Alkeus Pharmaceuticals, Inc. reported positive interim data from its TEASE-3 phase 3 clinical trial evaluating gildeuretinol acetate (ALK-001) for the treatment of Stargardt disease.
Quick company refresh, please.
Founded in 2010 and headquartered in Cambridge, Massachusetts, Alkeus Pharmaceuticals is a late-stage, private biopharmaceutical company currently developing a molecular therapy for the potential treatment of degenerative eye diseases, including:
- Stargardt disease (we’ll get to that in a moment)
- Geographic atrophy (GA)
Let’s talk Stargardt.
The cause of this disease—prevalent and a leading cause for blindness among children and young adults—is due to mutations in the ABCA4 gene, which typically is responsible for making sure a vitamin A isomer called n-retinylidene-PE flows through the photoreceptor membrane.
For patients with Stargardt, the ABCA4 protein is either absent or defective—leading to an excess amount of vitamin A concentration and dimerization, a biological process that involves two molecular entities joining together via bonds.
The result of this: Toxic byproducts that “irreversibly damage the RPE [retinal pigment epithelium] layer, leading to progressive vision loss,” according to Alkeus.
Now this therapy.
Alkeus’s lead investigational candidate, gildeuretinol acetate (ALK-001) is a novel, selectively-modified version of vitamin A.
The once-daily oral, investigational therapy is intended to selectively address the underlying cause of Stargardt by reducing the rate of vitamin A dimerization within the eye.
To note, gildeuretinol has already received Breakthrough Therapy designation and Orphan Drug Designation (ODD).
How does it work?
Per Alkeus, the molecular therapy is intended to substitute vitamin A and perform all of its functions—without any dimerization or clumping.
This then leads to reduced toxic byproduct production and, as a result, retinal health and vision preservation.
Any prior data on it?
Oh yes … the TEASE trials are made up of four independent clinical studies on gildeuretinol for Stargardt:
- TEASE-1
- TEASE-2
- TEASE-3
- TEASE-4
Positive data was previously reported from the TEASE-1 study—a double-blind, placebo-controlled, randomized phase 2 trial that evaluated gildeuretinol in 50 patients with advanced Stargardt vs a placebo.
Give me specifics.
The trial met its pre-specified primary efficacy endpoint with a high statistical significance and consistent trend of clinical benefit, as observed in secondary efficacy analyses.
Gildeuretinol was founded to be well-tolerated with a safety profile consistent with that of vitamin A, as well 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.
What about the other trials?
Currently ongoing, the TEASE-2 trial (NCT02402660)—a fully enrolled, randomized, triple-masked, placebo-controlled trial—is evaluating 80 participants diagnosed with Stargardt.
The company expects to report topline data in 2025.
And the TEASE-4 trial is being designed as an open-label extension study.
Tell me about this new phase 3 trial.
Also ongoing, the TEASE-3 study is the first open-label clinical trial on early-stage Stargardt evaluating five patients treated with a daily oral administration of gildeuretinol.
Per the company, the first three teenage patients (out of 200 total participants) enrolled and treated in the study have remained asymptomatic with no disease progression throughout their respective treatment duration:
- 2 years (one patient)
- 6 years (two patients)
And what was the original expectation?
Investigators had projected these patients to “begin experiencing vision loss within 2 years.”
This would have aligned with the disease trajectory of these patients’ respective older siblings, who also contained identical genetic mutations but had not received gildeuretinol treatment.
And the significance of this?
According to Alkeus co-founder, President, and CEO Leonard Saad, PhD, the early results from the TEASE-3 study—coupled with data from the TEASE-1 study—”show great promise for all patients.”He further stated that the company is looking forward to submitting a new drug application (NDA) for the indication of gildeuretinol to treat Stargardt.
Gotcha. So what’s next?
With supporting positive data from two phase 2 studies, the company intends to discuss the results with the FDA and “advance our phase development program,” stated Gleeson.