FDA 批准替诺福韦艾拉酚胺用于患有慢性乙型肝炎病毒的青少

StephenW

FDA 批准替诺福韦艾拉酚胺用于患有慢性乙型肝炎病毒的青少年
2022 年 12 月 6 日
PT员工

替诺福韦艾拉酚胺（Tenofovir alafenamide）（Vemlidy；Gilead Science）获批用于治疗 12 岁及以上代偿性肝病儿科患者的慢性乙型肝炎病毒感染。

FDA 已批准替诺福韦艾拉酚胺（Vemlidy；Gilead Science）的补充新药申请，用于治疗 12 岁及以上代偿性肝病青少年的慢性乙型肝炎病毒 (HBV) 感染。 替诺福韦艾拉酚胺是替诺福韦的一种新型靶向膦酰胺前体药物，最初于 2016 年获得 FDA 批准，用于治疗慢性 HBV 感染伴代偿性肝病的成人，每日一次。

吉利德科学公司首席医疗官 Merdad Parsey 医学博士在一份新闻稿中说：“虽然美国儿童乙型肝炎患病率已显着下降，但在急性感染后发展为慢性乙型肝炎的儿童可能会受到终生健康影响。” “吉利德专注于应对肝病领域的最大挑战并影响疾病进程。 凭借既定的安全性和每日一次的剂量，Vemlidy 为医生提供了一个新的选择来满足患有乙型肝炎的儿科患者的治疗需求。”

HBV 通过性接触、共用注射器或出生时母婴传播，通过体液从病毒感染者身上传播。 对某些人来说，HBV 是一种短期疾病，而对另一些人来说，它可能会成为一种长期的慢性感染，这与他们感染时的年龄有关。 与成人的 2% 至 6% 相比，大约 90% 的 HBV 婴儿会发展为慢性感染。

1092 试验调查员 Kathleen Schwarz 说：“慢性乙型肝炎会对儿童的健康产生重大的长期影响，包括如果不及时治疗这种疾病，会在以后的生活中发展为肝癌，而这一人群的治疗挑战会加剧这种情况，” 医学博士，圣地亚哥拉迪儿童医院的儿科胃肠病学家，在一份新闻稿中。

替诺福韦艾拉酚胺是一种核苷类似物逆转录酶抑制剂，专门用于治疗 HBV 代偿性肝病。 由于替诺福韦不易穿过细胞膜且吸收不良，因此需要替诺福韦的前药来增加其细胞渗透性和口服生物利用度。

新的儿科适应症的批准是基于试验 1092 的 24 周数据，该试验是一项 2 期研究，招募了 70 名 12 至 18 岁的患者。 该试验在 70 名年龄在 12 岁至 18 岁以下且体重至少 35 公斤的未接受过治疗和接受过治疗的患者中比较了 25 毫克替诺福韦艾拉酚胺与安慰剂的治疗效果。

该研究达到了治疗 24 周时 HBV DNA 水平低于 20 IU/mL 的患者百分比的主要终点。 总体而言，21% 的服用替诺福韦艾拉酚胺 25 mg 的患者在 24 周时达到 HBV DNA <20 IU/mL，而安慰剂队列中这一比例为 0%。

“作为一名临床医生，我认识到尽快治疗这种疾病的重要性，这有助于避免并发症和对肝脏的潜在损害，”施瓦茨在新闻稿中说。 “在临床试验中，我们发现替诺福韦阿拉芬胺可能是年仅 12 岁的慢性病患者的一种有效治疗选择。”

最常见的不良事件包括头痛、上呼吸道感染、腹痛、咳嗽、背痛、关节痛、疲劳、恶心、腹泻、消化不良和发热。

警告和预防措施包括 HBV/HIV-1 合并感染、新发或恶化的肾功能损害、乳酸性酸中毒和伴有脂肪变性的严重肝肿大患者产生 HIV-1 耐药性的风险。

参考

美国食品和药物管理局批准 Vemlidy®（替诺福韦艾拉酚胺）用于治疗儿科患者的慢性乙型肝炎病毒感染。 吉利德科学。 新闻发布。 2022 年 12 月 2 日。https://www.gilead.com/news-and- ... nofovir-alafenamide -用于治疗儿科患者的慢性乙型肝炎病毒感染

StephenW

FDA Approves Tenofovir Alafenamide for Adolescents With Chronic Hepatitis B Virus
December 6, 2022
PT Staff

Tenofovir alafenamide (Vemlidy; Gilead Science) approved for the treatment of chronic hepatitis B virus infection in pediatric patients aged 12 years and older with compensated liver disease.

The FDA has approved a supplemental new drug application for tenofovir alafenamide (Vemlidy; Gilead Science) for the treatment of chronic hepatitis B virus (HBV) infection in adolescents aged 12 years and older with compensated liver disease. Tenofovir alafenamide is a novel, targeted phosphonamidate prodrug of tenofovir that was initially approved by the FDA in 2016 for the once-daily treatment of adults with chronic HBV infection with compensated liver disease.

“While pediatric hepatitis B prevalence has dropped significantly in the US, children who develop chronic hepatitis B following an acute infection can experience lifelong health impact,” said Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, in a press release. “Gilead is focused on meeting the biggest challenges in liver disease and impacting the course of disease. With an established safety profile and once-daily dosing, Vemlidy provides physicians a new option to address the treatment needs of pediatric patients living with hepatitis B.”

HBV is transmitted via bodily fluids from a person infected with the virus through sexual contact, by sharing syringes, or from mother to baby at birth. In some people, HBV is a short-term illness, whereas in others, it could become a long-term chronic infection, which is associated with their age at the time of infection. Approximately 90% of infants with HBV develop chronic infection compared with 2% to 6% of adults.

“Chronic hepatitis B can have a significant long-term health impact on children, including the development of liver cancer later in life if the disease is left untreated, which is compounded by treatment challenges in this population,” said Trial 1092 investigator Kathleen Schwarz, MD, pediatric gastroenterologist at Rady Children’s Hospital-San Diego, in a press release.

Tenofovir alafenamide is a nucleoside analog reverse transcriptase inhibitor specifically indicated to treat HBV with compensated liver disease. Because tenofovir does not readily cross cell membranes and is poorly absorbed, prodrugs of tenofovir are needed to increase its cellular permeability and oral bioavailability.

The approval for the new pediatric indication was based on 24-week data from Trial 1092, a phase 2 study that enrolled 70 patients between 12 and 18 years of age. The trial compared treatment with tenofovir alafenamide 25 mg vs placebo among 70 treatment-naïve and treatment-experienced patients aged 12 to less than 18 years of age and weighing at least 35 kg.

The study met the primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy. Overall, 21% of patients administered tenofovir alafenamide 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% of patients in the placebo cohort.

“As a clinician, I recognize the critical importance of treating this disease as quickly as possible to help avoid complications and potential damage to the liver,” Schwarz in the release. “In the clinical trial, we saw that tenofovir alafendamide may represent an effective treatment option for people as young as 12 years of age living with chronic disease.”

The most common adverse events included headache, upper respiratory tract infection, abdominal pain, cough, back pain, arthralgia, fatigue, nausea, diarrhea, dyspepsia, and pyrexia.

Warnings and precautions include risk of development of HIV-1 resistance in patients with HBV/HIV-1 coinfection, new onset or worsening renal impairment, and lactic acidosis and severe hepatomegaly with steatosis.

Reference

U.S. Food and Drug Administration Approves Vemlidy® (tenofovir alafenamide) for Treatment of Chronic Hepatitis B Virus Infection in Pediatric Patients. Gilead Sciences. News release. December 2, 2022. https://www.gilead.com/news-and- ... -pediatric-patients