Healthcare Industry News: tenofovir
News Release - August 1, 2008
Gilead Sciences and Merck & Co., Inc. Enter Into an Agreement to Register and Distribute HIV Medication Atripla(R) (Efavirenz 600 mg/ Emtricitabine 200 mg/ Tenofovir Disoproxil Fumarate 300 mg) in Twelve CountriesAgreement Includes Countries in Latin America and the Asia-Pacific Region
Under Agreement, Gilead Will Lead Regulatory and Distribution Processes
FOSTER CITY, Calif. & WHITEHOUSE STATION, N.J.--(HSMN NewsFeed)--Gilead Sciences, Inc. (Nasdaq:GILD ) and Merck & Co., Inc. (NYSE:MRK ) today announced that the companies have entered into an agreement through which Gilead will assume the lead role for the distribution of Atripla® (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) in 12 countries located primarily in Latin America and the Asia-Pacific region.
Atripla is the first once-daily single tablet regimen for HIV. It contains three HIV medicines: efavirenz, emtricitabine and tenofovir disoproxil fumarate. Efavirenz is marketed by Merck under the tradename Stocrin® in some territories outside of the United States, Canada and certain European countries. Emtricitabine and tenofovir disoproxil fumarate are commercialized by Gilead Sciences under the tradenames Emtriva® and Viread®, respectively, and together as the fixed-dose combination Truvada®.
Under the terms of the agreement, Gilead will assume the lead role in the registration, manufacturing and distribution of Atripla in Argentina, Australia, Chile, Hong Kong, Israel, Mexico, New Zealand, Russia, Taiwan, Thailand, Turkey and Uruguay. The companies will make Atripla available in the 12 countries covered by this agreement as rapidly as feasible, and will share the revenues and costs associated with registering and distributing the product. Going forward, additional countries may be added to this new agreement by mutual consent.
“This new agreement reflects Gilead’s ongoing commitment to ensuring global access to the first and only single tablet regimen for the treatment of HIV,” said Kevin Young, Executive Vice President, Commercial Operations, Gilead Sciences. “Gilead has established an international infrastructure of wholly-owned operations and distributor partnerships that will allow us to advance the registration and distribution of Atripla. We are pleased to extend our partnership with Merck to further progress toward our shared goal of expanding access for patients in need.”
With today’s announcement, 138 countries are now covered under agreements between Gilead and Merck or Bristol-Myers Squibb. In August 2006, Gilead and Merck entered into an agreement under which Merck distributes Atripla at substantially discounted pricing in 94 developing nations. That agreement includes some of the countries most heavily affected by the AIDS epidemic, including nations in sub-Saharan Africa. Atripla is commercialized in the United States, Canada and Europe through a partnership between Bristol-Myers Squibb and Gilead.
“For more than 20 years, Merck has made significant contributions to the fight against HIV and AIDS by discovering and developing antiretroviral medicines and creating programs to foster access in both the developed and the developing world,” said Patrick Bergstedt, General Manager, Infectious Diseases, Merck & Co., Inc. “We are pleased to continue this tradition by partnering with Gilead Sciences to make this important medicine available to patients who need it.”
IMPORTANT SAFETY INFORMATION ABOUT ATRIPLA
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.
Atripla is not approved 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-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Emtriva (emtricitabine) or Viread (tenofovir DF), which are components of Atripla. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Atripla. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Coadministration of Atripla with bepridil, cisapride, midazolam, pimozide, triazolam, or ergot derivatives is contraindicated, since competition for CYP3A by efavirenz could result in inhibition of metabolism of these drugs and create the potential for serious or life-threatening adverse reactions. Concomitant use of Atripla with voriconazole, atazanavir (with or without ritonavir), St. John’s wort (Hypericum perforatum) or St. John’s wort-containing products is not recommended.
Since Atripla contains efavirenz, emtricitabine, and tenofovir DF, Atripla should not be coadministered with Sustiva® (efavirenz), Emtriva, Viread, or Truvada (emtricitabine/tenofovir DF). Due to similarities between emtricitabine and lamivudine, Atripla should not be coadministered with drugs containing lamivudine, including Combivir® (lamivudine/zidovudine), Epivir® or Epivir-HBV® (lamivudine), Epzicom® (abacavir sulfate/lamivudine), or Trizivir® (abacavir sulfate/ lamivudine/zidovudine).
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 receiving 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 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 4 weeks of therapy, the prevalence of 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.
It is recommended that creatinine clearance (CrCl) be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy with Atripla, and routine monitoring of CrCl and serum phosphorus be performed for patients at risk of renal impairment. Atripla should not be given to patients with CrCl <50 mL/min. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir DF. 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 breast-feed while taking Atripla. Barrier contraception must always be used in combination with other methods of contraception (e.g., oral or other hormonal contraceptives). Because of the long half-life of efavirenz, adequate contraceptive measures are recommended for 12 weeks after discontinuation of Atripla. 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. Atripla should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. Skin discoloration, associated with emtricitabine, may also occur.
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.
Bone mineral density (BMD) monitoring should be considered for patients who have a history of pathologic bone fracture or are at risk for ostopenia. Decreases in BMD have been seen with tenofovir DF. Cases of osteomalacia (associated with proximal renal tubulopathy) have been reported in association with the use of tenofovir DF.
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.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of Atripla.
Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.
Saquinavir should not be used as the only protease inhibitor in combination with Atripla.
Coadministration of Atripla and atazanavir is not recommended. Atazanavir and lopinavir/ritonavir have been shown to increase tenofovir concentrations. Patients on atazanavir or 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 with didanosine should be undertaken with caution. Patients receiving this combination should be monitored closely for didanosine-associated adverse events.
In Study 934, through 144 weeks, the most frequently reported Grades 2-4 adverse reactions reported in =5% of patients receiving efavirenz + emtricitabine + tenofovir DF were diarrhea (9%), nausea (9%), fatigue (9%), depression (9%), dizziness (8%), sinusitis (8%), upper respiratory tract infection (8%), rash event (7%), headache (6%), insomnia (5%), anxiety (5%), and nasopharyngitis (5%).
The dose of Atripla is one tablet (containing 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir DF) 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 <18 years of age, or in patients with CrCl <50 mL/min.
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. Visit Gilead on the World Wide Web at www.gilead.com.
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.
Gilead Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians, regulatory agencies and payers may not see advantages of Atripla over other antiretrovirals and may therefore be reluctant to approve, prescribe or provide reimbursement for the product. 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 the Gilead Annual Report on Form 10-K for the year ended December 31, 2007 and the Quarterly Report for the quarter ended March 31, 2008, 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.
Merck 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 risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
Full U.S. prescribing information, including Boxed WARNINGS, 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
Atripla is a registered 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.
Source: Gilead Sciences
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