The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Atsena Therapeutic’s X-linked retinoschisis (XLRS) gene therapy candidate: ATSN-201.
This latest designation follows last month’s news of ATSN-201 receiving Fast Track designation from the federal agency for this same indication, which currently has no approved treatment.
Lots of developments for this therapy! Start with its background.
ATSN-201 is part of Atsena’s pipeline of novel next-generation treatments based on adeno-associated virus (AAV) technologies such as laterally-spreading capsids, intravitreal (IVT) capsids, and dual vectors.
These therapeutics’ targets: Inherited forms of blindness (think: XLRS, Leber congenital amaurosis, and Usher syndrome).
Circle back to that technology. How does that factor into ATSN-201?
Atsena’s dual vector technology is what powers this gene therapy.
About the tech: This is designed to tackle two major drawbacks to standard AAVs—a limited packaging capacity and an incapacity to deliver gene constructs greater than 5 kilobases (kb).
- The delivery process for this involves using dual AAV vectors to deliver larger (+5 kb) payloads for genetic mutations that are usually too large to treat via just one AAV vector.
- Check out how this works—and see a visual.
And the candidate itself?
The unique foundation for ATSN-201 involves one of Atsena’s aforementioned laterally-spreading capsids with a prominent role in treating XLRS: AAV.SPR.
Its mechanism of action (MOA): The capsid spreads laterally beyond the subretinal injection site (bleb margins) to safely deliver retinoschisin (RS1) to photoreceptors within the central retina / fovea.
- Refresher: RS1 is a protein produced by photoreceptors; when mutated, it results in the development of XLRS.
Due to this MOA: AAV.SPR isn’t associated with “vision-compromising limitations” often reported with IVT-delivered AAVs or with the surgical risks of foveal detachment.
- The result: The capsid regulates therapeutic levels of gene expression in photoreceptors, leading to retinal structure and function restoration for XLRS patients.
Now to this FDA designation … what does it mean for ATSN-201?
RMAT designation is one of several potential designations included in the FDA’s expedited program for investigational drugs classified as (and meeting the definition of) a regenerative medicine therapy.
- Take note: The program also includes Rare Pediatric Disease and Fast Track designations—both of which ATSN-201 has already received, along with Orphan Drug designation—in the last 8 months.
To be eligible: A candidate must be intended to treat, modify, reverse, or cure a serious condition and have supporting preclinical evidence indicating its potential to address unmet medical needs for such a condition (XLRS, for example).
And the advantages of this?
With RMAT, sponsors (such as Atsena) are provided with “intensive FDA guidance on efficient drug development” as well as key insights into how to achieve accelerated regulatory approval, such as:
- Meeting post-approval requirements
- Potential Priority Review of a Biologics License Application (BLA)
Nice! So what clinical data is available on the candidate?
Preliminary data (released in May 2024) clinically validated AAV.SPR and reported that ATSN-201 was well tolerated in all patients. See here for more details.
More recently: ATSN-201 is currently under clinical evaluation in the ongoing two-part phase 1/2 LIGHTHOUSE trial involving an estimated 21 male XLRS patients (aged 6 to 64).
- What we know so far: Part A of the study completed its enrollment and dosing, with early safety data determining that Part B (initiated earlier this year) will focus on the 1.0 E11 vg/mL concentration of ATSN-201 after it was found to provide “the optimal balance of tolerability and efficacy based on preliminary clinical results.”
- To note: The study is expected to conclude in October 2029.