孤儿药物名称授予小儿乙型肝炎治疗

StephenW

Orphan Drug Designation Granted to Pediatric Hepatitis B TherapyFEBRUARY 22, 2018
Mathew Shanley
This morning, ContraVir Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to tenofovir exalidex (TXL), an investigational drug candidate for the potential treatment of chronic hepatitis B infection in a pediatric patient population.

The pediatric population indication is important because it pertains to children from ages 0 years to 11, in whom infection rates related to chronic hepatitis B virus (HBV) are especially prevalent. Currently available treatment options for those infected with HBV at birth or in early childhood have had limited success.

HBV is a rare liver disease that can become chronic and lead to more severe diseases, including cirrhosis, hepatocellular carcinoma and early death. According to the Centers for Disease Control and Prevention (CDC), in the United States there are approximately 20,000 HBV infections that are diagnosed annually – most of which, however, occur in adults.

As of the announcement, TXL is the only investigational or approved HBV treatment that has been granted orphan drug designation for the pediatric patient population.

“This designation underscores the significant unmet need in this highly vulnerable patient population and provides a critical development path for TXL to bring to market a new treatment option for this under-served patient population,” said James Sapirstein, Chief Executive Officer at ContraVir in a press release.  “We look forward to continued collaboration with the FDA addressing the urgency of successfully developing treatments for hepatitis B in the pediatric and adult populations.”

TXL is being developed as a highly potent prodrug of the antiviral tenofovir (TFV), which is an active component of both tenofovir alafenamide (Vemlidy) and tenofovir disoproxil fumarate (Viread). The drug’s unique liver-targeting prodrug structure is intended to decrease systemic circulating levels of TFV, thus reducing the potential for renal and skeletal side effects.

A Phase 2 randomized, open-label, ascending, sequential dose group, multiple dose study was recently completed of TXL in HBV-infected subjects. Primary objectives included safety and tolerability of multiple oral doses of TXL at multiple ascending dose levels, and a comparison of TXL versus TFV disproxil fumarate. The study’s secondary objective was to evaluate the pharmacokinetics of multiple doses of TXL at multiple dose levels in a fasted state.

In the study, HBV-infected subjects were administered doses up to 100 mg for 28 days and ContraVir is now augmenting its formulation to further enhance delivery of the drug. To date, TXL has achieved clinical proof of concept for antiviral activity and displayed an exceptional safety, tolerability, and pharmacokinetic profile.

In September, the FDA approved an Investigational New Drug Application (IND) for TXL as a potential treatment for HBV.

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StephenW

孤儿药物名称授予小儿乙型肝炎治疗
2018年2月22日
Mathew Shanley
今天上午，ContraVir制药公司宣布，美国食品和药物管理局（FDA）已授予tenofovir exalidex（TXL）的孤儿药物名称，TXF是潜在治疗儿童患者群中慢性乙型肝炎感染的研究候选药物。

儿科人群适应症很重要，因为它适用于0岁至11岁的儿童，其中与慢性乙型肝炎病毒（HBV）相关的感染率尤其普遍。目前在出生或儿童早期感染HBV的患者的治疗选择取得了有限的成功。

HBV是一种罕见的肝脏疾病，可以变成慢性并导致更严重的疾病，包括肝硬化，肝细胞癌和早期死亡。根据美国疾病控制和预防中心（CDC）的数据，在美国，每年约有2万名乙型肝炎病毒感染者被诊断出来 - 然而，其中大部分发生在成年人身上。

截至公告显示，TXL是唯一获批准用于儿科患者群体的孤儿药物研究或批准的HBV治疗药物。

“这一称号突显了在这个极为脆弱的患者群体中尚未满足的重大需求，并为TXL为这一服务不足的患者群体提供了新的治疗方案提供了重要的发展途径，”ContraVir首席执行官James Sapirstein说。新闻稿。 “我们期待与FDA继续合作，解决在儿科和成人人群中成功开发乙型肝炎治疗的紧迫性。”

TXL正在开发作为抗病毒替诺福韦（TFV）的高度有效前体药物，其是替诺福韦艾拉酚胺（Vemlidy）和替诺福韦二吡呋酯富马酸盐（Viread）的活性成分。该药独特的肝靶向前药结构旨在降低全身循环水平的TFV，从而减少肾和骨骼副作用的可能性。

一项2期随机，开放标签，上行，顺序剂量组的多次剂量研究最近在HBV感染者中完成了TXL。主要目标包括在多个递增剂量水平下多次口服TXL剂量的安全性和耐受性，以及TXL与TFV双丙戊酸富马酸酯的比较。该研究的第二个目标是评估禁食状态下多剂量TXL的药代动力学。

在该研究中，HBV感染者在28天内服用剂量高达100mg，而ContraVir现在增加其制剂以进一步增强药物的递送。迄今为止，TXL已经获得了抗病毒活性概念的临床证明，并显示出卓越的安全性，耐受性和药代动力学特征。

9月份，FDA批准了TXL的研究性新药申请（IND）作为HBV的潜在治疗药物。

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