The wAMD treatment is expected to require only one injection!

On September 13, AbbVie and Regenxbio announced that they have reached the development and commercialization of the gene therapy RGX-314 for the treatment of age-related macular degeneration (wet AMD), diabetic retinopathy (DR) and other chronic eye diseases Chemical cooperation agreement
.
AbbVie will pay Regenxbio US$370 million in down payment and US$1.

RGX-314 is a gene therapy that uses Regenxbio’s NAV technology platform to deliver genes encoding antibody Fab fragments that can neutralize VEGF activity into cells through the AAV8 vector.
Currently, a subretinal pass is being carried out in patients with wet AMD.
Key clinical trials of injection administration, and two phase II clinical studies of administration through suprachoroidal injection in wet AMD patients and DR patients
.

According to the agreement, Regenxbio will be responsible for completing the clinical trials of RGX-314 currently in progress
.
AbbVie and Regenxbio will jointly be responsible for other clinical trials to be launched in the future and jointly bear the cost of clinical trials, including the second key clinical trial that was originally planned to be carried out in AMD patients through subretinal injection

VEGF is a protein that stimulates the growth of blood vessels.
The pathology of wAMD is that new and abnormal blood vessels grow uncontrollably under the macula, leading to swelling, bleeding and/or fibrosis, resulting in rapid and severe vision loss.
Departmental injection of anti-VEGF drugs is also the main clinical treatment for wAMD, including ranibizumab (Roche/Novartis), aflibercept (Bayer/Regeneron), and Conbercept (Kanghong Pharmaceutical)
.

Anti-VEGF therapy greatly reduces the risk of vision loss associated with wAMD, and at the same time, it is also upgrading to a long-lasting effect and reducing the frequency of injections
.
Aflibercept is an Fc fusion protein that can bind to all subtypes of VEGF-A and can maintain anti-VEGF activity in the eye for a long time

Roche's faricimab (RG7716), currently in Phase III, is the world's first bispecific antibody developed for ophthalmic diseases, and it targets two different signaling pathways, VEGF-A and Angiopoietin 2 (Ang-2).
, While blocking the VEGF/VEGFR signal to effectively control the formation of new blood vessels, it can also inhibit the Ang-2 signal to improve blood vessel stability and reduce retinal inflammation.
Compared with pure anti-VEGF therapy, it can be used to treat a variety of retinal diseases.
It is possible to reduce the frequency of ocular injections and it is expected to achieve one injection in 4 months
.

As a gene therapy, RGX-314 delivers genes encoding anti-VEGF antibody fragments into cells, providing the possibility of treating wAMD with only one injection
.
In addition, in addition to the standard subretinal injection administration route, RGX-314 also provides a less risky delivery method through the suprachoroidal space.

Regenxbio is currently conducting a phase I/IIa study to evaluate the efficacy and safety of RGX-314.
A total of 42 patients with severe wAMD who require frequent anti-VEGF injections were divided into 5 cohorts and received 3x109~2.
5x1011 GC/ Eye dose of medication
.
On February 16 this year, Regenxbio updated the latest positive interim data of cohort 4 and cohort 5 and the three-year follow-up data of cohort 3 in this phase I/IIa study

Cohort 4 and Cohort 5 received 1.
6x1011 and 2.
5x1011 GC/eye doses, respectively
.
As of January 22, 2021, patients have been well tolerated 1.

Compared with the pre-administration of RGX-314, the annualized anti-VEGF therapy injection burden of the two cohorts has a clinically significant reduction
.
Among them, cohort 4 patients received an average of 4.

The 6 patients in cohort 3 still achieved a stable treatment effect after receiving RGX-314 for 3 years.
The average best corrected visual acuity improved by 12 letters from the baseline, and the central retinal thickness remained stable compared to the measured value at 2 years
.
The average annualized anti-VEGF injection of patients was 2.

After AbbVie acquired Allergan, its business line was expanded, and ophthalmic diseases became an important layout direction
.
In terms of sales revenue, AbbVie’s ophthalmology business revenue in 2020 will be 2.
184 billion U.
S.
dollars, and its revenue in the first half of 2021 will be 1.
736 billion U.
S.
dollars, a strong growth
.
Considering the huge number of wAMD patients worldwide, blockbuster drugs such as aflibercept and ranibizumab have been born, and AbbVie’s existing ophthalmic drugs are mainly for glaucoma and dry eye.
-314 gene therapy is not only a powerful supplement to the product pipeline, but also a place in the cutting-edge field of gene therapy
.