Alkeus' oral eye drug fails in phase 3 to reduce lesion growth

Alkeus Pharmaceuticals is pressing forward with the development of its oral eye disease treatment, despite a recent phase 3 trial setback. The company’s candidate, gildeuretinol acetate (ALK-001), was tested in a 24-month study known as SAGA, which involved 198 patients suffering from geographic atrophy (GA) due to age-related macular degeneration (AMD). GA is a chronic condition that leads to vision loss.

The primary goal of the study was to measure the growth rate of GA lesions from the start of the trial to 24 months, using Fundus Autofluorescence imaging. Unfortunately, the study did not meet its primary efficacy endpoint. The reduction in the growth rate of GA lesions noted in the trial was 0.25 square millimeters per year compared to a placebo, which was not statistically significant (p=0.07).

Despite this, Alkeus remains optimistic, citing "clinically meaningful" trends and a win on a secondary endpoint as encouragement for further development. Dr. Seemi Khan, the chief medical officer of Alkeus, emphasized the importance of the results, noting that the data showed a "clinically meaningful trend in slowing the growth rate of GA lesions." Khan also highlighted that this study is the first to demonstrate that slowing vitamin A dimerization might be beneficial for treating GA secondary to AMD. This builds on positive data from previous studies of gildeuretinol in Stargardt disease.

The trial did show a statistically significant reduction in the loss of low luminance visual acuity, which is a risk factor for disease progression and a secondary endpoint. The candidate also displayed a favorable safety and tolerability profile, in line with previous studies in Stargardt disease, another severe eye condition caused by genetic factors.

GA is a progressive disease leading to irreversible central vision loss, and currently, there are no oral therapies approved by the FDA for this condition. Dr. David Boyer, a principal investigator and retina specialist, expressed his optimism in the company's press release, stating that the results of the oral treatment are promising for patients in desperate need of a therapy to slow disease progression. He believes that these findings mark a significant advancement in understanding the GA disease mechanism.

Although the future of gildeuretinol acetate in treating GA remains uncertain, Alkeus CEO Michel Dahan is committed to advancing the treatment, particularly for individuals with Stargardt disease, pending regulatory approval. The candidate has already received breakthrough therapy and orphan drug designations from the FDA for this rare genetic eye disease. A previous phase 2 study demonstrated significant slowing of retinal lesion growth over two years in patients with late-stage Stargardt disease.

Alkeus Pharmaceuticals, based in Massachusetts and backed by Bain Capital Life Sciences, is continuing its clinical trials for gildeuretinol in Stargardt disease. The biotech firm remains hopeful that their oral treatment will provide much-needed relief for patients suffering from debilitating eye diseases.