Sanofi Pharmaceuticals has received Fast Track designation from the FDA for its gene therapy SAR446597, an investigational gene therapy for the treatment of geographic atrophy (GA) due to age-related macular degeneration (AMD).
Let’s start with the significance of Fast Track.
This designation is granted to companies seeking to expedite the development and regulatory review process of an investigational drug candidate to treat serious medical conditions and fill an unmet need.
Notably: This designation can be requested and granted to a company without the submission of non-clinical data and/or preliminary clinical evidence.
- Also: Fast Track is part of an FDA program for investigational drugs that also includes Regenerative Medicine Advanced Therapy (RMAT) and Breakthrough designations (BTD).
Duly noted. Next up: this company.
Headquartered in Paris, France, Sanofi is an artificial intelligence (AI)-based biopharma company involved in the research, development, manufacturing, and marketing of therapeutic solutions across the globe.
Its target therapeutic areas: Immunology and inflammation, rare diseases, neurology, oncology, and other medicines / vaccines.
- In regards to our topic of discussion: Sanofi is researching therapies with the potential to address serious neuroinflammatory and neurodegenerative diseases—including retinal diseases with unmet needs (such as AMD).
Let’s talk about GA (and dry AMD).
To understand GA, we’ll need to talk about the complement system.
Considered a major component of innate immunity within the human body, the complement system is known for its direct involvement in the pathogenesis of GA and dry AMD (via the overactivation and the triggering of certain proteins, as we explain below).
- To note: The complement system consists of three pathways (alternative, classical, or lectin) that work to ensure homeostasis.
However: Evidence has found that overactivity in the complement system can lead to drusen formation—a notable “hallmark lesion” in AMD and GA.
- Specifically: During this overactivity, plasma and membrane-associated serum proteins are also triggered, causing abnormalities in their function, an imbalance in homeostasis, and damage to healthy tissue—leading to retinal damage and vision loss.
Go on …
These protein abnormalities have been implicated in both the development and progression of dry AMD.
- As such, targeting the complement system to treat dry AMD is where current research is focused—though researchers are still exploring which of those three pathways has the most potential.
And that brings us to … Sanofi’s gene therapy?
Correct. SAR446597 is designed to deliver genetic material encoding two therapeutic antibody fragments that, in turn, target and block two of the three pathways: classical and alternative.
And those two therapeutic antibody fragments include:
- C1s in the classical pathway
- The C1 complex is a protein complex (serin protease) that, when activated, plays a critical role in the complement system by initiating the classical pathway
- Factor Bb in the alternative pathway
- This is a fragment of Factor B (a protein), considered a key component of the alternative pathway’s complement activation
And the potential?
By adopting a dual-targeting approach, the intent is for SAR446597 to enable “sustained complement suppression within the retinal microenvironment" while simultaneously leading to a significant reduction in treatment burden.
Note: This “burden” refers to a reduced or completely eliminated need for frequent intravitreal (IVT) injections—such as those required by current FDA-approved medications for GA.
So how is SAR446597 administered?
Via a single (one-time) IVT injection (hence the company’s emphasis on its potential to reduce that treatment burden).
Got it. Now about its new designation … what does it mean moving forward?
Fast Track gives Sanofi several advantages for SAR446597, including more frequent meetings and communications with the FDA to go over the gene therapy’s:
- Development plans (such as proposed clinical trial designs and biomarker use)
- Potential eligibility for accelerated approval and priority review (if criteria are met)
- Rolling review of a future new drug application (NDA)
- This would allow Sanofi to submit complete sections of its NDA in stages rather than waiting until all sections are completed (as per standard, non-expedited practice)
Nice! And where is the company in the development process?
In announcing this new designation, Sanofi also reported plans to initiate a phase 1/2 study on SAR446597 to evaluate its safety, tolerability, and efficacy.
- At the time of publication, no further details have been released.
In other related news: The company shared that it is currently conducting a phase 1/2 study (NCT06660667) on a separate gene therapy candidate (SAR402663, also administered as a one-time injection) for wet AMD.
The study kicked off in November 2024 and is estimated to conclude in 2031 (with primary completion in 2027).