Medical Drug Criteria (MDC)

Policy Num:       M5.001.029
Policy Name:     Foscarbidopa-Foslevodopa (Vyalev) 
Policy ID:          [M5.001.0029] [Ac/ L /M+ / P+ ]FB 09-J5000-09]

Last Review:       May 19, 2026
Next Review:      May15, 2027
Issue:                   June, 2027

Related Policies: None

 Foscarbidopa-Foslevodopa (Vyalev)

Summary

Parkinson’s disease is a progressive neurodegenerative condition caused by a loss of dopaminergic neurons in the substantia nigra and dopamine depletion, which unbalances oscillatory neural transmission through the basal ganglia, resulting in bradykinesia. Risk factors for Parkinson’s disease include older age, genetics (e.g., family history), and environmental factors (e.g., exposure to certain pesticides and solvents). 

On October 17, 2024, the FDA approved foscarbidopa-foslevodopa (Vyalev) subcutaneous infusion for the treatment of motor fluctuations in adults with advanced Parkinson’s disease. Foscarbidopafoslevodopa (Vyalev) is a prodrug combination of foscarbidopa (carbidopa-4´-monophosphate) and foslevodopa (levodopa-4´-monophosphate). Foscarbidopa and foslevodopa are converted in vivo to carbidopa and levodopa, respectively. 

Policy Statements

Initiation of foscarbidopa-foslevodopa (Vyalev) meets the definition of medical necessity for members meeting ALL of the following criteria (“1” to “6”):

1. Diagnosis of advanced Parkinson’s disease

2. Experiencing persistent motor fluctuations including a minimum of 2.5 hours of “off” time per day while receiving carbidopa/levodopa therapy – documentation must be provided

3. The member is taking at least 400 mg of levodopa daily – documentation must be provided

4. Documentation of an inadequate response, intolerance, or contraindication to at least TWO medications from at least TWO of the following medication classes - documentation must be provided

a. COMT inhibitors (e.g., entacapone, tolcapone, opicapone)

b. MAO-B inhibitors (e.g., rasagiline, selegiline, safinamide)

c. Dopamine agonists (e.g., pramipexole, ropinirole, rotigotine)

d. Amantadine

5. Foscarbidopa-foslevodopa (Vyalev) is prescribed by, or in consultation with, a specialist who treats Parkinson’s disease (e.g., neurologist, neuromuscular or geriatric specialist)

6. The maximum dose does not exceed 3,525 mg of foslevodopa (approximately 2,500 mg levodopa) daily 

Duration of approval: 6 months 

Policy Guidelines

Continuation of foscarbidopa-foslevodopa (Vyalev) meets the definition of medical necessity for members meeting ALL of the following criteria (“1” to “4”): 

1. Authorization or reauthorization for foscarbidopa-foslevodopa (Vyalev) has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of motor fluctuations associated with advanced Parkinson’s disease (if another health plan, documentation of a health plan-paid claim for foscarbidopa-foslevodopa (Vyalev) during the 90 days immediately before the authorization request must be submitted); OR the member previously met ALL indication-specific initiation criteria

2. The member has had a beneficial response to therapy such as improvement or stabilization in motor fluctuations and/or “off” time per day – documentation must be provided

3. Foscarbidopa-foslevodopa (Vyalev) is prescribed by, or in consultation with, a specialist who treats Parkinson’s disease (e.g., neurologist, neuromuscular or geriatric specialist)

4. The maximum dose does not exceed 3,525 mg of foslevodopa (approximately 2,500 mg levodopa) daily

Duration of approval: 1 year 

DOSAGE/ADMINISTRATION

FDA-approved

 Foscarbidopa-foslevodopa (Vyalev) is indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease with a maximum recommended daily dosage of 3,525 mg of the foslevodopa component (equivalent to approximately 2,500 mg levodopa). Refer to the foscarbidopa-foslevodopa (Vyalev) prescribing information for calculation of the base continuous dosage, hourly infusion rate, optional loading dose, and extra doses.

 Foscarbidopa-foslevodopa (Vyalev) is administered as a subcutaneous infusion with the Vyafuser pump. Patients should be trained on the proper use of the delivery system prior to initiating treatment and, as necessary, thereafter. In preparing foscarbidopa-foslevodopa (Vyalev), use aseptic technique and the sterile, single-patient-use infusion components (syringe, infusion set, and vial adapter) qualified for use with the pump.  Do not dilute or mix foscarbidopa-foslevodopa (Vyalev) with other products.  Foscarbidopa-foslevodopa (Vyalev) should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

 Foscarbidopa-foslevodopa (Vyalev) vials are for single dose only, and the entire contents of the vial should be transferred into a syringe for administration. Discard the vial after transfer of the product to the syringe and discard the syringe and any unused medication in the syringe after the product has been in the syringe for 24 hours. Keep the medication vials in the outer carton to protect the vials from breaking and store them refrigerated at 2°C to 8°C (36°F to 46°F). Foscarbidopafoslevodopa (Vyalev) may be stored at room temperature up to a maximum of 30°C (86°F) for a single period of up to 28 days. Once the product has been stored at room temperature, do not return the product to the refrigerator. If stored at room temperature, discard the product if not used within 28 days. Do not freeze or shake the product.

 Foscarbidopa-foslevodopa (Vyalev) administration is subcutaneously, preferably in the abdomen, avoiding the area with a 2-inch radius from the navel. The infusion set (cannula) can remain in place for up to 3 days when the product is infused continuously. Rotate the infusion site and use a new infusion set at least every 3 days. Select new infusion sites at least 1 inch from sites used within the previous 12 days. Do not infuse the product into areas where the site is tender, bruised, red, or hard to the touch.

 If interruption of foscarbidopa-foslevodopa (Vyalev) therapy occurs, a backup oral carbidopa and levodopa product is recommended, which may result in underdosing. Sudden discontinuation or rapid dose reduction of foscarbidopa-foslevodopa (Vyalev), without administration of alternative dopaminergic therapy, should be generally avoided.  Following interruptions of more than 1 hour, a new infusion set (tubing and cannula) should be used and rotated to a different infusion site. If the infusion has been interrupted for longer than 3 hours, the patient may also self-administer a loading dose, if enabled by their healthcare professional. 

Dose Adjustments

 None

Drug Availability

 Foscarbidopa-foslevodopa (Vyalev) injection contains 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL).

 Each single-dose vial contains 10 mL of a colorless to yellow to brown (may have a purple or red tint) and clear to slightly opalescent solution and is fitted with a grey rubber stopper, aluminum crimp cap, and turquoise plastic flip-off cap. The rubber stopper on the vial does not contain natural rubber latex. Carton of 7 vials: NDC 0074-0501-01. 

REQUIRED MEDICAL INFORMATION

Submission of medical records (chart notes) related to the medical necessity criteria is REQUIRED on all requests for authorizations. Records will be reviewed at the time of submission. Please provide documentation related to diagnosis, step therapy, and clinical markers (i.e. genetic and mutational testing) supporting initiation when applicable. Medical records may be submitted via direct upload through the PA web portal or by fax.

EXCLUSION CRITERIA

Text

BENEFIT APPLICATION

As stated in the policy.

OTHER CRITERIA

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Practice Guidelines and Position Statements

Analysis of Evidence (Rationale for Determination)

Foslevodopa/Foscarbidopa

Parkinson’s disease is a slowly progressive neurodegenerative disease of adult-onset caused by the loss of dopaminergic neurons leading to motor and non-motor symptoms. Levodopa is the most effective drug for the management of motor symptoms related to PD; however, the half-life of the drug is short, resulting in fluctuations in blood levels and motor symptom control. A novel prodrug of levodopa (foslevodopa/foscarbidopa) has been developed to be delivered by 24-hour continuous subcutaneous infusion and has been FDA approved for the treatment of motor fluctuations not adequately controlled by oral medications in patients with advanced Parkinson's disease. The aim of this summary of evidence was to determine if the use of foslevodopa/foscarbidopa was associated with improved health outcomes (e.g., motor control, QoL, treatment-emergent AEs). An analysis of the literature revealed that there were statistical and clinically meaningful47 improvements in the number of “on” time hours without troublesome dyskinesia (24% to 30% increase compared to baseline; 20% differential treatment effect in favor of CSCI compared to control) and the number of “off”­ time hours (42% to 43% decrease compared to baseline; 27% differential treatment effect in favor of CSCI compared to control) with continuous subcutaneous infusion of foslevodopa/foscarbidopa compared with oral levodopa with or without concomitant therapies. Treatment with foslevodopa/foscarbidopa also resulted in an at least 50% reduction in the number of patients reporting morning akinesia. Quality of life (measured by the EQ-5D-5L and PDQ-39), motor experiences of daily living (measured by the MDS-UPDRS part II), and non-motor symptoms (measured by the PDSS-2) were also improved. The reported AE profile for foslevodopa/foscarbidopa was consistent with other levodopa-containing medications and/or other subcutaneous therapies, and most AEs were mild to moderate in severity.

Based on a review of the best available literature, there is sufficient evidence to support that continuous subcutaneous infusion of foslevodopa/foscarbidopa may improve health outcomes in individuals with a diagnosis of Parkinson’s disease whose motor control symptoms are not adequately controlled with their baseline treatment regimen (e.g., oral levodopa/carbidopa, dopamine agonists, MAO-B inhibitors). Therefore, the External Infusion Pumps LCD (L33794) will be updated to allow coverage for infusion-based therapy for the treatment of Parkinson’s Disease, such as continuous subcutaneous infusion of foslevodopa/foscarbidopa, for Medicare beneficiaries with levodopa-responsive idiopathic Parkinson’s Disease when non-infusion-based Parkinson’s Disease therapy dosage and/or dosing interval cannot be further optimized due to intolerance, dyskinesia and/or other side effects/adverse events, and the beneficiary continues to experience inadequate control of motor fluctuation symptoms affecting daily living (e.g., unpredictable increase in stiffness, tremor, bradykinesia), as well as a minimum of 2.5 hours of “off” time per day.

As summarized in the prescribing information, the efficacy and safety of foscarbidopa-foslevodopa (Vyalev) was evaluated in a 12-week, randomized, double-blind, double-dummy, active-controlled, multicenter study (Study 1; NCT04380142) in patients with advanced Parkinson’s disease. Enrolled patients included those who were responsive to levodopa treatment (i.e., taking ≥ 400 mg/day of levodopa), had motor fluctuations inadequately controlled by their current medications, and who experienced a minimum of 2.5 hours of “off” time per day as assessed by patient diaries. A total of 141 patients were randomized in 1:1 ratio and received either 24-hour/day continuous subcutaneous administration of foscarbidopa-foslevodopa (Vyalev) plus oral placebo capsules (N=74) or 24-hour/day continuous subcutaneous administration of placebo solution plus oral encapsulated carbidopa-levodopa immediate-release (IR) tablets (N=67). Patients had a mean age of 66.4 years and a mean disease duration of 8.6 years. Most (93%) of the patients were Caucasian, 2% were Asian, 3% African-American and 70% of the patients were male. At baseline, approximately 74% of patients in the foscarbidopafoslevodopa (Vyalev) group and 66% of patients in the oral immediate release carbidopa-levodopa group were taking at least one or more classes of Parkinson’s disease medications other than carbidopalevodopa. The primary clinical outcome measure was the mean change from baseline to Week 12 in the total daily mean “on” time without troublesome dyskinesia (defined as "on" time without dyskinesia plus "on" time with non-troublesome dyskinesia) based on patient diary. The key secondary clinical outcome measure was the mean change from baseline to Week 12 in the total daily mean “off” time. The “on” and “off” time were normalized to a daily 16-hour awake period. Daily normalized "off" and "on" times are averaged over valid patient diary days for each visit to obtain the average daily normalized times. Foscarbidopa-foslevodopa (Vyalev) demonstrated improvements from baseline to Week 12 in "on" time without troublesome dyskinesia compared with the oral immediate release carbidopa-levodopa group (p=0.0083; Table 1). Foscarbidopa-foslevodopa (Vyalev) also demonstrated improvements from baseline to Week 12 in “off” time compared with the oral immediate release carbidopa-levodopa group (p=0.0054; Table 1). 

Table 1: Change from Baseline to Week 12 in Primary and Key Secondary Measures  

Medicare National Coverage

 No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of guideline creation. 

References

1. Clinical Pharmacology powered by ClinicalKey [Internet]. Tampa, FL: Elsevier.; 2026. Available at: https://www.clinicalkey.com/pharmacology/. Accessed 1/29/26.

2. DRUGDEX System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2026 Jan 29].

3. DynaMed [database online]. Ipswich, MA: EBSCO Information Services.; 2025. URL http://www.dynamed.com. Accessed 1/30/25.

4. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2026 [cited 2026 Jan 29]. Available from:

http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

5. Vyalev (foscarbidopa-foslevodopa) [package insert]. North Chicago, IL: AbbVie Inc., October 2024. 

Codes

Policy History