminary results during the first quarter 2011
• Pharmasset expects to initiate a phase 2 study with PSI-7977 and PSI-938 in the second quarter 2011
• Pharmasset expects to initiate an interferon sparing trial in genotype 2/3 patients with PSI-7977 in the fourth quarter 2010
• Pharmasset plans to file an IND for PSI-661 in the first quarter 2011 and to initiate a phase 1 trial in the second quarter 2011
• Roche expects to initiate a phase 2 study with RG7128 in genotype 2/3 patients in the first half 2011
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in HCV genotype 1, 2, and 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Pegasys(R) and Copegus(R) are registered trademarks of Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q for the periods ended December 31, 2009, March 31, 2010 and June 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
Source
November 24, 2010
Gilead Sciences Submits New Drug Application to U.S. FDA for Once-Daily Single-Tablet Regimen of Truvada(R) and TMC278 for HIV
- Product Would Be Second Complete Single-Tablet Antiretroviral Regimen -
FOSTER CITY, Calif., Nov 23, 2010 (BUSINESS WIRE) --
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for marketing approval of the single-tablet regimen of Truvada(R) (emtricitabine and tenofovir disoproxil fumarate) and Tibotec Pharmaceuticals' investigational non-nucleoside reverse transcriptase inhibitor TMC278 (rilpivirine hydrochloride) for HIV-1 infection in adults. If approved, this would be the second product that contains a complete HIV treatment regimen in a single once-daily tablet.
"Combination antiretroviral therapy has dramatically advanced the field of HIV medicine, but the need remains for new single-tablet regimens that are effective, safe and well tolerated," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "Gilead is committed to helping advance HIV treatment by pursuing both scientific research and innovative partnerships that will deliver more options to the healthcare community. We are pleased to work with Tibotec to bring this potentially important new therapy to people living with HIV."
On July 23, 2010, Tibotec submitted an NDA for U.S. marketing approval of TMC278 for once-daily use with other antiretroviral agents. That NDA is supported by 48-week data from two Phase III double-blind, randomized studies (ECHO and THRIVE) that evaluated the safety and efficacy of TMC278 in treatment-naive HIV-1 infected adults, the majority of whom received TMC278 in combination with Truvada. The Gilead NDA for Truvada/TMC278 is supported by a bioequivalence study conducted by Gilead demonstrating that the formulation of the single-tablet regimen achieved the same levels of medication in the blood as the component products dosed simultaneously as individual pills.
On September 3, 2010, the European marketing applications for TMC278 and for the Truvada/TMC278 single-tablet regimen were filed simultaneously by Tibotec and Gilead, respectively.
Gilead entered into a license and collaboration agreement with Tibotec for the development and commercialization of the single-tablet regimen in July 2009. Subject to regulatory approval, Gilead will assume the lead role in the manufacturing, registration, distribution and commercialization of the single-tablet regimen worldwide, excluding the developing world and Japan. Tibotec will be responsible for the commercialization of TMC278 as a stand-alone product and will hold rights to co-promote the single-tablet regimen in these territories. The companies are currently working on an agreement to make the combination product available in the developing world.
Truvada/TMC278 is an investigational product and its safety and efficacy have not yet been established.
Important Product Safety Information About Truvada
Truvada is a fixed-dose combination tablet containing 200 mg of emtricitabine (Emtriva(R)) and 300 mg of tenofovir disoproxil fumarate (Viread(R)). In the United States, Truvada is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals including Viread (tenofovir disoproxil fumarate), a component of Truvada.Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection and its safety and efficacy has not been established in patients co-infected with HBV and HIV-1.Severe acute exacerbations of hepatitis B have been reported in patients co-infected with HIV-1 and HBV who have discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HBV and HIV-1 and discontinue Truvada. If appropriate, initiation of anti-hepatitis B treatment may be warranted.
It is important for patients to be aware that anti-HIV medicines including Truvadado not cure HIV infection or AIDS and do not reduce the risk of transmitting HIV to others.
