Atsena Therapeutics has received Rare Pediatric Disease designation (RPD) from the FDA for ATSN-201, its investigational gene therapy candidate, to treat X-linked retinoschisis (XLRS).
First up: Atsena.
The Durham, North Carolina-based clinical-stage gene therapy company targets the development of novel, next-generation treatments for inherited forms of blindness:
- XLRS
- GUCY2D-associated Leber congenital amaurosis (LCA1)
- MYO7A-associated Usher syndrome (USH1B)
And key to this is …
Atsena’s next-generation, adeno-associated virus (AAV) technologies that feature novel, laterally-spreading capsids, dual vectors, and intravitreal capsids.
- The dual vector technology is designed to deliver larger payloads for genetic mutations that are too large to treat with a single AAV vector, Atsena stated.
Now explain this gene therapy candidate.
ATSN-201 utilizes AAV.SPR, one of Atsena’s novel capsids that spreads laterally beyond the subretinal injection site (bleb margins) to ensure the safe delivery of retinoschisin (RS1) to photoreceptors within the central retina/fovea.
- Note: RS1 is a protein secreted primarily by photoreceptors that, when mutated, causes XLRS.
Give me a rundown on AAV.SPR.
The AAV.SPR vector reaches therapeutic levels of gene expression in photoreceptors within the central retina—all without the surgical risks associated with foveal detachment to potentially restore retinal structure and function.
- Its clinical status: The capsid is currently being investigated in Atsena’s XLRS and USH1B programs.
And what makes this gene therapy so unique?
It really all comes down to the use of the AAV.SPR, according to Atsena Founder and Director Shannon Boye, PhD.
Dr. Boye previously noted that, while AAVs delivered intravitreally have limitations that could lead to vision-compromising inflammation, that isn’t the case with Atsena’s vector.
“AAV.SPR is well-suited for use in XLRS [because] it 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.”
Got it. Back to ATSN-201: What clinical data is available?
The gene therapy is currently being studied in the ongoing phase 1/2 LIGHTHOUSE study (NCT05878860).
- The design: open-label, dose-escalation, dose-expansion, randomized trial
- The participants: Estimated 21 participants (male; aged 6-64) diagnosed with XLRS caused by pathogenic or likely pathogenic mutations in the RS1 gene
- The setup: Four aged-based cohorts
- The dosages: Subretinal administration of varying injection levels of ATSN-201
- The outcome measures:
- Primary: ATSN-201 safety and tolerability from baseline to Week 52
- Secondary: Best-corrected visual acuity (BCVA); low-luminance visual acuity (LLVA); contrast sensitivity. See the complete lineup.
Any clinical findings thus far?
None so far, unfortunately. The company reported that enrollment is still ongoing (first patient dosing was back in August 2023).
However: This study’s initiation was possible due to the FDA clearing Atsena’s investigational new drug (IND) application for ATSN-201 in May 2023.
- To note: While the study is expected to conclude in October 2029, we can likely expect interim data in the near future.
Alrighty then. Now to this new designation … what does it mean?
A Rare Pediatric Disease Designation (RPDD) is granted by the FDA for drugs under development for rare childhood diseases when the following criteria has been met:
- The drug must be intended for preventing or treating a rare pediatric disease (defined as a life-threatening or serious condition primarily affecting patients aged 18 and under)
- Adequate documentation or prevalence data must demonstrate that the intended pediatric disease or condition is rare (and the overall patient population for that disease must be 200,000 or less patients in the United States)
- Must not be for an active ingredient that is already approved for use
- Supportive data must suggest that the drug may be effective in the rare pediatric disease or condition.
Why is it critical?
Companies with drugs in the RPDD program that have received an approval to qualify for a priority review voucher (PRV) may also be eligible to receive an expedited 6-month priority review for any marketing applications that follow (such as an IND or new drug application [NDA]).
And for Atsena?
Thanks to this designation, ATSN-201 will now be eligible to receive a priority review voucher (PRV) if approved, as well as an expedited 6-month priority review for any marketing applications that follow (including a new drug application [NDA]).
Plus, Atsena noted that this voucher could also be used to “advance another internal program or be sold to an outside company” to generate additional revenue or for use on a commercial disease.