A Multi-Center, Randomized, Double-Masked, Active-Comparator-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (ARTEMIS)

This is a multi-center, randomized, double-masked, active-comparator-controlled, Phase 3 study in a broad participant population (treatment-naïve and treatment-experienced) with neovascular (wet) age-related macular degeneration (nAMD). The study will evaluate a single intravitreal (IVT) injection of Ixo-vec compared to an active comparator. The primary endpoint of this study is the mean change in best corrected visual acuity (BCVA) of Ixo-vec compared to an active comparator measured at an average of Weeks 52 and 56.
Safety, tolerability, and efficacy will be evaluated throughout the study.

开始日期2025-02-28

申办/合作机构

Adverum Biotechnologies, Inc.

NCT05536973

/ Active, not recruiting临床2期

A Multi-Center, Randomized, Double-Masked Phase 2 Study to Assess Safety and Efficacy of ADVM-022 (AAV.7m8-aflibercept) in Anti-VEGF Treatment-Experienced Patients With Neovascular (Wet) Age-related Macular Degeneration (nAMD) [LUNA]

Neovascular or wet age-related macular degeneration (nAMD) is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.

开始日期2022-08-23

申办/合作机构

Adverum Biotechnologies, Inc.

NCT05607810

/ Enrolling by invitationN/A

A Long-Term Follow-Up Study of ADVM-022 in Diabetic Macular Edema- INFINITY Extension

This is a prospective, observational study designed to evaluate the long-term safety and tolerability of ADVM-022 in participants with diabetic macular edema (DME). Participants who previously participated in the INFINITY parent study and received a single unilateral intravitreal dose of ADVM-022 are eligible for enrollment upon completion of the end of study visit in the parent study.

开始日期2022-08-10

申办/合作机构

Adverum Biotechnologies, Inc.

100 项与 Ixoberogene soroparvovec 相关的临床结果

登录后查看更多信息

100 项与 Ixoberogene soroparvovec 相关的转化医学

登录后查看更多信息

100 项与 Ixoberogene soroparvovec 相关的专利（医药）

登录后查看更多信息

项与 Ixoberogene soroparvovec 相关的文献（医药）

2025-01-01·EYE

Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues

Review

作者: Shirian, Jonathan D ; Shirian, Jonathan D. ; Shukla, Priya ; Singh, Rishi P. ; Singh, Rishi P

Abstract:

Neovascular age-related macular degeneration (nAMD) can lead to significant vision impairment through the growth of abnormal neovascular membranes in the choroid. Despite advancements with current anti-vascular endothelial growth factor (VEGF) therapies, challenges such as frequent injections, inadequate response, and patient-related concerns persist. Emerging therapeutics aim to reduce vision-loss through a variety of mechanisms. Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951.

2024-01-01·EClinicalMedicine

Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study

Article

作者: Kiss, Szilárd ; Wykoff, Charles C ; Danzig, Carl J ; Major, James C ; Joondeph, Brian C ; Turpcu, Adam ; Boyer, David S ; Regillo, Carl D ; Khanani, Arshad M ; Pieramici, Dante ; Busbee, Brandon G

Background:

Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD.

Methods:

In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to anti-VEGF were assigned to four cohorts differing by ixo-vec dose (2 × 10¹¹ vs 6 × 10¹¹ vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov, NCT03748784.

Findings:

Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020 at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6 × 10¹¹ dose group and in 7 participants in the 2 × 10¹¹ dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2 × 10¹¹ vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2 × 10¹¹ vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6 × 10¹¹ vg/eye cohorts.

Interpretation:

Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions.

Funding:

Adverum Biotechnologies.

2022-02-01·Eye (London, England)3区 · 医学

Review of gene therapies for age-related macular degeneration

3区 · 医学

Review

作者: Danzig, Carl J ; Yiu, Glenn ; Kaiser, Peter K ; Waheed, Nadia K ; Aziz, Aamir A ; Weng, Christina Y ; Khanani, Arshad M ; Thomas, Mathew J ; Kiss, Szilárd

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.

112

项与 Ixoberogene soroparvovec 相关的新闻（医药）

2025-03-04

·PipelineReview

Adverum Biotechnologies Initiates ARTEMIS Phase 3 Study Evaluating Ixo-vec for Wet AMD

REDWOOD CITY, CA, USA I March 03, 2025 I Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy to preserve sight for life in highly prevalent ocular diseases, today announced the initiation of the ARTEMIS Phase 3 study. This pivotal trial is designed to evaluate the efficacy and safety of Ixo-vec (ixoberogene soroparvovec) as a one-time intravitreal (IVT) injection for patients with neovascular (wet) age-related macular degeneration (AMD). ARTEMIS is a US-based study evaluating a single administration of Ixo-vec (6E10 vg/eye) compared to aflibercept (2mg) every 8 weeks in approximately 284 patients with wet AMD, including both treatment-naïve and previously treated patients. The primary endpoint is mean change from baseline in best corrected visual acuity (BCVA) at one year (average of weeks 52 and 56) with a non-inferiority (NI) margin of -4.5 letters. Per FDA guidance, all patients will receive three loading doses of aflibercept prior to receiving Ixo-vec. Patients in both arms will be eligible for supplemental injections of aflibercept and will receive prophylactic steroid eye drops. ARTEMIS is the first of two planned Phase 3 registrational trials to evaluate Ixo-vec in patients with wet AMD. Details on the second study, named AQUARIUS and to be conducted globally, will be forthcoming. “Gene therapy is recognized as the most exciting modality on the horizon for the treatment of wet AMD. Initiation of the Phase 3 ARTEMIS trial demonstrates our commitment to transforming the landscape with a one-time IVT injection to help restore vision and prevent blindness,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “With over 4 years of experience, we are at the forefront and believe Ixo-vec is positioned as a best-in-class therapy to provide potentially lifelong benefit to patients who depend on frequent injections to preserve their sight. Huge kudos to my colleagues at Adverum who have worked expeditiously to initiate ARTEMIS, a pioneering effort, and who have consistently outperformed our ambitious timelines.” “Leveraging our robust data for Ixo-vec, the ARTEMIS Phase 3 trial was designed to enhance the potential for clinical, regulatory and commercial success,” stated Rabia Gurses Ozden, MD, Chief Medical Officer at Adverum. “We have been thrilled by the enthusiasm of retina specialists for this design, including studying Ixo-vec in both treatment-naïve and previously treated patients, which we expect will increase the speed of enrollment and generate a registrational dataset representative of real-world patient demographics. We are eager to generate the data necessary to seek regulatory approval and ultimately establish Ixo-vec as a transformative treatment option for a broad spectrum of wet AMD patients.” “There continues to be tremendous unmet need for longer-acting anti-VEGF therapies. Underscoring the unmet need, recent data indicate that up to 42% of patients stop treatment for wet AMD after 2 years, which results in poor long-term vision outcomes. Ixo-vec’s potential to dramatically reduce treatment burden, provide lifelong injection freedom and enhance long-term vision outcomes could deliver a compelling benefit for a large proportion of wet AMD patients,” said Dr. Dante Pieramici, Medical Director of Research, California Retina Consultants and an investigator for ARTEMIS. “Consistent with the strong patient preference for Ixo-vec indicated by LUNA patients, there is great interest from my patients when they hear about a therapy like Ixo-vec that has the potential to treat their disease with a single injection. I’m delighted to have served as an investigator for both OPTIC and LUNA, and I look forward to working with the Adverum team on the ARTEMIS pivotal study.” “When designing registrational trials for patients with wet AMD, it’s not always feasible to study the therapeutic agent in a patient population that closely represents the real-world. Adverum’s inclusion in ARTEMIS of both treatment-naive and treatment-experienced patients is intended to address a broad patient population, including those with the highest treatment burden,” said Dr. Sean Adrean, Partner, Retina Consultants of Orange County and an investigator for ARTEMIS. “Based on its design, I expect the data coming out of the ARTEMIS trial will be highly informative and answer the key question of how Ixo-vec is expected to perform in those patients with high injection burdens and would most benefit from gene therapy. Looking back over 2 years ago, it was a pleasure to kick-off enrollment in LUNA, Ixo-vec’s Phase 2 clinical trial, and be part of that successful trial. Now today, it’s a thrill to be one of the first sites to begin screening patients and contribute to Ixo-vec’s Phase 3 clinical trial.” “Delivering continuous levels of aflibercept to reduce treatment burden and improve visual outcomes may be even more profound in treatment naïve patients,” said Dr. Carl Danzig, Rand Eye Institute and an investigator for ARTEMIS. “In OPTIC and LUNA, Ixo-vec has demonstrated the ability to durably produce therapeutic levels of aflibercept with an acceptable long-term safety profile, suggesting a potential lifelong benefit with a therapy that is well tolerated. It’s a great pleasure to be a part of this registrational program, and I look forward to working with the Adverum team to generate data to more fully elucidate Ixo-vec’s therapeutical potential for my patients.” About the ARTEMIS Phase 3 Study The Phase 3 ARTEMIS trial (NCT06856577) is designed to evaluate the safety and efficacy of Ixo-vec in a randomized (1:1), double-masked, sham-controlled, two-arm study. The US-based trial is intended to randomize approximately 284 patients, including both patients who are treatment naïve and patients who have been previously treated. The primary endpoint, measured at an average of weeks 52 and 56, is NI in mean BCVA change from baseline with a NI margin of -4.5 letters. The key secondary endpoint is reduction of injection burden as measured by mean number of injections received. All patients will receive three monthly loading doses of aflibercept prior to receiving Ixo-vec. Patients in both arms will be eligible for supplemental injections of aflibercept and will receive topical steroid eye drops. About Wet Age-Related Macular Degeneration Wet AMD, also known as neovascular AMD or nAMD, is a VEGF driven advanced form of AMD affecting approximately 10% of patients living with AMD associated with the build-up of fluid in the macula and the retina. Wet AMD is a leading cause of blindness in people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases. Additionally, wet AMD is a bilateral disease, and incidence of nAMD in the second eye is up to 42% in the first two to three years. The current standard of care requires frequent life-long repeated bolus injections of anti-VEGF in the eye. IVT gene therapy has the promise to preserve vision and reduce most or all injections for the life of the patient by delivering stable therapeutic levels of anti-VEGF to control macular fluid. About Ixo-vec in Wet AMD Adverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-VEGF, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, FDA granted Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations for Ixo-vec for the treatment of wet AMD. Ixo-vec has also received PRIME designation from the EMA and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD. About Adverum Biotechnologies Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures to restore vision and prevent blindness. Leveraging the capabilities of its proprietary IVT platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. Additionally, by overcoming the challenges associated with current treatment paradigms for debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit www.adverum.com. SOURCE: Adverum Biotechnologies

临床3期快速通道基因疗法临床2期

2024-12-06

·GlobeNewswire-Health Care

Adverum Biotechnologies Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

REDWOOD CITY, Calif., Dec. 06, 2024 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM) today announced that on December 4, 2024, the Compensation Committee of Adverum’s Board of Directors granted inducement awards consisting of non-qualified stock options to purchase 68,640 shares of common stock and restricted stock units (RSUs) for 34,920 shares of common stock to 13 new employees under Adverum’s 2017 Inducement Plan. The Compensation Committee of Adverum’s Board of Directors approved the awards as an inducement material to the new employees’ employment in accordance with Nasdaq Listing Rule 5635(c)(4). Each stock option has an exercise price per share equal to $6.00 per share, Adverum’s closing trading price on December 4, 2024, and will vest over four years, with 25% of the underlying shares vesting on the first anniversary of the applicable vesting commencement date and, 1/48th of the balance of the underlying shares vesting monthly thereafter over 36 months, subject to the new employee’s continued service relationship with Adverum through the applicable vesting dates. Each of the RSUs will vest over three years, with 33 1/3% of the underlying shares vesting on each anniversary of December 4, subject to the new employee’s continued service relationship with Adverum through the applicable vesting dates. The awards are subject to the terms and conditions of Adverum’s 2017 Inducement Plan and the terms and conditions of an applicable award agreement covering the grant. About Adverum Biotechnologies Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy to preserve sight for life in highly prevalent ocular diseases with the aspirations of developing functional cures to restore vision and prevent blindness. Leveraging the capabilities of its proprietary intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. Additionally, by overcoming the challenges associated with current treatment paradigms for debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit www.adverum.com. Inquiries: Adverum Investor Relations Email: ir@adverum.com

基因疗法

2024-11-27

·派真生物PackGene

聚焦眼科基因治疗：AAV的潜力与突破-临床试验进展篇

眼科疾病一直是rAAV基因治疗的前沿领域。截至2023年12月，已有78项临床试验正在进行或已完成，旨在研究rAAV在治疗眼科疾病中的应用（图1）。其中，15%的试验针对新生血管性年龄相关性黄斑变性（neovascular AMD），14%的试验与莱伯先天性黑蒙2型（LCA2）相关。超过60%的试验处于早期阶段（Ⅰ期和Ⅰ/Ⅱ期），主要关注治疗的安全性；此外，15%的试验已进入Ⅲ期阶段，与2019年之前的分析相比，数量有了显著增加。在这些试验中，rAAV2是最常用的血清型，成为基因治疗的主导载体。图1 基于rAAV的眼科基因治疗临床试验分析。通过检索ClinicalTrials.gov，共筛选出78项基于rAAV的眼科基因治疗相关临床试验（包括正在进行和已完成的）。需要注意的是，该图表特别筛选了同一疾病类别中、处于相同研究阶段的不同研究药物（即，如果某一特定研究药物涉及多个处于同一阶段的试验，则仅统计一次）。因此，这一图表提供的是一个经过筛选的视角，并未涵盖rAAV眼科基因治疗临床试验的全部数据。遗传性视网膜疾病（IRDs） IRDs是一类具有高度遗传异质性的疾病，可导致视力逐渐丧失，最终发展为失明。目前，尚无针对IRDs的有效治疗手段。然而，基于rAAV的基因治疗为恢复视网膜功能提供了有前景的解决方案，这种方法可以通过递送缺陷基因的功能性拷贝、引入治疗性基因，或直接编辑基因组DNA以纠正突变，从而实现治疗目标。已有多项临床试验正在进行或已完成，为患者带来了希望。莱伯先天性黑蒙2型（LCA2） >>> LCA2是一种由RPE65基因突变引起的严重遗传性视网膜疾病。基于AAV的基因治疗Ⅰ/Ⅱ期临床研究结果证明了其在治疗LCA2方面的安全性和有效性，为更进一步的临床试验奠定了坚实基础。在LCA2的AAV基因治疗中，最重要的突破是voretigene neparvovec-rzyl（商品名：Luxturna）的开发，这是一种携带RPE65基因功能拷贝的AAV2载体，也是首个获美国FDA批准用于治疗遗传性疾病的基因疗法。在一项具有里程碑意义的Ⅲ期研究中，共有31名与RPE65相关的IRD患者参与了试验。研究结果显示，voretigene neparvovec显著改善了患者的功能性视力。干预组患者在接受治疗后1年的多亮度移动性测试（MLMT）得分平均提高了1.8个光级，而对照组仅提高了0.2个光级（p=0.0013）。此外，65%的接受治疗的患者在最低光级下达到了最大改善。值得注意的是，该疗法未报告与产品相关的严重不良事件。这些改善效果在后续的3至4年长期随访中得以持续保持，进一步证明了voretigene neparvovec在安全性和疗效上的可靠性。脉络膜病变（CHM） >>> CHM是一种由CHM基因突变引起的X连锁隐性遗传性疾病，主要病理特征是光感受器、RPE和脉络膜逐渐退化。2011年，首项使用编码Rab伴随蛋白1（REP1）的rAAV2载体进行CHM基因治疗的临床试验启动，此后多项多中心临床试验陆续开展。在首项临床试验中，六名患者接受了眼底注射治疗，结果显示治疗后6个月内，患者平均视力提高了3.8个字母，视网膜敏感性的改善与每平方毫米存活视网膜的给药剂量呈剂量依赖关系。在为期3.5年的随访中，2/6患者的视力改善得以维持，而未治疗眼的视力在基线时表现更好。另一项研究对12名患者的疗效进行了评估，发现患者的最佳矫正视力（BCVA）平均提高了5.5个字母，但有两名患者出现了并发症，分别导致视力下降了15个字母和14个字母。此外，其他三项使用相同载体但更高剂量的临床试验报告了不同的视力改善结果，改善范围从0±7.5个字母到2±4个字母不等，这些变化在治疗后2年内发生。然而，在另一项临床试验中，治疗后2年内未见显著视力改善，但有两名患者报告出现了不良反应，包括结膜下出血和眼内压变化等。尽管各项试验结果差异较大，CHM的基因治疗研究已进入随机、双盲的Ⅲ期试验阶段，即STAR研究，这项研究评估了timrepigene emparvovec（BIIB111/AAV2-REP1）的安全性和疗效，研究对象为成年男性CHM患者，分为高剂量组（1.0×10^¹¹ vg/眼；n=69）、低剂量组（1.0×10^10 vg/眼；n=34）和未治疗对照组（n=66）三组，随访期为12个月。结果显示，试验未能达到主要终点，即BCVA的显著改善。在高剂量组中，65名患者中有3名（5%）改善了至少15个字母，低剂量组34名患者中有1名（3%）达到该标准，而对照组的62名患者中无人达到上述改善。安全性结果与之前的研究一致，但疗效的差异性仍是未来研究的重要关注点。视网膜色素变性（RP） >>> RP是一类具有遗传异质性的遗传性视网膜病，由80多个不同基因的突变引起，其主要特征是光感受器的逐渐退化，最终导致视力丧失甚至失明。 RPGR基因突变是X连锁视网膜色素变性（XLRP）最常见的原因。XLRP主要影响男性，表现为光感受器和RPE细胞功能受损，导致视力的逐渐下降。近年来，针对RPGR基因的AAV基因治疗取得了显著进展，目前已有多项临床试验正在进行。其中最具代表性的是一项Ⅰ/Ⅱ期研究，使用AAV8载体递送经过密码子优化的RPGR基因（AAV8-RPGR）。初步结果显示，该疗法具有良好的安全性和潜在的疗效，多名参与者的视力和视网膜敏感性均有所改善。重要的是，该疗法具有良好的耐受性，未观察到剂量限制性毒性。