Clinical Profile

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VYALEV™ Clinical Studies

The efficacy and safety of 24-hour continuous levodopa-based therapy with VYALEV™ were demonstrated in 2 trials.^1-3

12-week

Pivotal Phase 3, randomized, double-blind, double-dummy, active-controlled study evaluating the efficacy and safety of 24‑hour daily continuous subcutaneous infusion of VYALEV™ compared with oral IR levodopa/carbidopa^1,3

Study Design Details

52-week

Phase 3, single-arm, open-label study evaluating the safety and efficacy of 24-hour daily exposure with a continuous subcutaneous infusion of VYALEV™^,2

Study Design Details

IR=immediate-release.

Study Design
Motor Symptoms

VYALEV™ 12-Week Efficacy and Safety Study Design^1,3

VYALEV™ 12‑Week Efficacy and Safety Study Design^1,3

Aim: Evaluate the efficacy and safety of VYALEV™ to oral IR levodopa/carbidopa in patients with advanced PD.

Duration: 12 weeks.

Study type: Phase 3, 1:1 randomized, double-blind, double-dummy, active-controlled.

Patient population: Evaluation of 141 patients. The target population was levodopa-responsive patients with advanced PD whose motor symptoms were inadequately controlled with current treatment and experienced minimum daily average of 2.5 hours of “Off” time per day, as assessed by PD diaries.*

Of the 74 patients receiving VYALEV™, 48 completed the study and 26 discontinued treatment.

Of the 67 patients receiving optimized oral IR levodopa/carbidopa, 62 completed treatment and 5 discontinued.

*Based on the PD diary, the average daily normalized “On” time for patients on VYALEV™ was 9.20 (+/−2.42) hours at baseline and increased by 2.72 (+/−0.52) hours at Week 12 compared with an increase of 0.97 (+/−0.50) hours at Week 12 from a baseline of 9.49 (+/−2.62) hours for patients taking optimized oral IR LD/CD. This resulted in a statistically significant increase of 1.75 (+/−0.65) hours in daily normalized “On” time without troublesome dyskinesia in patients on VYALEV™ vs oral IR LD/CD (LS mean of difference [SE]; P=0.0083). Average daily normalized “Off” time for patients on VYALEV™ was 6.34 (+/−2.27) hours at baseline and decreased by 2.75 (+/−0.50) hours at Week 12 compared with a decrease of 0.96 (+/−0.49) hours at Week 12 from a baseline of 5.91 (+/−1.88) hours for patients taking optimized oral IR LD/CD (LS mean change [SE]). This resulted in a statistically significant reduction of 1.79 (+/−0.63) hours in “Off” time in patients on VYALEV™ vs oral IR LD/CD (LS mean of difference [SE]; P=0.0054).

CI=confidence interval; IR=immediate-release; LD/CD=levodopa/carbidopa; PD=Parkinson’s disease; LS=least squares.

See Trial Endpoints

Please refer to the VYALEV™ SmPC for full study data.

See Trial Endpoints

Please refer to the VYALEV™ SmPC for full study data.

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Reduction in morning “Off” time (morning akinesia)^1*

Less “Off” time and more good “On” time during morning, day, and night^1,3†‡

Fewer interruptions over 24 hours morning, day, and night^3†

More “On” time and less “Off” time over 24 hours means more for patients^1‡

*As demonstrated by a reduction in the number of patients reporting morning “Off” (morning akinesia) in their PD diaries from baseline to Week 52. Morning akinesia was defined as reporting “Off” status as the first morning symptom upon awakening.³

^†In the clinical trials, patients recorded their PD symptoms in a PD diary, which was completed for a full 24-hour period. Patients made an entry upon waking and every 30 minutes during their normal waking time. Patients recorded whether they were “On,” “Off,” or “Asleep” and what the severity of their dyskinesia (troublesome or not troublesome) was.³

^‡More refers to “On” time compared to oral IR levodopa/carbidopa. Patients in the VYALEV™ study experienced significant improvements compared with oral IR levodopa/carbidopa at Week 12, including “On” time without troublesome dyskinesia and “Off” time.³

IR=immediate-release; PD=Parkinson’s disease.

