ABBV-951 (foslevodopa/foscarbidopa) for Parkinson's Disease

ABBV-951 (foslevodopa/foscarbidopa) Subcutaneous Infusion for Parkinson's Disease

<div class="infobox infobox-trial">
<div class="infobox-header">Pivotal Phase 3 Trial</div>
<div class="infobox-row">
<div class="infobox-label">NCT Number</div>
<div class="infobox-value">NCT04380142</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Phase</div>
<div class="infobox-value">Phase 3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Status</div>
<div class="infobox-value">Completed</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Sponsor</div>
<div class="infobox-value">AbbVie</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Intervention</div>
<div class="infobox-value">foslevodopa/foscarbidopa (ABBV-951) continuous subcutaneous infusion</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Indication</div>
<div class="infobox-value">Advanced Parkinson's Disease (Motor Complications)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Enrollment</div>
<div class="infobox-value">141 participants (74 ABBV-951, 67 control)</div>
</div>
</div>

Overview

ABBV-951 (brand name: Crexonti in EU, known as levodopa/carbidopa subcutaneous suspension in US) is a 24-hour continuous subcutaneous infusion of soluble levodopa (foslevodopa) and carbidopa (foscarbidopa) developed by AbbVie for the treatment of advanced Parkinson's disease with motor complications[@abbv][@foslevodopafoscarbidopa2022].

ABBV-951 (foslevodopa/foscarbidopa) Subcutaneous Infusion for Parkinson's Disease

<div class="infobox infobox-trial">
<div class="infobox-header">Pivotal Phase 3 Trial</div>
<div class="infobox-row">
<div class="infobox-label">NCT Number</div>
<div class="infobox-value">NCT04380142</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Phase</div>
<div class="infobox-value">Phase 3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Status</div>
<div class="infobox-value">Completed</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Sponsor</div>
<div class="infobox-value">AbbVie</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Intervention</div>
<div class="infobox-value">foslevodopa/foscarbidopa (ABBV-951) continuous subcutaneous infusion</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Indication</div>
<div class="infobox-value">Advanced Parkinson's Disease (Motor Complications)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Enrollment</div>
<div class="infobox-value">141 participants (74 ABBV-951, 67 control)</div>
</div>
</div>

Overview

ABBV-951 (brand name: Crexonti in EU, known as levodopa/carbidopa subcutaneous suspension in US) is a 24-hour continuous subcutaneous infusion of soluble levodopa (foslevodopa) and carbidopa (foscarbidopa) developed by AbbVie for the treatment of advanced Parkinson's disease with motor complications[@abbv][@foslevodopafoscarbidopa2022].

ABBV-951 provides continuous dopaminergic stimulation through a subcutaneous pump system, addressing the motor fluctuations (OFF time) and dyskinesias that develop with long-term oral levodopa therapy. The FDA approved ABBV-951 in 2024 for the treatment of Parkinson's disease in patients with motor fluctuations who are inadequately controlled with oral levodopa/carbidopa[@fda].

Parkinson's disease affects approximately 10 million people worldwide and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. While oral levodopa/carbidopa is the gold standard treatment, long-term use leads to motor complications including:

• OFF episodes: Periods when medication wears off and motor symptoms return
• Dyskinesias: Involuntary movements caused by pulsatile dopaminergic stimulation
• Wearing-off phenomenon: Progressive shortening of the response to each levodopa dose

Mechanism of Action

Continuous Subcutaneous Delivery

ABBV-951 delivers a continuous subcutaneous infusion of two key components:

Advantages Over Oral Levodopa

| Feature | Oral Levodopa/Carbidopa | ABBV-951 Subcutaneous Infusion |
|---------|------------------------|-------------------------------|
| Delivery | Oral, pulsatile | Continuous subcutaneous |
| Plasma levels | Variable, peaks/troughs | Stable |
| Dosing frequency | 3-5x daily | 24-hour continuous |
| OFF time | 2-4+ hours/day | Significantly reduced |
| Dyskinesias | Progressive increase | Reduced with CDS |

The continuous delivery system mimics physiological dopamine signaling more closely than oral medications, potentially reducing the development of motor complications[@pharmacokinetics2020][@continuous].

Clinical Development Program

Key Clinical Trials

| Trial | Phase | NCT Number | Status | Key Findings |
|-------|-------|-------------|--------|--------------|
| M15-738 | Phase 1 | NCT03033498 | Completed | Safety, PK, dose escalation |
| M15-739 | Phase 1 | NCT03374917 | Completed | 4-week outpatient safety/tolerability |
| M15-736 | Phase 3 | NCT03781167 | Completed | Safety and tolerability |
| Pivotal Phase 3 | Phase 3 | NCT04380142 | Completed | Efficacy vs oral LD/CD |
| ROSSINI | Observational | NCT06107426 | Recruiting | Real-world effectiveness |

Pivotal Phase 3 Trial Results (NCT04380142)

The pivotal 12-week randomized, double-blind, double-dummy, active-controlled phase 3 trial compared ABBV-951 subcutaneous infusion to standard oral levodopa/carbidopa in patients with advanced Parkinson's disease and motor fluctuations[@soileau2022]:

