Proven to help patients
achieve more “On” time

Superior improvement in daily good “On” time and “Off” time vs oral IR CD/LD¹*^†

ON TIME ON TIME

OFF TIME OFF TIME

Clinically proven to help patients achieve more “On” time without troublesome dyskinesia

Primary endpoint:
Mean change from baseline to week 12 in total daily mean “On” time without
troublesome dyskinesia^‡§

VYALEV

+ hours

Baseline:
9.20 hours
(n=73)

Oral IR CD/LD

+ hours

Baseline:
9.49 hours
(n=67)

~3x

increase in daily
good “On” time
vs oral IR CD/LD¹*^†

Mean difference=1.75 hours; P=0.0083

*Good “On” time (“On” time without troublesome dyskinesia) was defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia and was assessed using a PD diary.¹

^†2.80x increase.¹

^‡The “On” and “Off” time were normalized to a daily 16-hour awake period. Daily normalized "Off" and "On" times are averaged over valid PD diary days for each visit to obtain the average daily normalized times.¹

^§Data based on least squares mean.¹

Clinically proven to help patients reduce their daily “Off” time

Secondary endpoint:
Mean change from baseline to week 12 in hours of averaged daily normalized "Off" time^‡§

VYALEV

– hours

Baseline:
6.34 hours
(n=73)

Oral IR CD/LD

– hours

Baseline:
5.91 hours
(n=67)

~3x

decrease in daily
“Off” time vs
oral IR CD/LD^1†

Mean difference=–1.79 hours; P=0.0054

^†2.86x decrease.¹

^§Data based on least squares mean.¹

Study Design: VYALEV was studied in a phase 3, randomized, double-blind, double-dummy, active-controlled, 12-week, multicenter study in 141 patients^|| with advanced PD whose motor fluctuations were inadequately controlled by their current medication. One VYALEV patient was not evaluable for the efficacy analysis.¹

See full study design

^||Of the 141 patients who were randomly assigned in the trial, 110 completed the study. Of the 74 patients randomized to receive VYALEV, 48 completed the study and 26 discontinued treatment. Of the 67 patients randomized to receive oral IR CD/LD, 62 completed the study and 5 discontinued treatment.²

Good “On” time throughout the day at week 12³*

83% of VYALEV patients reported waking up in the good “On” state at week 12

Post hoc analysis

Percentage of Patients (n=46)

Hours After Waking

Study Design: A 12-week, randomized, double-blind, active-controlled study. Reported is good “On” time throughout the day at week 12 normalized to a 16-hour awake period.

Limitations: Data are from a post hoc analysis; no conclusions of statistical significance can be drawn.

“On” status was self-reported by a cohort of study participants. Patients recorded their status only during waking hours. Waking time was defined as the first diary entry that did not report "asleep" (recorded within 30 minutes of waking).

Observed reduction in sleep disturbances at week 12⁴

In patients with advanced Parkinson's disease

LS mean change from baseline to week 12 in PDSS-2 total score

0
-1
-2
-3
-4
-5
-6
-7
-8
-9

Oral IR CD/LD

(n=59)

-2.52

13^%

Change

from BL of 18.71

VYALEV

(n=44)

-7.92

36^%

Change

from BL of 21.70

Change from baseline to week 12 in sleep symptoms as assessed by the PDSS-2 was a prespecified secondary endpoint.²

VYALEV is indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease.¹

Limitations: PDSS-2 was a ranked secondary endpoint in the registrational 12-week study. Due to nonsignificant results for endpoints higher in the testing hierarchy, these results are observational in nature and any comparisons between treatment arms should be interpreted with caution.

The Parkinson’s Disease Sleep Scale-2 (PDSS-2) is a patient-completed clinical rating scale that assesses the frequency of sleep disturbances in patients with PD. Total scores range from 0 to 60, with lower scores indicating fewer sleep disturbances. The scale consists of 15 questions that are grouped into 3 subdomains:

Motor symptoms
at night

PD symptoms
at night

Disturbed sleep

VYALEV is indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease.¹

See full study design

In the pivotal study, oral IR CD/LD was converted to VYALEV, so

VYALEV replaced all oral IR CD/LD^1,2,5

On average, VYALEV patients were taking 12 IR CD/LD pills per day at baseline^¶ and 0 IR CD/LD pills per day at 12-week study end^#

Average number of IR CD/LD pills per month (30 days)

During a 30 day average, VYALEV™ patients were taking 360 IR CD/LD pills per month at baseline and 0 IR CD/LD pills per month at 12-week study end.