VYALEV™ Provided a Superior Improvement in Good “On” Time vs Oral IR Levodopa/Carbidopa^1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

VYALEV™ Provided a Superior Improvement in Good “On” Time vs Oral IR Levodopa/Carbidopa^1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

Change from baseline to Week 12 in “On” time*

(LS mean of difference between the two treatment arms=1.75 hours; P=0.0083 [95% CI, 0.46, 3.05])

*Based on the PD diary, the average daily normalized “On” time without troublesome dyskinesia for patients on VYALEV™ was 9.20 (+/-2.42) hours at baseline and increased by 2.72 (+/-0.52) hours at Week 12 compared with an increase of 0.97 (+/-0.50) hours at Week 12 from a baseline of 9.49 (+/-2.62) hours for patients taking optimized oral IR levodopa/carbidopa (LS mean change [SE]). This resulted in a statistically significant increase of 1.75 (+/-0.65) hours in patients on VYALEV™ vs oral IR LD/CD (LS mean of difference [SE]; P=0.0083). “On” time without troublesome dyskinesia/good “On” time is the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia.

^†Model-based least square mean (standard error) of change.

^‡Calculated by dividing the change in hours from baseline by the number of hours reported at baseline ([2.72/9.2] x 100 = 29.57%).

^§A total of 110 patients (oral IR LD/CD n=62; VYALEV™ n=48) completed the study. During the double-blind treatment period, 5 patients in the oral IR LD/CD group and 26 in the VYALEV™ group prematurely discontinued. One of the patients in the VYALEV™ group was excluded from the analysis because the patient did not have valid baseline data for the efficacy model.

IR=immediate-release; LD/CD=levodopa/carbidopa; LS=least squares; PD=Parkinson’s disease; SE=standard error.

VYALEV™ Provided a Superior Improvement in Daily “Off” Time vs Oral IR Levodopa/Carbidopa^1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

VYALEV™ Provided a Superior Improvement in Daily “Off” Time vs Oral IR Levodopa/Carbidopa^1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

Change from baseline to Week 12 in “Off” time*

(LS mean of difference between the two treatment arms=-1.79 hours; P=0.0054 [95% CI, -3.03, -0.54])

^*Based on the PD diary, the average daily normalized “Off” time for patients on VYALEV™ was 6.34 (+/-2.27) hours at baseline and decreased by 2.75 (+/-0.50) hours at Week 12 compared with a decrease of 0.96 (+/-0.49) hours at Week 12 from a baseline of 5.91 (+/-1.88) hours for patients taking optimized oral IR levodopa/carbidopa (LS mean change [SE]). This resulted in a statistically significant reduction of 1.79 (+/-0.63) hours in patients on VYALEV™ vs oral IR LD/CD (LS mean of difference [SE]; P=0.0054).

^†Model-based least square mean (standard error) of change.

^‡Calculated by dividing the change in hours from baseline by the number of hours reported at baseline ([2.75/6.34] x 100 = 43.38%).

CI=confidence interval; IR=immediate-release; LD/CD=levodopa/carbidopa; LS=least squares; PD=Parkinson’s disease; SD=standard deviation.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Percentage of patients without morning akinesia at Week 12*^†‡

*Morning akinesia was defined as reporting “Off” status as the first morning symptom upon awakening.

^†Percentage of patients without morning akinesia is the sum of patients reporting “On” time without dyskinesia, “On” time with non-troublesome dyskinesia, and “On” time with troublesome dyskinesia upon awakening.

^‡For patients on VYALEV™, based on PD diary, “On” time without dyskinesia was reported in 70% (N=33/47) of patients; “On” with non-troublesome dyskinesia in 8% (N=4/47) of patients; “On” with troublesome dyskinesia was reported in 4% (N=2/47) of patients at Week 12. For patients on oral IR LD/CD, based on the PD diary, “On” time without dyskinesia was reported in 37% (N=22/66) of patients at Week 12. For patients on VYALEV™, based on the PD diary, morning akinesia was reported in 79% (N=56/71) of patients at baseline and in 17% (N=8/47) of patients at Week 12. For patients on oral IR LD/CD, based on the PD diary, morning akinesia was reported in 76% (N=51/67) of patients at baseline and in 63% (N=38/60) of patients at Week 12.

IR=immediate-release; LD/CD=levodopa/carbidopa; PD=Parkinson’s disease.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Change from baseline to Week 12 in PDSS-2 total score*

The secondary endpoint of sleep did not meet statistical significance based on the hierarchical testing procedure.¹

See 52-week Sleep Data

*For patients on VYALEV™, the PDSS-2 total score was 21.19 (n=72) at baseline with a change of -7.92 (n=44) at Week 12. For patients on oral IR LD/CD the PDSS-2 total score was 18.88 (n=66) at baseline with a change of -2.52 (n=59) at Week 12.

^†Calculated by dividing the change in score from baseline by the score reported at baseline.

IR=immediate-release; LD/CD=levodopa/carbidopa; PDSS-2=Parkinson’s Disease Sleep Scale-2.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Change from baseline to Week 12 in PDQ-39 summary index*

The secondary endpoint of
QoL did not meet statistical significance based on the hierarchical testing procedure.¹

*For patients on VYALEV™, the mean (SD) PDQ-39 summary index value was 30.68 (n=73) at baseline with a change of -6.38 (n=45) at Week 12. For patients on oral IR LD/CD the mean (SD) PDQ-39 summary index value was 26.15 (n=66) at baseline with a change of -2.28 (n=59) at Week 12.

^†Calculated by dividing the change in score from baseline by the score reported at baseline.

IR=immediate-release; LD/CD=levodopa/carbidopa; PDQ-39=39-item Parkinson’s Disease Questionnaire; QoL=quality of life; SD=standard deviation.

Study Design
Motor Symptoms

VYALEV™ 52-Week Safety Study Design^1,2

VYALEV™ 52‑Week Safety Study Design^1,2

Aim: Evaluate the safety and tolerability of 24-hour daily exposure with a continuous subcutaneous infusion of VYALEV™. Secondary efficacy endpoints were also evaluated.

Duration: 52 weeks (this study is ongoing).

Study type: Phase 3, single-arm, open-label.

Patient population: Evaluation of 244 patients. 137 patients completed the 52-week study. The target population was levodopa-responsive patients with PD whose motor symptoms were inadequately controlled with current treatment and experienced a minimum of 2.5 hours of “Off” time per day as assessed by PD diaries.

PD=Parkinson’s disease.

See Trial Endpoints

Please refer to the VYALEV™ SmPC for full study data.

See Trial Endpoints

Please refer to the VYALEV™ SmPC for full study data.

VYALEV™ subcutaneous administration and DUODOPA^® (levodopa/carbidopa intestinal gel) enteral administration were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, which support a comparable efficacy profile.¹

View PK Comparability Data

AUC=area under the curve; C_max=peak concentration.

VYALEV™ subcutaneous administration and DUODOPA^® (levodopa/carbidopa intestinal gel) enteral administration were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, which support a comparable efficacy profile.¹

View PK Comparability Data

AUC=area under the curve; C_max=peak concentration.

Patients Treated With VYALEV™ Experienced MORE “On” Time Without Troublesome Dyskinesia vs Baseline^1,2*

Secondary Efficacy Endpoints From the 52-Week Safety Study

Patients Treated With VYALEV™ Experienced MORE “On” Time Without Troublesome Dyskinesia vs Baseline^1,2*

Secondary Efficacy Endpoints From the 52-Week Safety Study

*"On" time without troublesome dyskinesia is the sum of "On" time without dyskinesia and "On" time with non-troublesome dyskinesia.

^†Values represent unadjusted mean hours (+/-standard deviation) assessed using a 24-hour PD diary and normalized to a 16-hour waking day. Only patients who completed each study visit were included in the efficacy analysis, and no adjustments were made to account for premature discontinuation.

^‡52-week value is the sum of 10.8 hours ("On" time without dyskinesia) and 2.3 hours ("On" time with non-troublesome dyskinesia).

^§Calculated by dividing the change in hours from baseline by the number of hours reported at baseline.

Patients Treated With VYALEV™ Experienced Less “Off” Time^1,2

Secondary Efficacy Endpoints From the 52-Week Safety Study

Patients Treated With VYALEV™ Experienced Less “Off” Time^1,2

Secondary Efficacy Endpoints From the 52-Week Safety Study

*“Oﬀ” time was decreased by an average of 3.5 hours by Week 52 (average 2.5 hours) compared to baseline (average 5.9 hours) as demonstrated by a the average daily normalized “Oﬀ” time for patients in their PD diaries from baseline to study end (n=116).²

^†Calculated by dividing the change in hours from baseline by the number of hours reported at baseline.

Continue to Safety page

Safety

Please refer to the VYALEV™ SmPC for complete Prescribing and Safety Infomation.

REFERENCES:

VYALEV™ (foslevodopa/foscarbidopa solution for infusion) Summary of Product Characteristics-MAY 03,2023.
Aldred J, Freire-Alvarez E, Amelin AV, et al. Neurol Ther. 2023;12:1937-1958. (incl. suppl.).
Soileau MJ, Aldred J, Budur K, et al. Lancet Neurol. 2022;21:1099-1109 (incl. suppl.).
Rosebraugh M, Liu W, