The wind of ophthalmic CGT is rising.

Ophthalmic CGT has become another emerging trend pursued by pharmaceutical companies.

In the past month, Eli Lilly has completed two consecutive deals. In mid - October, it acquired Adverum for up to $262 million to obtain the gene therapy Ixo - vec for wet age - related macular degeneration (wAMD). On November 10th, it reached a cooperation with MeiraGTx, paying an upfront payment of $75 million and up to $475 million in milestone payments to acquire the global rights to a gene therapy for Leber congenital amaurosis type 4 (LCA4).

While the CGT industry as a whole is experiencing a "recession period", giants such as Roche and Pfizer have scaled back their AAV gene therapy layouts, and Vertex Pharmaceuticals has even completely abandoned AAV vector research. However, the ophthalmic field has witnessed a boom in transactions. Before Eli Lilly, Otsuka Pharmaceutical paid an upfront payment of $85 million to obtain the Asia - Pacific rights to 4D - 150 from 4D Molecular. AbbVie has been continuously promoting its acquired ABBV - RGX - 314 into Phase III clinical trials.

Behind this differentiation lies the unique advantage of the eye as an "immune - privileged organ", and more importantly, the disruptive potential of gene therapy in treating blinding ophthalmic diseases, which has won the real - money recognition of multinational pharmaceutical companies.

From rare diseases to common diseases, and from gene replacement to gene regulation, the ophthalmic field is becoming the best testing ground for the implementation of CGT technology. The trend has arrived. As companies like Eli Lilly use capital to accelerate the implementation of technology and multiple therapies enter Phase III clinical trials, has the golden age of ophthalmic CGT arrived?

/ 01 / Eli Lilly's consecutive bets

Eli Lilly's consecutive bets are not blind following of the trend. Instead, it has targeted two core tracks in ophthalmic CGT: rare hereditary ophthalmic diseases and common blinding ophthalmic diseases, while also hiding a dual - layout logic of assets and technology.

In its cooperation with MeiraGTx, Eli Lilly is targeting the gene therapy AAV - AIPL1 for the treatment of Leber congenital amaurosis type 4 (LCA4).

LCA is a severe type of hereditary retinal disease. Patients show severe vision loss at birth or shortly after birth. LCA4 is an extremely rare subtype, a severe retinal disease caused by mutations in the AIPL1 gene. Most LCA4 children lose almost all of their photoreceptor cells around the age of four.

"Restoring the vision of those children who are destined to be blind at birth," this is how Andrew Adams, vice - president of Eli Lilly's Molecular Discovery Department, describes AAV - AIPL1.

AAV - AIPL1 injects the drug beneath the retina, using a synthetic adeno - associated virus (AAV) to deliver a copy of the therapeutic gene (AIPL1) into the remaining photoreceptors. It has proven its strength in clinical trials: to date, all 11 LCA4 children who have received treatment have achieved significant vision improvement after a single treatment, and the safety is also good.

Beyond this revolutionary drug, the value of this deal also lies in the fact that Eli Lilly has obtained the right to use MeiraGTx's gene therapy tools and its advanced "riboswitch" gene regulation technology. This technology can precisely regulate gene expression, solving the key challenge of controlling the expression of target genes in AAV vector delivery, which lays a technological foundation for its future development of treatment plans for other complex ophthalmic diseases.

The acquisition of Adverum to obtain lxo - vec shows Eli Lilly's ambition in the market for common ophthalmic diseases. Macular degeneration (AMD) is a highly age - related disease and the main cause of blindness in the elderly. In 2020, there were up to 190 million patients globally. Existing anti - VEGF drugs such as aflibercept require frequent injections, resulting in poor patient compliance.

Lxo - vec carries the aflibercept coding sequence through the AAV7 vector. A single intravitreal injection can achieve continuous expression, shifting from "lifelong injection treatment" to "one - time cure". The Phase III trial launched in March this year is verifying its efficacy in a large - scale patient population.

