huperzine A (SPN-817) / Supernus Pharma - LARVOL DELTA

817P203: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults with Focal Onset Seizures (clinicaltrialsregister.eu) - P1/2 | N=100 | Not yet recruiting | Sponsor: Supernus Pharmaceuticals Inc. | N=45 ➔ 100

Enrollment change • CNS Disorders • Epilepsy

RENAISSANCE 2: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults With Focal Onset Seizures (clinicaltrials.gov) - P2 | N=216 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Trial completion date: Oct 2026 ➔ Aug 2027 | Trial primary completion date: Oct 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Safety and Tolerability Study of SPN-817 in Adult Patients With Treatment Resistant Epilepsy (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | N=35 ➔ 60 | Trial completion date: Jan 2025 ➔ Dec 2027 | Trial primary completion date: Oct 2024 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

817P203: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults with Focal Onset Seizures (clinicaltrialsregister.eu) - P1/2 | N=45 | Not yet recruiting | Sponsor: Supernus Pharmaceuticals Inc.

New P1/2 trial • CNS Disorders • Epilepsy

SPN-817 Open-Label Extension Study in Adults With Focal Onset Seizures (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Phase classification: P3 ➔ P2

Phase classification • CNS Disorders • Epilepsy

SPN-817 Open-Label Extension Study in Adults With Focal Onset Seizures (clinicaltrials.gov) - P3 | N=100 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc.

New P3 trial • CNS Disorders • Epilepsy

RENAISSANCE 2: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults with Focal Onset Seizures (clinicaltrials.gov) - P2 | N=258 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc.

New P2 trial • CNS Disorders • Epilepsy

The RENAISSANCE Study: Interim Results of a Phase 2 Study of SPN-817 in Adults with Treatment Resistant Epilepsy (AES 2024) - "Adverse events were common during SPN-817 titration and largely cholinergic in nature. The potential benefit of a peripherally-acting antiemetic on medication tolerability should be evaluated. Individuals with treatment‑resistant epilepsy, including focal seizures, who underwent maintenance treatment with huperzine A showed meaningful seizure reductions, with over half experiencing ≥ 50% reduction in seizure frequency."

Clinical • P2 data • Absence Seizure Disorder • CNS Disorders • Epilepsy • Pain

Effects of SPN-817 on Hippocampal Paroxysmal Discharge Occurrence in the Mesial Temporal Lobe Epilepsy Mouse Model (AES 2024) - "SPN-817 (0.1, 0.25, and 0.5 mg/kg, PO), vehicle (10% HPβCD in 0.9% NaCl, PO), diazepam (DZP; 2 mg/kg; IP), or carbamazepine (CBZ; 40 mg/kg; IP) were administered in a crossover design... SPN-817 significantly suppressed HPD numbers at 0.25 and 0.5 mg/kg in the MTLE model without changes in mean event duration. The highest dose resulted in a net HPD suppression comparable to DZP. Seizure suppression by SPN-817 was obtained with low unbound SPN‑817 brain concentrations."

Preclinical • CNS Disorders • Epilepsy

Huperzine A suppresses absence seizures in the genetic absence epilepsy rat from Strasbourg (GAERS) model of genetic generalized epilepsy with absence seizures. (PubMed, Epilepsia Open) - "This study looked at how huperzine A affects seizures in rats with similar abnormal brain activity as seen in humans with absence epilepsy. Rats received different treatments, placebo (i.e., saline solution), huperzine A, and ethosuximide. Ethosuximide is considered a gold standard treatment for absence epilepsy. We recorded brain activity to measure seizures before and after each treatment. We found that huperzine A (3.0 mg/kg) reduced seizures soon after treatment, like ethosuximide. Both treatments appeared safe, causing only mild sleepiness. The study shows that huperzine A could be a good new treatment for a type of absence epilepsy."

Journal • Preclinical • Absence Seizure Disorder • Anesthesia • CNS Disorders • Epilepsy

Supernus Announces Second Quarter 2023 Financial Results (GlobeNewswire) - "SPN-817 – A novel product candidate for the treatment of epilepsy: The open-label Phase II clinical study of SPN-817 in patients with treatment-resistant seizures is ongoing. Depending on the rate of enrollment, the Company expects to have data in the first half of 2024."

