suvecaltamide (JZP385) / Jazz, Merck (MSD) - LARVOL DELTA

Non-surgical treatment of essential tremor: What's in store? (PubMed, Parkinsonism Relat Disord) - "While ACP-711 is a newly investigated positive allosteric modulator (PAM) of GABA-A receptors, other PAMs (SAGE-324 and PRAX-114) have been withdrawn after failure to demonstrate statistically significant effects in clinical trials. This has also extended to include highly selective Cav3 antagonists (T-type calcium channel blockers): suvecaltamide (JZP385) and NBI-827104/ACT-7099478. By contrast, ulixacaltamide (PRAX-944) has been recently found to be effective and safe in a large phase 3 trial. ES-481, a novel selective antagonist of transmembrane AMPA receptor regulatory protein (TARP)-γ8-dependent AMPA receptors, has been tested in a small trial in Canada, complicated by early participant drop-out...Although many compounds have failed during advanced clinical development, others remain in the pipeline. This renewed interest in the treatment of ET, along with a better understanding of its pathophysiology and clinical trial design, could ultimately lead to newer..."

Journal • Review • Essential Tremor • Movement Disorders • Orthopedics • CAV3

A double-blind, randomized, multicenter, phase 2b study of the safety and efficacy of suvecaltamide in essential tremor. (PubMed, Parkinsonism Relat Disord) - P2 | "Suvecaltamide did not achieve statistically significant improvements on the primary or key secondary efficacy endpoints compared with placebo."

Clinical • Journal • P2b data • CNS Disorders • Essential Tremor • Fatigue • Insomnia • Movement Disorders • Sleep Disorder

A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease (clinicaltrials.gov) - P2 | N=169 | Completed | Sponsor: Jazz Pharmaceuticals | Recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

The Pharmacological Management of Essential Tremor and Its Long-Term Effects on Patient Quality of Life: A Systematic Review. (PubMed, Cureus) - "Based on the studies, pharmacological treatments such as alprazolam, primidone, propranolol, and CX-8998 were found to be efficient in the management of ET...Novel approaches like low-intensity focused ultrasound (LIFU), transcutaneous afferent patterned stimulation (TAPS), and incobotulinumtoxinA injections presented promising results with improved tremor control and minimal side effects. In conclusion, pharmacological treatments for ET provide symptomatic relief but are limited by side effects and reduced long-term efficacy, significantly impacting QoL. Surgical and novel therapeutic options offer enhanced motor control and durability of effects, though they are not universally applicable."

HEOR • Journal • Review • CNS Disorders • Essential Tremor • Movement Disorders

Treatment for essential tremor: a systematic review and Bayesian Model-based Network Meta-analysis of RCTs. (PubMed, EClinicalMedicine) - "However, GRADE assessment indicated that the evidence level for these conclusions was "low" or "very low." According to SUCRA rankings, DBS (0.97) ranked first in relative efficacy, followed by CX-8998 (0.80), thalamotomy (0.79), atenolol (0.76), metoprolol (0.66), propranolol (0.64), magnetic resonance guided focus ultrasound (MR-FUS) (0.624), ICI-118551 (0.620), nimodipine (0.61) and phenobarbitone (0.59). This work was supported by grants from the National Nature Science Foundation of China (Grant No. 82271459)."

Journal • Retrospective data • Review • Essential Tremor • Movement Disorders

Contribution to Efficacy by Active Metabolites of Suvecaltamide in a Preclinical Rat Model of Essential Tremor (MDS Congress 2024) - P2 | "These results illustrate contributions to efficacy by active suvecaltamide metabolites in rats, which must be considered clinically given they are predicted to translate to human efficacy. These data support the continued clinical development of suvecaltamide for adults with moderate-to-severe ET (NCT05122650) or residual Parkinson's disease tremor (NCT05642442)."

Preclinical • CNS Disorders • Essential Tremor • Parkinson's Disease • CAV3

Suvecaltamide Metabolites Are CaV3 Modulators and Contribute to Pharmacological Effect (MDS Congress 2024) - P2 | "Suvecaltamide and its active metabolites demonstrate selective, state-dependent modulation of all CaV3 subtypes with markedly higher affinity for partially inactivated channels. Modelling TAM shows that, at clinically relevant concentrations, suvecaltamide and its metabolites may selectively inhibit channels enriched under hyperexcitable conditions (eg, pathological neuronal firing) while sparing channels involved in normal signalling, which may contribute to a more optimal clinical profile. Two ongoing phase 2 studies are evaluating suvecaltamide in adults with moderate-to-severe ET (NCT05122650) or residual Parkinson's disease tremor (NCT05642442)."

CNS Disorders • Essential Tremor • Parkinson's Disease • CAV3 • PPARG

Once-Daily Suvecaltamide Pharmacokinetics, Safety, & Tolerability–Phase 1, Randomized, Double-Blind, Multiple Ascending Dose Study (MDS Congress 2024) - P2 | "Results from this Phase 1 study expand our understanding of suvecaltamide PK, safety, and tolerability, supporting further clinical development of the QD formulation of suvecaltamide."

Clinical • P1 data • PK/PD data • CNS Disorders • Essential Tremor • Insomnia • Pain • Parkinson's Disease • Sleep Disorder • CAV3

A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET) (clinicaltrials.gov) - P2 | N=420 | Completed | Sponsor: Jazz Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Essential Tremor • Movement Disorders

Contribution to Efficacy by Active Metabolites of Suvecaltamide in a Preclinical Rat Model of Essential Tremor (EAN 2024) - P2 | "These results illustrate contributions to efficacy by active suvecaltamide metabolites in rats, which must be considered clinically given they are predicted to translate to human efficacy. These data support continued clinical development of suvecaltamide for adults with moderate-to-severe ET (NCT05122650) or residual Parkinson's disease tremor (NCT05642442)."

Preclinical • CNS Disorders • Essential Tremor • Movement Disorders • Parkinson's Disease • CAV3

Suvecaltamide Metabolites Are CaV3 Modulators and Contribute to Pharmacological Effect (EAN 2024) - P2 | "Suvecaltamide and its active metabolites demonstrate selective, state-dependent modulation of all CaV3 subtypes with markedly higher affinity for partially inactivated channels. Modelling TAM shows that, at clinically relevant concentrations, suvecaltamide and its metabolites may selectively inhibit channels enriched under hyperexcitable conditions (eg, pathological neuronal firing) while sparing channels involved in normal signalling, which may contribute to a more optimal clinical profile. Two ongoing phase 2 studies are evaluating suvecaltamide in adults with moderate-tosevere ET (NCT05122650) or residual Parkinson's disease tremor (NCT05642442)."

CNS Disorders • Essential Tremor • Movement Disorders • Parkinson's Disease • CAV3 • PPARG

Suvecaltamide Pharmacokinetics, Safety, & Tolerability–Phase 1, Randomized, Double-Blind, Multiple Ascending Dose Study (EAN 2024) - P2 | "Results from this Phase 1 study expand our understanding of suvecaltamide PK, safety, and tolerability, supporting further clinical development of the QD formulation of suvecaltamide."

Clinical • P1 data • PK/PD data • CNS Disorders • Essential Tremor • Insomnia • Movement Disorders • Pain • Parkinson's Disease • Sleep Disorder • CAV3

Jazz Pharmaceuticals Provides Update on Phase 2b Trial of Investigational Suvecaltamide (JZP385) in Essential Tremor (PRNewswire) - "'We are evaluating the data to better understand the trial results and await the results of the suvecaltamide trial in Parkinson's disease tremor to determine next steps for the program. The Phase 2 Parkinson's disease tremor trial is ongoing with results expected first quarter 2025.'"

P2 data • CNS Disorders • Parkinson's Disease

A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Jazz Pharmaceuticals | Trial completion date: May 2024 ➔ Dec 2024 | Trial primary completion date: May 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Design of a Phase 2 Study of Suvecaltamide in Moderate-to-severe Parkinson's Disease Tremor (AAN 2024) - P2 | "The phase 2 proof-of-concept study for the efficacy of suvecaltamide to treat the functional impact of PDT represents the first large clinical study informing the use of TETRAS to assess tremor in this population."

P2 data • CNS Disorders • Essential Tremor • Movement Disorders • Parkinson's Disease

A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET) (clinicaltrials.gov) - P2 | N=420 | Active, not recruiting | Sponsor: Jazz Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Essential Tremor • Movement Disorders

Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers. (PubMed, Chem Biodivers) - "Despite the clinical trials of TTCC blockers like Z944 and MK8998, none are currently available on the market. The most potent derivative, compound 7, exhibited an IC50 value of 0.19 ± 0.03 μM and was further analyzed through molecular docking, revealing key interactions with Cav3.1. These findings provide a foundation for the structural optimization of Cav3.1 calcium channel blockers and present compound 7 as a promising lead compound for drug development and a tool for chemical biology research."

Journal • CNS Disorders • Epilepsy • Oncology • Pain • CAV3

JZP385-201 Phase 2b Study (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: Jazz Pharmaceuticals | Phase classification: P2b ➔ P2 | Trial completion date: Dec 2023 ➔ May 2024 | Trial primary completion date: Nov 2023 ➔ May 2024

Phase classification • Trial completion date • Trial primary completion date • Essential Tremor • Movement Disorders

Design of a Phase 2 Study of Suvecaltamide in Moderate to Severe Parkinson’s Disease Tremor (MDS Congress 2023) - P2 | "The phase 2 study will serve as proof-of-concept for the efficacy of suvecaltamide to treat the functional impact of tremor in Parkinson’s disease and represents the first large clinical study to inform the use of TETRAS to assess tremor in this patient population."

P2 data • CNS Disorders • Parkinson's Disease

Jazz Pharmaceuticals Announces Full Year and Fourth Quarter 2022 Financial Results and Provides 2023 Financial Guidance (PRNewswire) - “Suvecaltamide (JZP385): Suvecaltamide, a highly selective modulator of T-type calcium channels, is in clinical development for the treatment of essential tremor (ET) and Parkinson's disease tremor. Patient enrollment is ongoing in the Phase 2b ET trial and top-line data read-out is anticipated in 1H24.”

P2b data • CNS Disorders • Essential Tremor

A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Jazz Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Anti-tremor efficacy of suvecaltamide in a rat model of essential tremor (Neuroscience 2022) - P2, P2b | "Oral suvecaltamide effectively reduced tremor in rats pre- or post-harmaline, and in a manner superior to propranolol, supporting the continued development of suvecaltamide for the treatment of ET. An ongoing phase 2b trial (NCT05122650) will further evaluate the safety and efficacy of suvecaltamide for adults with moderate to severe ET."

Preclinical • CNS Disorders • Essential Tremor

In vitro pharmacological characterization of suvecaltamide: a potent, selective, and state-dependent modulator of voltage-gated T-type calcium channels CaV3.1, CaV3.2, and CaV3.3 (Neuroscience 2022) - P2, P2b | "This may engender an optimal clinical profile. An ongoing phase 2b clinical trial (NCT05122650) will further evaluate the safety and efficacy of suvecaltamide for adults with moderate to severe ET."

Preclinical • CNS Disorders • Essential Tremor

Jazz Pharmaceuticals Announces Third Quarter 2022 Financial Results and Raises Total Revenue Guidance Mid-point (PRNewswire) - “Suvecaltamide (JZP385): Suvecaltamide...is in clinical development for the treatment of essential tremor (ET) and Parkinson's disease tremor….The Company initiated a Phase 2 trial in patients with Parkinson's disease tremor and expects the first patient to be enrolled by year end.”

Enrollment status • CNS Disorders • Essential Tremor • Parkinson's Disease