PARSIPPANY, N.J.--(BUSINESS WIRE)--Ferring Pharmaceuticals today announced the presentation of three-year follow-up data from the Phase 3 study1 at the 39th Annual European Association of Urology (EAU) Congress demonstrating a sustained durable response of ADSTILADRIN (nadofaragene firadenovec-vncg) in two cohorts of adult patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC).

新泽西州帕西帕尼（商业新闻短讯）--费林制药公司今天宣布，在第39届欧洲泌尿外科协会（EAU）年会上，提交了3期研究1的三年随访数据，证明阿德拉林（nadofaragene firadenovec vncg）在两组高风险卡介苗（BCG）无反应性非肌肉浸润性膀胱癌（NMIBC）成年患者中具有持续的持久反应。

Follow-up data from the high-grade Ta/T1 papillary disease cohort were presented for the first time at the EAU meeting and interim data from the cohort of patients with carcinoma in situ (CIS) with or without papillary tumors were reported in November 2023. Results from both patient cohorts are available at clinicaltrials.gov/study/NCT02773849..

在EAU会议上首次介绍了高级Ta/T1乳头状疾病队列的随访数据，并于2023年11月报告了有或没有乳头状肿瘤的原位癌（CIS）患者队列的中期数据。两个患者队列的结果均可在clinicaltrials.gov/study/NCT02773849获得。。

ADSTILADRIN is the first and only intravesical non-replicating gene therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors.

ADSTILADRIN是美国食品和药物管理局（FDA）批准的第一种也是唯一一种膀胱内非复制基因疗法，用于治疗患有或不患有乳头状肿瘤的高危BCG无反应性NMIBC的成年患者。

“While radical cystectomy provides excellent cancer control for NMIBC patients who no longer respond to standard therapy, most are elderly with significant comorbidities or are unwilling to undergo a life-altering procedure,” said Colin P.N. Dinney, M.D., Chairman of the Department of Urology, Division of Surgery, at the University of Texas MD Anderson Cancer Center, Houston, and a lead investigator of the Phase 3 study.

“虽然根治性膀胱切除术为不再对标准治疗有反应的NMIBC患者提供了极好的癌症控制，但大多数是患有严重合并症或不愿意接受改变生活的手术的老年人，”科林·P.N·丁尼医学博士说，科林·P.N·丁尼是休斯顿德克萨斯大学安德森癌症中心泌尿外科主任，也是第三阶段研究的首席研究员。

“Intravesical gene therapy represents an important innovative treatment option for these patients. In this follow-up analysis of the Phase 3 study, we demonstrated a sustained response to ADSTILADRIN treatment over three years, allowing more than half of the patients in the study to remain cystectomy free for at least 36 months.”.

“膀胱内基因治疗对于这些患者来说是一种重要的创新治疗选择。在这项3期研究的后续分析中，我们证明了对ADSTILADRIN治疗的持续反应超过了三年，使研究中超过一半的患者至少36个月不进行膀胱切除术。”。

Ongoing Follow-up of Patients in Phase 3 Study

正在进行的3期研究患者随访

The follow-up analysis is part of a Phase 3 study in which patients received ADSTILADRIN 75 mL intravesical instillation (3x1011 viral particles/mL) once every three months for up to 12 months (four doses) or until signs of toxicity or recurrent high-grade (HG) NMIBC. The trial enrolled 157 patients with BCG-unresponsive NMIBC and included two cohorts: 107 patients with CIS ±Ta/T1 (CIS cohort) and 50 patients with high-grade Ta/T1 without CIS (papillary disease [PD]).

随访分析是第三阶段研究的一部分，患者每三个月接受一次75 mL ADSTILADRIN膀胱内滴注（3x1011病毒颗粒/mL），持续12个月（四剂），或直至出现毒性迹象或复发性高级别（HG）NMIBC。该试验招募了157例卡介苗无反应的NMIBC患者，包括两个队列：107例CIS±Ta/T1患者（CIS队列）和50例无CIS的高级别Ta/T1患者（乳头状病[PD]）。

The efficacy analysis included 103 and 48 patients in the CIS and PD cohorts, respectively, who met the protocol definition of BCG-unresponsive NMIBC..

疗效分析分别包括CIS和PD队列中的103名和48名患者，他们符合BCG无反应性NMIBC的方案定义。。

Patients who were high-grade recurrence free (HGRF) at Month 12 were allowed to continue ADSTILADRIN treatment every three months as part of an ongoing follow-up analysis. In total, 12.1% (13/107) and 20.0% (10/50) of patients in the CIS and PD cohorts, respectively, received ADSTILADRIN at three years..

作为正在进行的随访分析的一部分，允许在第12个月时高度无复发（HGRF）的患者每三个月继续阿德替拉林治疗。总共，CIS和PD队列中分别有12.1%（13/107）和20.0%（10/50）的患者在三年内接受了ADSTILADRIN。。

Follow-up Analysis Shows Durable Response

后续分析显示持久的反应

In the CIS cohort, about 53% achieved a complete response (CR) at Month 3 in the primary analysis. By 36 months, more than 25% of these patients (14/55) remained HGRF. In the high-grade PD cohort in a secondary analysis, nearly 73% were HGRF at Month 3 and of these patients, about 31% (11/35) remained HGRF through three years..

在CIS队列中，大约53%在初步分析的第3个月达到了完全缓解（CR）。到36个月时，这些患者中有25%以上（14/55）仍然是HGRF。在二次分析的高级PD队列中，近73%的患者在第3个月时为HGRF，在这些患者中，约31%（11/35）的患者在三年内仍为HGRF。。

The median duration of CR in both cohorts was nearly 10 months (9.2 – 24.0), with an approximately 34% (21.6% – 47.1%) Kaplan-Meier (KM)-estimated probability of duration of CR for at least three years. The estimated median (95% CI) duration of HGRF survival was six months (3.4 – 8.3) in the CIS cohort and about 12 months (6.7 – 20.3) in the PD cohort.

两个队列中CR的中位持续时间接近10个月（9.2–24.0），Kaplan-Meier（KM）估计CR持续至少三年的概率约为34%（21.6%–47.1%）。在CIS队列中，HGRF生存期的估计中位数（95%CI）为6个月（3.4-8.3），在PD队列中为约12个月（6.7-20.3）。

The KM-estimated cystectomy-free survival (95% CI) at three years was nearly 54% (43.3 – 63.1) in the CIS cohort and nearly 64% (48.0 – 75.6) in the PD cohort, and the three-year overall survival was about 90% (82.3 – 94.9) and about 91% (78.5 – 96.7) in the CIS and PD cohorts, respectively..

KM估计的三年无膀胱切除术生存率（95%CI）在CIS队列中接近54%（43.3-63.1），在PD队列中接近64%（48.0-75.6），三年总生存率在CIS和PD队列中分别约为90%（82.3-94.9）和约91%（78.5-96.7）。。

“ADSTILADRIN is a novel therapy that has demonstrated its value as an effective and well-tolerated standard-of-care treatment for high-risk NMIBC patients with CIS ± Ta/T1 who have BCG-unresponsive disease,” said Pierre-Yves Berclaz, M.D., PhD., Executive Vice President and Chief Science and Medical Officer, Ferring Pharmaceuticals.

医学博士皮埃尔·伊夫·贝克拉兹（PierreYves-Berclaz）说：“阿德替拉林是一种新型疗法，已证明它是一种有效且耐受性良好的标准治疗方法，可用于卡介苗无反应性疾病的高危NMIBC患者。”。，费林制药公司执行副总裁兼首席科学和医学官。

“This 3-year analysis provides further evidence for the durable efficacy and long-term safety of ADSTILADRIN in this on-label patient population, as well as additional data showing its therapeutic potential in a separate population of NMIBC patients with papillary disease. We look forward to continuing patient follow up as we work to redefine the treatment of NMIBC.”.

“这项为期3年的分析为ADSTILADRIN在这一标签上的患者人群中的持久疗效和长期安全性提供了进一步的证据，并提供了额外的数据，显示其在单独的乳头状疾病NMIBC患者群体中的治疗潜力。我们期待着在重新定义NMIBC治疗的同时继续进行患者随访。”。

The treatment was well-tolerated and no new safety signals were observed during this three-year long-term follow-up analysis. Over the course of three years, only three patients discontinued treatment due to an adverse event (AE), including two in the CIS cohort because of Grade 3 bladder spasm (n=1) and Grade 2 instillation site discharge (n=1), and one in the PD cohort due to Grade 2 benign neoplasm of the bladder.

治疗耐受性良好，在这三年的长期随访分析中未观察到新的安全信号。在三年的过程中，只有三名患者因不良事件（AE）停止治疗，其中两名患者因3级膀胱痉挛（n=1）和2级滴注部位放电（n=1）而在CIS队列中停止治疗，一名患者因2级膀胱良性肿瘤而在PD队列中。

No events leading to discontinuation were considered serious AEs..

没有导致停药的事件被认为是严重的不良事件。。

About ADSTILADRIN

关于ADSTILADRIN

ADSTILADRIN® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

ADSTILADRIN®（nadofaragene firadenovec vncg）是FDA批准的第一种也是唯一一种膀胱内基因疗法，用于治疗成人高危卡介苗（BCG）-无反应性非肌层浸润性膀胱癌（NMIBC）原位癌（CIS）伴或不伴乳头状肿瘤。

It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer.

它是一种基于非复制腺病毒载体的疗法，含有干扰素α-2b基因，每三个月通过导管直接进入膀胱一次。该载体进入膀胱壁细胞，释放活性基因，使膀胱细胞壁分泌大量干扰素α-2b蛋白，这是一种人体用于抗癌的天然蛋白质。

This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer..

这种方法实质上是将膀胱壁细胞转化为干扰素微工厂，增强人体自身对癌症的自然防御能力。。

ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849).1.

ADSTILADRIN已经在一项临床试验计划中进行了研究，该计划包括157名高度BCG无反应的NMIBC患者，这些患者之前曾接受过足够的BCG治疗，但没有从额外的BCG治疗中获益（完整纳入标准发表在clinicaltrials.gov上：NCT02773849）。

About Non-Muscle Invasive Bladder Cancer (NMIBC)

关于非肌层浸润性膀胱癌（NMIBC）

NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.2 In the United States, bladder cancer is the seventh most common cancer, fourth among men3-4, and it is estimated that there will be approximately 83,190 new cases of bladder cancer in the U.S.

NMIBC是一种膀胱癌，存在于膀胱的浅层，没有深入膀胱或扩散到身体的其他部位。2在美国，膀胱癌是第七大最常见的癌症，在men3-4中排名第四，据估计，美国将有大约83190例新发膀胱癌病例。

in 2024.5 Historically, 75% of bladder cancer presents as NMIBC.6 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard-of-care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.5 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder).7.

从历史上看，2024.5年，75%的膀胱癌表现为NMIBC[6]。在高危NMIBC患者中，膀胱内卡介苗仍然是一线护理标准。然而，超过50%接受卡介苗初始治疗的患者将在一年内经历疾病复发和进展，许多患者发展为卡介苗无反应性疾病[5]。目前卡介苗无反应患者的治疗选择非常有限，国家综合癌症网络（NCCN）指南建议膀胱切除术（部分或完全切除膀胱）。

INDICATION

指示

ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

ADSTILADRIN是一种基于非复制腺病毒载体的基因疗法，适用于治疗高危卡介苗（BCG）-无反应性非肌肉浸润性膀胱癌（NMIBC）伴原位癌（CIS）伴或不伴乳头状肿瘤的成年患者。

IMPORTANT SAFETY INFORMATION

重要安全信息

CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

禁忌症：ADSTILADRIN禁用于先前对干扰素α或产品任何成分有超敏反应的患者。

WARNINGS AND PRECAUTIONS:

警告和注意事项：

Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy..

延迟膀胱切除术的风险：BCG无反应的CIS患者延迟膀胱切除术可能导致肌肉浸润性或转移性膀胱癌的发展，这可能是致命的。如果CIS患者在3个月后对治疗没有完全反应，或者CIS复发，请考虑膀胱切除术。。

Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.

播散性腺病毒感染的风险：由于复制能力低的腺病毒水平，免疫功能低下或免疫缺陷的人可能有从ADSTILADRIN传播感染的风险。避免ADSTILADRIN暴露于免疫功能低下或免疫缺陷的个体。

DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

剂量和给药：仅通过膀胱内滴注给予ADSTILADRIN。ADSTILADRIN不用于静脉注射，局部使用或口服给药。

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose..

在特定人群中使用：建议具有生殖潜力的女性在ADSTILADRIN治疗期间和最后一剂后6个月内使用有效的避孕方法。建议有生殖潜力的女性伴侣的男性患者在阿德替拉林治疗期间和最后一剂后3个月内使用有效的避孕措施。。

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination)..

不良反应：最常见的不良反应（>10%），包括实验室异常（>15%），包括血糖升高，滴注部位排出，甘油三酯升高，疲劳，膀胱痉挛，排尿（尿急），肌酐升高，血尿（尿中有血），磷酸盐减少，寒战，发热（发烧）和排尿困难（排尿疼痛）。。

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

鼓励您向FDA报告处方药的负面副作用。访问www.FDA.gov/medwatch或致电1-800-332-1088。您也可以通过1-888-Ferring联系Ferring Pharmaceuticals。

Please click to see the full Prescribing Information.

