Gilead Announces 48-Week Data Evaluating Switching from Combivir(R) To Truvada(R) Among Virologically-Suppressed HIV Patients.-- Results From Phase III 'SWEET' Study Presented at the 11(th) European AIDS Conference -- FOSTER CITY, Calif. -- Gilead Sciences, Inc. (Nasdaq:GILD) today announced 48-week data from a Phase III clinical trial Noun 1. phase III clinical trial - a large clinical trial of a treatment or drug that in phase I and phase II has been shown to be efficacious with tolerable side effects; after successful conclusion of these clinical trials it will receive formal approval from the evaluating virologically-suppressed patients with HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. who switched from treatment with twice-daily Combivir([R]) (lamivudine/zidovudine) to treatment with Gilead's once-daily Truvada([R]) (emtricitabine and tenofovir disoproxil fumarate emtricitabine and tenofovir disoproxil fumarate Truvada Pharmacologic class: Nucleoside/nucleotide reverse-transcriptase inhibitor combination Therapeutic class: Antiretroviral Pregnancy risk category B ) as part of their combination drug therapy. In the SWEET (Simplification With Easier Emtricitabine and Tenofovir) study, patients who switched from Combivir to Truvada, both in combination with once-daily Sustiva([R]) (efavirenz efavirenz /ef·a·vi·renz/ (ef´ah-vi?renz) an antiretroviral, inhibiting reverse transcriptase; used in the treatment of HIV infection. e·fa·vir·enz n. ), experienced improvements in a number of treatment-related side effects. Patients in both study arms maintained virological suppression at 48 weeks. The data were presented at the 11th European AIDS Conference (EACS), held October 24-27 in Madrid, Spain. "As HIV patients live longer and remain on therapy for extended periods of time, the long-term side effect profile of treatment is increasingly more important," said Martin Fisher, MD, Brighton and Sussex University Hospitals, Brighton, United Kingdom and the principal investigator for the SWEET study. "Data from this study indicate that patients on long-term Combivir therapy without clinical lipoatrophy may benefit from switching to Truvada, as virological control can be maintained and limb fat loss and recovery may be improved. These data support the new EACS 2007 guidelines regarding proactive switching." New European HIV treatment guidelines issued this week at EACS list Truvada among the recommended components of a first-line treatment regimen for antiretroviral naive patients. Combivir, previously recommended as a first-line treatment option, is now listed as an alternative treatment option. In the United States, the components of Truvada and Sustiva are available in a fixed-dose combination tablet called Atripla([R])(efavirenz 600mg / emtricitabine 200mg / tenofovir disoproxil fumarate tenofovir disoproxil fumarate Viread Pharmacologic class: Nucleoside analog reverse transcriptase inhibitor Therapeutic class: Antiretroviral Pregnancy risk category B 300 mg). Atripla is currently the first and only once-daily single tablet regimen approved for the treatment of HIV-1 infection in adults in the United States for use either as stand-alone therapy or in combination with other antiretroviral agents. On October 18, 2007, the Committee for Medicinal Products for Human Use “CHMP” redirects here. For French language Canadian radio station, see CHMP-FM.CPMP, Committee for Proprietary Medicinal Products, now CHMP Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency The European Medicines Agency (EMEA) is a European agency for the evaluation of medicinal products. Until 2004, the European Medicines Agency was known as The European Agency for the Evaluation of Medicinal Products. Roughly parallel to the U.S. (EMEA) recommended that Atripla be approved for use in the European Union. A final decision on Atripla by the European Commission is expected by the end of the year. About The SWEET Study SWEET was a 48-week, multicenter, prospective, open-label study evaluating 250 HIV-infected patients. At study entry, patients received a treatment regimen of Combivir and Sustiva and were virologically controlled with HIV RNA of less than 50 copies/mL for the last two consecutive testings and less than 400 copies/mL for more than three months. Of the 250 patients enrolled in the study, 234 received at least one dose of study drug. Subjects were randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. 