Study Design

• Sites: 65 centers in USA and Australia
• Duration: 12 weeks
• Patients: 141 randomized (74 ABBV-951, 67 oral levodopa/carbidopa)
• Population: Advanced PD with motor fluctuations inadequate controlled on oral levodopa

Efficacy Results

| Endpoint | ABBV-951 | Oral Levodopa/Carbidopa | Treatment Difference | p-value |
|----------|----------|------------------------|---------------------|---------|
| ON time without troublesome dyskinesia (hours) | +2.72 | +0.97 | +1.75 | p=0.0083 |
| OFF time reduction (hours) | -2.75 | -0.96 | -1.79 | p=0.0054 |

Key Findings:

• ABBV-951 demonstrated statistically significant improvements in both ON time and OFF time compared to oral levodopa/carbidopa
• Patients gained an additional 1.75 hours of "ON time" without troublesome dyskinesia per day
• Patients experienced 1.79 hours less "OFF time" per day compared to oral therapy

Safety Profile

| Adverse Event | ABBV-951 (n=74) | Control (n=67) |
|---------------|-----------------|----------------|
| Any adverse event | 85% | 63% |
| Serious adverse events | 8% | 6% |
| Discontinuations due to AEs | 22% | 1% |

Most Common ABBV-951 Adverse Events:

• Infusion site erythema: 27%
• Infusion site pain: 26%
• Cellulitis (infusion site): 19%
• Infusion site edema: 12%

Long-term Safety Study (NCT03781167)

The 52-week open-label safety study (M15-736) demonstrated:

• Sustained efficacy over 52 weeks
• No new safety signals with long-term use
• Infusion site reactions remained the most common adverse event

Regulatory Status

• FDA Approval: 2024 - Approved for treatment of Parkinson's disease in patients with motor fluctuations who are inadequately controlled with oral levodopa/carbidopa[@fda]
• European Approval: Marketed as Crexonti in EU (approval 2024)
• Japan: Under review

Real-World Evidence (ROSSINI Study)

The ongoing ROSSINI study (NCT06107426) is a global real-world evidence study evaluating the long-term effectiveness of ABBV-951 in routine clinical practice[@rossini]:

• Enrollment: ~450 participants (300 new to ABBV-151, 150 continuing from OLE studies)
• Sites: ~60 sites globally
• Duration: Up to 3 years
• Primary outcome: Change from baseline in OFF time (hours)
• Status: Recruiting

Comparison with Other Advanced PD Therapies

| Treatment | Mechanism | OFF Time Reduction | Route | Key Considerations |
|-----------|-----------|-------------------|-------|---------------------|
| ABBV-951 | Continuous levodopa delivery | 1.79 hrs | Subcutaneous infusion | 24/7 pump, skin reactions |
| Duodopa/Duopa | Continuous levodopa delivery | 1.5-2 hrs | Intestinal gel | Requires PEG-J tube surgery |
| Apomorphine infusion | D1/D2 agonist | 2-4 hrs | Subcutaneous infusion | Pump + rescue pen |
| Apomorphine intermittent | D1/D2 agonist | 1-2 hrs | Subcutaneous injection | Rescue for OFF episodes |
| Oral levodopa/carbidopa | Dopamine replacement | Baseline | Oral | Gold standard, motor fluctuations |

ABBV-951 offers a less invasive alternative to intestinal delivery (Duodopa) while providing continuous dopaminergic stimulation comparable to other device-assisted therapies[@continuous].

Cross-References

Related Mechanisms

• Basal Ganglia Motor Circuit in Parkinson's Disease
• Motor Complications in Parkinson's Disease
• Dopaminergic Signaling in Movement Control

Related Treatments

• Parkinson's Disease Treatment Overview
• Carbidopa
• [Dopamine Agonists](/therapeutics/dopamine-agonists)
• Apomorphine Therapy
• Duodopa Intestinal Gel

Related Conditions

• Parkinson's Disease Subtypes
• Motor Complications in Parkinson's Disease
• Levodopa-Induced Dyskinesia

Company Information

AbbVie is a global biopharmaceutical company headquartered in North Chicago, Illinois, with a focus on developing advanced therapies for neurological disorders. ABBV-951 was developed through AbbVie's neuroscience pipeline, representing a significant advancement in continuous dopaminergic delivery for Parkinson's disease[@abbv].

External Links

• [ClinicalTrials.gov - NCT04380142](https://clinicaltrials.gov/study/NCT04380142)
• [ClinicalTrials.gov - NCT03781167](https://clinicaltrials.gov/study/NCT03781167)
• [ClinicalTrials.gov - NCT06107426 (ROSSINI)](https://clinicaltrials.gov/study/NCT06107426)
• [AbbVie Pipeline - ABBV-951](https://www.abbvie.com/)](/companies/abbvie)
• [Parkinson's Foundation - Motor Fluctuations](https://www.parkinson.org/)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving ABBV-951 (foslevodopa/foscarbidopa) for Parkinson's Disease discovered through SciDEX knowledge graph analysis: