Gilead’s Biktarvy Maintained High Efficacy With No Cases of Treatment-Emergent Resistance Through Three Years in Phase 3 HIV Clinical Trials


2019-11-08 17:21:46 BioSpace


Data from the Two 144-week Studies in Treatment-naïve Adults Living with HIV Presented at European AIDS Conference FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced findings from two randomized, double-blind, active-controlled Phase 3 studies (Study 1489 and Study 1490) evaluating the safety and efficacy of Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets) compared with dolutegravir (DTG)-containing regimens for the treatment of HIV-1 infection in adults new to HIV therapy. In both studies, Biktarvy was well-tolerated and demonstrated high rates of virologic suppression through Week 144. These data are being presented at the 17th European AIDS Conference (EACS) in Basel, Switzerland. “The findings presented today support the value of Biktarvy as an effective treatment that offers durable viral suppression and maintains a high barrier to resistance,” said Diana Brainard, MD, Senior Vice President, HIV and Emerging Viruses, Gilead Sciences. “These longer-term data reaffirm Biktarvy’s role as a first-line treatment option for appropriate adults who are living with HIV and are starting therapy.” Biktarvy is indicated in the United States as a complete regimen for the treatment of HIV-1 infection in patients who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. Biktarvy carries a Boxed Warning in its U.S. product label regarding the risk of post-treatment acute exacerbation of hepatitis B. See below for Important Safety Information. Studies 1489 and 1490 randomized 1,274 treatment-naïve adults to receive Biktarvy or either dolutegravir/ abacavir/lamivudine (50/600/300 mg, DTG/ABC/3TC) (Study 1489) or DTG + emtricitabine/tenofovir alafenamide (50/200/25 mg, F/TAF) (Study 1490). The primary endpoint of both studies was virologic suppression, defined as the proportion of participants who were virologically suppressed (HIV-1 RNA levels <50 copies/mL) at Week 48. At the primary endpoint, noninferior efficacy was achieved in both studies and has been previously presented. At Week 144, non-inferiority was maintained from the primary endpoint measurement in both studies at Week 48, with a similar proportion of the Biktarvy group achieving virologic suppression (82 percent; n=518/634) as those taking DTG/ABC/3TC (84 percent; n=265/315) and DTG + F/TAF (84 percent; n=273/325). Across all treatment groups no participants developed treatment failure with treatment-emergent resistance. “Developing new HIV treatment regimens that can be used in a wide range of people living with HIV is very important,” said Chloe Orkin, MBBCH, FRCP, Clinical Professor of HIV Medicine at Queen Mary University of London. “The three-year results from both Biktarvy studies provide further evidence that it is potent and effective, enabling people living with HIV to maintain an undetectable viral