London, England - Gilead Sciences, Inc. (Nasdaq: GILD) today announced that Stribild® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil (as fumarate) 245 mg), a once-daily single tablet regimen for the treatment of HIV, is now available in the United Kingdom. Stribild® was granted a license by the European Commission on May 27, 2013 for the treatment of HIV-1 infection in adult patients aged 18 and over who are antiretroviral treatment-naïve or are infected with HIV-1 without known mutations associated with resistance to any of the product's three antiretroviral agents.
"Treatment guidelines from the British HIV Association recommend HIV regimen simplification to help enhance patient adherence. This can keep the virus under control, which may improve long-term health benefits for patients," said Dr. Anton Pozniak, Director, HIV Service, Chelsea and Westminster Hospital, London. "In pivotal studies, once-daily Stribild was highly effective and generally well tolerated with a favorable safety profile, and is an important advance for HIV patients in the United Kingdom."
The license is supported by 48-week data from two pivotal Phase 3 studies in which Stribild met its primary objective of non-inferiority compared to Atripla® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil (as fumarate) 245 mg) (Study 102) and to a regimen containing ritonavir-boosted atazanavir plus Truvada® (emtricitabine/tenofovir disoproxil (as fumarate)) (Study 103).
The product has also been granted a license in the United States, Canada, Australia, South Korea, Japan and Turkey.
Stribild is the third single tablet HIV regimen developed by Gilead to become available in Europe. The first, Atripla, was granted a license in the European Union in 2007 and is marketed by Gilead in partnership with Bristol-Myers Squibb and Merck & Co. The second, Eviplera®▼ (emtricitabine 200mg/rilpivirine 25mg/tenofovir disoproxil (as fumarate) 245mg), is marketed by Gilead and Janssen R&D Ireland and received European marketing authorization in November 2011.
About Stribild®
Stribild contains four Gilead compounds in a complete once-daily, single tablet regimen: elvitegravir 150 mg; cobicistat 150 mg; emtricitabine 200 mg; and tenofovir disoproxil (as fumarate) 245 mg.
Elvitegravir is a member of the integrase inhibitor class of antiretroviral compounds. Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead's agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights.
Cobicistat is Gilead's proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body.
Marketing applications for elvitegravir and cobicistat as standalone agents are currently under review in the European Union. In the United States, on April 29, 2013, Gilead announced it had received Complete Response Letters from the U.S. Food and Drug Administration (FDA) on its New Drug Applications for elvitegravir and cobicistat as standalone agents. The company is working to address the questions raised in FDA's letters as quickly as possible.
Elvitegravir and cobicistat as standalone agents are investigational products and their safety and efficacy have not yet been established.
EU Important Product Information About Stribild
Lactic acidosis, usually associated with hepatic steatosis, has been reported with the use of nucleoside analogues. Lactic acidosis has a high mortality and patients at increased risk should be followed closely.
Stribild should not be taken with any of the following due to the potential for serious and/or life-threatening events or loss of virologic response and possible resistance to Stribild:
• alpha 1-adrenoreceptor antagonists: alfuzosin
• antiarrhythmics: amiodarone, quinidine
• anticonvulsants: carbamazepine, phenobarbital, phenytoin
• antimycobacterials: rifampicin
• ergot derivatives: dihydroergotamine, ergometrine, ergotamine
• gastrointestinal motility agents: cisapride
• herbal products: St. John's wort (Hypericum perforatum)
• HMG Co-A reductase inhibitors: lovastatin, simvastatin
• neuroleptics: pimozide
• PDE-5 inhibitors: sildenafil for treatment of pulmonary arterial hypertension
• sedatives/hypnotics: orally administered midazolam, triazolam
As a fixed combination, Stribild should not be administered concomitantly with other medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of hepatitis B virus infection.
Emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion. Renal failure, renal impairment, elevated creatinine, hypophosphataemia and proximal tubulopathy (including Fanconi syndrome) have been reported with the use of tenofovir disoproxil fumarate.
Patients who have previously discontinued treatment with tenofovir disoproxil fumarate due to renal toxicity should not be treated with Stribild.
Patients should have creatinine clearance calculated and urine glucose and urine protein determined prior to initiating Stribild therapy.
Stribild should not be initiated in patients with creatinine clearance below 70 mL/min. It is recommended that Stribild is not initiated in patients with creatinine clearance < 90 mL/min unless, after review of the available treatment options, it is considered that Stribild is the preferred treatment for the individual patient.
Creatinine clearance, serum phosphate, urine glucose and urine protein should be monitored every 4 weeks during the first year and then every 3 months. More frequent monitoring of renal function should be considered in patients at risk for renal impairment.