Note: Additional doses of rescue IR CD/LD may be needed if the VYALEV Pump is not working or is disconnected for a prolonged period. Refer to the VYALEV Pump Instructions for Use for more information.^††

Limitations: Patients in the pivotal study were required to convert all levodopa-containing medications and COMT inhibitors to IR CD/LD prior to randomization. This led to a reduction, on average, of 12 levodopa pills per day at baseline to 0.9 rescue levodopa pill per day at week 12; based on oral levodopa dose of Sinemet^® 25/100 (25 mg carbidopa/100 mg levodopa).

^¶Mean daily dose of oral levodopa at baseline was 1202.7 mg.

^#Mean daily dose of levodopa from all sources at week 12 was 1793.3 mg (levodopa delivered through the pump as VYALEV: 1703.7 mg; levodopa taken orally: 89.6 mg).

**For illustrative purposes. Exact dosage as well as dose frequency and timing varied among patients in the pivotal study.

^††The maximum recommended daily dosage of VYALEV is 3525 mg of the foslevodopa component (equivalent to approximately 2500 mg levodopa). Prescribing a backup oral carbidopa and levodopa product is recommended in the event that delivery of VYALEV is interrupted, which may result in underdosing.¹

Study Design: A phase 3, randomized, double-blind, active-controlled study to evaluate the efficacy and safety of VYALEV vs oral IR CD/LD over 12 weeks in 141 patients with advanced PD. In this study, concomitant PD medications were allowed; however, no changes were permitted. Patients could take oral IR CD/LD as needed for rescue. Mean daily dose of levodopa at the end of the study: 1793 mg with VYALEV; 1213 mg with oral IR CD/LD.

Review the safety profile of VYALEV.

See safety information

BL=baseline; CD=carbidopa; COMT=catechol-O-methyltransferase; IR=immediate release; LS=least squares; LD=levodopa; PD=Parkinson’s disease.

Proven to help patients
achieve more “On” time

Superior improvement in daily good “On” time and “Off” time vs oral IR CD/LD¹*^†

Clinically proven to help patients achieve more “On” time without troublesome dyskinesia

~3x

Clinically proven to help patients reduce their daily “Off” time

~3x

Good “On” time throughout the day at week 12³*

83% of VYALEV patients reported waking up in the good “On” state at week 12

Post hoc analysis

Observed reduction in sleep disturbances at week 12⁴

VYALEV replaced all oral IR CD/LD^1,2,5

On average, VYALEV patients were taking 12 IR CD/LD pills per day at baseline^¶ and 0 IR CD/LD pills per day at 12-week study end^#

Average number of IR CD/LD pills per month (30 days)

IMPORTANT SAFETY INFORMATION AND INDICATION

INDICATION¹

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION AND INDICATION

INDICATION¹

IMPORTANT SAFETY INFORMATION

Proven to help patients achieve more “On” time

Superior improvement in daily good “On” time and “Off” time vs oral IR CD/LD1*†

Clinically proven to help patients achieve more “On” time without troublesome dyskinesia

~3x

Clinically proven to help patients reduce their daily “Off” time

~3x

Good “On” time throughout the day at week 123*

83% of VYALEV patients reported waking up in the good “On” state at week 12

Post hoc analysis

Observed reduction in sleep disturbances at week 124

VYALEV replaced all oral IR CD/LD1,2,5

On average, VYALEV patients were taking 12 IR CD/LD pills per day at baseline¶ and 0 IR CD/LD pills per day at 12-week study end#

Average number of IR CD/LD pills per month (30 days)

IMPORTANT SAFETY INFORMATION AND INDICATION

INDICATION1

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION AND INDICATION

INDICATION1

IMPORTANT SAFETY INFORMATION

Proven to help patients
achieve more “On” time

Superior improvement in daily good “On” time and “Off” time vs oral IR CD/LD¹*^†

Good “On” time throughout the day at week 12³*

Observed reduction in sleep disturbances at week 12⁴

VYALEV replaced all oral IR CD/LD^1,2,5

On average, VYALEV patients were taking 12 IR CD/LD pills per day at baseline^¶ and 0 IR CD/LD pills per day at 12-week study end^#

INDICATION¹

INDICATION¹