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[1][2].
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[3].
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:
ABBV-951 delivers a continuous subcutaneous infusion of two key components:
| 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[4:1][5].
| 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 |
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[6]:
| 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:
| 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:
The higher discontinuation rate in the ABBV-951 arm was primarily due to infusion site reactions, which are manageable but require careful monitoring and proper site rotation[6:1].
The 52-week open-label safety study (M15-736) demonstrated:
The ongoing ROSSINI study (NCT06107426) is a global real-world evidence study evaluating the long-term effectiveness of ABBV-951 in routine clinical practice[7]:
| 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[5:1].
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[1:1].
ABBV-951 (foslevodopa/foscarbidopa) Clinical Development. ↩︎ ↩︎
Foslevodopa/Foscarbidopa (ABBV-951) for Advanced Parkinson's Disease - Soileau et al. Lancet Neurology 2022. 2022. ↩︎
FDA Approves Continuous Subcutaneous Infusion of Levodopa/Carbidopa for Advanced Parkinson's Disease. ↩︎ ↩︎
Pharmacokinetics of foslevodopa and foscarbidopa - Hill et al. Movement Disorders 2020. 2020. ↩︎ ↩︎
Continuous Subcutaneous Levodopa Therapies for Parkinson's Disease - Systematic Review. ↩︎ ↩︎
Soileau et al. Lancet Neurology 2022 - ABBV-951 Phase 3 Results. 2022. ↩︎ ↩︎