Opthea’s Phase 3 COAST Trial for Wet AMD Fails to Meet Primary Endpoint

Opthea的湿性AMD三期COAST试验未能达到主要终点

March 25, 2025

2025年3月25日

Opthea Limited has announced that its global Phase 3 clinical trial, known as COAST (Combination OPT-302 with Aflibercept Study), did not meet its primary endpoint for the treatment of wet age-related macular degeneration (AMD).

Opthea Limited 宣布其全球三期临床试验（称为 COAST，即 OPT-302 与阿柏西普联合研究）未达到治疗湿性年龄相关性黄斑变性（AMD）的主要终点。

COAST Trial Design and Objectives

COAST试验设计与目标

The COAST trial evaluated the efficacy and safety of sozinibercept—a first-in-class VEGF-C/D trap inhibitor—administered intravitreally at a dose of 2 mg every 4 or 8 weeks, in combination with aflibercept (2 mg) administered every 8 weeks, following a loading phase. The objective was to determine whether this combination therapy could deliver superior best corrected visual acuity (BCVA) improvements over aflibercept monotherapy..

COAST 试验评估了首类 VEGF-C/D 陷阱抑制剂——索齐尼贝塞普（sozinibercept）——以 2 mg 的剂量每 4 周或每 8 周玻璃体内注射，与每 8 周注射一次的阿柏西普（aflibercept，2 mg）联合使用的疗效和安全性，试验在加载阶段后进行。目标是确定这种联合疗法是否能在最佳矫正视力（BCVA）改善方面优于阿柏西普单药治疗。

Primary Endpoint Results

主要终点结果

The primary endpoint, defined as mean change in BCVA from baseline to week 52, was not met. Among patients with minimally classic and occult lesions:

主要终点，定义为从基线到第52周BCVA的平均变化，并未达到。在具有最小经典性和隐匿性病灶的患者中：

•

Sozinibercept combination therapy administered every 4 weeks (n=296) or every 8 weeks (n=297) yielded a mean BCVA gain of 13.2 letters in both groups.

每4周（n=296）或每8周（n=297）给予索齐尼贝普联合治疗，两组的平均BCVA增益均为13.2个字母。

•

This compared with 13.8 letters in the aflibercept monotherapy group (n=299), with P-values of 0.59 and 0.62, respectively.

相比之下，阿柏西普单药治疗组（n=299）为13.8个字母，P值分别为0.59和0.62。

In the overall population:

在总体人群中：

•

Participants receiving combination therapy every 4 weeks (n=333) gained 13.5 letters.

每4周接受联合治疗的参与者（n=333）获得了13.5个字母。

•

Those on the 8-week regimen (n=330) gained 12.8 letters.

那些采用8周疗程的患者（n=330）获得了12.8个字母。

•

The aflibercept monotherapy group (n=330) gained 13.7 letters, with P-values of 0.86 and 0.42, respectively.

阿柏西普单药治疗组（n=330）获得了13.7个字母，P值分别为0.86和0.42。

Secondary Endpoints and Safety Profile

次要终点和安全性特征

Opthea reported no numerical differences in key secondary endpoints between treatment arms. Despite the lack of efficacy differentiation, sozinibercept combination therapy was well tolerated, with no safety concerns reported.

Opthea 报告称，治疗组之间的关键次要终点没有数值差异。尽管缺乏疗效差异，但索齐尼贝塞普联合疗法耐受性良好，未报告任何安全性问题。

Opthea’s Response and Next Steps

Opthea的回应与下一步措施

Following the trial outcome, Opthea conducted a thorough review of the data to confirm its accuracy and integrity. According to the company, no anomalies were identified that would warrant an alternate interpretation of the trial results.

根据试验结果，奥普萨公司对数据进行了彻底的审查，以确认其准确性和完整性。据该公司称，未发现任何异常情况，这使得试验结果有了另一种解释。

As of now, no decision has been made regarding the continuation of the COAST trial or the potential acceleration and unmasking of the parallel ShORe trial. Discussions are ongoing with Opthea’s Development Funding Agreement (DFA) investors to evaluate future strategies.

截至目前，尚未就继续进行COAST试验或加速和揭盲平行的ShORe试验做出决定。与Opthea的发展资助协议（DFA）投资者的讨论正在进行中，以评估未来的策略。

Financial Update and Trading Suspension

财务更新与交易暂停

As of February 28, 2025, Opthea reported an unaudited cash and cash equivalents balance of $113.8 million. The company has requested that trading of its listed securities remain suspended on both the ASX and Nasdaq until an official announcement can be made, or until Monday, March 31, 2025, when trading will resume automatically..

截至2025年2月28日，Opthea报告的未经审计的现金及现金等价物余额为1.138亿美元。该公司已要求其上市证券在澳大利亚证券交易所（ASX）和纳斯达克的交易继续暂停，直至官方公告发布，或至2025年3月31日星期一自动恢复交易为止。