load over the long term.” There were no discontinuations due to renal events and no cases of proximal renal tubulopathy or Fanconi syndrome in the Biktarvy treatment group. Similar reductions in median estimated glomerular filtration rate (eGFR) were observed across groups (-9.2 mL/min in patients taking Biktarvy vs. -11.7 mL/min in participants taking ABC/DTG/3TC vs. -11.0 mL/min in participants taking DTG + F/TAF) at Week 144. Study 1489 also assessed other laboratory markers of renal and bone safety in patients taking Biktarvy and DTG/ABC/3TC. Participants in both treatment arms demonstrated similar median changes in proteinuria and mean percentage changes in hip and spine bone mineral density (BMD) from baseline. Small, statistically significant differences in the median change from baseline favoring DTG/ABC/3TC were observed for LDL, HDL and total cholesterol to HDL ratio. Biktarvy was well tolerated through Week 144. Discontinuations due to adverse events were low across all groups (1 percent (n=6/634) for Biktarvy vs. 2 percent (n=5/315) for DTG/ABC/3TC and 2 percent (n=6/325) for DTG + F/TAF). The proportion of drug-related adverse events (all grades) was 26 percent in the Biktarvy arm (n=165/634) vs. 42 percent (n=132/315) for DTG/ABC/3TC and 29 percent (n=94/325) for DTG + F/TAF). The incidence of drug-related nausea was 4 percent for Biktarvy vs. 18 percent for DTG/ABC/3TC and 5 percent for DTG + F/TAF (p<0.0001 for Biktarvy vs. DTG/ABC/3TC). The most commonly reported treatment-emergent adverse events (all grades) were diarrhea (19 percent for Biktarvy vs. 18 percent for DTG/ABC/3TC and 16 percent for DTG + F/TAF), headache (16 percent for Biktarvy vs. 18 percent for DTG/ABC/3TC and 18 percent for DTG + F/TAF) and nasopharyngitis (14 percent for Biktarvy vs.17 percent for DTG/ABC/3TC and 19 percent for DTG + F/TAF). Study 1489 and Study 1490 are ongoing. Beyond Week 144, study participants will have the option to receive Biktarvy in an open-label extension for up to 96 weeks. Biktarvy does not cure HIV infection or AIDS. Important U.S. Safety Information and Indication for Biktarvy BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted. Contraindications Coadministration: Do not use BIKTARVY with dofetilide or rifampin. Warnings and precautions Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions. Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported. New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of BIKTARVY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus. Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. Adverse reactions Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%). Drug interactions Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments. Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1. Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions. Dosage and administration Dosage: Patients weighing ≥25 kg: 1 tablet taken once daily with or without food. Renal impairment: Not recommended in patients with CrCl <30 mL/min. Hepatic impairment: Not recommended in patients with severe hepatic impairment. Prior to or when initiating: Test patients for HBV infection. Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus. Prior to or when initiating: Test patients for HBV infection. Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus. Pregnancy and lactation Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population. Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission. INDICATION Biktarvy is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Biktarvy. About Gilead Sciences Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California. For more than 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention, testing and linkage to care, and cure research. Today, it’s estimated that more than 12 million people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners. For more information on Gilead Sciences, please visit the company’s website at 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 possibility of unfavorable results from ongoing and additional clinical trials involving Biktarvy. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. 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, 2019, 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 Biktarvy, including BOXED WARNING, is available at Biktarvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc. or its related companies.
欧洲艾滋病会议上发表的两项144周治疗感染艾滋病毒的成年人研究数据 加利福尼亚州福斯特市.(商业前景)--吉利德科学(Gilead Sciences), Inc .( NASDAQ : GILD )今天公布了两项随机双盲的研究结果。主动控制的第三阶段研究(研究1489和研究1490)评估比卡托维®(比特格拉夫50mg / emtripatine 200mg /替诺福韦 alafenami 25mg 片)的安全性和有效性,与含有多氯雷他韦( DTG )的治疗 HIV-1感染的新的成人艾滋病毒治疗方案相比。在这两项研究中, Bitarvy 都得到了良好的耐受性,并在144周期间表现出高度的病毒学抑制率。这些数据正在瑞士巴塞尔举行的第十七届欧洲艾滋病会议上公布。 吉利德科学(Gilead Sciences)的 HIV 和新兴病毒高级副总裁 Diana Brainard 医学博士说:“今天公布的研究结果支持了 Bitarvy 作为一种有效的治疗方法的价值,它能提供持久的病毒抑制,并保持高的耐药性。”“这些长期数据重申了 Bitarvy 作为一种一线治疗选择的作用,适用于感染艾滋病毒并开始治疗的合适成年人。” Bitarvy 在美国被认为是治疗没有抗逆转录病毒治疗历史的患者的 HIV-1感染的完整方案,或者是在那些在稳定的抗逆转录病毒养生法方案上至少3个月受到病毒学抑制的患者中替代目前的抗逆转录病毒治疗方案,并且没有治疗失败的病史,也没有已知的替代方案与 Bitarvy 个别成分的耐药性有关。Bitarvy 在其美国产品标签中带有关于治疗后急性乙型肝炎恶化风险的 Boxed 警告。有关重要安全信息,请参见下文。 1489和1490项随机对照研究1274名治疗偏头痛的成年人接受比托韦或多氯雷韦酯/阿贝卡韦/拉米夫定(50/600/300毫克, DTG / ABC /3TC )(研究1489)或 DTG + emittripine /替诺福韦胺(50/200/25毫克, F / TAF )(研究1490)。两项研究的主要终点都是病毒学抑制,即48周被病毒学抑制的参与者( HIV-1 RNA 水平<50拷贝/ mL )的比例。在主要终点,在两项研究中都取得了非劣效性的疗效,并且之前已经提出。在144周,在48周的两项研究中,从主要终点测量中保持了非劣效性,与 DTG / ABC /3TC (84%; n =265/315)和 DTG + F / TAF (84%; n =273/325)相比, Bitarvy 组的病毒学抑制比例相似(82%; n =518/634)。在所有治疗小组中,没有任何参与者出现治疗失败和紧急抵抗。 伦敦玛丽女王大学( Queen Mary University ) HIV 医学临床教授克洛伊·奥尔金( Chloe Orkin )表示:“开发新的艾滋病毒治疗方案,可用于广泛的艾滋病毒感染者非常重要。”“这两项 Bistavy 研究的三年结果进一步证明,它是有效的,使艾滋病毒感染者能够长期保持无法检测的病毒载量。” 比克托维治疗组无因肾事件而中断,无肾近端肾小管病变或范尼综合征病例。在144周进行 ABC / DTG /3TC 和 DTG + F / TAF 的受试者中,在各组中位估计的肾小球滤过率( eGFR )也有类似的降低(-9.2 mL / min Bitarvy 患者中,降低-11.7 mL / min )。1489项研究还评估了 Bistavy 和 DTG / ABC /3TC 患者肾脏和骨骼安全的其他实验室指标。两个治疗手臂的参与者在蛋白尿和髋关节和脊柱骨密度( BMD )的平均百分比变化方面显示出相似的中位数变化。