Cobicistat inhibits the tubular secretion of creatinine and may cause modest increases in serum creatinine and modest declines in creatinine clearance. Patients who experience a confirmed increase in serum creatinine of greater than 26.5 µmol/L (0.3 mg/dL) from baseline should be closely monitored for renal safety.
Renal function should be re-evaluated within 1 week if serum phosphate is < 0.48 mmol/L (1.5 mg/dL) or creatinine clearance decreases to < 70 mL/min during Stribild therapy.
If creatinine clearance is confirmed as < 50 mL/min or serum phosphate decreases to < 0.32 mmol/L (1.0 mg/dL) then Stribild should be discontinued.
There are currently inadequate data to determine whether co-administration of tenofovir disoproxil fumarate and cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that include tenofovir disoproxil fumarate without cobicistat.
Stribild should be avoided with concurrent or recent use of a nephrotoxic medicinal product due to the increased risk of renal adverse reactions (with the TDF component of Stribild).
Bone abnormalities (infrequently leading to fractures) may be associated with proximal renal tubulopathy and appropriate consultation should be obtained if suspected.
Patients with chronic hepatitis B or C treated with antiretrovirals are at an increased risk for severe and potentially fatal hepatic adverse reactions. Stribild has not been studied in patients with severe hepatic impairment (CPT Score C) and is therefore not recommended in these patients. If Stribild is discontinued in patients co infected with HIV and hepatitis B virus (HBV), these patients should be closely monitored for evidence of exacerbation of hepatitis. In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post treatment exacerbation of hepatitis may lead to hepatic decompensation.
Immune Reactivation Syndrome has been reported in patients treated with combination therapy, including the components of Stribild.
Combination therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients. The long-term consequences of these events are currently unknown.
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 Asia Pacific.
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 in Europe may not see advantages of Stribild over other HIV therapies and may therefore be reluctant to prescribe the product. In addition, pending marketing applications for elvitegravir and cobicistat as standalone agents in Europe may not be approved or approval may be delayed, and marketing approvals, if granted, may have significant limitations on their use. 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 March 31, 2013, 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.
###
EU Summary of Product Characteristics for Atripla, Eviplera, Stribild and Truvada are available at http://www.ema.europa.eu/ema/index.jsp?curl=/pages/home/Home_Page.jsp
Complera, Eviplera, Stribild and Truvada 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 www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574- 3000.
UK Job bag number: HIV1/UK/13-04/MI/1066
Date of preparation: May 2013
Contacts:
Patrick O'Brien (Investors)
(650) 522-1936
Stephen Head, Media (Media, Europe)
+44 (208) 587-2359
Erin Rau (Media, U.S.)
(650) 522-5635
"Treatment guidelines from the British HIV Association recommend HIV regimen simplification to help enhance patient adherence. This can keep the virus under control, which may improve long-term health benefits for patients," said Dr. Anton Pozniak, Director, HIV Service, Chelsea and Westminster Hospital, London. "In pivotal studies, once-daily Stribild was highly effective and generally well tolerated with a favorable safety profile, and is an important advance for HIV patients in the United Kingdom."
The license is supported by 48-week data from two pivotal Phase 3 studies in which Stribild met its primary objective of non-inferiority compared to Atripla® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil (as fumarate) 245 mg) (Study 102) and to a regimen containing ritonavir-boosted atazanavir plus Truvada® (emtricitabine/tenofovir disoproxil (as fumarate)) (Study 103).
The product has also been granted a license in the United States, Canada, Australia, South Korea, Japan and Turkey.
Stribild is the third single tablet HIV regimen developed by Gilead to become available in Europe. The first, Atripla, was granted a license in the European Union in 2007 and is marketed by Gilead in partnership with Bristol-Myers Squibb and Merck & Co. The second, Eviplera®▼ (emtricitabine 200mg/rilpivirine 25mg/tenofovir disoproxil (as fumarate) 245mg), is marketed by Gilead and Janssen R&D Ireland and received European marketing authorization in November 2011.
About Stribild®
Stribild contains four Gilead compounds in a complete once-daily, single tablet regimen: elvitegravir 150 mg; cobicistat 150 mg; emtricitabine 200 mg; and tenofovir disoproxil (as fumarate) 245 mg.
Elvitegravir is a member of the integrase inhibitor class of antiretroviral compounds. Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead's agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights.
Cobicistat is Gilead's proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body.
Marketing applications for elvitegravir and cobicistat as standalone agents are currently under review in the European Union. In the United States, on April 29, 2013, Gilead announced it had received Complete Response Letters from the U.S. Food and Drug Administration (FDA) on its New Drug Applications for elvitegravir and cobicistat as standalone agents. The company is working to address the questions raised in FDA's letters as quickly as possible.
