Published in Pipeline

FDA grants Orphan Drug designation for Atsena's XLRS gene therapy

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3 min read

Atsena Therapeutics announced the FDA has granted Orphan Drug designation (ODD) for ATSN-201, a gene therapy candidate intended to treat X-linked retinoschisis (XLRS), just one month after receiving Rare Pediatric Disease designation (PDD).

First an ODD rundown.

Orphan drug designation (ODD) is granted to certain orphan drugs showing promise for the treatment, prevention, or diagnosis of “orphan” diseases—rare serious or life-threatening diseases or conditions that affect <200,000 patients in the United States.

  • To note: Drugs in this category go through the same scientific review process as any other drug seeking approval for licensing, and are qualified to receive:
    • Tax credits for qualified clinical trials
    • Exemption from user fees
    • Potential 7 years of market exclusivity following approval

Now the basis for this candidate.

To understand ATSN-201, you’ll need to know about Atsena’s next-generation, adeno-associated virus (AAV) technologies, which include novel, laterally-spreading capsids, dual vectors, and intravitreal capsids.

Zeroing in on dual vectors: These are designed to “deliver larger payloads for genetic mutations that are too large to treat with a single AAV vector,” according to the company.

  • Such genetic mutations translate to diseases like XLRS, an early onset form of macular degeneration.

And ATSN-201?

This gene therapy utilizes AAV.SPR, a laterally-spreading capsid that reaches beyond the subretinal injection site (bleb margins) to ensure the safe delivery of the retinoschisin (RS1) gene to photoreceptors within the central retina/fovea.

Catch me up on RS1 and AAV.SPR.

What to know about RS1: This is a protein secreted primarily by photoreceptors (and bipolar cells) that, when mutated, causes XLRS.

All about AAV.SPR: This vector reaches therapeutic levels of gene expression in photoreceptors within the central retina without the surgical risks typically associated with foveal detachment to potentially restore retinal structure and function.

  • Clinically-speaking: It’s currently being investigated in Atsena’s XLRS program as well as its MYO7A-associated Usher syndrome (USH1B) program.

Alrighty, now to this ODD … why is it significant?

With no treatment currently approved for XLRS, this latest designation for ATSN-201—as well as its RPD last month—”mark a significant inflection point for the potential of this ocular gene therapy,” noted Atsena CEO Patrick Ritschel.

  • Note: The FDA previously approved an investigational new drug (IND) application for the XLRS indication of ATSN-201 in May 2023.

And what’s next for the candidate?

As we last reported, ATSN-201 is being studied in the ongoing phase 1/2 LIGHTHOUSE trial (NCT05878860).

The details: An estimated 21 male participants (aged 6 to 64) diagnosed with XLRS caused by pathogenic or likely pathogenic mutations in the RS1 gene.

As far as clinical data: With that phase 1/2 study still enrolling, Clinical Trials estimates its conclusion for October 2029 (although interim data will likely be released before then).

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