Frontera Therapeutics' FT-002 Becomes First Domestic rAAV Gene Therapy Cleared by FDA for Phase II Trial in the U.S.

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On September 23, 2024, Frontera Therapeutics announced that its self-developed recombinant adeno-associated virus (rAAV) gene therapy product, FT-002 injection, received Phase II clinical trial authorization (IND) from the U.S. Food and Drug Administration (FDA). The approval of this IND marks FT-002 injection as the first China-produced rAAV gene therapy drug to obtain FDA authorization for direct entry into Phase II clinical trials in the United States, representing a milestone event in the overseas development of China's rAAV gene ophthalmology treatment drugs.

FT-002 Aims to Treat X-linked Retinitis Pigmentosa (XLRP) Caused by RPGR Gene Mutations. XLRP is a progressive disease leading to vision loss and represents the most severe form of inherited retinal disorders. The primary affected population is male, with clinical manifestations typically presenting as night blindness during childhood (~10 years old), followed by a gradual narrowing of the visual field. Severe vision loss or even blindness often occurs in middle adulthood (~40 years old), significantly impacting patients' lives. Currently, clinical management for XLRP patients is limited to supportive care and alleviating measures, with no effective treatment drugs approved for marketing in China or globally. Statistics indicate that there are approximately 60,000 to 70,000 patients in China and around 20,000 patients in the United States, reflecting a significant unmet clinical need. The development of FT-002 carries the hope of restoring vision for these patients.

FT-002 is a recombinant adeno-associated virus serotype 5 vector containing a codon-optimized coding gene for the retinitis pigmentosa GTPase regulator (rAAV5-hRPGRORF15). It is produced using an optimized Sf9 baculovirus expression vector system (Sf9 BEVS) and manufactured in the GMP facility of Frontera Therapeutics, Inc. in Suzhou for clinical trial use. Sf9 BEVS is one of the mainstream platform technologies for rAAV production, offering advantages such as high yield, low empty capsid rate, low process-related impurities, linear scalability, and cost-effectiveness. Through innovative production and purification processes, Frontera Therapeutics has successfully reduced the empty capsid rate of the bulk drug substance to less than 1%, far surpassing the industry average and significantly enhancing product safety.

FT-002, as a novel rAAV gene therapy drug, has a very clear mechanism of action: through subretinal injection, it delivers the functional target gene it carries into the patient's retinal photoreceptor cells, enabling them to express active functional proteins, thereby repairing the structure and function of damaged retinal cells. FT-002 requires only a single injection, with the expectation of fundamentally reversing the patient’s vision loss. FT-002 Injection is China’s first rAAV gene therapy drug to enter human trials for XLRP patients and is currently advancing in Phase II clinical research. The Phase II clinical study will continue to observe the effects of FT-002 on the retinal structure and visual function of XLRP patients.

In January 2024, FT-002 injection received FDA Orphan Drug Designation (ODD). In May 2024, Frontera Therapeutics presented clinical research data on FT-002 involving 18 patients with the longest follow-up of one year at the "2024 Retina Cell & Gene Therapy Innovation Summit" held in Seattle, USA. The study results showed that all subjects had good safety and tolerability, and subjects in a certain dose group demonstrated significant improvements in retinal sensitivity, visual function, and other indicators. FT-002 injection is expected to become a First-in-Class rAAV gene therapy drug.

"FT-002 Receives FDA Approval for Direct Entry into Phase II Clinical Trials in the United States, Marking Another Milestone for Frontera Therapeutics. After Four Years of Rapid Development, the Company Has Now Entered a New Stage, with Its First Product Set to Initiate Phase III Clinical Studies in China and Three Projects Advancing to Phase II Clinical Stages." Dr. Li Xinyan, Co-founder and CEO of Frontera Therapeutics, stated, "This approval represents the FDA’s full recognition of Frontera Therapeutics’ innovative capabilities, CMC technology platform, and preclinical and IIT clinical data. We will continue our relentless efforts to bring safe, innovative, and accessible rAAV gene therapy products to market as soon as possible."

AAV vectors have become one of the popular carriers in the field of gene therapy due to their high safety, good tissue targeting, stable and continuous expression of exogenous genes, and low immunogenicity. In recent years, AAV gene therapy has shown promising application prospects in the field of rare diseases, including age-related macular degeneration (AMD), hemophilia, spinal muscular atrophy, frontotemporal dementia, glycogen storage disease, Huntington's disease, and other indications, all of which have made certain progress in clinical trials.

As a research hotspot in the field of gene therapy, the AAV gene therapy sector has attracted a large number of pharmaceutical companies. Currently, over 70% of gene delivery drugs use AAV vectors for delivery. Driven by broad market prospects and significant patient demand, companies in China have also begun to seize opportunities and expand their presence in this area.

Article Reference: Frontera Therapeutics

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