Rare Disease Data Center

Gene therapy primarily utilizes viral vector technology for gene delivery. In recent years, adeno-associated virus (AAV) vectors have gained significant traction and are developing rapidly.

AAV is a small, non-enveloped virus with numerous advantages, such as non-pathogenicity, high sustained expression efficiency, user-friendliness, and low immunogenicity. These features make it one of the most promising vectors in gene therapy. Once the therapeutic gene carried by the AAV vector enters the cell, it is transcribed and translated into functional proteins, offering the potential to treat various diseases. The advancements in gene therapy also provide hope for cures for many rare diseases.

The Secretariat of the Alliance closely monitors progress in AAV-related research. To date, seven AAV gene therapies have received global market approval, as summarized below:

Table 1: AAV Gene Therapies Approved for Global Market

Serial Number	Medication	Launch Date and Location	Enterprise	Indication
1	Elevidys	In June 2023, in the US.	Sarepta Therapeutics and Roche collaborate on development.	Used for the treatment of Duchenne muscular dystrophy (DMD) in 4-5-year-old children who are capable of independent walking. Additionally, this medication is contraindicated in DMD children with deletions in exon 8 and/or exon 9.
2	Hemgenix	In November 2022, in the US. In February 2023, in the EU.	UniQure	Adult patients with hemophilia B.
3	Roctavian	In August 2022, in the EU	BioMarin Pharmaceutical	Severe hemophilia A adult patients without a history of FVIII inhibitor and negative for AAV5 antibodies.
4	Upstaza	In June 2022, in the US. In November 2022, in the EU.	PTC Therapeutics	Patients with aromatic Lamino acid decarboxylase (AADC) deficiency who are 18 months of age and older.
5	Zolgensma	In May 2019, in the US.	Avexis, a subsidiary of Novartis.	Patients with Spinal Muscular Atrophy (SMA) who are under 2 years old.
6	Luxturna	In 2017, in the US. In 2018, in the EU.	Spark Therapeutics, a subsidiary of Roche.	Used for the treatment of children and adult patients with vision loss due to biallelic RPE65 gene mutations, who have sufficient viable retinal cells.
7	Glybera	In 2012, in the EU	UniQure	Patients with Lipoprotein Lipase Deficiency (LPLD) who experience severe or recurring pancreatitis despite strict dietary fat restriction.

Furthermore, a total of 22 AAV gene therapy drugs have been approved for Investigational New Drug (IND) applications in China. Among them, three have entered Phase III clinical trials (NR082 by Neufutures, BBM-H901 by Qilu Pharmaceutical, and OAV101 by Novartis). The summary is as follows:

Table 2: AAV Gene Therapy Clinical Trials Approved in China

Serial Number	Medication	Enterprise	Indication	CDE Approval Date	Clinical Progress	Types of Carriers	Recent Clinical Advancements Overseas
1	ZS802	REAL AND BEST	Haemophilia A	2023/6/28	Phase 1/2	rAAV	-
2	EXG102-031	Exegenesis Bio	wAMD	2023/6/1	Phase 1/2	rAAV	Obtained FDA new drug clinical trial approval on January 19, 2023.
3	AL-001	Beijing Anlong Biomedical Co., Ltd.	wAMD	2023/4/27	Phase 1/2	AAV	-
4	HG004	HuidaGene	LCA2	2023/4/18	Phase 2	rAAV	-
5	NFS-02	Neurophth	G3460A	2023/4/14	Phase 1/2	rAAV2	Obtained FDA new drug clinical trial approval on December 19, 2022.
6	GS1191-0445	Suzhou Huayilejian Biotechnology Co., Ltd.	Haemophilia A	2023/1/16	Phase 2	AAV	-
7	LX102	Innostellar Biotherapeutics Co.,Ltd	wAMD	2022/12/23	Phase 1/2	AAV	-
8	GC301	GeneCradle	IOPD	2022/12/20	Phase 1/2	AAV9	-
9	ZVS101e	ChinaGene Tech	BCD	2022/12/6	Phase 1/2	AAV8
10	GC304	GeneCradle	HTG-AP	2022/11/15	Phase 1/2	AAV	-
11	KH631	Chengdu Kanghong Pharmaceutical Group Co.,Ltd.	wetAMD	2022/11/15	Phase 1/2	AAV	-
12	VGR-R01	Vitalgene	BCD	2022/11/1	Phase 1/2	rAAV2/8	-
13	GC101	GeneCradle	SMA-1	2022/10/9	Phase 1/2	AAV	-
14	FT-001	Frontera Therapeutics	LCA	2022/9/17	Phase 1/2	AAV	Obtained FDA new drug clinical trial approval on April 2022.
15	ZS801	REAL AND BEST	Haemophilia B	2022/9/1	Phase 1/2	rAAV	-
16	EXG001-307	Exegenesis Bio	SMA-1	2022/6/21	Phase 1/2	AAV	-
17	VGR-R04	Vitalgene	Haemophilia B	2022/4/20	Phase 1/2	AAV	-
18	LX101	Innostellar Biotherapeutics Co.,Ltd	IRD	2022/4/19	Phase 1/2	rAAV	-
19	OAV101	Novartis	SMA-1	2022/1/7	Phase 3 (This clinical trial is the Chinese segment of the global Phase 3 clinical STEER study.)	AAV	Obtained FDA approval for market launch in May 2019.
20	BBM-H901	Belief BioMed	Haemophilia B	2021/8/9	Phase 3	AAV	-
21	NR082	Neurophth	LHON	2021/3/30	Phase 3	rAAV	-
22	STSG-0002	Staidson	HBV	2019/9/19	Phase 1/2	rAAV	-

In conclusion, the rapid developments in AAV gene therapy are promising, both for existing treatments and those still in the experimental stages. Continued research and investment in this field are likely to yield even more groundbreaking therapies, transforming the treatment landscape for a range of diseases, including rare genetic disorders.

A Review of AAV Gene Therapy