Healthcare Industry News:  Viread 

Biopharmacetuicals HIV/AIDS

 News Release - February 16, 2007

Merck & Co., Inc. (1) To Distribute ATRIPLA(TM) in Developing Countries

New once-daily, single tablet combination regimen may simplify HIV treatment and care Not-for-profit price to poorest countries and those hardest hit by HIV/AIDS

WHITEHOUSE STATION, N.J.--(HSMN NewsFeed)--Merck & Co., Inc. today announced that it has begun to file registrations for ATRIPLA(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg), a once-daily, single tablet regimen for the treatment of HIV-1 infection in adults, with health authorities in those developing countries around the world where many HIV-positive people live.

Merck began to file registrations for ATRIPLA in November 2006 (beginning with Ethiopia). ATRIPLA will be filed in 45 countries in the Middle East & Africa and an additional nine countries in Latin America, the Caribbean and Asia Pacific through the first half of 2007. Its availability to patients in these countries will depend on the pace of national regulatory processes. In an additional 11 countries, ATRIPLA can be imported based on the U.S. registration. Merck is also pursuing an application for WHO pre-qualification.

"This new single-tablet regimen, which can simplify HIV treatment for people living with HIV infection, exemplifies our mission of putting patients first," said Merck Chief Executive Officer and President Richard T. Clark. "Merck has long been a leader in efforts to broaden access to medicines and vaccines around the world. We look forward to collaborating with Gilead and national health authorities to deliver ATRIPLA to those who need it most as quickly as possible."

"Fixed dose combination drugs (FDCs) have revolutionized antiretroviral therapy in the developing world and brought treatment to millions," said Professor Sir Richard G. A. Feachem, Executive Director, The Global Fund to Fight AIDS, TB and Malaria. "ATRIPLA is a valuable addition to the FDC armory and requires only one pill per day. It is also the first triple drug FDC for HIV/AIDS developed by a consortium of originator companies. Merck and Gilead are to be congratulated on bringing to the market this new weapon in the fight against HIV/AIDS in developing countries."

ATRIPLA pricing in developing countries

For countries in the Low Human Development Index (HDI) category and countries in the Medium HDI category, with adult HIV prevalence of 1% or greater, ATRIPLA will be available to all purchasers at a price of US $1.68 per tablet, or US $50.40 per pack (ex-manufacturer). Sixty-seven countries are eligible for this pricing. For countries in the Medium HDI with adult HIV prevalence of less than 1%, ATRIPLA will be available to all purchasers at a price of US $2.83, or US $84.90 per pack (ex-manufacturer). Twenty-two countries are in this category.

Background on ATRIPLA

ATRIPLA contains 600 mg of efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate, both nucleoside reverse transcriptase inhibitors (NRTIs). Efavirenz is marketed by Merck under the tradename STOCRIN® in all territories outside of the United States, Canada and certain European countries (where it is commercialized by Bristol-Myers Squibb under the tradename Sustiva®). Emtricitabine and tenofovir disoproxil fumarate are commercialized by Gilead Sciences under the tradenames Emtriva® and Viread®, respectively. The compounds are commonly prescribed together as a once-daily, fixed-dose tablet, marketed under the tradename Truvada®.

ATRIPLA was approved by the U.S. Food and Drug Administration (FDA) on July 12, 2006. ATRIPLA was developed through a collaboration between Bristol-Myers Squibb and Gilead. In the United States, the product is commercialized by Bristol-Myers Squibb and Gilead Sciences through a joint venture between the companies. The FDA also granted approval of an alternate tradedress of ATRIPLA for developing countries, where ATRIPLA will be made available as a white-colored tablet to distinguish it from the salmon-colored version currently available in the United States.

Gilead and Merck reached agreement in August 2006 to work together to pursue registration of the product with individual country health authorities in the developing world. The component therapies are already registered, or in the process of being registered, in many of these countries. Under the terms of the agreement, Gilead will manufacture ATRIPLA using efavirenz supplied by Merck. Merck in turn will handle distribution of the product in the countries covered by the agreement. Discussions on distribution of ATRIPLA in Europe and the rest of the world continue among Merck, Gilead and Bristol-Myers Squibb.

Important Safety Information About ATRIPLA, Truvada, Viread and Emtriva

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. ATRIPLA, Truvada, Viread and Emtriva are not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of these drugs have not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Emtriva or Viread (components of ATRIPLA and Truvada). Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue ATRIPLA, Truvada, Emtriva or Viread and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Additional Important Information About ATRIPLA

ATRIPLA is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.

It is important for patients to be aware that ATRIPLA does not cure HIV infection or AIDS. ATRIPLA has not been shown to reduce the risk of transmission of HIV to others through sexual contact or blood contamination.

ATRIPLA is not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of ATRIPLA have not been established in patients coinfected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Emtriva or Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue ATRIPLA and are coinfected HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

ATRIPLA is contraindicated for use with astemizole, bepridil, cisapride, midazolam, pimozide, triazolam, ergot derivatives, or voriconazole. Concomitant use of ATRIPLA and St. John's wort (Hypericum perforatum) or St. John's wort-containing products is not recommended. Since ATRIPLA contains efavirenz, emtricitabine and tenofovir disoproxil fumarate, it should not be coadministered with efavirenz, Emtriva, Viread, or Truvada. Due to similarities between emtricitabine and lamivudine, ATRIPLA should not be coadministered with drugs containing lamivudine, including Combivir, Epivir®, Epivir-HBV®, EpzicomTM, or Trizivir®.

Serious psychiatric adverse experiences, including severe depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%) and manic reactions (0.2%) have been reported in patients treated with efavirenz. In addition to efavirenz, factors identified in a clinical study that were associated with an increase in psychiatric symptoms included a history of injection drug use, psychiatric history and use of psychiatric medication. There have been occasional reports of suicide, delusions, and psychosis-like behavior, but it could not be determined if efavirenz was the cause. Patients with serious psychiatric adverse experiences should be evaluated immediately to determine whether the risks of continued therapy outweigh the benefits. Fifty-three percent of patients reported central nervous system symptoms including dizziness (28.1%), insomnia (16.3%), impaired concentration (8.3%), somnolence (7.0%), abnormal dreams (6.2%) and hallucinations (1.2%) when taking efavirenz compared to 25% of patients receiving control regimens. These symptoms usually begin during the first or second day of therapy and generally resolve after the first two to four weeks of therapy; they were severe in 2.0% of patients and 2.1% of patients discontinued therapy. After four weeks of therapy, the prevalence of central nervous system symptoms of at least moderate severity ranged from 5% to 9% in patients treated with regimens containing efavirenz. Nervous system symptoms are not predictive of the less frequent psychiatric symptoms.

ATRIPLA should not be given to patients with creatinine clearance below 50 mL/min. 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 tenofovir disoproxil fumarate, most often in patients with underlying systemic or renal disease, or in patients taking concomitant nephrotoxic agents. Some cases have occurred in patients with no identified risk factors. ATRIPLA should be avoided with concurrent or recent use of a nephrotoxic agent.

ATRIPLA may cause fetal harm when administered during the first trimester to a pregnant woman. Women should not become pregnant or breastfeed while taking ATRIPLA. Barrier contraception must always be used in combination with other methods of contraception such as oral or other hormonal contraceptives. If the patient becomes pregnant while taking ATRIPLA, she should be apprised of the potential harm to the fetus.

Mild to moderate rash is a common side effect of efavirenz. In controlled clinical trials, 26% of patients treated with efavirenz experienced new-onset skin rash compared with 17% of patients treated in control groups. Skin discoloration, associated with emtricitabine, may also occur. ATRIPLA should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. Liver enzymes should be monitored in patients with known or suspected hepatitis B or C and when ATRIPLA is administered with ritonavir or other medications associated with liver toxicity. Decreases in bone mineral density have been seen with tenofovir disoproxil fumarate. Use ATRIPLA with caution in patients with a history of seizures. Convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history of seizures. Redistribution and/or accumulation of body fat have been observed in patients receiving antiretroviral therapy. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of ATRIPLA.

Saquinavir should not be used as the only protease inhibitor in combination with ATRIPLA. Coadministration of ATRIPLA and atazanavir is not recommended due to concerns regarding decreased atazanavir concentrations. Atazanavir and lopinavir/ritonavir have been shown to increase tenofovir concentrations. Patients on lopinavir/ritonavir plus ATRIPLA should be monitored for tenofovir-associated adverse events. ATRIPLA should be discontinued in patients who develop tenofovir-associated adverse events. Coadministration of ATRIPLA and didanosine should be undertaken with caution. Patients receiving this combination should be monitored closely for didanosine-associated adverse events. See full prescribing information for complete list of drug-drug interactions.

In a large controlled clinical trial (Study 934), adverse events observed in greater than or equal to 5% of patients in the Viread/Emtriva/efavirenz group include dizziness, nausea, diarrhea, fatigue, headache, and rash, sinusitis, depression, insomnia, and abnormal dreams.

The dose of ATRIPLA is one tablet once daily taken orally on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms. ATRIPLA is not recommended for use in patients younger than 18 years of age.

Important Information About Efavirenz

Efavirenz in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on two clinical trials of at least one year duration that demonstrated prolonged suppression of HIV RNA.

Coadministration with astemizole, cisapride, midazolam, triazolam, ergot derivatives, or voriconazole is contraindicated. Concomitant use of efavirenz and St. John's wort (Hypericum perforatum) or St. John's wort-containing products is not recommended. This list of medications is not complete. Coadministration of efavirenz with ATRIPLA is not recommended, since efavirenz is one of its active ingredients.

Serious psychiatric adverse experiences, including severe depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%) and manic reactions (0.2%) have been reported in patients treated with efavirenz. In addition to efavirenz, factors identified in a clinical study that were associated with an increase in psychiatric symptoms included history of injection drug use, psychiatric history, and use of psychiatric medication. There have been occasional reports of suicide, delusions, and psychosis-like behavior, but it could not be determined if efavirenz was the cause. Patients with serious psychiatric adverse experiences should be evaluated immediately to determine whether the risks of continued therapy outweigh the benefits. Fifty-three percent of patients reported central nervous system symptoms including dizziness (28.1%), insomnia (16.3%), impaired concentration (8.3%), somnolence (7.0%), abnormal dreams (6.2%) and hallucinations (1.2%) when taking efavirenz compared to 25% of patients receiving control regimens. These symptoms usually begin during Days 1-2 of therapy and generally resolve after the first 2-4 weeks of therapy; they were severe in 2.0% of patients and 2.1% of patients discontinued therapy. After four weeks of therapy, the prevalence of central nervous system symptoms of at least moderate severity ranged from 5% to 9% in patients treated with regimens containing efavirenz. Nervous system symptoms are not predictive of the less frequent serious psychiatric symptoms.

Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Women should not become pregnant or breastfeed while taking efavirenz. Barrier contraception must always be used in combination with other methods of contraception (e.g. oral or other hormonal contraceptives). If the patient becomes pregnant while taking efavirenz, she should be apprised of the potential harm to the fetus.

Mild to moderate rash is a common side effect of efavirenz. In controlled clinical trials, 26% of patients treated with efavirenz experienced new-onset skin rash compared with 17% of patients treated in control groups. Efavirenz should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. Rash is more common and often more severe in pediatric patients.

Liver enzymes should be monitored in patients with known or suspected hepatitis B or C, in patients treated with other medications associated with liver toxicity, and when efavirenz is administered with ritonavir. Use efavirenz with caution in patients with a history of seizures. Convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history of seizures. Redistribution and/or accumulation of body fat have been seen in patients receiving antiretroviral therapy. A causal relationship has not been established. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including efavirenz.

