tavapadon (CVL-751) / AbbVie - LARVOL DELTA

Tavapadon as adjunct to levodopa increases daily ON time in Parkinson's disease (Medical Xpress) - P3 | N=507 | TEMPO-3 (NCT04542499) | Sponsor AbbVie | "For patients with Parkinson's disease with motor fluctuations, the oral once-daily, selective D1/D5 partial dopamine agonist tavapadon as an adjunct to levodopa increases total daily ON time versus placebo, according to a study presented at the annual meeting of the American Academy of Neurology, held from April 5 to 9 in San Diego....A total of 507 patients (aged 40 to 80 years) were enrolled and randomly assigned to adjunctive tavapadon...or placebo in a 1:1 ratio. The researchers found that tavapadon treatment significantly increased total daily ON time without troublesome dyskinesia (1.7 hours versus 0.6 hours with placebo). There was also a significant reduction in the change from baseline in daily OFF time compared with placebo. The safety profile of tavapadon was consistent with that seen in previous clinical trials; most adverse events were mild to moderate in severity."

P3 data • Parkinson's Disease

A Study to Assess the Relative Bioavailability of Oral Tavapadon in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

Efficacy and Safety of Fixed-Dose Tavapadon, an Oral, Once-Daily, Selective D1/D5 Partial Dopamine Agonist for the Treatment of Early Parkinson's Disease (AAN 2025) - P3 | "Conclusions In individuals with early PD, tavapadon as monotherapy was effective with an acceptable safety profile. Other trials evaluating tavapadon as flexible-dose monotherapy (TEMPO-2) or adjunctive therapy (TEMPO-3) are completed, and an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing."

Clinical • Late-breaking abstract • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy and Safety of Flexible-Dose Tavapadon, an Orally Administered, Once-Daily, Selective D1/D5 Partial Dopamine Agonist for the Treatment of Early Parkinson's Disease (AAN 2025) - P3 | "Conclusions TEMPO-2 results demonstrate the efficacy and acceptable safety profile of flexible-dose tavapadon as monotherapy in adults with early PD. Trials evaluating tavapadon as fixed-dose monotherapy (TEMPO-1) or adjunctive therapy (TEMPO-3) are completed; an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing."

Clinical • Late-breaking abstract • CNS Disorders • Movement Disorders • Parkinson's Disease

Managing impulse control and related behavioral disorders in Parkinson's disease: where we are in 2025? (PubMed, Expert Rev Neurother) - "Insights into ICDs pathophysiology and DA-specific pharmacodynamics indicate safer profiles for certain preparations (e.g. rotigotine patches) and possibly for D1/D5 agonists like tavapadon. Invasive treatments, including deep brain stimulation and infusion therapies, should be prioritized in advanced-stage PD complicated by ICBDs."

Journal • Review • Behavior Disorders • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry

A Study to Assess the Relative Bioavailability of Oral Tavapadon in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=84 | Not yet recruiting | Sponsor: AbbVie

New P1 trial

Efficacy and Safety of Tavapadon, an Orally Administered, Once-daily, Selective D1/D5 Partial Dopamine Agonist, Adjunctive to Levodopa for Treatment of Parkinson's Disease with Motor Fluctuations (AAN 2025) - P3 | "These findings in adults with PD and motor fluctuations demonstrate the efficacy and acceptable safety profile of tavapadon as adjunctive therapy to levodopa. Tavapadon as monotherapy in early PD (TEMPO-1 and TEMPO-2) and the long-term use of tavapadon (open-label extension; TEMPO-4) are being evaluated in ongoing phase 3 trials."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson’s Disease (PRNewswire) - P3 | N=304 | TEMPO-2 (NCT04223193) | Sponsor: Cerevel Therapeutics, LLC | "AbbVie...today announced positive topline results from its pivotal Phase 3 TEMPO-2 trial evaluating investigational tavapadon as a flexible-dose monotherapy in early Parkinson's disease...The trial met its primary endpoint – patients treated with tavapadon experienced a statistically significant reduction (improvement) from baseline compared to placebo (placebo: -1.2; tavapadon 5-15 mg: -10.3; p-value <0.0001 versus placebo) in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26...Full results from the TEMPO-2 trial will be submitted for presentation at a future medical meeting. AbbVie is on track to submit the New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) in 2025."

FDA filing • P3 data: top line • CNS Disorders • Parkinson's Disease

TEMPO-2: Flexible-Dose Trial in Early Parkinson's Disease (PD) (clinicaltrials.gov) - P3 | N=304 | Completed | Sponsor: Cerevel Therapeutics, LLC | Active, not recruiting ➔ Completed

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

TEMPO-4: Open-label Trial in Parkinson's Disease (PD) (clinicaltrials.gov) - P3 | N=992 | Active, not recruiting | Sponsor: Cerevel Therapeutics, LLC | Enrolling by invitation ➔ Active, not recruiting

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

Efficacy and Safety of Tavapadon, an Orally Administered, Once-Daily, Selective D1/D5 Partial Dopamine Agonist, Adjunctive to Levodopa for Treatment of Parkinson’s Disease With Motor Fluctuations (MDS Congress 2024) - P3 | "Overall, 507 adults aged 40-80 years were enrolled. Participants receiving tavapadon (5–15 mg once daily) demonstrated a significant increase of 1.1 hours in total daily ON time without troublesome dyskinesia vs participants receiving placebo (1.7 hours vs 0.6 hours, respectively; P<0.0001). Change from baseline in daily OFF time also showed a significant reduction versus placebo."

Clinical • Late-breaking abstract • CNS Disorders • Parkinson's Disease

AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as a Monotherapy for Parkinson’s Disease (PRNewswire) - "P3 | N=522| TEMPO-1 (NCT04201093) | Sponsor: Cerevel Therapeutics, LLC | "The trial met its primary endpoint – patients treated with tavapadon in both dose groups experienced a statistically significant reduction (improvement) from baseline compared to placebo (placebo: +1.8; 5 mg: -9.7; 15 mg: -10.2; p-value <0.0001 each dose versus placebo) in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26. The TEMPO-1 trial also met the key secondary endpoint, demonstrating a statistically significant and clinically meaningful improvement in motor aspects of experiences of daily living (MDS-UPDRS Part II) in both tavapadon dose groups compared to placebo at week 26...The safety profile observed in the TEMPO-1 trial was consistent with prior clinical trials. The majority of adverse events reported were mild to moderate in severity...Topline results from TEMPO-2...are expected by the end of 2024."

P3 data: top line • CNS Disorders • Parkinson's Disease

Discovery and structure - activity relationships of 2,4,5-trimethoxyphenyl pyrimidine derivatives as selective D5 receptor partial agonists. (PubMed, Bioorg Chem) - "Previously, PF-06649751 (tavapadon), PF-2562 and PW0464 have been discovered as potent and selective G protein-biased D1/D5 receptor agonists with optimal pharmacokinetic properties...We observed that 5j (10 mg/kg, p.o) alleviated scopolamine-induced impairment in short-term memory and social recognition, which were blocked by D1/D5 antagonist SCH23390 (0.1 mg/kg, i.p.). Furthermore, 5j did not exhibit any cytotoxicity (up to 10 µM) or in vivo acute toxicity up to 200 mg/kg (p.o). These results strongly suggest that 5j could be further developed for treating neurological disorders wherein the D5 receptors play pivotal roles."

Journal • Alzheimer's Disease • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry

AbbVie Completes Acquisition of Cerevel Therapeutics (PRNewswire) - "AbbVie...today announced that it has completed its acquisition of Cerevel Therapeutics...With the completion of the acquisition, Cerevel is now part of AbbVie...There are multiple programs in Cerevel's pipeline across several neurological and psychiatric conditions such as schizophrenia, Parkinson's disease and mood disorders, where there continues to be significant unmet need for patients."

M&A • CNS Disorders • Parkinson's Disease

TEMPO-1: Fixed-Dose Trial in Early Parkinson's Disease (PD) (clinicaltrials.gov) - P3 | N=522 | Completed | Sponsor: Cerevel Therapeutics, LLC | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Jun 2024

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

Cerevel Therapeutics Announces Positive Topline Results for Tavapadon in Phase 3 Adjunctive Trial for People Living with Parkinson’s Disease (Yahoo Finance) - P3 | N=507 | TEMPO-3 (NCT04542499) | Sponsor: Cerevel Therapeutics, LLC | "Cerevel Therapeutics...announced positive topline results from its pivotal Phase 3 TEMPO-3 trial for tavapadon, the first and only D1/D5 receptor partial agonist being studied as a once-daily treatment for Parkinson’s disease....The trial met its primary endpoint - patients treated with tavapadon adjunctive to LD experienced a clinically meaningful and statistically significant increase of 1.1 hours in total 'on' time without troublesome dyskinesia compared to those treated with LD and placebo (1.7 hours vs. 0.6 hours, p <0.0001). A statistically significant reduction in 'off' time, the key secondary endpoint, was also observed for the tavapadon treatment arm....Additional data from the trial will be presented at a future medical meeting; results from the tavapadon Phase 3 monotherapy trials (TEMPO-1 and TEMPO-2) are expected in the second half of 2024."

P3 data • P3 data: top line • Parkinson's Disease

TEMPO-3: Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations (clinicaltrials.gov) - P3 | N=507 | Completed | Sponsor: Cerevel Therapeutics, LLC | Active, not recruiting ➔ Completed

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

TEMPO-2: Flexible-Dose Trial in Early Parkinson's Disease (PD) (clinicaltrials.gov) - P3 | N=296 | Active, not recruiting | Sponsor: Cerevel Therapeutics, LLC | Recruiting ➔ Active, not recruiting

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

To Evaluate Pharmacokinetics (PK) and Safety of Tavapadon in Participants With Severe Renal Impairment Compared to Participants With Normal Renal Function (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Cerevel Therapeutics, LLC | Active, not recruiting ➔ Completed | N=20 ➔ 14 | Trial completion date: Dec 2023 ➔ Aug 2023

Enrollment change • Trial completion • Trial completion date • Renal Disease

Dopamine Receptors and Clinical Efficacy/Tolerability? Expert Panel Discussion (CONy 2024) - "However D1-specific dopamine agonis_The use of dopamine agonists for the initial and adjunctive treatment of PD has become controversial, largely due to D2-family recptor related adverse effects, incts such as tavapadon are in late-stage development and lack these D2-family associated side effects. Should dopamine agonists continue to play a role in PD?"

Clinical

Dopamine agonists remain an important therapeutic option for PD (CONy 2024) - "However some dopamine agonists with dopamine-like receptor activity (i.e. apomorphine) and emerging D1-specific dopamine agonists (i.e. tavapadon) do not have D2-family predominant receptor side effects. Should dopamine agonists remain part of the therapeutic armamentarium?"

CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

HOW PARKINSON'S DISEASE TREATMENT WILL CHANGE IN THE NEXT FUTURE (ADPD 2024) - "A new dopamine agonist, tavapadon. Two different studies on dyskinesia are ongoing with a combination of buspirone and zolmitriptan and another with mesdopetam."

CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • GBA

Multiple-dose Trial to Determine the Clinical Bioequivalence Between Tavapadon Tablets in Participants With Parkinson's Disease (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Cerevel Therapeutics, LLC | Recruiting ➔ Completed

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

TEMPO-1: Fixed-Dose Trial in Early Parkinson's Disease (PD) (clinicaltrials.gov) - P3 | N=522 | Active, not recruiting | Sponsor: Cerevel Therapeutics, LLC | Recruiting ➔ Active, not recruiting

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