Currently,A Total of 26 AAV Gene Therapy Drugs IND Applications Approved in China, three of which have entered Phase III clinical trials.According to its INDSummary of Approval Timeline in Chronological Order:
1. SKG0106 by Nine Skies Biotech
Skyline Therapeutics' AAV ophthalmology gene therapy SKG0106 has recently been approved for clinical trials by the National Medical Products Administration, with indications for neovascular age-related macular degeneration (nAMD). Additionally, SKG0106 received FDA approval in June this year to conduct global Phase I/IIa clinical trials for the treatment of nAMD.SKG0106 is an innovative ophthalmic gene therapy drug under research. This therapy uses AAV as a vector to overexpress anti-vascular endothelial growth factor (VEGF) protein, administered via intravitreal injection, and theoretically has long-term efficacy with a single dose.2、Janssen's JNJ-81201887
In early August 2023, Janssen, a subsidiary of Johnson & Johnson, received the CDE's implied permission for clinical trials of its AAV gene therapy JNJ-81201887 (AAVCAGsCD59), which is being developed to treat adult patients with geographic atrophy secondary to age-related macular degeneration.
JNJ-81201887 (JNJ-1887, AAVCAGsCD59) is an investigational gene therapy based on an AAV vector, designed to increase the expression of soluble CD59 (sCD59) to protect retinal cells, thereby slowing and preventing disease progression.
3、Xin Zhi PharmaceuticalsTheBBM-H803
On July 24, 2023, the clinical trial application for "BBM-H803 Injection" submitted by Shanghai Xinzhi Biomedical Technology Co., Ltd. and Shanghai Mianyi Biotechnology Co., Ltd., wholly-owned subsidiaries of Belief BioMed (BBM), received tacit approval for clinical trials. The indication is Hemophilia A.
BBM-H803 is an AAV gene therapy drug with independent intellectual property rights developed by Belief BioMed. It delivers the human coagulation factor VIII gene into patients with hemophilia A through intravenous administration, thereby increasing and maintaining the level of coagulation factor in patients over the long term.
On July 12, 2023, Factore Biotherapeutics (Suzhou) Co., Ltd. (hereinafter referred to as "Factore Biotherapeutics") developed a treatment targetingHemophilia B(Endogenous FIX activity ≤2%)) ofAAV Gene Therapy Drug FT-004 Receives CDE Clinical Trial Approval.
FT-004 is a gene therapy drug based on the AAV vector. Preclinical data shows that FT-004 can efficiently enter liver cells, sustainably and stably express and secrete functional hFIX protein into the blood, effectively enhance the coagulation ability of model animals over the long term, and has demonstrated good safety.5、 ZS802 by Zhishan Weixin
On June 28, 2023, Sichuan Zhishan Weixin Biotechnology Co., Ltd. (hereinafter referred to as "Zhishan Weixin") received CDE approval for its AAV gene therapy drug "ZS802 Injection" for Hemophilia A, and will soon commence clinical Phase I/II trials.
ZS802 is an AAV gene therapy drug independently developed by ZhiShan WeiXin, utilizing the company's self-developed smallest liver-specific promoter globally, which solves the challenge of packaging large gene capacity and significantly improves product quality. Additionally, ZS802 adopts an optimized and modified FVIII gene sequence developed by ZhiShan WeiXin, effectively enhancing its efficacy. Currently, the ZS802 project has initiated IIT research at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, with preliminary results demonstrating the drug’s safety and efficacy.6. EXG102-031 by Jiayin Bio
On June 1, 2023, the AAV gene therapy drug EXG102-031 ophthalmic injection developed by Hangzhou Jiayin Biotechnology Co., Ltd. ("Jiayin Bio" for short) was approved by the CDE for the indication of wet age-related macular degeneration (wAMD).
This therapy uses AAV as a vector to overexpress a therapeutic fusion protein, which can bind/neutralize all known vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG2) subtypes, theoretically providing long-term efficacy with a single dose.7. AL-001 by Anlong BiotechOn April 27, 2023, Beijing Anlong Biomedical Co., Ltd. ("Anlong Biomedical") announced that the IND for its ophthalmic gene therapy product "AL-001 Ophthalmic Injection" has been approved by the CDE, with the indication for: wet age-related macular degeneration (wAMD).On May 29, 2023, Anlong Biotechnology announced that the project had received approval from the Institutional Project Initiation and Ethics Committee of Peking Union Medical College Hospital, the leading research institution, marking the official entry of this project into the clinical trial phase.。
This therapy is targeted in ChinawAMDThe first approved gene therapy administered via suprachoroidal space (SCS) injection,The therapyOverexpression of anti-VEGF protein using AAV as a vector is theoretically effective for a long term with a single administration. This product utilizes an advanced, self-developed rAAV production process employing Sf9 suspension cells free of helper virus.8. HuigeneTheHG004
On April 18, 2023, Huigene (Shanghai) Biotechnology Co., Ltd. (referred to as "Huigene") announced thatThe IND for HG004, the company's first self-developed ophthalmic AAV gene therapy drug, has been approved by the CDE. The indication is Type 2 Leber's Congenital Amaurosis (LCA2). Additionally, in January this year, HG004 received IND approval from the FDA.
HG004 is an AAV-mediated gene replacement therapy designed to treat RPE65 mutation-associated retinopathy. Mutations in the RPE65 gene can lead to severe early-onset childhood retinal dystrophy, early-onset severe retinal dystrophy, Leber congenital amaurosis (LCA), or retinitis pigmentosa (RP). The AAV vector used in HG004 demonstrates a transduction efficiency in retinal pigment epithelium at least 10 times higher than that of AAV2, with an effective starting dose significantly lower than the marketed AAV2-hRPE65 (LUXTURNA). In the IIT clinical study conducted at Xinhua Hospital in Shanghai, China, HG004 achieved positive clinical outcomes, with patients experiencing significant and substantial recovery in vision.April 14, 2023Neurophth Biotechnology Co., Ltd.The IND application for NFS-02 ophthalmic injection, an AAV gene therapy drug, has received tacit approval from the CDE, with indications for Leber's hereditary optic neuropathy (G3460A). In addition, last year, NFS-02 received FDA approval for a new drug clinical trial (IND).NFS-02 is a novel intravitreal gene therapy drug based on AAV2. The therapeutic gene can be delivered to the patient's damaged retinal ganglion cells through a single intravitreal injection of the drug, repairing the mitochondrial bio-respiratory chain impaired by genetic mutations and thereby restoring visual function in the retinal ganglion cells.10、Huayi LejianTheGS1191-0445On January 16, 2023, the clinical trial application for GS1191-0445 Injection, an AAV gene therapy drug for treating Hemophilia A developed by Suzhou Huayi Lejian Biotechnology Co., Ltd., was approved by the CDE.Huayi Lejian formally submitted the IND application for this therapy to the CDE in November 2022 and received approval, becoming the hemophilia A treatment drug in China to enter the IND stage. In addition, the drug has been studied in an IIT research conducted by the Tianjin Blood Research Institute., nine patients have been enrolled, and after medication, good safety and exciting efficacy data were obtained.On December 23, 2022, Langxin Bio announced that its subsidiary, Apexigen Langxin (Suzhou) Biopharmaceutical Co., Ltd.(Langsheng Bio)The IND application for the AAV gene therapy product LX102 injection has been approved by the CDE for the treatment ofWet Age-related Macular Degeneration (wAMD).This therapy is based on AAV vector-mediated in vivo gene therapy.Method, capable of expressing anti-VEGF fusion proteinThe purpose of introducing the target gene into the patient's retinal cells is to achieve long-term effectiveness with a single dose. In previously conducted IIT clinical studies, this therapy demonstrated good safety and efficacy.。