P2 data • CNS Disorders • Epilepsy

Safety and Tolerability Study of SPN-817 in Adult Patients With Treatment Resistant Epilepsy (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2022 ➔ Feb 2023

Enrollment open • Trial initiation date • CNS Disorders • Epilepsy

Supernus Pharmaceuticals Announces Fourth Quarter and Full Year 2022 Financial Results (Market Screener) - "SPN-817 - A novel product candidate for the treatment of epilepsy; The Company has commenced an open-label Phase II clinical study of SPN-817 in patients with treatment-resistant seizures. Depending on the rate of enrollment, the Company expects to have data in the first half of 2024."

P2 data • CNS Disorders • Epilepsy

Safety and Tolerability Study of SPN-817 in Adult Patients With Treatment Resistant Epilepsy (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: Supernus Pharmaceuticals, Inc.

New P2 trial • CNS Disorders • Epilepsy

Evaluating the Safety and Relative Bioavailability of Three SPN-817 Treatments (A, B and C) in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Supernus Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion

Supernus Announces Second Quarter 2022 Financial Results (Streetinsider.com) - "SPN-817 – A novel product candidate for the treatment of epilepsy; An open-label Phase II clinical study of SPN-817 in patients with treatment-resistant seizures is expected to start in the fourth quarter of 2022....For the three months ended June 30, 2022, net product sales were $165.5 million, a 19% increase over $138.6 million for the same period in 2021. For the six months ended June 30, 2022, net product sales were $312.9 million, a 17% increase over $267.0 million for the same period in 2021. The increases in both periods were primarily due to net product sales of GOCOVRI and growth in net product sales of Qelbree and Oxtellar XR."

Commercial • New P2 trial • CNS Disorders • Epilepsy

Evaluating the Safety and Relative Bioavailability of Three SPN-817 Treatments (A, B and C) in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2022 ➔ Aug 2022

Enrollment closed • Trial completion date

Evaluating the Safety and Relative Bioavailability of Three SPN-817 Treatments (A, B and C) in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Dec 2021 ➔ Apr 2022

Enrollment open • Trial primary completion date

Epilepsy: Expert opinion on emerging drugs in phase 2/3 clinical trials. (PubMed, Expert Opin Emerg Drugs) - "Novel mechanisms of action involve cholesterol degradation, mitochondrial pathways, anti-inflammation and neuro-regeneration. Earlier identification of genetic conditions through genetic testing will allow for earlier use of disease specific and disease-modifying therapies."

Journal • P2/3 data • CNS Disorders • Epilepsy • Immunology • Inflammation

An Open-Label Pilot Trial Assessing the Safety and Efficacy of SPN-817 (Huperzine A Extended-Release) in Adults with Treatment-Resistant Focal Impaired Awareness Seizures (AAN 2022) - "SPN-817 was well tolerated and has an anticonvulsant effect in three subjects with drug-resistant FIAS."

Clinical • CNS Disorders • Epilepsy • Ophthalmology • Psychiatry

Supernus Announces Preliminary Fourth Quarter and Full Year 2021 Financial Results (GlobeNewswire) - "SPN-817 – A novel product candidate for the treatment of epilepsy; A randomized Phase II clinical study of SPN-817 for the treatment of focal seizures is expected to start in the second half of 2022."

New P2 trial • CNS Disorders • Epilepsy

Supernus Announces Third Quarter 2021 Financial Results (BioSpace) - "SPN-817 – A novel product candidate for the treatment of epilepsy; A randomized Phase II clinical study of SPN-817 for the treatment of focal seizures is expected to start in the second half of 2022."

New P2 trial • CNS Disorders • Epilepsy

Evaluating the Safety and Relative Bioavailability of Three SPN-817 Treatments (A, B and C) in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: Supernus Pharmaceuticals, Inc.

Clinical • New P1 trial

FIAS: BIS-001-ER for the Treatment of Adult Focal Impaired Awareness Seizures (clinicaltrials.gov) - P1/2; N=16; Active, not recruiting; Sponsor: Supernus Pharmaceuticals, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Nov 2018 ➔ Dec 2026; Trial primary completion date: Nov 2018 ➔ Dec 2026

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

The effects of Huperzine A on dementia and mild cognitive impairment: An overview of systematic reviews. (PubMed, Phytother Res) - "Despite the promising effects of Hup A on cognition and ADLs, there is insufficient evidence to support the effectiveness of Hup A in cognitive impairments due to the high heterogeneity of SRs and the low quality of primary studies. High-quality, large multicenter RCTs with long-term follow-up in different settings are warranted."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders