What Is ALKS 2680?
ALKS 2680 is an investigational drug, classified as a DRUG type, currently being studied in clinical trials. It is being developed as an oral tablet designed for once-daily administration. The medication is sponsored by Alkermes, Inc. and is under investigation for its potential to treat various sleep disorders.
Clinical trials are exploring ALKS 2680 as a potential treatment for conditions such as Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia. Participants in some studies receive ALKS 2680 tablets orally, once daily, for a duration of 12 weeks. A total of 7 trials are underway or completed for ALKS 2680, involving a total of 1,013 participants across these studies. The first trial for ALKS 2680 began on April 11, 2024, with the latest trial starting on April 21, 2026.
Uses and Conditions Under Study
ALKS 2680 is currently under investigation for its potential to treat several sleep disorders. These conditions are characterized by excessive daytime sleepiness and other disruptions to the sleep-wake cycle. The drug is being studied in a total of 7 clinical trials, sponsored by Alkermes, Inc., with an overall enrollment of 1,013 participants.
The primary conditions being studied are Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia. These conditions often lead to significant impairment in daily functioning due to persistent drowsiness.
- Narcolepsy Type 1: This condition involves chronic, excessive daytime sleepiness often accompanied by cataplexy, which is a sudden loss of muscle tone triggered by strong emotions. ALKS 2680 is being studied in 4 trials for Narcolepsy Type 1, aiming to address the core symptoms of this disorder.
- Narcolepsy Type 2: Similar to Type 1, Narcolepsy Type 2 also presents with chronic excessive daytime sleepiness but without cataplexy. ALKS 2680 is being investigated in 3 trials for Narcolepsy Type 2, seeking to improve wakefulness and reduce sleepiness.
- Idiopathic Hypersomnia: This rare, chronic neurological condition is characterized by an overwhelming need to sleep during the day, even after adequate or prolonged nighttime sleep. ALKS 2680 is being explored in 2 trials for Idiopathic Hypersomnia, with the goal of alleviating the severe daytime sleepiness associated with this disorder.
Dosing
ALKS 2680 is administered as an oral tablet, designed for once-daily use. Clinical trials have explored various dosages and strengths of ALKS 2680 to determine its efficacy and safety profile for different sleep disorders, including Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia.
The investigational dosage forms and strengths studied in trials include a range of specific amounts. These include:
- ALKS 2680 Dose 1, ALKS 2680 Dose 2, and ALKS 2680 Dose 3, which represent different investigational dose levels.
- Specific strengths of ALKS 2680 at 4 mg, 6 mg, 8 mg, 10 mg, 14 mg, and 18 mg.
Participants in some studies receive ALKS 2680 tablets orally, once daily, for a duration of 12 weeks. These varied dosages are being evaluated across the clinical program to identify the optimal therapeutic dose for managing symptoms associated with Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH).
Side Effects
The most common side effect reported in clinical trials for ALKS 2680 was headache, experienced by 14.2% of patients taking the drug, compared to 10.9% of those on placebo. Other common side effects included:
- Nausea: 11.5% of patients taking ALKS 2680 experienced nausea, compared to 5.4% on placebo.
- Insomnia: 9.7% of patients taking ALKS 2680 experienced insomnia, compared to 4.3% on placebo.
- Anxiety: 7.1% of patients taking ALKS 2680 experienced anxiety, compared to 3.3% on placebo.
- Dizziness: 6.2% of patients taking ALKS 2680 experienced dizziness, compared to 2.2% on placebo.
- Dry Mouth: 5.3% of patients taking ALKS 2680 experienced dry mouth, compared to 2.2% on placebo.
Fatigue was reported by 4.4% of patients taking ALKS 2680, which was lower than the 6.5% of patients on placebo who experienced fatigue. Serious adverse events occurred in 1.8% of patients receiving ALKS 2680, compared to 1.1% of those on placebo. Discontinuation from the study due to adverse events was reported by 7.1% of patients taking ALKS 2680, versus 3.3% of patients on placebo.
Clinical Trial Results
Clinical trials for ALKS 2680 have investigated its efficacy in patients with Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia. A Phase 1b open-label study (NCT05707722) enrolled 27 patients, including 10 with Narcolepsy Type 1, 10 with Narcolepsy Type 2, and 7 with Idiopathic Hypersomnia. This study primarily assessed safety and tolerability, but also evaluated changes in sleepiness and wakefulness from baseline.
Patients showed significant improvements in wakefulness as measured by the Maintenance of Wakefulness Test (MWT). An increase in MWT minutes indicates improved ability to stay awake. At Day 8, patients with Narcolepsy Type 1 experienced a mean increase of +18.7 minutes from baseline. Patients with Narcolepsy Type 2 saw a mean increase of +18.4 minutes, and those with Idiopathic Hypersomnia had a mean increase of +16.6 minutes.
Subjective sleepiness, measured by the Epworth Sleepiness Scale (ESS), also improved across all groups. A decrease in ESS points indicates reduced sleepiness. At Day 8, patients with Narcolepsy Type 1 experienced a mean reduction of -7.5 points from baseline. Patients with Narcolepsy Type 2 had a mean reduction of -5.9 points, and patients with Idiopathic Hypersomnia showed a mean reduction of -5.3 points.
Patient Global Impression of Change (PGIC) scores indicated that a majority of patients felt their condition had improved. Among patients with Narcolepsy Type 1, 80% rated themselves as "much improved" or "very much improved." For Narcolepsy Type 2, 70% of patients reported being "much improved" or "very much improved," and for Idiopathic Hypersomnia, 71% of patients reported similar improvements.
Currently Recruiting Trials
ALKS 2680 is currently being investigated in several clinical trials for its potential to treat sleep disorders. These studies are seeking adult participants to evaluate the drug's effectiveness and safety.
One ongoing Phase 3 study, known as Brilliance NT1 - 304 (NCT07540897), is evaluating ALKS 2680 in adults with Narcolepsy Type 1. This trial aims to enroll approximately 150 participants to measure how ALKS 2680 tablets compare to placebo in reducing daytime sleepiness, cataplexy (sudden loss of muscle tone), and other disease symptoms.
Another Phase 3 study (NCT07455383) also focuses on adults with Narcolepsy Type 1. This study, targeting 150 participants, similarly investigates the reduction of daytime sleepiness, cataplexy, and disease symptoms with ALKS 2680 tablets versus placebo.
For individuals with Narcolepsy Type 2, a separate Phase 3 study (NCT07502443) is underway. This trial plans to enroll around 176 adults to assess the efficacy and safety of ALKS 2680 tablets in decreasing daytime sleepiness and other disease symptoms compared to placebo.
ALKS 2680 is also being studied for Idiopathic Hypersomnia. A Phase 2 trial (NCT06843590) is recruiting approximately 96 subjects to evaluate the safety and effectiveness of ALKS 2680 tablets at various dosages (10 mg, 14 mg, 18 mg) in reducing daytime sleepiness compared to placebo.
Finally, a long-term study (NCT06767683) is enrolling approximately 256 participants across Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia. This Phase 2/3 trial aims to continue monitoring the safety, tolerability, and sustained treatment effects of ALKS 2680 over an extended period.
Where to Participate
Clinical trials for ALKS 2680 are actively recruiting participants across a wide geographic area within the United States. Currently, there are 2 sites spanning 37 cities across 19 states.
To be eligible for participation in these studies, individuals must generally be between 18 and 70 years of age. All genders are welcome, but these trials are not designed for healthy volunteers or children. Specific eligibility criteria will vary by study.
Some of the cities with multiple participating sites include:
- Cincinnati, Ohio
- Brandon, Florida
- Macon, Georgia
- Wyomissing, Pennsylvania
- Columbia, South Carolina
- Austin, Texas
- Sugar Land, Texas
- Lansing, Michigan
Development Timeline
The journey of ALKS 2680 in clinical development began with its first trial initiated on April 11, 2024, with the latest trial projected to conclude around April 21, 2026. This investigational medicine is being developed by Alkermes, Inc., who has sponsored all seven clinical trials for ALKS 2680 to date.
Initially, ALKS 2680 was explored for conditions such as IBS-C and hyperphosphatemia. However, its development pipeline has since expanded, with a significant focus now on sleep disorders, including Idiopathic Hypersomnia and Narcolepsy.
Across its development, ALKS 2680 has progressed through various stages. The program includes three Phase 2 studies, three Phase 3 studies, and one study that spans both Phase 2 and Phase 3. These trials have collectively aimed to enroll a total of 1,013 participants, evaluating the drug's safety and efficacy in addressing unmet medical needs.