Emtricitabine and tenofovir are principally eliminated by the kidneys. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Truvada and as clinically appropriate during therapy. Routine monitoring of calculated creatinine clearance and serum phosphorous should be performed in patients at risk for renal impairment including patients who have previously experienced renal events while receiving Hepsera(R) (adefovir dipivoxil).
Dosing interval adjustment and close monitoring of renal function are recommended in all patients with creatinine clearance 30-49 ml/min. Truvada should be avoided with concurrent or recent use of a nephrotoxic agent. Truvada should not be administered with Hepsera.
Truvada should not be coadministered with Emtriva, Viread, Atripla(R) (efavirenz 600 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) or lamivudine-containing products, including Combivir(R) (lamivudine/zidovudine), Epivir(R) or Epivir-HBV(R) (lamivudine), Epzicom(R) (abacavir sulfate/lamivudine) or Trizivir(R) (abacavir sulfate/lamivudine/zidovudine). In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effect on long-term bone health and future fracture risk is unknown. BMD monitoring should be considered in patients with a history of pathologic fractures or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
Redistribution/accumulation of body fat has been observed in patients taking antiretroviral medicines. Immune Reconstitution Syndrome has been reported in patients treated with combination therapy, including Viread and Emtriva, and may necessitate further evaluation and treatment. Early virologic failure has been reported in HIV-infected patients on regimens containing only three nucleoside reverse transcriptase inhibitors. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.
Coadministration of Truvada and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events and didanosine should be discontinued if these occur. Dose reduction of didanosine should be considered, if warranted. Patients on atazanavir and lopinavir/ritonavir plus Truvada should be monitored for Truvada-associated adverse events and Truvada should be discontinued if these occur. When co-administered with Truvada, it is recommended that atazanavir be boosted with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Truvada.
The most common adverse reactions (incidence greater-than or equal to 10 percent) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams and rash.
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium. The inventors of Viread have agreed to waive their right to a royalty on sales of Viread and Truvada in the Gilead Access Program countries to ensure that the product can be offered at a no-profit price in parts of the world where the HIV/AIDS epidemic has hit the hardest.
For complete prescribing information for Truvada, visit http://www.truvada.com/.
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 America, Europe and Australia.
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 risks related to Gilead's ability to successfully commercialize the single-tablet regimen of Truvada/TMC278. For example, the FDA, European Medicines Agency or other regulatory agencies may not approve TMC278 or the single-tablet regimen of Truvada/TMC278 for the treatment of HIV-1 infection in adults, and any marketing approval, if granted, may have significant limitations on its use. Further, Gilead and Tibotec may make a strategic decision to discontinue development of the combination product 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 detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Truvada is available at http://www.truvada.com/.
U.S. full prescribing information for Atripla is available at http://www.atripla.com/.
U.S. full prescribing information for Viread is available at http://www.viread.com/.
U.S. full prescribing information for Emtriva is available at http://www.gileadhiv.com/.
U.S. full prescribing information for Hepsera is available at http://www.hepsera.com/.
Truvada, Viread, Emtriva and Hepsera are registered trademarks of Gilead Sciences, Inc.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com/ or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.Susan Hubbard, 650-522-5715 (Investors)Cara Miller, 650-522-1616 (Media)
Source
FOSTER CITY, Calif., Nov 23, 2010 (BUSINESS WIRE) --
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for marketing approval of the single-tablet regimen of Truvada(R) (emtricitabine and tenofovir disoproxil fumarate) and Tibotec Pharmaceuticals' investigational non-nucleoside reverse transcriptase inhibitor TMC278 (rilpivirine hydrochloride) for HIV-1 infection in adults. If approved, this would be the second product that contains a complete HIV treatment regimen in a single once-daily tablet.
"Combination antiretroviral therapy has dramatically advanced the field of HIV medicine, but the need remains for new single-tablet regimens that are effective, safe and well tolerated," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "Gilead is committed to helping advance HIV treatment by pursuing both scientific research and innovative partnerships that will deliver more options to the healthcare community. We are pleased to work with Tibotec to bring this potentially important new therapy to people living with HIV."