低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和总胆固醇与高密度脂蛋白比率的中位数变化与支持 DTG / ABC /3TC 的基线相比差异较小,具有统计学意义。 在144周期间,比克托维是很好的耐受性.在所有组中,由于不良事件引起的停赛发生率都较低(1%( n =6/634)。DTG / ABC /3TC 为2%( n =5/315), DTG + F / TAF 为2%( n =6/325)。与药物相关的不良事件(所有级别)在比克托维手臂( n =165/634)中所占比例为26%。DTG / ABC /3TC 的42%( n =132/315)和 DTG + F / TAF 的29%( n =94/325)。与毒品相关的恶心的发生率为百分之4比比克托维。DTG / ABC /3TC 为18%, DTG + F / TAF 为5%( Bitarvy 与 DTG / ABC /3TC 为0.0001)。最常见的治疗突发不良事件(所有级别)是腹泻(比克托维19%, DTG / ABC /3TC 18%, DTG + F / TAF 16%)。头痛(比克托维16%, DTG / ABC /3TC 18%, DTG + F / TAF 18%)和鼻咽炎(比克托维14%, DTG / ABC /3TC 17%, DTG + F / TAF 19%)。 研究1489和研究1490正在进行中。除了144周之外,研究参与者还可以选择在开放标签的扩展中接受比克托维长达96周。 比克托维不能治愈 HIV 感染或艾滋病。 美国重要的自行车安全信息和标志 boxed warning : post TREANT ACEUTIES EXPETIS B 与 HIV-1和 HBV 同时感染且已停用含有 emtripatine ( FTC )和/或富马酸替诺福韦二吡呋酯( TDF )的产品的患者报告了乙型肝炎的严重急性加重,并可能因 BIKTRVY 的中止而发生。密切监测与 HIV-1和 HBV 同时感染和终止 BIKTARVY 的患者的肝功能,并进行至少几个月的临床和实验室随访。如果合适,抗乙肝治疗可能是必要的。 对比适应症 给药:不要使用多胎或利福平. 警告及预防措施 药物相互作用:见对比适应症和药物相互作用部分。在 BIKTARVY 治疗前和治疗期间考虑药物相互作用的可能性,并监测不良反应。 免疫重建综合征,包括发生自身免疫性疾病的时间可变,以开始,已报告。 新发病或恶化的肾损害:急性肾功能衰竭和范可尼综合征已报告使用替诺福韦前药。在 BIKTARVY 的临床试验中,没有发生范可尼综合征或肾小管近端病变( PRT )的病例。对于估计肌酐清除率小于30 mL / min 的患者,不要启动 BIKTRVY 。肾功能受损和/或服用肾毒性药物(包括非甾体抗炎药)的患者发生肾相关不良反应的风险增加。停用 BIKTARVY 对肾功能明显下降的患者或范可尼综合征的证据。 肾脏监测:在开始 BIKTARVY 之前或在治疗期间,评估所有患者的血清肌酐、 CrCl 、尿葡萄糖和尿蛋白。慢性肾病患者血清磷的测定. 乳酸酸中毒和严重的肝巨脂肪变性:脂肪病例已报告使用核苷类似物,包括 FTC 和 TDF 。如果临床或实验室发现提示乳酸中毒或明显的肝毒性发展,包括在没有明显转氨酶升高的情况下肝肥大和脂肪变性,则终止 BIKTARVY 。 不良反应 临床研究至144周最常见的不良反应(发病率≥5%;所有级别)为腹泻(6%)、恶心(6%)和头痛(5%)。 药物相互作用 处方信息:请参阅 BIKTARVY 的完整处方信息,了解更多有关禁忌症、警告和潜在的重要药物相互作用的信息,包括临床评论。 酶/转运体:诱导 P-gp 或同时诱导 CYP3A 和 UGT1A1的药物可以显著降低 BIKTRVY 组分的浓度。抑制 P-gp 、 BCRP 或抑制 CYP3A 和 UGT1A1的药物可能会显著增加 BIKTRVY 组分的浓度。BIKTARVY 可增加 OCT2或 MATE1底物药物的浓度。 影响肾功能的药物: BIKTARVY 与减少肾功能或竞争有活性肾小管分泌物的药物合用,可能会增加 FTC 和替诺福韦的浓度和不良反应的风险。 剂量和管理 剂量:体重≥25公斤的患者:每日服用一次含或不含食物的片剂. 肾损害:不推荐 CrCl <30mL / min 患者使用。 肝损害:不推荐严重肝损害患者使用. 启动前或启动时:检测 HBV 感染患者。 在开始治疗之前或开始治疗时,以及在治疗期间:临床上适当,评估所有患者的血清肌酐、铬、尿葡萄糖和尿蛋白。慢性肾病患者血清磷的测定. 启动前或启动时:检测 HBV 感染患者。 在开始治疗之前或开始治疗时,以及在治疗期间:临床上适当,评估所有患者的血清肌酐、铬、尿葡萄糖和尿蛋白。慢性肾病患者血清磷的测定. 怀孕和哺乳 怀孕:在怀孕期间使用 BIKTARVY 的人类数据不足。另一种整合酶抑制剂杜鲁特格拉韦与神经管缺陷有关。探讨孕期和怀孕期间使用 BIKTRVY 的益处风险。建立了抗逆转录病毒怀孕登记处。来自 FTC APR 的现有数据显示,与美国参考人口相比,出生缺陷率没有差异。 哺乳:由于 HIV-1传染的可能性,应指示感染 HIV-1的妇女不要母乳喂养。 索引 Bitarvy 被认为是治疗成人和儿童 HIV-1感染的完整方案,这些成人和儿童的体重至少为25公斤,没有抗逆转录病毒( ARV )治疗的历史,或取代目前的 ARV 方案,在那些谁是病毒抑制( HIV-1 RNA <50拷贝每毫升)的稳定的 ARV 养生法,没有治疗失败的历史,也没有已知的抵抗任何成分 Bitarvy 。 关于吉利德科学(Gilead Sciences) 吉利德科学(Gilead Sciences), Inc .是一家以研究为基础的生物制药公司,在未满足医疗需求的领域发现、开发和商业化创新药物。该公司致力于改造和简化世界各地患有危及生命的疾病的人的护理。吉利德(Gilead)的业务遍及全球35个国家,总部位于加利福尼亚州的福斯特。 30多年来,吉利德(Gilead)一直是艾滋病毒领域的领先革新者,推动了治疗、预防、检测和保健联系以及治疗研究的进展。今天,据估计全球有超过1200万艾滋病毒感染者接受吉利德(Gilead)或该公司的一个制造伙伴提供的抗逆转录病毒治疗。 有关吉利德科学(Gilead Sciences)的更多信息,请访问公司网站 。 前瞻性陈述 本新闻稿包括1995年《私人证券诉讼改革法案》含义内的前瞻性陈述,这些陈述存在风险、不确定性和其他因素,包括必拓维正在进行的和额外的临床试验可能产生不利结果。除历史事实陈述以外的所有陈述均可视为前瞻性陈述。这些风险、不确定性和其他因素可能导致实际结果与前瞻性陈述中提及的结果存在重大差异。读者应注意不要依赖这些前瞻性陈述。这些风险和其他风险在吉利德(Gilead)提交给美国证券交易委员会的截至2019年9月30日的季度10-Q 季报中详细描述。所有前瞻性陈述均基于 Gilead 目前可获得的信息,吉利德(Gilead)不承担更新任何此类前瞻性陈述的义务。