Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
SAGE-718 · 7 trials · 8 indications
The WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with real-world functional outcomes (e.g., the ability to accomplish everyday tasks) and recovery from functional disability, used to assess processing speed. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 120-second time limit. Higher scores indicate better processing speed. Positive change from baseline indicates better processing speed. Least Squares (LS) Means were calculated using a mixed-effects model for repeated measures (MMRM) approach.
HD-CAB assesses cognitive function using 6 subtests:Symbol Digit Modalities Test-correctly coded items(0-110); One Touch Stockings of Cambridge(OTS)-mean time to reach correct response(range not defined); Trail Making Test Trail B (TMT-B)-time to complete task(0-240 sec); Hopkins Verbal Learning Test Revised-total correct recall trials(0-48); Paced Tapping Test-reciprocal of standard deviation(SD) of intertap intervals (range not defined); Emotion Recognition Test-negative emotions correctly identified(0-24). Values of OTS \& TMT B are multiplied by -1 to represent higher is better direction as other tests. Each of 6 subtests scores was transformed to z-score(range not defined;low negative value represents cognitive impairment), which is calculated by subtracting mean and dividing by SD of HP at baseline. HD-CAB composite=average of 6 z-scores. Negative HD-CAB of HD participants=decline in cognitive function relative to HP. Assessment is relative to reference group(healthy population).
The SDMT evaluates the tracking of cognitive function over time and for the early detection of cognitive impairment. The test assesses sustained attention, processing speed, visual scanning, and psychomotor speed, with the total score reflecting the number of correct pairings (out of 110 possible) completed within 90 seconds. Scores range from 0 to 110, with higher scores indicating better cognitive performance.
An adverse event (AE) was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.
An adverse event (AE) was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.
An AE was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.
| Arm | Type | Description |
|---|---|---|
| SAGE-718 | EXPERIMENTAL | Participants will receive SAGE-718, 1.2 milligrams (mg), orally, once daily (QD) for the first 6 weeks (Days 1 to 42), followed by 0.9 mg of SAGE-718 for the remainder of the treatment period up to Day 84. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84. |
| Healthy Participants | NO_INTERVENTION | HP enrolled in this study will not receive any investigational product (IP) (SAGE-718 or placebo). |
| Part A: SAGE-718 3 mg | EXPERIMENTAL | Participants received SAGE-718 3 milligrams (mg) tablets, once daily with food in the morning for 14 days. |
| Part B: SAGE-718 3 mg | EXPERIMENTAL | Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days. |
| Name | Type | Description |
|---|---|---|
| SAGE-718 | DRUG | Softgel lipid capsules. |
| SAGE-718-matching Placebo | DRUG | Softgel lipid capsules. |
| Placebo | DRUG | SAGE-718-matching oral capsules |
Inclusion Criteria: 1. Meet the following criteria for mild cognitive impairment (MCI) or mild dementia due to Alzheimer's Disease (AD) at Screening: 1. A memory complaint reported by the participant or their study partner 2. A Clinical Dementia Rating (CDR) score of 0.5 to 1.0 (inclusive) w...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Novartis AG Sponsored ADR | NVS | 2 | PHASE3 | Votoplam |
| Neurocrine Biosciences, Inc. | NBIX | 1 | PHASE3 | Valbenazine |
| Hoffmann-La Roche | RHHBY | 3 | PHASE2 | Tominersen, RG6496, SPK-10001 |
| Alnylam Pharmaceuticals, Inc | ALNY | 1 | PHASE1 | ALN-HTT02 |
| uniQure N.V. | QURE | 2 | PHASE1 | AMT-130 |
| Sarepta Therapeutics, Inc. | SRPT | 1 | PHASE1 | SRP-1005 |
SAGE-718 is an investigational small molecule being developed by Supernus Pharmaceuticals for cognitive impairment associated with neurological conditions. It has been studied in Alzheimer disease, Huntington disease, Parkinson disease cognitive impairment, and mild cognitive impairment. It is a Phase 2 clinical-stage candidate and has not been approved by the FDA.
SAGE-718 has been studied in people with mild cognitive impairment or mild dementia due to Alzheimer disease. A Phase 2 trial, NCT05619692, evaluated its effects in 174 participants aged 50 and older in the United States and Puerto Rico. SAGE-718 is investigational and is not approved for any use.
SAGE-718 is being developed by Supernus Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker SUPN. The company is the sponsor behind the clinical program evaluating the drug across several neurological indications, including Alzheimer disease, Huntington disease, and Parkinson disease cognitive impairment.
SAGE-718 is in Phase 2 clinical development. All four listed studies of the drug are Phase 2 trials, and all have completed. SAGE-718 is investigational and has not been approved by the FDA for any indication.
SAGE-718 has been evaluated in completed Phase 2 trials including NCT05619692 in Alzheimer disease, NCT05358821 and NCT05107128 in Huntington disease, and NCT05318937 in Parkinson disease cognitive impairment. These studies enrolled participants across the United States, Canada, Puerto Rico, Australia, and the United Kingdom.
Across the four listed Phase 2 studies, 518 participants have been enrolled in SAGE-718 trials. Enrollment ranged from 69 participants in the Huntington disease functioning capacity study, NCT05358821, to 189 participants in the Huntington disease cognitive function study, NCT05107128.