Replimune secures FDA approval for melanoma therapy Tudriqev after long regulatory battle

来源：Fiercepharma | 发布时间：2026-08-31

摘要：美国FDA加速批准Replimune公司基于HSV-1改造的溶瘤免疫疗法Tudriqev联合纳武利尤单抗，用于抗PD-1方案治疗后进展的不可切除晚期皮肤黑色素瘤成人患者，该批准基于1/2期临床24.2%的客观缓解率数据，确证性3期试验正在进行中。

In a remarkable turnaround, Replimune has reversed the fortune of its melanoma therapy, winning FDA approval after two prior rejections and agency leadership shakeups.

Thursday, the FDA granted accelerated approval to Replimune’s engineered viral immunotherapy Tudriqev (vusolimogene oderparepvec) in combination with Bristol Myers Squibb’s Opdivo for adults with unresectable advanced cutaneous melanoma whose disease progressed on prior anti-PD-1 therapy.

The go-ahead is supported by results from the phase 1/2 Ignyte trial, in which the combo delivered a 24.2% objective response rate and a median duration of response of 14.1 months among 91 efficacy-evaluable patients.

The green light marks a dramatic regulatory turnaround for Massachusetts-based Replimune following two high-profile FDA rejections accompanied by intense debate over the interpretability of the drug’s clinical data. Former FDA Commissioner Marty Makary, M.D., previously defended the agency’s decision to reject Tudriqev, as The Wall Street Journal’s editorial board used the case to criticize his leadership.

The approval comes shortly after an FDA advisory committee voted 10 to 3 in favor of the drug’s profile, even though the FDA’s reviewers had raised significant concerns about the trial results. The agency had questioned that, without a comparator arm, the contribution of Tudriqev, previously known as RP1, couldn’t be isolated from Opdivo. Because the drug is injected directly into the tumor, the FDA also raised doubts about its systemic treatment effect.

Although external advisors to the FDA shared some of the agency’s concerns, they also believed that Replimune has shown enough data to support an approval. For example, even after excluding patients without enough tumor lesions to assess systemic response, the drug’s response rate remains notably above historical experience in this patient population.

“This is a transformative moment for Replimune, marking years of pioneering research to bring Tudriqev to patients desperately in need of new treatment options for advanced melanoma,” Sushil Patel, Ph.D., CEO of Replimune, said in an Aug. 6 statement, as he also thanked the FDA for “recognizing the urgency to get this therapy to patients.”

Thursday’s approval, though hard-won, does not mean Replimune’s fate has completely reversed. Because the approval was granted under the accelerated pathway based on surrogate endpoints, Replimune remains on the hook to confirm Tudriqev’s clinical benefit in a confirmatory trial, which currently looks to be the ongoing phase 3 Ignyte-3 study.

The trial, which compares the Tudriqev-Opdivo cocktail against physician’s choice of therapy, has enrolled about a third of its target population, with a readout from its primary endpoint of overall survival expected in 2030, Replimune management said on an investor call Thursday. As Leerink analysts pointed out in an Aug. 6 note, Replimune will need those randomized overall survival data to secure approvals outside the U.S.

Before that, Leerink Partners analysts projected “strong demand for the regimen given its relative ease of access and benign safety profile,” according to an Aug. 3 note. Most treatment-related adverse reactions observed so far from the combo were grade 1 and 2 and transient.

Another option for post-PD-1 cutaneous melanoma, Iovance Biotherapeutics’ cell therapy Amtagvi, comes with a cumbersome treatment process with logistical challenges and potentially intense side effects from various components of the therapy.

“Tudriqev is an off-the-shelf treatment, practically for everyday clinical practice, that minimizes logistical complexity and treatment delays, and ensures that patients with aggressive disease receive immediate care,” Replimune’s chief medial officer, Kostas Xynos, M.D., Ph.D. said on the Thursday call.

美国FDA加速批准创新溶瘤免疫疗法

Replimune近日宣布，美国FDA已加速批准Tudriqev（vusolimogene oderparepvec，此前称为RP1）联合纳武利尤单抗，用于治疗接受以抗PD-1抗体为基础的治疗方案后疾病进展的不可切除晚期皮肤黑色素瘤成人患者。

这一批准主要基于1/2期IGNYTE研究中2期黑色素瘤队列的数据。IGNYTE试验共纳入140例患者，其中91例患者至少有1个未接受瘤内注射的病灶，构成疗效可评价人群。在该人群中，Tudriqev联合纳武利尤单抗取得了24.2%的客观缓解率（ORR），中位缓解持续时间为14.1个月。该联合疗法总体耐受性良好，不良事件大多为轻度至中度。IGNYTE研究数据已发表于Journal of Clinical Oncology。

晚期黑色素瘤患者的治疗选择有限。Replimune在新闻稿中指出，超过一半的晚期黑色素瘤患者在接受抗PD-1疗法等免疫检查点抑制剂治疗后6个月内出现疾病进展。这些患者预后较差，疾病进展后的中位总生存期不足1年。

为验证Tudriqev的临床获益，一项名为IGNYTE-3的确证性3期临床试验正在进行中，旨在评估Tudriqev联合纳武利尤单抗的疗效和安全性。

Tudriqev是一种基于1型单纯疱疹病毒（HSV-1）开发的溶瘤病毒免疫疗法。该疗法经过基因工程改造，可表达融合性糖蛋白GALV-GP R-和粒细胞-巨噬细胞集落刺激因子（GM-CSF），旨在增强对肿瘤细胞的直接裂解作用，提高肿瘤细胞死亡的免疫原性，并激活全身性抗肿瘤免疫应答。