The FDA has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to Atsena Therapeutics’ ATN-101, an investigational gene therapy candidate for autosomal recessive guanylate cyclase 2D (GUCY2D)-associated Leber congenital amaurosis (LCA1).
Refresh me on RMAT.
RMAT designation is a dedicated FDA program designed to expedite the development and review process of investigational drug candidates intended to treat, modify, reverse, or cure a serious or life-threatening condition. The designation is based on preliminary clinical evidence that indicates the specific therapy could potentially address an unmet need for the condition.
This is part of the agency’s expedited programs for therapies, which include:
- Fast Track designation
- Breakthrough Therapy designation
- Accelerated approval
- Priority Review designation
See here for a comprehensive rundown on each.
And this company?
The clinical-stage gene therapy company targets the development of novel treatments for inherited forms of blindness, including LCA1, X-linked retinoschisis (XLRS), and MYO7A-associated Usher syndrome 1B (USH1B).
Atsena’s next-generation, adeno-associated virus technologies feature laterally spreading capsids (AAV.SPR), dual vectors, and intravitreal capsids.
Now talk about ATSN-101.
ATSN-101 is an investigational gene therapy candidate developed to introduce the functional human copy of the GUCY2D gene to photoreceptors—potentially treating LCA1.
Administered via a single subretinal injection, the therapy is an AAV5 capsid and human rhodopsin promoter.
To note, ATSN-101 was previously granted Orphan Drug designation (ODD) for LCA1.
Gotcha. So what was this RMAT designation based on?
Positive 6-month data—released in April 2023—from an ongoing phase 1/2 trial (NCT03920007) that enrolled 15 patients (including three pediatric) divided into three adult cohorts (with three patients each) treated with three ascending doses of ATSN-101 via subretinal injection.
And the findings?
For the nine patients receiving a high dose in the main trial, the mean change from baseline in retinal sensitivity was reported to be significantly greater in treated eyes vs untreated eyes at Day 28 (as well as later follow-up visits) using dark-adapted, full-field stimulus testing (FST).
Further, two high-dose patients achieved an improvement in best-corrected visual acuity (BCVA) that was greater than 0.3 logMAR or approximately 20/40 Snellen equivalent (compared to none in untreated eyes).
For the five high-dose patients tested with the Multi-Luminance Mobility Test (MLMT), four presented with a maximum MLMT score of 6 or a ≥2 level improvement compared to baseline.
See our Glance coverage here for details on adverse reactions.
Gotcha. So about this designation … what’s the significance?
With no FDA-approved treatment for LCA1 on the market, ATSN-101 has the potential to fill an unmet need for pediatric and adult LCA1 patients.
Per Atsena CEO Patrick Ritschel, MBA, the company is planning to explore options for advancing ATSN-101 into a pivotal trial.
And in the meantime, 12-month data from the ongoing phase 1/2 trial is expected to be released by the end of 2023.