1:1 to continue with a regimen of Combivir and Sustiva (n=117) or switch to a regimen of Truvada and Sustiva (n=117). Baseline characteristics were well matched between study arms. The median prior use of Combivir among patients was 36 months. Among patients who switched to Truvada and Sustiva, 88 percent were suppressed to less than 50 copies/mL at 48 weeks, compared to 85 percent of patients who continued with Combivir (intent-to-treat, missing = failure analysis; 95% CI: -6% to +11%; p=0.70). In addition, median CD4 counts remained comparable between the study arms. Limb fat was measured using DEXA scans in a subset of 100 study participants, of whom 74 had both baseline and 48-week data available. In this sub-study, a median increase in limb fat of 0.21 kg was observed among patients who switched to Truvada and a median decrease of 0.14 kg was observed among patients who continued on Combivir (p=0.025). Differences in limb fat were more pronounced among patients who had less experience with AZT AZT or zidovudine (zīdō`vy  dēn'), drug used to treat patients infected with the human immunodeficiency virus (HIV), which causes AIDS; also called (zidovudine).
At week 48, a median increase in hemoglobin of 0.5 g/dL was observed among Truvada patients and a median decrease of 0.1 g/dL was observed among those taking Combivir (p < 0.001). Twenty-two percent of patients who switched to Truvada (n=22) experienced an increase in hemoglobin greater than 1 g/dL at 48 weeks compared to 2 percent of Combivir patients (n=2). Conversely, 9 percent of patients who remained on Combivir (n=8) experienced a reduction in hemoglobin greater than 1 g/dL, compared to 2 percent of patients who switched to Truvada (n=2). Truvada patients in the study also experienced improvements across a number of lipid parameters. After 48 weeks of treatment, fasting total cholesterol fell by a median of 0.22 mmol/L (8.46 mg/dl) among Truvada patients, compared to a reduction of 0.06 mmol/L (2.30 mg/dl) among Combivir patients (p=0.23; Truvada vs. Combivir comparison). Fasting triglycerides fell by a median of 0.17 mmol/L (15.45 mg/dl) among Truvada patients, but increased by 0.04 mmol/L (3.63 mg/dl) among those who continued treatment with Combivir (p=0.11; Truvada vs. Combivir comparison). Renal function remained within normal ranges in both treatment arms after 48 weeks of treatment, as measured by creatinine clearance (Cockroft-Gault) and estimated glomerular filtration rate The Estimated Glomerular Filtration Rate (eGFR) is a calculated estimate of the actual glomerular filtration rate and is based on your serum creatinine concentration; the calculation uses a formula that also can include your age, gender, height, and weight; in some formulas, race may also (MDRD). Median creatinine increased by 3 umol/L (less than 0.01 mg/dl) among Truvada patients (p < 0.001), and declined by 1 umol/L (less than 0.01 mg/dl) among patients in the Combivir group (p=0.57). Five percent of Combivir patients and 3 percent of Truvada patients discontinued study drug due to adverse events. These included dizziness, insomnia, nausea, depression and sleep disorder in the Truvada arm and angiosarcoma angiosarcoma /an·gio·sar·co·ma/ (an?je-o-sahr-ko´mah) a malignant neoplasm arising from vascular endothelial cells; the term may be used generally or may denote a subtype, such as hemangiosarcoma. , pulmonary embolism, pulmonary hypertension, weight loss of arms and legs, syncope syncope Effect of temporary impairment of blood circulation to a part of the body. It is often used as a synonym for fainting, which is loss of consciousness due to inadequate blood flow to the brain. , worsening of lipoatrophy and depression in the Combivir arm. Important Product Safety Information About Truvada and Atripla Lactic acidosis and severe hepatomegaly hepatomegaly /hep·a·to·meg·a·ly/ (hep?ah-to-meg´ah-le) enlargement of the liver. hep·a·to·meg·a·ly n. The abnormal enlargement of the liver. Also called megalohepatia. with steatosis steatosis /ste·a·to·sis/ (ste?ah-to´sis) fatty change. ste·a·to·sis n. See fatty degeneration. steatosis fatty degeneration. See also muscular steatosis. , including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Truvada and Atripla are not approved for the treatment of chronic hepatitis B virus (HBV HBV hepatitis B virus. HBV abbr. hepatitis B virus ) infection and their safety and efficacy 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 Viread([R]) (tenofovir disoproxil fumarate) or Emtriva([R]) (emtricitabine), which are components of Truvada and Atripla. In some of these patients treated with Emtriva, the exacerbations of hepatitis B were associated with liver decompensation decompensation /de·com·pen·sa·tion/ (de?kom-pen-sa´shun) 1. inability of the heart to maintain adequate circulation, marked by dyspnea, venous engorgement, and edema. 2. and liver failure. 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 HIV and HBV and discontinue Truvada or Atripla. If appropriate, initiation of anti-hepatitis B treatment may be warranted. It is important for patients to be aware that anti-HIV medicines including Truvada and Atripla do not cure HIV infection or AIDS and do not reduce the risk of transmitting HIV to others. Additional Important Information About Truvada Truvada is a fixed-dose combination tablet containing 200 mg of emtricitabine (Emtriva) and 300 mg of tenofovir disoproxil fumarate (Viread). In the United States, Truvada is indicated in combination with other antiretroviral agents, such as non-nucleoside reverse transcriptase inhibitors Non-Nucleoside Reverse Transcriptase Inhibitors Definition This type of drug interferes with an enzyme that is key to the replication (reproduction) of the human immunodeficiency virus (HIV). or protease inhibitors, for the treatment of HIV-1 infection in adults. It is not recommended that Truvada be used as a component of a triple nucleoside regimen. Truvada should not be coadministered with Atripla, Emtriva, Viread or lamivudine-containing products, including Combivir (lamivudine/zidovudine), Epivir([R]) or Epivir-HBV([R]) (lamivudine), Epzicom([TM]) (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. Emtricitabine and tenofovir are principally eliminated by the kidneys. Renal impairment, including cases of acute renal failure acute renal failure Acute kidney failure Nephrology An abrupt decline in renal function, triggered by various processes–eg, sepsis, shock, trauma, kidney stones, drug toxicity-aspirin, lithium, substances of abuse, toxins, iodinated radiocontrast. and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of Viread, a component of Truvada. 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 phos·pho·rous adj. Of, relating to, or containing phosphorus, especially with a valence of 3 or a valence lower than that of a comparable phosphoric compound. should be performed in patients at risk for renal impairment. Dosing interval adjustment and close monitoring of renal function are recommended in all patients with creatinine clearance of 30-49 ml/min. Truvada should be avoided with concurrent or recent use of a nephrotoxic nephrotoxic /neph·ro·tox·ic/ (nef´ro-tok?sik) destructive to kidney cells. Nephrotoxic Toxic, or damaging, to the kidney. agent. No drug interaction studies have been conducted using Truvada. The U.S. package insert advises that co-administration of Truvada and didanosine didanosine /di·dan·o·sine/ (-dan´o-sen) 2, an analogue of dideoxyadenosine; an antiretroviral agent used for the treatment of advanced HIV-1 infection and acquired immunodeficiency syndrome, administered orally. should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events and didanosine should be discontinued if these occur. 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 given with ritonavir ritonavir /ri·to·na·vir/ (ri-to´nah-vir) an HIV protease inhibitor used in treatment of HIV infection and AIDS. ri·ton·a·vir n. 100 mg. Atazanavir without ritonavir should not be co-administered with Truvada. Decreases in bone mineral density bone mineral density n. See bone density. bone mineral density A measurement of bone mass, expressed as the amount of mineral–in grams divided by the area scanned in cm2. See Bone densitometry. (BMD BMD In currencies, this is the abbreviation for the Bermudian Dollar. Notes: The currency market, also known as the Foreign Exchange market, is the largest financial market in the world, with a daily average volume of over US $1 trillion. ) 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. Cases of osteomalacia osteomalacia /os·teo·ma·la·cia/ (os?te-o-mah-la´shah) inadequate or delayed mineralization of osteoid in mature cortical and spongy bone; it is the adult equivalent of rickets and accompanies