Elvitegravir and cobicistat as standalone agents are investigational products and their safety and efficacy have not yet been established.
EU Important Product Information About Stribild
Lactic acidosis, usually associated with hepatic steatosis, has been reported with the use of nucleoside analogues. Lactic acidosis has a high mortality and patients at increased risk should be followed closely.
Stribild should not be taken with any of the following due to the potential for serious and/or life-threatening events or loss of virologic response and possible resistance to Stribild:
• alpha 1-adrenoreceptor antagonists: alfuzosin
• antiarrhythmics: amiodarone, quinidine
• anticonvulsants: carbamazepine, phenobarbital, phenytoin
• antimycobacterials: rifampicin
• ergot derivatives: dihydroergotamine, ergometrine, ergotamine
• gastrointestinal motility agents: cisapride
• herbal products: St. John's wort (Hypericum perforatum)
• HMG Co-A reductase inhibitors: lovastatin, simvastatin
• neuroleptics: pimozide
• PDE-5 inhibitors: sildenafil for treatment of pulmonary arterial hypertension
• sedatives/hypnotics: orally administered midazolam, triazolam
As a fixed combination, Stribild should not be administered concomitantly with other medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of hepatitis B virus infection.
Emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion. Renal failure, renal impairment, elevated creatinine, hypophosphataemia and proximal tubulopathy (including Fanconi syndrome) have been reported with the use of tenofovir disoproxil fumarate.
Patients who have previously discontinued treatment with tenofovir disoproxil fumarate due to renal toxicity should not be treated with Stribild.
Patients should have creatinine clearance calculated and urine glucose and urine protein determined prior to initiating Stribild therapy.
Stribild should not be initiated in patients with creatinine clearance below 70 mL/min. It is recommended that Stribild is not initiated in patients with creatinine clearance < 90 mL/min unless, after review of the available treatment options, it is considered that Stribild is the preferred treatment for the individual patient.
Creatinine clearance, serum phosphate, urine glucose and urine protein should be monitored every 4 weeks during the first year and then every 3 months. More frequent monitoring of renal function should be considered in patients at risk for renal impairment.
Cobicistat inhibits the tubular secretion of creatinine and may cause modest increases in serum creatinine and modest declines in creatinine clearance. Patients who experience a confirmed increase in serum creatinine of greater than 26.5 µmol/L (0.3 mg/dL) from baseline should be closely monitored for renal safety.
Renal function should be re-evaluated within 1 week if serum phosphate is < 0.48 mmol/L (1.5 mg/dL) or creatinine clearance decreases to < 70 mL/min during Stribild therapy.
If creatinine clearance is confirmed as < 50 mL/min or serum phosphate decreases to < 0.32 mmol/L (1.0 mg/dL) then Stribild should be discontinued.
There are currently inadequate data to determine whether co-administration of tenofovir disoproxil fumarate and cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that include tenofovir disoproxil fumarate without cobicistat.
Stribild should be avoided with concurrent or recent use of a nephrotoxic medicinal product due to the increased risk of renal adverse reactions (with the TDF component of Stribild).
Bone abnormalities (infrequently leading to fractures) may be associated with proximal renal tubulopathy and appropriate consultation should be obtained if suspected.
Patients with chronic hepatitis B or C treated with antiretrovirals are at an increased risk for severe and potentially fatal hepatic adverse reactions. Stribild has not been studied in patients with severe hepatic impairment (CPT Score C) and is therefore not recommended in these patients. If Stribild is discontinued in patients co infected with HIV and hepatitis B virus (HBV), these patients should be closely monitored for evidence of exacerbation of hepatitis. In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post treatment exacerbation of hepatitis may lead to hepatic decompensation.
Immune Reactivation Syndrome has been reported in patients treated with combination therapy, including the components of Stribild.
Combination therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients. The long-term consequences of these events are currently unknown.
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 Asia Pacific.
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 in Europe may not see advantages of Stribild over other HIV therapies and may therefore be reluctant to prescribe the product. In addition, pending marketing applications for elvitegravir and cobicistat as standalone agents in Europe may not be approved or approval may be delayed, and marketing approvals, if granted, may have significant limitations on their use. 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 March 31, 2013, 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.
###
EU Summary of Product Characteristics for Atripla, Eviplera, Stribild and Truvada are available at http://www.ema.europa.eu/ema/index.jsp?curl=/pages/home/Home_Page.jsp
Complera, Eviplera, Stribild and Truvada 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 www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574- 3000.
UK Job bag number: HIV1/UK/13-04/MI/1066
Date of preparation: May 2013
Contacts:
Patrick O'Brien (Investors)
(650) 522-1936
Stephen Head, Media (Media, Europe)
+44 (208) 587-2359
Erin Rau (Media, U.S.)
(650) 522-5635