此外，XIRIUS基因治疗试验的事后分析以及XOLARIS XLRP自然病史研究显示，一些患者在接受cotoretigene toliparvovec（BIIB112/rAAV8-RPGR）视网膜下注射后，视网膜敏感性和低亮度视力在12个月内表现出持续的改善。然而，Ⅱ/Ⅲ期XIRIUS试验未能达到主要终点，即治疗后12个月内，通过微视野检查（10-2网格）在16个中心点中至少5个点的视力提高7 dB以上。目前，其他临床试验正在积极探索不同的AAV载体，以进一步优化RPGR基因治疗在XLRP中的疗效。一项Ⅰ/Ⅱ期试验（NCT03252847）研究了AAV5-hRKp.RPGR在与RPGR相关的XLRP男性患者中的效果，研究结果表明，该疗法安全且耐受性良好，未观察到剂量限制性事件，大多数不良事件为短暂性且与手术操作相关。在治疗第26周，与对照组相比，治疗组的视网膜敏感性和功能性视力均有改善，第52周也观察到了类似趋势。这些结果支持进一步的Ⅲ期临床试验研究。由核受体亚家族2组E成员3（NR2E3）基因突变引起的常染色体隐性视网膜色素变性以光感受器退化为主要特征，导致视力逐渐丧失。NR2E3基因在维持视杆细胞和视锥细胞的平衡中发挥关键作用，其突变可能导致夜盲、周边视力下降，最终影响中心视力。针对NR2E3相关RP和视紫红质（RHO）相关RP的基因治疗药物OCU400（AAV5-hNR2E3），在Ⅰ/Ⅱ期临床试验中共招募了18名受试者。研究结果表明，低剂量和中等剂量治疗具有相对良好的安全性，大多数不良事件在几周内得到缓解。疗效方面，86%的RHO相关RP受试者在视觉功能上表现出稳定或改善，在移动性测试中亮度级别提升了多达3个等级。然而，对于NR2E3突变的受试者，尚未观察到显著改善。这些结果需要进一步研究和验证。与磷酸二酯酶6B（PDE6B）相关的视网膜色素变性由PDE6B基因突变引起，该基因编码视杆细胞cGMP磷酸二酯酶的β亚单位。PDE6B基因的突变会导致视杆细胞功能障碍和退化，表现为视力的逐渐丧失，早期症状包括夜盲和周边视力下降，最终可能发展为完全失明。基于AAV5载体的基因治疗药物CTx-PDE6b在Ⅰ/Ⅱ期临床试验中的12个月随访结果显示，该疗法在所有17名患者中均具有良好的耐受性。在病情相对较轻的六名患者中，接受较高剂量治疗的亚组在多个临床终点上表现出显著的视觉功能改善，包括最佳矫正视力、视野范围、微视野检查结果，以及光学相干断层扫描（OCT）显示的视网膜结构改善。这些结果为该疗法的进一步临床开发提供了有力支持。另一个正在开发基因治疗策略的遗传性视网膜疾病是由MER酪氨酸激酶（MERTK）基因突变引起的疾病。MERTK在RPE的吞噬作用中起关键作用，其功能缺失会导致光感受器退化，最终引发视网膜色素变性。这种常染色体隐性遗传疾病约占视网膜色素变性病例的3%。一项Ⅰ期研究评估了通过眼底注射递送rAAV2-VMD2-hMERTK的安全性，受试者为6名患者，给药剂量分别为150μL和450μL。在长达2年的随访中，结果显示该治疗安全性良好，未观察到与基因载体相关的重大并发症，尽管部分患者出现了轻微的眼部不适。在疗效方面，3名患者在手术后视力有所改善，但其中2名患者在2年时失去了这种改善。这表明该治疗可能具有一定的效果，但临床表现存在不确定性。视黄醛结合蛋白1（RLBP1）基因的双等位基因突变会导致罕见的常染色体隐性视网膜营养不良，包括视网膜色素变性及其他相关疾病，主要特征为夜盲、暗适应时间延长，以及视力逐渐丧失。目前，报道了约160例病例，主要集中在瑞典和加拿大。由于缺乏自然病史研究，对疾病进展的了解有限，患者预后仍然不理想。目前正在开展针对CPK-850的临床试验。这是一种基于AAV的基因治疗，旨在验证其在人体中的应用效果。研究通过单次眼底注射，评估CPK-850的最大耐受剂量，并探讨其在改善RLBP1相关RP患者视觉功能方面的安全性和潜在疗效。截至目前，该试验暂未公布明确的研究结果。除了基因替代或基因编辑方法外，光遗传学等独立于遗传突变的治疗策略也被用于研究治疗视网膜色素变性。光遗传学通过将光敏蛋白引入存活的视网膜细胞（如双极细胞或神经节细胞），使这些细胞能够对光刺激产生反应。借助外部光源，这些经过修饰的细胞可以被激活，从而有可能恢复光感受器退化患者的视力。在一项针对RP患者的开创性临床试验中，患者接受了递送光遗传学基因的载体GS030-DP（rAAV2.7m8-CAG-ChrimsonR-tdTomato）治疗，并通过工程化眼镜提供光刺激。结果显示，患者能够感知、定位、计数并触摸各种物体。同时，多通道脑电图记录显示治疗眼在视觉皮层上方检测到与物体相关的活动。近期的研究进展包括一项2b期临床试验的初步结果，试验中使用编码视蛋白的MCO-010（通过rAAV2载体），通过玻璃体内注射递送至RP患者，特异性靶向ON双极细胞。结果令人鼓舞，该干预显著改善了患者的视力，且未报告严重的眼部或全身不良事件。这些研究结果表明，光遗传学策略在治疗RP导致的视力丧失方面具有创新性和潜在的有效性。此外，这种策略还可能适用于其他眼科疾病的治疗，以及不同致盲原因的干预。 Leber遗传性视神经病变（LHON） >>> LHON是一种母系遗传的线粒体疾病，主要导致视力逐渐丧失甚至失明，通常发生在年轻男性中。约90%的LHON病例由三种关键的点突变引起，这些突变位于MT-ND1、MT-ND4和MT-ND6线粒体基因中，导致视网膜神经节细胞凋亡，最终引发严重的视力损害。早期的基因治疗试验中，研究评估了通过玻璃体内注射递送编码密码子优化的MT-ND4基因的rAAV2载体的治疗效果。该载体包含CMV启动子、人类细胞色素c氧化酶10（COX10）基因的顺式作用元件，以及5'端的线粒体定位序列，确保mRNA翻译及蛋白的线粒体共定位。在一项Ⅰ期临床试验中，28名患者接受了单侧玻璃体内scAAV2(Y444,500,730F)-P1ND4v2基因治疗，剂量分别为5×10^9、2.46×10^10和1×10^11 vg/眼，总共三组。视力结果显示差异：部分患者的最佳矫正视力有所改善，但同时观察到显著的视网膜变薄，且稳态视觉诱发电位的振幅未见明显变化。此外，29%的患者发生偶然性葡萄膜炎，主要集中在高剂量组，但未引发长期视力丧失。在一项命名为REVERSE的Ⅲ期临床试验中，37名在过去6至12个月内出现视力丧失的LHON患者接受了lenadogene nolparvovec（rAAV2/2-ND4）的玻璃体内注射治疗。到96周时，25名受试者至少有一只眼睛的最佳矫正视力较基线期有显著的恢复，而29名受试者在两只眼睛的视力均有改善，且未报告严重不良事件。另一项名为RESCUE的Ⅲ期临床试验的结果与此类似，38名患者接受lenadogene nolparvovec注射，96周随访显示，注射眼与未注射眼的视力改善情况相当。此外，一项使用rAAV2/2-ND4的长期研究中，对9名LHON患者的随访结果显示，疾病发作后1至2年的较年轻患者的视力恢复程度更加显著。这些研究结果突出了治疗慢性LHON的挑战，并强调了需要更多对照试验以明确基因治疗的真实效果。目前LHON基因治疗试验结果的差异性，可能部分来源于患者群体、治疗介入的疾病阶段以及试验设计的差异。因此，未来有必要进行更大规模的随机对照试验，以全面评估LHON基因治疗的安全性和有效性。全色盲 >>> 全色盲，也称为全色觉缺失，是一种常染色体隐性遗传的遗传性视网膜病，主要影响负责高分辨率昼视觉的视锥细胞。高达90%的全色盲患者携带循环核苷酸门控通道亚单位α3（CNGA3）或β3（CNGB3）基因的突变，这些基因分别编码循环核苷酸门控（CNG）通道的关键亚单位，而这些通道对视锥细胞的光转导功能至关重要。基因替代疗法策略通过rAAV载体递送编码CNGA3或CNGB3的基因，已在多种动物模型中成功进行概念验证，结果显示能够恢复视锥细胞的功能。在评估AAV8.CNGA3基因治疗针对CNGA3相关全色盲的临床试验中，九名患者接受了单次不同剂量的眼底注射，并进行了12个月的随访，结果表明治疗具有良好的安全性，未发生严重不良事件，所有治疗眼均显示视锥细胞功能改善，平均视力提高了2.9个字母，对比敏感度平均增加0.33 log单位，显示出该疗法对治疗此类疾病的潜在益处。在一项关于CNGA3相关全色盲基因治疗后皮层可塑性的研究中，两名成年患者显示了轻微的改善，包括光敏感度降低和周边视力增强，其中一名患者获得了检测红光的能力。功能性磁共振成像（fMRI）分析显示，治疗眼的感受野大小有所缩小，表明皮层发生了一定程度的适应。然而，未观察到特定颜色相关皮层区域的激活，这可能是由于视锥细胞功能未完全恢复，或是成人皮层处理新输入的视锥细胞信号存在难度。一种新兴的多模态研究方法表明，基因治疗可以在10至15岁患有CNGA3和CNGB3相关全色盲的儿童中激活休眠的视锥细胞介导通路，恢复视锥细胞的功能。在接受了表达密码子优化人类CNGA3基因的rAAV载体治疗（启动子为PR1.7视锥视蛋白启动子，载体名称为rAAV2tYF-PR1.7-hCNGAco）的四名患者中，有两名患者在治疗后视锥细胞介导的视觉功能和视觉皮层的视网膜拓扑结构显著改善，而未治疗对照组未观察到类似效果。这些证据表明基因治疗可在儿童时期诱导神经可塑性，并部分恢复视锥细胞功能。莱伯先天性黑蒙10型（LCA10） >>> LCA10是一种常染色体隐性遗传的纤毛病，导致儿童早期出现严重的视力损害或失明。在LCA10患者中，最常见的突变是c.2991+1655A>G，该突变位于中心体蛋白290（CEP290）基因的内含子区域，形成了一个隐秘剪接供体位点。CEP290是一种大型蛋白，位于视锥和视杆细胞的纤毛过渡区，在初级纤毛的形成和稳定中起着至关重要的作用，它调控光感受器内外节之间的蛋白质运输，这对于光转导和光感受器功能非常关键。由于CEP290基因的尺寸较大，传统的基因替代疗法并不适合治疗LCA10，而CRISPR/Cas9基因编辑技术提供了一种有前景的方法，用于纠正该剪接突变。在一项研究中，利用携带自限制CRISPR/Cas9系统的双rAAV载体成功敲除了小鼠视网膜中CEP290基因的一个内含子片段。 2020年，一项具有里程碑意义的临床试验启动，通过眼底注射递送CRISPR/Cas9系统（EDIT-101），旨在去除LCA10患者视网膜细胞中的CEP290突变。这是一项Ⅰ/Ⅱ期、开放标签、单剂量递增研究，共招募了14名3岁及以上因IVS26变异导致CEP290相关LCA10的患者。主要研究目标是评估治疗的安全性，结果显示未观察到严重不良事件或剂量限制性毒性效应。在12名成人和2名儿童中，有64%的患者在关键的次要指标上取得了显著改善，包括最佳矫正视力、视网膜敏感性和移动性测试得分。此外，6名患者在与视力相关的生活质量上也表现出改善。这些结果为进一步研究CRISPR/Cas9体内基因编辑技术治疗由IVS26变异引起的遗传性视网膜疾病提供了有力支持。 X连锁视网膜劈裂症（XLRS） >>> XLRS是一种发育性遗传性视网膜病，主要表现为视网膜腔隙形成、突触功能障碍和视力下降，并易导致视网膜脱落，最终严重损害视力。该病通常在年轻男性中发病，并随着年龄增长逐渐加重。XLRS由视网膜劈裂蛋白1（RS1）基因突变引起，而RS1基因在视网膜结构的正常发育和维持中发挥着重要的细胞粘附功能。 XLRS的基因治疗旨在将RS1基因的功能拷贝递送至受影响的视网膜细胞。目前已有多项临床试验评估了相关基因治疗的安全性和疗效。在一项Ⅰ/Ⅱa期临床试验中，9名男性XLRS患者接受了玻璃体内递送的AAV8-RS1治疗，剂量分别为1.0×10^9、1.0×10^10或1.0×10^11 vg/眼。研究结果显示，该疗法总体耐受性良好，与剂量相关的炎症可以通过使用皮质类固醇得到有效控制。尽管未检测到针对RS1的抗体，但随着剂量增加，抗AAV8的系统性抗体水平有所升高。在一名患者中，视网膜腔隙曾暂时闭合，这提示需要进一步优化剂量和免疫抑制方案，以提升治疗的安全性和有效性。一种新的治疗XLRS的方案ATSN-201正在被开发。该疗法采用一种新型AAV.SPR衣壳，用于高效特异性递送RS1基因至视网膜，尤其是靶向通常发生劈裂腔隙的中央视网膜区域。AAV.SPR衣壳能够从眼底注射点向侧方扩散，因此无需直接注射至黄斑这一敏感区域，从而减少视网膜损伤的风险。在正在进行的Ⅰ/Ⅱ期LIGHTHOUSE研究中，ATSN-201显示出良好的安全性，未报告严重不良事件。在首批接受治疗的3名患者中，有2人在给药后8周内显示出视网膜劈裂的显著改善，这种改善持续至24周。这些结果表明，ATSN-201有潜力成为一种安全有效的XLRS治疗方案。比埃蒂结晶样营养不良（BCD） >>> BCD是一种进行性、罕见的常染色体隐性遗传性视网膜病，其主要特征是在视网膜色素上皮层形成大量闪亮的黄白色结晶沉积物。BCD的发生是由于细胞色素P450家族4亚家族V多肽2（CYP4V2）基因的功能丧失突变，该基因参与脂肪酸和类固醇的ω-羟基化代谢。在体外和体内模型中，研究者已尝试通过基因替代策略，利用rAAV2递送功能性CYP4V2基因，成功恢复基因功能。一项临床研究评估了NGGT001（一种基于AAV的基因治疗方案）用于治疗BCD的疗效和安全性。结果显示，治疗后9个月内，患者的平均视力提高了12.8 ± 3.7 ETDRS字母，其中46%的患者视力提升超过了15个字母。此外，该疗法耐受性良好，仅观察到与眼底注射相关的轻微、自限性不良事件，未发生眼内炎症。在另一项使用rAAV2/8-hCYP4V2进行BCD基因治疗的试验中，结果同样令人鼓舞：77.8%的治疗眼在治疗第180天时显示出最佳矫正视力的改善，平均提升9.0 ± 10.8个字母；到第365天，80%的治疗眼进一步改善，平均增加11.0 ± 10.6个字母。研究中共记录了73起治疗过程中出现的不良事件，但大多数为轻度至中度，并未观察到严重的治疗相关不良事件或免疫毒性。值得注意的是，在未治疗的对侧眼也观察到了轻微的BCVA改善。这一现象在此前几项IRD基因治疗临床试验中也有类似报告，可能与以下因素相关：视觉皮层的激活、大脑的可塑性反应，或基因载体扩散至对侧眼的影响。这些发现为BCD基因治疗的进一步研究提供了重要支持。常见获得性或多因素视网膜疾病尽管许多临床试验的结果令人鼓舞，但由于每种罕见的单基因遗传性视网膜病患者数量较少，基因治疗的成本显著偏高。相比之下，针对常见的获得性视网膜疾病的基因治疗可能会为更多患者带来积极影响，同时也有望降低治疗成本，从而提高患者的可及性。 01 年龄相关性黄斑变性（AMD） AMD的晚期阶段通常表现为视网膜地理性萎缩（GA）和/或新生血管形成，是发达国家中导致失明的主要原因。对于新生血管性AMD，目前的主要治疗手段是靶向血管内皮生长因子（VEGF），这一关键的血管生成因子在视网膜新生血管形成的发病机制中起重要作用。尽管抗VEGF治疗在减缓许多AMD患者的疾病进展和改善视觉功能方面取得了显著成效，但其需要每月注射，这对患者和医疗系统都带来了较大的治疗负担。此外，部分患者对抗VEGF药物并无显著反应。基因添加疗法通过rAAV递送相关基因，有望提供持续的内源性生物因子，从而避免重复眼内注射，因此，针对地理性萎缩和新生血管性AMD的rAAV基因治疗正在成为研究热点。地理性萎缩是一种与AMD相关的晚期且不可逆的黄斑区病变。它是干性AMD的一种表现形式，主要特征是RPE、光感受器细胞以及脉络膜毛细血管的萎缩和丢失，这种病变通常表现为外层视网膜的进行性萎缩，导致患眼视力逐渐下降，直至中心视力不可逆性丧失。GA的病变区域形状不规则，类似地图，因此得名“地理性萎缩”。GT005 是一种一次性基因治疗方案，利用rAAV2递送编码补体因子I（CFI）的基因，旨在通过眼底注射治疗AMD继发的GA。在GT005的Ⅰ/Ⅱ期FOCUS研究中，结果显示该疗法的耐受性良好，并在少数患者中减缓了GA的进展。基于这些初步结果，又启动了两项更大规模的Ⅱ期试验，EXPLORE和HORIZON，以评估GT005在更广泛人群中的疗效，包括携带高风险CFI基因变异的患者。早期数据显示，GT005可能在遗传易感患者中减缓病变进展。然而，尽管结果令人鼓舞，进一步分析认为该疗法未能满足继续开发的效益-风险标准，因此GT005的开发已被终止。类似地，OCU410 基因治疗使用AAV载体，通过眼底注射递送RAR相关孤儿受体A（RORA）基因，以治疗干性AMD。RORA基因参与脂质代谢和炎症调节。OCU410目前正在进行Ⅰ/Ⅱ期临床试验，这是一个开放标签、剂量探索研究。试验设置了低（2.5×10^10 vg/mL）、中（5×10^10 vg/mL）和高（1.5×10^11 vg/mL）三个剂量水平，所有剂量队列均已完成给药。试验的主要目标是评估安全性，次要目标是探索该疗法在减缓GA进展方面的潜在疗效。目前长期研究仍在进行中，目的是监测视力保护和疾病进展的情况。