On July 23, 2010, Tibotec submitted an NDA for U.S. marketing approval of TMC278 for once-daily use with other antiretroviral agents. That NDA is supported by 48-week data from two Phase III double-blind, randomized studies (ECHO and THRIVE) that evaluated the safety and efficacy of TMC278 in treatment-naive HIV-1 infected adults, the majority of whom received TMC278 in combination with Truvada. The Gilead NDA for Truvada/TMC278 is supported by a bioequivalence study conducted by Gilead demonstrating that the formulation of the single-tablet regimen achieved the same levels of medication in the blood as the component products dosed simultaneously as individual pills.
On September 3, 2010, the European marketing applications for TMC278 and for the Truvada/TMC278 single-tablet regimen were filed simultaneously by Tibotec and Gilead, respectively.
Gilead entered into a license and collaboration agreement with Tibotec for the development and commercialization of the single-tablet regimen in July 2009. Subject to regulatory approval, Gilead will assume the lead role in the manufacturing, registration, distribution and commercialization of the single-tablet regimen worldwide, excluding the developing world and Japan. Tibotec will be responsible for the commercialization of TMC278 as a stand-alone product and will hold rights to co-promote the single-tablet regimen in these territories. The companies are currently working on an agreement to make the combination product available in the developing world.
Truvada/TMC278 is an investigational product and its safety and efficacy have not yet been established.
Important Product Safety Information About Truvada
Truvada is a fixed-dose combination tablet containing 200 mg of emtricitabine (Emtriva(R)) and 300 mg of tenofovir disoproxil fumarate (Viread(R)). In the United States, Truvada is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals including Viread (tenofovir disoproxil fumarate), a component of Truvada.Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection and its safety and efficacy has not been established in patients co-infected with HBV and HIV-1.Severe acute exacerbations of hepatitis B have been reported in patients co-infected with HIV-1 and HBV who have discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HBV and HIV-1 and discontinue Truvada. If appropriate, initiation of anti-hepatitis B treatment may be warranted.
It is important for patients to be aware that anti-HIV medicines including Truvadado not cure HIV infection or AIDS and do not reduce the risk of transmitting HIV to others.
Emtricitabine and tenofovir are principally eliminated by the kidneys. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Truvada and as clinically appropriate during therapy. Routine monitoring of calculated creatinine clearance and serum phosphorous should be performed in patients at risk for renal impairment including patients who have previously experienced renal events while receiving Hepsera(R) (adefovir dipivoxil).
Dosing interval adjustment and close monitoring of renal function are recommended in all patients with creatinine clearance 30-49 ml/min. Truvada should be avoided with concurrent or recent use of a nephrotoxic agent. Truvada should not be administered with Hepsera.
Truvada should not be coadministered with Emtriva, Viread, Atripla(R) (efavirenz 600 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) or lamivudine-containing products, including Combivir(R) (lamivudine/zidovudine), Epivir(R) or Epivir-HBV(R) (lamivudine), Epzicom(R) (abacavir sulfate/lamivudine) or Trizivir(R) (abacavir sulfate/lamivudine/zidovudine). In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effect on long-term bone health and future fracture risk is unknown. BMD monitoring should be considered in patients with a history of pathologic fractures or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
Redistribution/accumulation of body fat has been observed in patients taking antiretroviral medicines. Immune Reconstitution Syndrome has been reported in patients treated with combination therapy, including Viread and Emtriva, and may necessitate further evaluation and treatment. Early virologic failure has been reported in HIV-infected patients on regimens containing only three nucleoside reverse transcriptase inhibitors. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.
Coadministration of Truvada and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events and didanosine should be discontinued if these occur. Dose reduction of didanosine should be considered, if warranted. Patients on atazanavir and lopinavir/ritonavir plus Truvada should be monitored for Truvada-associated adverse events and Truvada should be discontinued if these occur. When co-administered with Truvada, it is recommended that atazanavir be boosted with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Truvada.
The most common adverse reactions (incidence greater-than or equal to 10 percent) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams and rash.
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium. The inventors of Viread have agreed to waive their right to a royalty on sales of Viread and Truvada in the Gilead Access Program countries to ensure that the product can be offered at a no-profit price in parts of the world where the HIV/AIDS epidemic has hit the hardest.
For complete prescribing information for Truvada, visit http://www.truvada.com/.
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 America, Europe and Australia.
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 risks related to Gilead's ability to successfully commercialize the single-tablet regimen of Truvada/TMC278. For example, the FDA, European Medicines Agency or other regulatory agencies may not approve TMC278 or the single-tablet regimen of Truvada/TMC278 for the treatment of HIV-1 infection in adults, and any marketing approval, if granted, may have significant limitations on its use. Further, Gilead and Tibotec may make a strategic decision to discontinue development of the combination product 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 detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Truvada is available at http://www.truvada.com/.
U.S. full prescribing information for Atripla is available at http://www.atripla.com/.
U.S. full prescribing information for Viread is available at http://www.viread.com/.
U.S. full prescribing information for Emtriva is available at http://www.gileadhiv.com/.
U.S. full prescribing information for Hepsera is available at http://www.hepsera.com/.
Truvada, Viread, Emtriva and Hepsera are registered trademarks of Gilead Sciences, Inc.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com/ or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.Susan Hubbard, 650-522-5715 (Investors)Cara Miller, 650-522-1616 (Media)
Source
Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: A meta-analysis of randomized controlled trials
Int J Cancer. 2010 Nov 12. [Epub ahead of print]
Zhang CH, Xu GL, Jia WD, Li JS, Ma JL, Ge YS.
Graduate School of Tianjin Medical University, Tianjin, People's Republic of China.
Abstract
Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified eleven RCTs including 1772 patients which met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients (relative risk [RR]=0.39; 95% confidence interval [CI]=0.26-0.59; p=0.000), subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR=0.44; 95% CI=0.28-0.68; p=0.000); but HCC incidence in non-responders to initial antiviral therapy did not be reduced by maintenance IFN therapy (RR=0.96; 95% CI=0.59-1.56; p=0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR=0.23; 95% CI=0.05-1.04; p=0.056). Besides, IFN did not improve 1-year overall survival of advanced HCC patients significantly (RR=1.61; 95% CI=0.96-2.69; p=0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising but its administration in other subpopulations still requires further exploration.
PMID: 21077159 [PubMed - as supplied by publisher]
Source
Zhang CH, Xu GL, Jia WD, Li JS, Ma JL, Ge YS.
Graduate School of Tianjin Medical University, Tianjin, People's Republic of China.
Abstract
Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified eleven RCTs including 1772 patients which met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients (relative risk [RR]=0.39; 95% confidence interval [CI]=0.26-0.59; p=0.000), subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR=0.44; 95% CI=0.28-0.68; p=0.000); but HCC incidence in non-responders to initial antiviral therapy did not be reduced by maintenance IFN therapy (RR=0.96; 95% CI=0.59-1.56; p=0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR=0.23; 95% CI=0.05-1.04; p=0.056). Besides, IFN did not improve 1-year overall survival of advanced HCC patients significantly (RR=1.61; 95% CI=0.96-2.69; p=0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising but its administration in other subpopulations still requires further exploration.
PMID: 21077159 [PubMed - as supplied by publisher]
Source
The Treatment of Autoimmune Hepatitis - a review of current and evolving therapies
J Gastroenterol Hepatol. 2010 Nov 15. doi: 10.1111/j.1440-1746.2010.06579.x. [Epub ahead of print]
Jothimani D, Cramp M, Mitchell J, Cross T.
The Southwest Liver Unit, Derriford Hospital, Plymouth, Devon, United Kingdom, PL6 8DH.
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune and histological parameters, and exclusion of other liver diseases. Standard therapy consists of combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil (MMF), cyclosporin (CyA), tacrolimus, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), rituximab, ursodeoxycholic acid (UDCA), rapamycin and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.
© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
PMID: 21073674 [PubMed - as supplied by publisher]
Source
Jothimani D, Cramp M, Mitchell J, Cross T.
The Southwest Liver Unit, Derriford Hospital, Plymouth, Devon, United Kingdom, PL6 8DH.
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune and histological parameters, and exclusion of other liver diseases. Standard therapy consists of combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil (MMF), cyclosporin (CyA), tacrolimus, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), rituximab, ursodeoxycholic acid (UDCA), rapamycin and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.
© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
PMID: 21073674 [PubMed - as supplied by publisher]
Source
Abnormal Liver Enzymes No Reason to Avoid Statins
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 23, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Statins are not only safe and effective for patients with liver enzyme abnormalities but also appear to improve their liver function, researchers found.
Liver test results in patients with moderately abnormal liver tests at baseline -- possibly associated with non-alcoholic fatty liver disease -- improved with statin treatment but continued to worsen on usual care without statin treatment (P<0.0001), Dimitri P. Mikhailidis, MD, of University College London, and colleagues reported online in The Lancet.
Their retrospective analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) trial showed a greater statin effect on cardiovascular risk reduction in these high-risk patients than in those with normal liver tests (P=0.0074).
The findings add to evidence that should render liver tests irrelevant when prescribing statins, Ted Bader, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City, argued in an accompanying commentary.
"Statin-induced hepatotoxicity is a myth," he wrote in Lancet.
About 10% of patients see liver enzymes rise after starting a statin, which can exceed the threshold of three times the upper limit of normal for 1%, but these eventually return to normal even when continuing the same statin, Bader noted.
His group reported a small pilot study in 2007 that actually suggested a liver function boost on statin treatment for patients with chronic hepatitis C infection.
Yet reluctance to start statins in patients with out-of-range alanine aminotransferase (ALT) levels, and discontinuation of statins for ALT increases, might keep statins from 10% to 30% of those who need them, he estimated.
The language of package inserts is likely to blame for the misperception that statins cause liver disease, according to Bader. He encouraged drug companies to request label modification for all the statins.
"Although most patients [in the trial] took atorvastatin, there is no reason to believe that other statins would behave differently," Bader wrote in the commentary.
The single-center, prospective GREACE trial originally compared statin treatment with usual care (which could include a statin) with regard to survival effects in 1,600 patients with coronary artery disease. Study participants were under age 75, had serum concentrations of LDL cholesterol over 2.6 mmol/L, and had triglycerides under 4.5 mmol/L.
The post-hoc analysis included the 437 patients in the study with moderately abnormal ALT, asparte aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) concentrations at baseline, all believed to be due to fatty liver or non-alcoholic steatohepatitis (NASH) since alcohol misuse and other liver diseases were excluded.
Of these participants, 227 received a statin, predominantly 24 mg daily of atorvastatin (Lipitor), in the trial.
The main analysis showed that statin treatment reduced the risk of first occurrence of any cardiovascular event -- defined as death from any cause or from coronary heart disease as well as nonfatal myocardial infarction, revascularization, unstable angina, congestive heart failure, and stroke.
Overall in the trial, statins were associated with a lower cardiovascular event rate (13% or 4.2 per 100 patient-years versus 25% or 8.3 per 100 patient-years) for a 49% relative risk reduction compared with the usual care group (P<0.0001).
The post-hoc analysis showed that the patients with abnormal liver tests gained proportionately more from statin treatment.
Among participants with abnormal liver tests, statins reduced the risk of a first cardiovascular event by a relative 68% compared with usual care (10% or 3.2 per 100 patient-years versus 30% or 10.0 per 100 patient-years, P<0.0001).
By comparison, statins produced a 39% relative risk reduction among patients with normal liver tests (14% or 4.6 per 100 patient-years versus 23% or 7.6 per 100 patient-years, P<0.0001).
The reason for the greater benefit might be the elevated cardiovascular risk of patients with nonalcoholic fatty liver disease, the researchers speculated.
In the overall study, liver enzyme concentration increases on statins led to dose reductions in three of 880 patients. Less than 1% (seven of 880) withdrew from the study because of liver-related adverse effects attributed to statin treatment.
No patients required liver biopsy because of elevated liver enzymes or developed an increase in bilirubin to more than 34.2 μmol/L or alkaline phosphatase concentrations to more than twice the upper limit of normal.
Estimated glomerular filtration rates (eGFRs) actually rose by the end of the study in statin-treated patients compared with the others (P<0.0001).
The researchers cautioned that their study was faced by the same limitations characteristic of post-hoc analyses generally, and the small number of patients with liver test abnormalities in the study.
Whether the results generalize to patients with more than moderately elevated liver test results still needs to be established, they added.
The researchers reported having no conflicts of interest to disclose but noted that some of the authors have attended conferences, given lectures, and participated in advisory boards or trials sponsored by various pharmaceutical companies.
Bader reported sharing a patent application with the University of Oklahoma for use of statins in viral hepatitis.
Primary source: The Lancet
Source reference:
Athyros VG, et al "Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis" Lancet 2010; DOI: 10.1016/S0140-6736(10)61272-X.
Additional source: The Lancet
Source reference:
Bader T "Liver tests are irrelevant when prescribing statins" Lancet 2010; DOI: 10.1016/S0140-6736(10)62142-3.
Source
Published: November 23, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Statins are not only safe and effective for patients with liver enzyme abnormalities but also appear to improve their liver function, researchers found.
Liver test results in patients with moderately abnormal liver tests at baseline -- possibly associated with non-alcoholic fatty liver disease -- improved with statin treatment but continued to worsen on usual care without statin treatment (P<0.0001), Dimitri P. Mikhailidis, MD, of University College London, and colleagues reported online in The Lancet.
Their retrospective analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) trial showed a greater statin effect on cardiovascular risk reduction in these high-risk patients than in those with normal liver tests (P=0.0074).
The findings add to evidence that should render liver tests irrelevant when prescribing statins, Ted Bader, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City, argued in an accompanying commentary.
"Statin-induced hepatotoxicity is a myth," he wrote in Lancet.
About 10% of patients see liver enzymes rise after starting a statin, which can exceed the threshold of three times the upper limit of normal for 1%, but these eventually return to normal even when continuing the same statin, Bader noted.
His group reported a small pilot study in 2007 that actually suggested a liver function boost on statin treatment for patients with chronic hepatitis C infection.
Yet reluctance to start statins in patients with out-of-range alanine aminotransferase (ALT) levels, and discontinuation of statins for ALT increases, might keep statins from 10% to 30% of those who need them, he estimated.
The language of package inserts is likely to blame for the misperception that statins cause liver disease, according to Bader. He encouraged drug companies to request label modification for all the statins.
"Although most patients [in the trial] took atorvastatin, there is no reason to believe that other statins would behave differently," Bader wrote in the commentary.
The single-center, prospective GREACE trial originally compared statin treatment with usual care (which could include a statin) with regard to survival effects in 1,600 patients with coronary artery disease. Study participants were under age 75, had serum concentrations of LDL cholesterol over 2.6 mmol/L, and had triglycerides under 4.5 mmol/L.
The post-hoc analysis included the 437 patients in the study with moderately abnormal ALT, asparte aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) concentrations at baseline, all believed to be due to fatty liver or non-alcoholic steatohepatitis (NASH) since alcohol misuse and other liver diseases were excluded.
Of these participants, 227 received a statin, predominantly 24 mg daily of atorvastatin (Lipitor), in the trial.
The main analysis showed that statin treatment reduced the risk of first occurrence of any cardiovascular event -- defined as death from any cause or from coronary heart disease as well as nonfatal myocardial infarction, revascularization, unstable angina, congestive heart failure, and stroke.
Overall in the trial, statins were associated with a lower cardiovascular event rate (13% or 4.2 per 100 patient-years versus 25% or 8.3 per 100 patient-years) for a 49% relative risk reduction compared with the usual care group (P<0.0001).
The post-hoc analysis showed that the patients with abnormal liver tests gained proportionately more from statin treatment.
Among participants with abnormal liver tests, statins reduced the risk of a first cardiovascular event by a relative 68% compared with usual care (10% or 3.2 per 100 patient-years versus 30% or 10.0 per 100 patient-years, P<0.0001).
By comparison, statins produced a 39% relative risk reduction among patients with normal liver tests (14% or 4.6 per 100 patient-years versus 23% or 7.6 per 100 patient-years, P<0.0001).
