Alkeus Pharmaceuticals Inc. announced new findings from the phase 2/3 SAGA study evaluating oral gildeuretinol acetate (ALK-001) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Let’s start with Alkeus.
The late-stage, private biopharmaceutical company is developing a molecular therapy to potentially treat degenerative ocular diseases—specifical retinal diseases—such as:
- Stargardt disease (SD)
- See here for details on the latest positive phase 3 data, reported in January 2024.
- GA
Now this candidate.
ALK-001 is a novel molecule in clinical development as “a specialized form of deuterated Vitamin A” that’s intended to reduce the dimerization (where two molecules join together to form a new compound) of Vitamin A—without any vision disruptions.
How it works: The molecule substitutes Vitamin A while retaining the vitamin’s functions and “safely reducing the production of toxic byproducts,” according to Alkeus.
- The intended result: Preservation of retinal health and vision
How is it administered?
The investigational therapeutic is intended to be administered orally, once a day.
What’s its regulatory status?
In the United States, ALK-001 has already received Breakthrough Therapy designation and Orphan Drug designation (ODD) from the FDA.
Alrighty, now to this SAGA trial.
The double-masked, multicenter, randomized, placebo-controlled clinical trial (NCT03845582) evaluated a total of 198 participants (aged 60+ and diagnosed with GA secondary to dry AMD in at least one eye).
The study design:
- One oral capsule of ALK-001 administered once daily for 24 months (n = TBD)
- One oral placebo capsule administered once daily for 24 months (n = TBD)
Note: While Clinical Trials indicated the estimated participant enrollment to be 300—with up to 200 in the ALK-001 group and 100 in the placebo group—Alkeus noted only 198 patients (and no specifics on participant numbers per each group).
And what was measured?
Measured from baseline to 24 months, the primary outcome was growth rate of GA lesions (determined via fundus autofluorescence [FAAF]).
Also measured from baseline to 24 months, secondary outcomes included:
- Safety and tolerability (adverse events [AEs])
- Pharmacokinetics, as determined by plasma concentrations of ALK-001 and metabolites
- Choroidal neovascularization
- Visual acuity (VA) changes
- Reading speed changes
Next: The findings.
While Alkeus reported ALK-001 demonstrated “a clinically meaningful reduction” in GA lesion growth at 24 months—a reduction of 0.25 sqmm/year vs placebo (p = 0.07)—it did not go so far as to say that reduction was “statistically significant.”
- Why this is important: This indicates that the study failed to meet its primary endpoint; in fact, the company noted it supported “further clinical development.”
Was there any statistical significance identified?
What was determined to be statistically significant was ALK-001’s slowing in the rate of decline in low luminance VA (LLVA) at 24 months (p = 0.03)—a key secondary endpoint.
And its safety and tolerability?
As with prior clinical findings, ALK-001 demonstrated a “favorable safety and tolerability,” according to the company.
Speaking of previous research, what has that clinical data found?
Take note: These findings were based on evaluating ALK-001 for SD (not GA).
So to start: Preclinical research found that ALK-001 decreased Vitamin A dimerization to a normal rate, leading to it preventing retinal degeneration and visual function loss in animal subjects diagnosed with SD.
And the human-based clinical data?
ALK-001 is currently undergoing clinical testing as part of Alkeus’s TEASE clinical trial program for SD.
Per the company: Data from a randomized, placebo-controlled, double-masked TEASE-1 study analyzing ALK-001 in patients diagnosed with late-stage SD found “clinically and statistically significant slowing of the growth of retinal lesions over 1 years of treatment.”
And earlier this year, Alkeus reported positive interim data from the phase 3 TEASE-3 trial, the first open-label clinical study on early-stage SD.
Tell me about that.
Following a once-daily oral administration of ALK-001, the first three participants (out of 200 in total) enrolled and treated remained asymptomatic with no disease progression throughout the following treatment durations:
- 2 years (n = 1)
- 6 years (n = 2)
This definitely sounds promising! So what’s next for this candidate?
Focusing on its GA indication: Alkeus announced that its SAGA topline data was just accepted as a late-breaker at the 2024 American Academy of Ophthalmology (AAO) meeting, scheduled for Oct. 18-21 in Chicago, Illinois.
What this means: Additional (and more detailed) clinical findings from the SAGA study will likely be presented.