Saquinavir should not be used as the only protease inhibitor in combination with efavirenz.

The most common adverse events (greater than or equal to 5%) observed in clinical studies with efavirenz include fatigue, pain, dizziness, headache, insomnia, impaired concentration, nausea, vomiting, diarrhea, depression, rash, and pruritis.

It is recommended that efavirenz be taken on an empty stomach, preferably at bedtime. The increased concentrations following administration of efavirenz with food may lead to an increase in frequency of adverse events. Dosing at bedtime may improve the tolerability of nervous system symptoms.

Additional Important Information About Truvada

Truvada is a fixed-dose combination product that combines 200 mg of Emtriva® and 300 mg of Viread in one tablet, taken once a day. 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. Truvada should not be coadministered with Emtriva, Viread or lamivudine-containing products and it is not recommended that Truvada be used as a component of a triple nucleoside regimen. In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.

Clinical Study 934 supports the use of Truvada tablets for the treatment of HIV-1 infection. Additional data in support of the use of Truvada are derived from Study 903, in which Viread and lamivudine were used in combination in treatment-naive adults, and clinical Study 303, in which Emtriva and lamivudine demonstrated comparable efficacy, safety and resistance patterns as part of multidrug regimens.

No drug interaction studies have been conducted using Truvada. Drug interactions have been observed when didanosine, atazanavir, or lopinavir/ritonavir are co-administered with Viread, a component of Truvada, and dose adjustments may be necessary. Data are not available to recommend a dose adjustment of didanosine for patients weighing less than 60 kg. Patients on atazanavir or lopinavir/ritonavir plus Truvada should be monitored for Truvada-associated adverse events that may require discontinuation. When co-administered with Truvada, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Truvada.

Four-hundred and forty-seven HIV-1 infected patients have received combination therapy with Emtriva and Viread with either a non-nucleoside reverse transcriptase inhibitor (Study 934) or protease inhibitor for 48 weeks in clinical studies. Adverse events observed in Study 934 were generally consistent with those seen in other studies in treatment-experienced or treatment-naive patients receiving Viread and/or Emtriva. Adverse events observed in more than 5% of patients in the Viread/Emtriva group in Study 934 include diarrhea, nausea, fatigue, headache, dizziness and rash.

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported among patients taking Viread, a component of Truvada (emtricitabine and tenofovir disoproxil fumarate). Renal impairment occurred most often in patients with underlying systemic or renal disease or in patients taking concomitant nephrotoxic agents, though some cases have appeared in patients without identified risk factors. Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. Redistribution and/or accumulation of body fat have been observed in patients receiving antiretroviral therapy. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy including Truvada, Viread and Emtriva.

The effects of Viread-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Skin discoloration, manifested by hyperpigmentation on the palms and/or soles, has been reported with the use of Emtriva, a component of Truvada. Skin discoloration was generally mild and asymptomatic and its mechanism and clinical significance are unknown.

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.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but also help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

Full prescribing information for ATRIPLA is available at www.atripla.com.

Full prescribing information for STOCRIN is available at http://www.emea.eu.int/humandocs/Humans/EPAR/Stocrin/Stocrin.htm

Full prescribing information for Truvada, Viread and Emtriva is available at www.gilead.com.

Full prescribing information for Sustiva is available at www.Sustiva.com.

ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.

STOCRIN is a registered trademark of Merck & Co., Inc.

Truvada, Viread and Emtriva are registered trademarks of Gilead Sciences, Inc.

Sustiva is a registered trademark of Bristol-Myers Squibb Pharma Company.

(1) Merck & Co., Inc., Whitehouse Station, NJ, USA, is known in most countries outside of the United States as Merck Sharp & Dohme, or MSD.


Source: Merck

Issuer of this News Release is solely responsible for its content.
Please address inquiries directly to the issuing company.



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