It can be seen that Eli Lilly has quickly entered the ophthalmic CGT field through two deals, completing the layout from rare diseases to common diseases and from late - stage clinical assets to platform technology.

/ 02 / The main battlefield of ophthalmic innovation

While gene therapy has encountered disputes over the safety of AAV vectors and setbacks in commercialization in other fields, ophthalmic CGT has risen against the trend.

This is because the blood - eye barrier makes the eye relatively independent from the immune system. To a certain extent, the eye is an immune - privileged area and is considered the most suitable target for gene therapy. At the same time, many blinding ophthalmic diseases are caused by single - gene mutations, with clear targets, providing a clear direction for gene replacement therapy.

In 2017, Luxturna developed by Spark Therapeutics became the first FDA - approved ophthalmic gene therapy. This AAV therapy targeting the RPE65 gene mutation successfully verified the effectiveness of the AAV vector as an ophthalmic gene therapy platform, subsequently attracting the layouts of many domestic and foreign pharmaceutical companies.

Now, more than 10 ophthalmic AAV gene therapies have entered Phase III clinical trials, and the indication layout features equal emphasis on rare diseases and common diseases. Among them, MCO - 010, the core investigational therapy of Nanosconpe Therapeutics, has started the rolling submission of a Biologics License Application (BLA) to the FDA, targeting retinitis pigmentosa (RP), a refractory ophthalmic disease.

RP involves more than a hundred pathogenic genes and thousands of mutations, and traditional therapies are helpless. The innovation of MCO - 010 lies in its use of optogenetic technology, which does not target specific mutation types and is expected to cover a wider patient population. Clinical data shows that 100% of the 18 patients who received treatment achieved clinically significant vision improvement, and the safety and tolerance were good within five years after a single injection.

Domestic pharmaceutical companies have also made layouts for this kind of universal gene therapy across gene mutations. On October 9th, Xingming Youjian reached a BD cooperation worth a total of $414 million with AviadoBio regarding the optogenetic pipeline UGX - 202.

According to Xingming Youjian, the therapeutic effect of UGX202 does not depend on the specific pathogenic gene mutation type of the patient and is applicable to multiple disease populations, including retinitis pigmentosa, Stargardt disease, choroideremia, and advanced dry age - related macular degeneration.

This means that technological development is breaking the limitations of rare diseases. Gene therapy has extended from single - gene rare diseases to multi - factor common diseases. Breakthroughs in indications such as wAMD and diabetic macular edema (DME) have expanded the market space from thousands of people to tens of millions. This leap from "curing the niche" to "benefiting the masses" is one of the core logics for the rising popularity of ophthalmic CGT against the trend.

In addition to AAV gene therapy, with the progress of small nucleic acid drug technology, it is also accelerating its entry into the ophthalmic field. In 2023, Izervay, an RNA aptamer therapy acquired by Astellas, was approved for marketing for the treatment of geographic atrophy (GA) secondary to AMD, with sales of approximately $340 million in 2024.

In 2024, Regeneron launched a Phase III clinical trial of the RNAi therapy cemdisiran ± the C5 monoclonal antibody pozelimab targeting C5 for the treatment of GA. Domestic pharmaceutical companies have also made layouts. For example, RBD1007 of Ruibo Biotech is an optic nerve - protecting siRNA drug targeting Caspases2. It inhibits the expression of the target gene through RNAi, preventing the apoptosis of retinal ganglion cells (RGC) and the secondary degeneration of nerve axons. The first indication being developed is non - arteritic anterior ischemic optic neuropathy, and it has now entered Phase III clinical trials.

The ophthalmic field has become an innovative testing ground for CGT technology. Whether it is delivering healthy genes through AAV or modifying gene expression through RNA, these innovative therapies are all trying to intervene in ophthalmic diseases at the root to achieve the goal of cure as much as possible.

Of course, as the entire track reaches the late - stage clinical phase, the commercialization challenges that gene therapy itself needs to face cannot be ignored.

/ 03 / The competition window has arrived

Undoubtedly, payment ability will become a key variable in the subsequent competition.

In this regard, the perfect rare - disease payment system in the United States makes it possible to commercialize high - priced CGT therapies. Large pharmaceutical companies such as Eli Lilly dare to place heavy bets precisely because they have taken a fancy to this market characteristic. Compared with gene therapies for diseases such as hemophilia A, a gene therapy that can "restore vision with one injection" is commercially feasible even if priced at one million dollars under a mature payment system.

Even in the field of retinal diseases such as AMD, the emergence of drugs such as aflibercept and faricimab has greatly improved the treatment of patients. However, due to the challenge of compliance, there is still a great unmet clinical treatment need. In the market expectation, gene therapy is expected to achieve commercial success through a compliance revolution.

Take Otsuka Pharmaceutical's acquisition of 4D - 150 from 4D Molecular with an upfront payment of $85 million and up to $336 million in milestone payments as an example. It is for the treatment of wet AMD and DME. The Phase I/II PRISM trial shows that the treatment burden is reduced by 78% - 94%, 97% of patients have no inflammatory reaction, and there are no serious adverse events. Currently, it is advancing into Phase III clinical trials, and the data is expected to be announced in the first half of 2027.

Since 4D - 150 can express aflibercept for a long time, patients may benefit for life after a single treatment. 4D Molecular believes that this compliance revolution has great potential and can also solve the problem of the capacity limitation of retinal clinics.

4D Molecular is full of confidence regarding the commercialization issue. At the 2025 fiscal year earnings conference call, company executives said that a survey by the American Society of Retina Specialists showed that 50% of doctors listed gene therapy as the preferred therapy for neovascular retinal diseases. At the same time, based on doctors' high demand for gene therapy, the company plans to promote 4D - 150 to all patients with wet AMD and DME in the future.

It should be noted that due to the clear market demand, the competition in this field is also relatively fierce. In addition to 4D - 4150 and lxo - vec acquired by Eli Lilly, there are also multiple gene therapies in the late - stage clinical phase. For example, in 2021, AbbVie acquired the global development and commercialization rights to ABBV - RGX - 314 for a total of $1.752 billion.

This is a gene therapy using AAV8 as a vector, which contains a gene sequence encoding an anti - VEGF monoclonal antibody fragment and has obtained positive results in multiple clinical studies. In a Phase II study for wAMD, after 14 patients received high - dose sub - retinal injection of ABBV - RGX - 314 for 6 months, the best - corrected visual acuity score increased by 8.6 letters.

In June 2025, AbbVie launched the first Phase III clinical trial of ABBV - RGX - 314, aiming to evaluate the efficacy and safety of ABBV - RGX - 314 (sub - retinal injection) compared with ranibizumab (intravitreal injection) in the treatment of patients over 50 years old with wAMD who have previously received treatment.

Domestic pharmaceutical companies are also accelerating their pursuit. In the Phase II trial of LX102 by Langxin Biotech for nAMD, more than 75% of patients achieved complete resolution of retinal edema at 36 weeks, significantly higher than the 20% in the aflibercept control group, and it is about to enter Phase III clinical trials.

This means that the next few years will be a critical window period for the industry. As multiple therapies strive for market approval, the pattern of the ophthalmic market may be reshaped.

Of course, behind the popularity of the track, technological challenges still persist. The delivery efficiency, long - term safety, and manufacturing cost of AAV vectors are all thresholds that the industry must cross. The failure of the Phase III trial of the gene therapy bota - vec acquired by Johnson & Johnson for $415 million also warns us that the path of ophthalmic CGT is not smooth.

The pace of technological progress will not stop due to setbacks. In the future, with industrial upgrading and continuous innovation by pharmaceutical companies, patients with ophthalmic diseases who once had no available treatment may welcome an era of "one - time treatment, regain vision".

This article is from the WeChat official account "Amino Observation" (ID: anjiguancha), author: Wu Yue, published by 36Kr with authorization.