请单击查看完整的处方信息。

About Ferring Pharmaceuticals

关于Ferring Pharmaceuticals

Ferring Pharmaceuticals is a privately-owned, research-driven, specialty biopharmaceutical group committed to building families and helping people live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, and in areas of gastroenterology and orthopaedics.

Ferring Pharmaceuticals是一家私营、以研究为导向的专业生物制药集团，致力于建立家庭，帮助人们过上更好的生活。在美国，费林是生殖医学和孕产妇健康以及胃肠病学和骨科领域的领导者。

We are at the forefront of innovation in microbiome-based therapeutics and uro-oncology intravesical gene therapy. Our company was founded in 1950 and is headquartered in Saint-Prex, Switzerland. Ferring employs more than 7,000 people worldwide and markets its medicines in over 100 countries. Ferring USA is based in Parsippany, New Jersey, and employs more than 900 employees..

我们处于基于微生物组的治疗和泌尿肿瘤膀胱内基因治疗创新的前沿。我们公司成立于1950年，总部位于瑞士圣普雷克斯。Ferring在全球拥有7000多名员工，其药品在100多个国家销售。Ferring USA总部位于新泽西州帕西帕尼，拥有900多名员工。。

For more information, please visit www.ferringusa.com, call 1-888-FERRING (1-888-337-7464), or connect with us on LinkedIn, and X (Twitter).

有关更多信息，请访问www.ferringusa.com，致电1-888-FERRING（1-888-337-7464），或通过LinkedIn和X（Twitter）与我们联系。

References:

参考文献：

ADSTILADRIN in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. https://clinicaltrials.gov/ct2/show/NCT02773849.

ADSTILADRIN治疗高级别卡介苗（BCG）无反应性非肌层浸润性膀胱癌（NMIBC）患者。政府标识符：NCT02773849。https://clinicaltrials.gov/ct2/show/NCT02773849.

Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 2021; 22: 107–17.

Boorjian SA，Alemozaffar M，Konety BR等。膀胱内nadofaragene-firadenovec基因治疗卡介苗无反应性非肌肉浸润性膀胱癌：单臂，开放标签，重复剂量临床试验。柳叶刀Oncol 2021；22:107-17。

Bladder Cancer Advocacy Network. Bladder Cancer Advocacy Network Responds to American Cancer Society’s 2024 Projections. Bladder Cancer Advocacy Network Responds to American Cancer Society's 2024 Projections – Bladder Cancer Advocacy Network (bcan.org), page last accessed: March 2024.

膀胱癌倡导网络。膀胱癌倡导网络响应美国癌症协会2024年的预测。膀胱癌倡导网络响应美国癌症协会2024年预测-膀胱癌倡导网络（bcan.org），最后访问页面：2024年3月。

American Cancer Society. Cancer Facts & Figures 2024 Report. Cancer Facts & Figures 2024, page last accessed: March 2024

美国癌症协会。2024年癌症事实与数字报告。癌症事实与数字2024，最后访问的页面：2024年3月

American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. Accessed April, 2024.

美国癌症协会。癌症事实与数字2024。亚特兰大：美国癌症协会；2024https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html.2024年4月访问。

Babjuk M, Burger M, Capoun O, European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer. Eur Urol. 2022 Jan;81(1):75-94.

Babjuk M，Burger M，Capoun O，欧洲泌尿外科协会非肌肉浸润性膀胱癌指南。Eur Urol公司。2022年1月；81（1）：75-94。

National Comprehensive Cancer Network. Bladder Cancer (Version 1.2024). www.nccn.org/professionals/physicians_gls/pdf/bladder.pdf. Accessed March 7, 2024.

国家综合癌症网络。膀胱癌（版本1.2024）。www.nccn.org/professionals/mediciners\u gls/pdf/bladder.pdf。2024年3月7日访问。

More information is available at the following:

有关更多信息，请访问以下网址：

Health Care Providers: If you are interested in ordering ADSTILADRIN, please sign up for information and updates at ADSTILADRINHCP.com.

医疗保健提供者：如果您有兴趣订购ADSTILADRIN，请在ADSTILADRINHCP.com注册以获取信息和更新。

Patients and Consumers: For more information about ADSTILADRIN, please call 1-888-FERRING (888-337-7464), and select option number one.

患者和消费者：有关ADSTILADRIN的更多信息，请致电1-888-FERRING（888-337-7464），然后选择选项1。