The FDA has granted Alkeus Pharmaceuticals, Inc. both Rare Pediatric Disease and Fast Track designation for gildeuretinol acetate (ALK-001), its investigational oral candidate intended for the treatment of Stargardt disease (SD).
Let’s start with this therapeutic.
ALK-001 is a small molecule designed to selectively address the underlying cause behind SD (and dry AMD, which it’s also under clinical investigation for) by reducing the rate of Vitamin A dimerization within the eye.
- Dimerization refresh: This is where two molecules join together to form a new compound.
And why focus on Vitamin A?
This nutrient plays a key role in vision and can form toxic byproducts in the natural visual cycle through a process called dimerization.
As such: ALK-001 works to replace Vitamin A while retaining the vitamin’s natural functions and reducing toxic byproduct production.
- The intended result: Preservation of retinal health and vision.
Gotcha. And how is ALK-001 administered?
Orally, just once a day.
Now talk about these designations.
Before we do: It’s important to note that the FDA has already granted ALK-001:
- Breakthrough Therapy designation
- Orphan Drug designation
As for these new additions:
- Rare Pediatric Disease designation is granted to drugs under development for rare childhood diseases (such as SD) when four key criteria have been met.
- Because of this: Alkeus could be eligible to receive a priority review voucher (RPV) pending FDA approval of ALK-001, which could then be used for another clinical indication (such as GA secondary to AMD)
- Breakthrough Therapy designation is intended to expedite the development and review process for drugs designed to treat a serious or life-threatening disease (i.e., SD, in this case).
- To note: Drugs in this category are also eligible for all Fast Track designations
Nice! Circling back to this candidate … what has clinical data shown?
The company reported new findings last month from its SD-focused Tolerability and Effects of ALK-001 on Stargardt diseasE (TEASE) program, consisting of four independent clinical studies on ALK-001.
About TEASE-1 (NCT04239625): multicenter, double-masked, randomized, placebo-controlled phase 2 study (n = 50).
Its performance: Over a 2-year period, ALK-001:
- Slowed the growth rate of atrophic retinal lesions area by 21.6% versus untreated patients
- Demonstrated a 29.5% reduction in growth rate of atrophic lesions
- Those growth rates were:
- 0.18 mm/year (0.87 mm²/year untransformed area) in the ALK-001-treated arm
- 0.23 mm/year (1.23 mm²/year) in the untreated arm
- Mean difference: 0.05 mm/year, 95% confidence interval (CI), 0.03 to 0.07, p<0.001
- Those growth rates were:
Any data from other TEASE studies?
Alkeus also noted previous interim data released from the TEASE-3 study (n = 200).
Those findings: Based on early-stage SD patients treated with ALK-001, there was no disease progression, and all patients remained asymptomatic while on the therapy for between 2 and 6 years.
- Plus: ALK-001 treatment was linked to “relatively stable visual acuity” among SD patients.
Go on …
We also covered this interim data (based on three out of the 200 enrolled participants) when it was reported in January 2024.
Our notes: ALK-001 resulted in a 21% reduction in the growth rate of retinal atrophic lesions (p<0.001, square root units, 28% effect for untransformed areas) against untreated patients.
And between both TEASE-1 and TEASE-3?
ALK-001 demonstrated both “safety and tolerability,” with no adverse events (AEs) in relation to “hyper- or hypovitaminosis A.” These included:
- Xerophthalmia
- Chromatopsia
- Dark adaptation delays
- Night blindness
Definition refresh: “Hypervitaminosis A and hypovitaminosis A refer to conditions in which there is too much and a deficiency of Vitamin A, respectively, within the body.”
Quick question: Any updates on the other TEASE trials?
TEASE-2: Randomized, double-masked, placebo-controlled trial (n = 80 moderate SD patients):
- Status: Currently ongoing
- Data timeframe: Topline data readout expected in 2025
TEASE-4: Open-label extension study for monitoring long-term SD effects (follow-up to earlier TEASE trials):
- Status: Designing stages
- Data timeframe: TBD
And lastly: Based on the data thus far, what significance could ALK-001 have?
As noted by Christine Nichols Kay, MD, presenter of the recently reported TEASE-3 data, the findings indicate ALK-001’s potential value in treating SD patients “as early as possible, before onset of progressive central vision loss.”
Supporting this potential: Check out the candidate’s recent performance in the phase 2/3 SAGA study for GA secondary to AMD.