The reason for the greater benefit might be the elevated cardiovascular risk of patients with nonalcoholic fatty liver disease, the researchers speculated.
In the overall study, liver enzyme concentration increases on statins led to dose reductions in three of 880 patients. Less than 1% (seven of 880) withdrew from the study because of liver-related adverse effects attributed to statin treatment.
No patients required liver biopsy because of elevated liver enzymes or developed an increase in bilirubin to more than 34.2 μmol/L or alkaline phosphatase concentrations to more than twice the upper limit of normal.
Estimated glomerular filtration rates (eGFRs) actually rose by the end of the study in statin-treated patients compared with the others (P<0.0001).
The researchers cautioned that their study was faced by the same limitations characteristic of post-hoc analyses generally, and the small number of patients with liver test abnormalities in the study.
Whether the results generalize to patients with more than moderately elevated liver test results still needs to be established, they added.
The researchers reported having no conflicts of interest to disclose but noted that some of the authors have attended conferences, given lectures, and participated in advisory boards or trials sponsored by various pharmaceutical companies.
Bader reported sharing a patent application with the University of Oklahoma for use of statins in viral hepatitis.
Primary source: The Lancet
Source reference:
Athyros VG, et al "Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis" Lancet 2010; DOI: 10.1016/S0140-6736(10)61272-X.
Additional source: The Lancet
Source reference:
Bader T "Liver tests are irrelevant when prescribing statins" Lancet 2010; DOI: 10.1016/S0140-6736(10)62142-3.
Source
Hepatitis C Treatment: New Drug Application by Vertex Pharmaceuticals
Hepatitis C is bound to receive another treatment, as Vertex Pharmaceuticals Inc (NASDAQ:VRTX) just submitted Telaprevir to regulatory approval. The new drug application was submitted to the US Food and Drug Administration to reduce the FDA’s review time from 10 months to six months. After a 15-year effort to change the way hepatitis C is treated, the new drug is expected to increase chances for a viral cure to millions of people. Vertex Pharmaceuticals Inc., a small molecule drug developer, is looking for this priority review as to offer a better alternative to the 48-week course of interferon and ribavirin.
This comes at the same time with global drug giant Merck & Co. developing their own hepatitis C drug candidate that could compete with telaprevir for the same market. The investigational compound VX-950, or Telaprevir, attacks the enzyme protease, which aids replication of the hepatitis C virus. It is being developed by Vertex, along with Tibotec Pharma and Mitsubishi Tanabe Pharma. Vertex had begun submitting completed sections of the NDA to the FDA on a rolling basis around the middle of 2010.
The company’s application is based primarily on a trio of Phase III clinical trials that enrolled more than 2,000 patients. One trial showed that the new drug, in addition to standard meds, was able to essentially cure three-fourths of patients getting their initial round of therapy for hepatitis C infections. The second study showed that the drug could shorten the standard treatment time by half. A third trial proved the new treatment could cure two-thirds of patients who failed to respond to a prior round of therapy. Taken together, Vertex hopes the body of evidence in this application will pave the way for a completely new treatment strategy that will roughly double the cure rate of the existing regimen, while requiring patients to put up with fewer of the nasty flu-like symptoms implied by the current standard of care.
Safety and tolerability data were consistent across the three trials for the new drug, with mild-to-moderate rash and anemia being the more common adverse effects in the telaprevir trials.
With 6 million patients in the U.S. and Europe have hepatitis C, out of an estimated 170 million worldwide. Provided that Vertex gets the FDA approval, it will be the first major product for this company founded in 1989, which has accumulated a deficit of $3.26 billion through the end of September. If Vertex wins market clearance in 2011, the payoff could come relatively quickly. U.S. sales alone could amount more than $2 billion after a couple years because of the pent-up demand built for the drug during the clinical trial process, analysts say. Vertex’s market valuation yesterday was about $7 billion, based mostly on the projected value of this new treatment for hepatitis C. VRTC closed Monday’s trading at $34.25 on a volume of 1.65 million shares.
Source
Also See: Vertex Completes New Drug Application for Telaprevir for Hepatitis C
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