The FDA has granted Fast Track designation to Atsena Therapeutics’ gene therapy candidate for X-linked retinoschisis (XLRS): ATSN-201.
So what exactly is Atsena’s purpose?
The company features a pipeline of clinical and preclinical, novel, next-generation treatments for inherited forms of blindness such as XLRS, GUYC2D-associated Leber congenital amaurosis (LCA1), and MYO7A-associated Usher syndrome (USH1B).
About these assets: Each is powered by adeno-associated virus (AAV) technologies that include novel, laterally-spreading capsids, intravitreal capsids, and dual vectors.
And the technology utilized with these?
That would be Atsena’s unique dual vector technology, which addresses major issues accompanying standard AAVs: limited packaging capacity and an inability to deliver gene constructs larger than 5 kilobases (kb).
How it does this: By using dual AAV vectors to deliver larger payloads for genetic mutations typically too large to treat with a single AAV vector.
Explain the delivery process.
First: A coding sequence is split in half (front and back), with each sharing a recombinogenic sequence to mediate recognition and recombination.
From there: Each half is packaged into a separate AAV vector and co-delivered via a subretinal injection to “co-infect” the same target cells in the front- and back-half coding sequences.
Then: Once both vectors are in the nucleus (and their respective genetic material is released), each half of the delivered gene re-combine to form a full-length construct—which ultimately generates a functional mRNA and produces a full-length therapeutic protein.
Now to this XLRS candidate.
To understand ATSN-201, you’ll need a rundown on AAV.SPR, one of Atsena’s novel capsids that plays a key role in treating XLRS.
What it does: Spreads laterally beyond the subretinal injection site (bleb margins) to ensure the safe delivery of retinoschisin (RS1)—a protein primarily secreted by photoreceptors that, when mutated, leads to XLRS—to photoreceptors within the central retina/fovea.
And this is what makes ATSN-201 unique?
Indeed. In fact, as we previously reported, Atsena’s Shannon Boye, PhD, founder and director, highlighted that AAV.SPR doesn’t come with the typical vision-compromising limitations associated with intravitreally-delivered AAV.
This makes it ideal for use in treating XLRS.
AAV.SPR “can drive therapeutic levels of gene expression in photoreceptors while avoiding the surgical risks of foveal detachment,” Boye stated, “which is important because XLRS patients have fragile retinas due to the presence of schisis lesions.”
- The potential result: Retinal structure and function restoration
Nice! So about this Fast Track designation …
What it is: A company request to the FDA to expedite the regulatory review process of a drug to treat serious medical conditions and fill an unmet need.
- In this case: XLRS is a rare inherited retinal disease with no FDA-approved treatment currently available.
And unlike Breakthrough Therapy designation: FTD can be requested with non-clinical data and/or preliminary clinical evidence.
What other advantages come with FTD?
Aside from more frequent interactions with the FDA through ATN-201’s development, the Fast Track program also gives Atsena the potential for priority review (pending relevant criteria are met) of a future new drug application (NDA) submission.
What this is: An expedited timeframe for the FDA’s review process, in which the agency makes it a “Priority” to review a drug’s NDA and make a decision within 6 months of submission (compared to the standard 10-month review period).
Got it. And this isn’t the first designation for ATSN-201, right?
It’s not! The gene therapy has already received two FDA designations:
- Rare Pediatric Disease designation: Granted in August 2024
- See our coverage and read up on what this entails.
- Orphan Drug designation: Granted in September 2024
This all sounds promising … and it’s under clinical investigation now, right?
Yes! The ongoing phase 1/2 LIGHTHOUSE study (NCT05878860) is evaluating its safety and tolerability (with enrollment ongoing).
The details: An estimated 21 patients (male; aged 6 to 64) diagnosed with XLRS caused by pathogenic or likely pathogenic mutations in the RS1 gene are divided into four cohorts to receive varying injection levels of ATSN-201
- See here for additional information.
Any data released yet?
Indeed there is. In May 2024, the company released positive preliminary data from the study's first cohort (n = 3), in which its AAV.SPR was clinically validated.
Those findings: ATSN-201 was well tolerated in all patients, with two of the three exhibiting extensive resolution of schisis starting at 8 weeks post-dosing.
“These results demonstrate, for the first time, the ability to safely administer subretinal injections in patients with extensive retinal schisis,” Atsena noted in its announcement.
- With no adverse events reported, the therapeutic also demonstrated a favorable safety profile.
And more recently?
Just last month, Atsena announced it had initiated Part B of the LIGHTHOUSE study following successful enrollment and dosing in Part A.
Also: Based on early safety data from Part A, the company reported that Part B will proceed with a 1.0 E11 vg/mL concentration of ATSN-201, which “offered the optimal balance of tolerability and efficacy based on preliminary clinical results.”
Learn more about the setup for Part B here.