On December 20, 2022, the IND application for GC301 Adeno-Associated Virus Injection, an AAV gene therapy drug developed by Beijing Jinlan Gene Technology Co., Ltd. (Jinlan Gene), received tacit approval from the CDE, with indications for Infantile-Onset Pompe Disease (IOPD).On June 2, 2023, the Phase I/II clinical trial kick-off meeting for GC301 was successfully held at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, marking the official launch of the clinical trial for GC301 injection in the treatment of infantile Pompe disease at the main research center.。Its treatment strategy is: after a single intravenous infusion, the therapeutic gene can be widely expressed throughout the body, with the aim of compensating for GAA enzyme gene defects in tissues such as the liver, muscles, and central nervous system. GC301 has demonstrated good safety and efficacy in an investigator-initiated clinical study (IIT).13、Zhongyin TechnologyTheZVS101e2022On December 6, Beijing Zhongyin Technology Co., Ltd. (referred to as "Zhongyin Technology") "ZVS101e Injection"IND Application Granted CDE Tacit Approval, Indication: Crystalline Retinopathy (carrying CYP4V2 biallelic mutations)）。On February 20, 2023, the first subject was successfully enrolled and dosed in the Phase I/II clinical trial of ZVS101e injection at the Tianjin Medical University Eye Hospital.。ZVS101e is a gene replacement therapy using AAV8 as the vector.The therapy, which targets the same indications and treatment principles as VGR-R01 developed by Tianze CloudTech that was approved for clinical trials in November 2022.November 2022, Beijing JinlanGene Technology Co., Ltd. (Jinlan Gene)'s AAV gene therapy drug GC304 Adeno-Associated Virus Injection ("GC304 Injection") IND application received tacit approval from the CDE for the treatment of patients with hypertriglyceridemia accompanied by recurrent acute pancreatitis.GC304 Gene Drug-Loaded Treatment BaseBecause of the lipoprotein lipase (LPL) gene, LPL is a key enzyme in hydrolyzing triglycerides (TG) in plasma lipoproteins.November 15, 2022KH631 Ophthalmic Injection, an AAV gene therapy drug developed by Chengdu Hongji Biotechnology Co., Ltd. (Hongji Bio), a subsidiary of Kanghong Pharmaceutical, has received five IND approvals through the implied consent of the National Medical Products Administration (NMPA) for the treatment of neovascular (wet) age-related macular degeneration (wet AMD).Early May 2023，The team of Professor Wei Wenbin from Beijing Tongren Hospital, Capital Medical University, has completedKH631 for the treatment of AMDFirst Patient Dosed in Phase I Clinical Trial。16. VGR-R01 by Tianzeyun TaiOn November 1, 2022, the IND application for VGR-R01 injection, an AAV gene therapy drug developed by Shanghai Tianze Cloud Biopharmaceutical Co., Ltd. (Tianze Cloud), received tacit approval from the CDE. Its indication is crystalline retinal dystrophy (Bietti crystalline dystrophy, BCD) caused by CYP4V2 gene mutations.(Full text link:Tianze Yuntai BCD Gene Therapy Drug IND Approved）。In October 2022, GC101 Injection, an AAV gene therapy drug developed by Beijing Jinlan Gene Technology Co., Ltd., received the CDE’s tacit approval for clinical trials. Its clinical indication is Type 1 Spinal Muscular Atrophy (Type 1 SMA). On November 15 of the same year, the IND application for "GC101 Injection" for Type 2 SMA indication also received tacit approval from the CDE.18. FT-001 by Fangtuo BiologicsIn September 2022, the Investigational New Drug (IND) application for FT-001 injection, a gene therapy drug developed by Frontera Therapeutics for RPE65 biallelic variant hereditary retinal degeneration, received tacit approval from the Center for Drug Evaluation (CDE). On January 9, 2023, Frontera Therapeutics announced that the first patient dosing of FT-001 injection was completed at Peking Union Medical College Hospital (Full text link:Frontera Therapeutics FT-001 Injection Completes First Patient Dosing）。19. ZS801 by Zhishan WeixinOn September 1, 2022, the clinical application of ZS801 Injection from Sichuan Zhishan Weixin Biotechnology Co., Ltd. was approved by the CDE for the control and prevention of bleeding in male patients aged 18 years and above with severe or moderately severe Hemophilia B (congenital Factor IX deficiency, Factor IX <2%).This is an AAV gene therapy. The serotype of the AAV vector used in this therapy has very low pre-existing neutralizing antibodies in patients, allowing it to cover more Chinese patients.。20. EXG001-307 by JiaYin BioOn June 21, 2022, Genebio announced that the clinical trial application for its self-developed AAV gene therapy EXG001-307 injection has been approved by the CDE for the treatment of Type 1 Spinal Muscular Atrophy (Type 1 SMA) with bi-allelic mutations (deletions) in the Survival Motor Neuron 1 (SMN1) gene.This is the first gene therapy product for the treatment of Type 1 SMA via intravenous injection to be approved for registration clinical trials in China (Full text link:Another AAV Gene Therapy IND Clinical Trial Approved by CDE in China）。EXG001-307 is an AAV-based gene therapy that has the potential to be effective for a long time with a single administration. Its mechanism of action and usage are similar to Novartis' Zolgensma. Hangzhou Jiayin has adopted an innovative design for EXG001-307, aiming to reduce side effects on the heart and liver, thereby enhancing its therapeutic efficacy.21. Tianzeyun TechnologyVGB-R04In April 2022, VGB-R04 Injection, the first AAV gene therapy candidate drug independently developed by Shanghai Tianze Cloud Biotechnology, received clinical trial approval for the treatment of Hemophilia B caused by congenital Factor IX deficiency.VGB-R04 is administered intravenously, delivering the target gene (therapeutic gene) to the liver cell nucleus mediated by the AAV capsid. It expresses a variant of coagulation factor IX (hFIX Padua) protein in liver cells. FIX-Padua is a naturally occurring, highly active FIX variant (R338L), with activity approximately 8 times that of normal wild-type FIX. This means it can achieve normal blood clotting function at lower expression levels, thereby reducing the dosage of the viral vector and enhancing the safety and efficacy of the viral vector administration.In April 2022, LX101 Ophthalmic Injection, an AAV2-RPE65 gene therapy formulation independently developed by Shanghai Langxin Qisheng (Langsheng Biopharmaceuticals) Co., Ltd. under Langxin Biologics, received clinical trial approval for the treatment of patients with inherited retinal degeneration (IRD) associated with biallelic RPE65 mutations.The gene therapy LX101, using AAV2 as a vector, delivers the optimized coding sequence of the functional RPE65 gene into retinal cells in the body, compensating for the loss of protein function caused by mutations in this gene and restoring vision. In previously conducted investigator-initiated clinical studies, this gene therapy demonstrated good safety and efficacy.23, Novartis' OAV101 (already entered Phase III clinical trials)In January 2022, Novartis (Novartis, NYSE: NVS) received clinical trial approval in China for its SMA gene therapy drug OAV101 injection (Zolgensma). On April 29, 2022, relevant databases showed that this therapy had initiated clinical trials in China for the first time, planning to enroll 20 participants in China as part of the global Phase 3 clinical STEER study. On the afternoon of June 20, 2022, Novartis (Novartis) gene therapy (OAV101) clinical trial in China.The kick-off meeting of the Research Center was successfully held at Peking University First Hospital, the group leader unit. This clinical trial is the China segment of the global Phase III clinical STEER study, led by Professor Xiong Hui from the Pediatrics Department of Peking University First Hospital, targeting treatment-naïve patients aged 2 to 18 with Type 2 Spinal Muscular Atrophy (SMA).。
Zolgensma is a gene replacement therapy for treating Type 1 SMA, which theoretically provides long-term or even lifelong efficacy with a single dose, representing a one-time treatment approach that addresses the root cause of the disease. This gene therapy uses an scAAV9 vector administered intravenously to deliver the normal SMN1 gene into the patient's body, producing normal SMN1 protein and thereby improving the function of affected cells such as motor neurons. In contrast, the drugs Spinraza and Evrysdi, used to treat SMA, require repeated long-term administration; Spinraza is administered via spinal injection every four months, while Evrysdi is an orally taken medication that must be taken daily.24. Sinocelltech'sBBM-H901 (Entered Phase III Clinical Trials)In August 2021, BBM-H901 Injection, a gene therapy drug for the treatment of Hemophilia B independently developed by Shanghai Xinzhi Pharmaceutical Technology Co., Ltd., a wholly-owned subsidiary of Belief BioMed, received clinical trial approval. By the end of December 2021, the clinical trial had successfully completed the first dosing of a subject.Currently in Phase III clinical trials，Expected to be launched for sale in the second half of 2024 to the first half of 2025.。
BBM-H901 is an intravenously administered AAV gene therapy, where the AAV carries the target gene (therapeutic gene) that can overexpress human coagulation factor IX (hFIX), thereby increasing and maintaining the patient's coagulation factor levels over the long term.For the prevention of bleeding in adult male patients with Hemophilia BBBM-H901 is one of the earliest AAV gene therapy drugs to enter clinical trials in China, having started IIT clinical research (NCT04135300) in 2019. The IIT clinical research results showed that this therapy has good safety and efficacy. After administration, the level of clotting factor IX (hFIX) in subjects significantly increased, with hFIX levels remaining stable in the blood over the long term. The annualized bleeding rate in patients was significantly reduced, with no significant adverse reactions observed.25. NeophrosNR082 (Entered Phase III Clinical Trial)In March 2021, Neopharm's NR082 ophthalmic injection received the Investigational New Drug (IND) approval from the National Medical Products Administration. On June 28, 2021, Neopharm announced that the first patient was enrolled and dosed in the Phase I/II/III first stage clinical trial of NR082, China’s first in vivo AAV gene therapy for ocular indications to reach the clinical stage. On February 22, 2023, Neopharm announced that all patients had been enrolled and dosed in the Phase III clinical trial of NR082 ophthalmic injection for the treatment of Leber’s Hereditary Optic Neuropathy (LHON) caused by ND4 mutations in China.。
NR082 Gene Therapy Drug Uses AAV as a Vector for Leber's Hereditary Optic Neuropathy (LHON) Caused by ND4 Mitochondrial Gene Mutations. The Administration Method is a Single Intravitreal Injection, Delivering the Therapeutic Gene to the Patient’s Damaged Retinal Ganglion Cells via Intravitreal Cavity Injection, Repairing the Mitochondrial Bioenergetic Respiratory Chain, and Restoring Vitality and Visual Function to the Retinal Ganglion Cells.In mid-June 2019, the hepatitis B AAV gene therapy STSG-0002 was applied for clinical trial by Staidson (Beijing) Bio-pharmaceutical Co., Ltd. In mid-September 2019, it was approved by the National Medical Products Administration for clinical trials targeting chronic hepatitis B treatment. In August 2020, the first subject was dosed.STSG-0002 is an AAV vector-based DNA gene therapy drug utilizing RNA interference technology, developed by Staidson. Compared to non-viral vector small nucleic acid RNA drugs, this drug demonstrates significantly longer efficacy and is expected to provide long-term effectiveness with a single administration.In addition, there are currently 7 AAV gene therapies on the market globally., as shown in the figure below:Among them, (1)Zolgensma SinceLaunched in May 2019, with first-year sales reaching 3.61 billion USD; 9.2 billion USD in 2020; 13.51 billion USD in 2021; and 13.7 billion USD in 2022.。（2）Luxturna，As of September 2019, a total of US$55 million in net sales was achieved (US$27 million and US$28 million for the period from 2018 to September 2019). In October 2019, Roche announced the acquisition of Spark, after which the sales performance of Luxturna was no longer reflected in Roche's financial reports.Source: Official WeChat Account "Cell and Gene Therapy Field", Official Reports from Listed Companies
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