that disorder in children. (associated with proximal renal tubulopathy) have been reported in association with the use of Viread. Changes in body fat have been observed in patients taking anti-HIV medicines. The mechanism and long-term health effect of these conditions are unknown. Immune Reconstitution Syndrome has been reported in patients treated with combination therapy, including Viread and Emtriva. Treatment-emergent adverse events occurring in at least 3 percent of patients receiving Viread and Emtriva in Study 934 included dizziness (8%), diarrhea (7%), nausea (8%), fatigue (7%), sinusitis sinusitis Inflammation of the sinuses. Acute sinusitis, usually due to infections such as the common cold, causes localized pain and tenderness, nasal obstruction and discharge, and malaise. (4%), upper respiratory tract infections (3%), nasopharyngitis (3%), somnolence somnolence /som·no·lence/ (som´no-lens) drowsiness or sleepiness, particularly in excess. som·no·lence n. 1. A state of drowsiness; sleepiness. 2. (3%), headache (5%), dizziness (8%), depression (4%), insomnia (4%), abnormal dreams (4%) and rash (5%). Skin discoloration has been reported with higher frequency among Emtriva-treated patients. Skin discoloration, manifested by hyperpigmentation Hyperpigmentation Definition Hyperpigmentation is the increase in the natural color of the skin. Description Melanin, a brown pigment manufactured by certain cells in the skin called melanocytes, is responsible for skin color. on the palms and/or soles was generally mild and asymptomatic. The 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 The Academy of Sciences of the Czech Republic Czech: Akademie věd České republiky, abbr. AV ČR (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research The Rega Institute for Medical Research is a Belgian scientific establishment that is part of the Catholic University of Leuven (Leuven) in central Belgium. The Rega Iinstitute is an interfacultary biomedical research institute of the Catholic University of Leuven and consists of , 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 the product can be offered at cost in parts of the world where the epidemic has hit the hardest. For complete prescribing information for Truvada, visit www.truvada.com. For full prescribing information outside of the United States, physicians should consult their local product labeling. Additional Important Information About Atripla In the United States, 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. Atripla contains the components Truvada (emtricitabine and tenofovir disoproxil fumarate) and Sustiva (efavirenz), co-formulated as a single tablet. As such, the important safety information appearing in the above Truvada section also applies to Atripla, in addition to the following important product information. As a fixed-dose regimen of Viread (tenofovir disoproxil fumarate), Emtriva (emtricitabine) and Sustiva (efavirenz), Atripla should not be coadministered with Viread, Emtriva, Truvada (emtricitabine and tenofovir disoproxil fumarate) or Sustiva. Due to similarities between Emtriva 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). Atripla should not be taken with Hismanal([R]) (astemizole), Vascor([R]) (bepridil), Propulsid([R]) (cisapride), Versed([R]) (midazolam), Orap([R]) (pimozide pimozide /pi·mo·zide/ an antipsychotic and antidyskinetic agent used in the treatment of Gilles de la Tourette's syndrome. pim·o·zide n. ), Halcion([R]) (triazolam triazolam /tri·a·zo·lam/ (tri-a´zo-lam) a benzodiazepine used as a sedative and hypnotic in the treatment of insomnia. tri·a·zo·lam n. ), ergot ergot (ûr`gət), disease of rye and other cereals caused by the fungus Claviceps purpurea. The cottony, matlike body, or mycelium, of the fungus develops in the ovaries of the host plant; it eventually turns into a hard pink or purple medicines (for example, Wigraine([R]) and Cafergot([R])), or Vfend([R]) (voriconazole) due to a contraindication contraindication /con·tra·in·di·ca·tion/ (-in?di-ka´shun) any condition which renders a particular line of treatment improper or undesirable. con·tra·in·di·ca·tion n. with efavirenz. Use of Atripla with St. John's wort St. John’s wort indicates animosity. [Flower Symbolism: Flora Symbolica, 177] See : Hatred St. John’s wort defense against fairies, evil spirits, the Devil. [Br. (Hypericum perforatum) or St. John's wort-containing products is not recommended. This list of medicines is not complete. Patients should discuss all prescription and non-prescription medicines, vitamin and herbal supplements, or other health preparations they are taking or plan to take with their healthcare provider. Atripla should not be given to patients with creatinine clearance less than 50 ml/min. 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, a component of Atripla. 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 death by 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. Patients should tell their doctor if they have a history of mental illness or are using drugs or alcohol. Fifty-three percent of patients in clinical studies have 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 Hallucinations Definition Hallucinations are false or distorted sensory experiences that appear to be real perceptions. These sensory impressions are generated by the mind rather than by any external stimuli, and may be seen, heard, felt, and even (1.2%) when taking efavirenz compared to 25 percent 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. After four weeks of therapy, the prevalence of central nervous system symptoms of at least moderate severity ranged from 5 to 9 percent in patients treated with regimens containing efavirenz. Nervous system symptoms are not predictive of the less frequent psychiatric symptoms. Women should not become pregnant or breastfeed while taking Atripla. Serious birth defects have been seen in children of women treated with efavirenz during pregnancy. Women must use a reliable form of barrier contraception, such as a condom, even if they also use other methods of birth control. Rash is a common side effect that usually goes away without any change in treatment. Rash may be a serious problem in some children. Patients with liver disease may require the healthcare provider to check liver function or check drug levels in the blood. Atripla should be used with caution in patients with a history of seizures. Convulsions Convulsions Also termed seizures; a sudden violent contraction of a group of muscles. Mentioned in: Heat Disorders have been observed in patients receiving efavirenz, generally in the presence of a known medical history of seizures. Invirase([R]) (saquinavir saquinavir /sa·quin·a·vir/ (sah-kwin´ah-vir) an HIV protease inhibitor that causes formation of immature, noninfectious viral particles; used as the base or the mesylate salt in treatment of HIV infection and AIDS. ) should not be used as the only protease inhibitor in combination with Atripla. The most significant adverse events observed in patients treated with Sustiva are nervous system symptoms, psychiatric symptoms and rash. The most common adverse events (at least 5%) observed in clinical studies with Sustiva include fatigue, pain, dizziness, headache, insomnia, impaired concentration, nausea, vomiting, diarrhea, depression, rash, and pruritus pruritus /pru·ri·tus/ (proo-ri´tus) itching.prurit´ic pruritus a´ni intense chronic itching in the anal region. pruritus hiema´lis xerotic eczema. . For complete prescribing information for Atripla, visit www.atripla.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
Forward-Looking Statement This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and of 1995, that are subject to risks, uncertainties and other factors, including the risk that as Truvada and Atripla are used over longer periods of time by many patients taking numerous other medicines, many of whom have underlying health problems, we may find new issues such as safety, resistance or drug interaction issues, which may require us to provide additional warnings or contraindications on our labels or narrow our approved indications, each of which could reduce the market acceptance of these products. 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 Annual Report on Form 10-K for the year ended December 31, 2006 and its Quarterly Reports on Form 10-Q for the first and second quarters of 2007, 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, Atripla, Viread and Emtriva are available at www.gilead.com. Truvada, Viread and Emtriva are registered trademarks of Gilead Sciences, Inc. Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. For more information on Gilead, please call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com. |
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