另一种针对新生血管性AMD的基因添加疗法，利用rAAV2通过玻璃体内或眼底注射递送sFlt-1基因，该基因的表达产物是VEGF的抑制蛋白，由Flt-1（VEGF受体1）的第2结构域与人类免疫球蛋白G1的Fc片段融合而成。在Ⅰ期剂量递增试验中，玻璃体内注射rAAV2-sFlt-1在52周随访中表现出良好的安全性和耐受性，但其sFlt-1的表达水平和治疗效果存在差异，这种差异可能与抗渗透性和抗AAV2血清抗体的存在有关。在Ⅰ期和Ⅱa期随机对照试验的合并分析中，相同载体通过玻璃体内注射给药，在老年患者中显示出良好的耐受性。试验暂未观察到显著的视力改善。 RGX-314是一种利用rAAV8递送编码抗VEGF单克隆抗体片段的基因疗法，通过眼底注射治疗新生血管AMD。在Ⅰ期ASCENT试验的初步评估中，该疗法显示出良好的安全性和耐受性。研究发现，治疗的有效性与剂量相关，部分患者在治疗后长达18个月无需额外的抗VEGF注射。 ADVM-022是一种通过玻璃体内注射，使用工程化的AAV2.7m8载体递送编码aflibercept蛋白cDNA的基因疗法。Aflibercept蛋白是一种阻断VEGF信号通路的可溶性诱饵蛋白。在Ⅰ期OPTIC试验中，92周随访数据显示，超过80%的患者在接受治疗后不再需要额外的抗VEGF注射。该疗法不仅表现出良好的安全性，还在治疗效果和持续性方面展现出显著优势，为新生血管AMD的治疗带来了潜在的变革。 4D-150是一种针对湿性AMD和糖尿病性黄斑水肿（DME）的基因疗法，利用工程化的R100 AAV衣壳，通过玻璃体内注射高效感染整个视网膜，递送表达aflibercept和VEGF-C抑制性RNAi的双重转基因载体，靶向VEGF A、B、C及胎盘生长因子（placental growth factor, PIGF）。在Ⅱ期PRISM试验中，共有51名高治疗负担（在之前的12个月里，平均接受了10次抗VEGF注射）的湿性AMD患者参与研究，接受高剂量（3×10^10 vg/眼）或低剂量（1×10^10 vg/眼）的4D-150治疗或aflibercept注射作为对照。结果显示，4D-150疗法具有良好的安全性，未发生显著眼内炎症，并成功减少了类固醇的使用。在高剂量组中，患者年度抗VEGF注射率减少了89%，其中84%的患者仅需0次或1次补充注射，63%的患者在24周内无需任何额外注射。此外，患者的视力和中心视网膜厚度（CST）均保持稳定。基于这些积极结果，该疗法计划在2025年第一季度启动Ⅲ期试验。 02 糖尿病性视网膜病变（DR） DR是糖尿病患者常见的并发症，也是发达国家主要致盲的原因之一。DR主要包括增殖性糖尿病视网膜病变（PDR）和糖尿病性黄斑水肿（DME）两种类型。其中，PDR的特征是视网膜内异常新生血管的生长，而DME的特点则是黄斑区域的视网膜血管发生渗漏，引发水肿。目前，针对DR的rAAV基因治疗的临床研究主要集中于通过内源性表达治疗性蛋白来干预，其中许多研究的靶点是VEGF。与新生血管性AMD类似，RGX-314也正在开发用于治疗糖尿病患者。在正在进行的Ⅱ期ALTITUDE试验中，通过脉络膜上注射给药，RGX-314在两个剂量水平的50名患者中显示了良好的安全性，未报告任何与药物相关的严重不良事件。治疗一年后，接受高剂量治疗的患者中有70.8%在糖尿病视网膜病变严重性评分（DRSS）上改善了至少1级，而对照组仅为25%。此外，该疗法将威胁视力事件的风险降低了89%，且没有接受治疗的患者在DRSS评分上恶化2级或以上，而对照组这一比例为37.5%。目前，RGX-314在DME中的应用也在进一步开发中。此外，ADVM-022也正在DME患者中开展研究，通过玻璃体内注射评估其安全性和疗效（INFINITY试验）。然而，一名接受高剂量（6.0×10^11 vg/眼）治疗的患者出现了低眼压的严重不良事件。在接受高剂量治疗的12名患者中，有5人在治疗后的16至32周内经历了额外的不良事件，包括快速且临床相关的眼内压下降，这些不良事件对类固醇治疗无反应。其中一例严重不良事件发生在高剂量组患者治疗后30周，使得试验申办方暂停试验并进行进一步分析。尽管如此，早期试验（如湿性AMD的OPTIC研究）显示，ADVM-022显著降低了治疗负担，且总体耐受性良好。然而，研究揭示了DME和新生血管性AMD患者之间的显著差异，尤其是在低剂量（2.0×10^11 vg/眼）和高剂量（6.0×10^11 vg/眼）水平下的表现也存在明显不同。这表明，湿性AMD和DME可能具有不同的病理生理机制及相关风险因素。目前，尽管ADVM-022的剂量限制性毒性的确切原因尚不明确，但推测与DME患者常见的基础疾病有关。DME患者通常伴有严重的血管病变，这可能引发炎症因子增加，导致血管通透性升高和血-眼屏障受损。一项研究发现，编码抗VEGF基因的AAV2.7m8载体在小鼠视网膜中对血管鞘病理具有剂量依赖性影响，这与人类的血管炎表现类似，血管炎症通常伴有免疫细胞浸润。这表明，在接受ADVM-022治疗的患者中观察到的严重不良事件，可能是基础疾病引发的炎症加剧和VEGF功能抑制共同作用的结果，这种双重影响可能随着时间的推移加重疾病相关的炎症反应。 AAV作为眼科基因治疗的主要平台，在临床试验中取得了显著成果，但仍面临诸多挑战，相信通过不断优化载体设计和递送技术，AAV将在眼科基因治疗领域发挥更大的潜力。派真CRO &CTDMO 一站式服务平台，提供从基因合成、载体构建，到病毒包装的整体解决方案，全面支持您基因编辑研究，还可提供从研究至GMP级别的多种AAV血清型载体，助力眼科疾病基因治疗。参考资料：https://doi.org/10.1016/j.ymthe.2024.10.017 关于派真生物

临床结果基因疗法临床3期临床2期临床1期

100 项与 Ixoberogene soroparvovec 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
湿性年龄相关性黄斑变性	临床3期	-	Adverum Biotechnologies, Inc.	2025-02-28
糖尿病性黄斑水肿	临床2期	美国	Adverum Biotechnologies, Inc.	2020-05-28
糖尿病性黄斑水肿	临床2期	波多黎各	Adverum Biotechnologies, Inc.	2020-05-28

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03748784 (OPTIC, GlobeNewswire) 人工标引	临床1期	湿性年龄相关性黄斑变性	30	Ixo-vec	積製觸艱壓襯憲淵積顧(構憲蓋構鑰顧餘艱網醖) = 獵鬱夢壓製觸積構夢鑰餘鏇鬱廠簾餘蓋簾糧鬱 (繭顧構膚窪醖鬱鏇淵膚 ) 更多	积极	2024-11-18
NCT05536973 (LUNA, GlobeNewswire) 人工标引	临床2期	湿性年龄相关性黄斑变性	60	6E10 Ixo-vec	鹹蓋鹽簾廠鏇鑰憲鹽廠(積鑰壓膚廠選簾鬱鏇襯) = 選襯網繭夢廠遞襯獵製繭齋鏇遞蓋憲範鹹選繭 (艱廠淵網積範壓鏇糧鏇, -4.8 ~ 0.7) 更多	积极	2024-11-18
				2E11 Ixo-vec	鹹蓋鹽簾廠鏇鑰憲鹽廠(積鑰壓膚廠選簾鬱鏇襯) = 鏇製鑰鬱顧顧醖觸艱襯繭齋鏇遞蓋憲範鹹選繭 (艱廠淵網積範壓鏇糧鏇, -4.6 ~ 0.9) 更多
NCT05536973 (LUNA, EURETINA2024)	临床2期	湿性年龄相关性黄斑变性 anti-VEGF therapy	60	Ixoberogene Soroparvovec (Ixo-vec) (Ixo-vec 6x10^10 vg/eye)	構膚鹽鏇鏇築憲艱壓範(淵鹹築選鏇壓製鬱繭網) = 壓觸構遞憲獵鹽膚遞簾蓋鑰獵顧蓋網壓繭選鹽 (鹽餘鬱簾網窪築願淵觸 ) 更多	积极	2024-09-19
				Ixo-vecgene Soroparvovec (Ixo-vec) (Ixo-vec 2x10^11 vg/eye)	構膚鹽鏇鏇築憲艱壓範(淵鹹築選鏇壓製鬱繭網) = 鏇遞鹽夢夢艱糧範選襯蓋鑰獵顧蓋網壓繭選鹽 (鹽餘鬱簾網窪築願淵觸 ) 更多
GlobeNewswire 人工标引	临床2期	湿性年龄相关性黄斑变性	60	Ixo-vec 6E10	簾夢餘願餘鹹淵鏇顧網(鹽願鹽鏇餘憲築願觸選) = 遞蓋簾壓築願顧遞鑰願鹹鏇範窪廠醖鑰製憲獵 (壓築製鹹齋膚觸選襯窪 ) 更多	积极	2024-07-17
				Ixo-vec 2E11	簾夢餘願餘鹹淵鏇顧網(鹽願鹽鏇餘憲築願觸選) = 齋衊顧蓋艱餘願製鬱遞鹹鏇範窪廠醖鑰製憲獵 (壓築製鹹齋膚觸選襯窪 ) 更多
NCT05536973 (LUNA, Biospace) 人工标引	临床2期	湿性年龄相关性黄斑变性	60	Ixo-vec 2E11 vg/eye	餘鑰選廠衊網鏇齋鹽夢(齋齋淵廠觸糧積簾鏇觸) = 膚憲膚壓獵夢網築齋願簾鏇鏇糧鏇獵齋獵觸餘 (醖鏇範糧齋廠繭繭醖範 ) 更多	积极	2024-02-08
				Ixo-vec 6E10 vg/eye	餘鑰選廠衊網鏇齋鹽夢(齋齋淵廠觸糧積簾鏇觸) = 鑰餘鬱積網構鹽膚顧艱簾鏇鏇糧鏇獵齋獵觸餘 (醖鏇範糧齋廠繭繭醖範 ) 更多
OPTIC extension (GlobeNewswire) 人工标引	临床2期	湿性年龄相关性黄斑变性	-	ADVM-022 2E11	艱選壓壓鬱壓觸蓋願築(範醖醖積淵鏇壓鏇醖襯) = 窪繭蓋選選淵艱淵餘糧壓選願獵範鏇觸窪齋鬱 (築憲構鏇範顧構淵膚製 )	积极	2023-11-04
EURETINA2023	N/A	湿性年龄相关性黄斑变性	-	Ixoberogene soroparvovecIxo-vecgene soroparvovec (Ixo-vec 6x10^11 vg/eye)	遞窪襯鏇網範觸鏇艱網(衊簾襯構膚窪鑰襯鑰選) = Ixo-vec related ocular adverse events were mild (84%) to moderate (16%). Ocular inflammation was mild to moderate, dose-dependent, and was responsive to topical corticosteroids. There were no cases of retinitis, vasculitis, choroiditis, or vascular occlusive events. 廠壓蓋齋壓憲壓鑰選製 (鏇鬱齋觸鬱鏇鑰築繭夢 )	-	2023-10-05
				Ixoberogene soroparvovecIxo-vecgene soroparvovec (Ixo-vec 2x10^11 vg/eye)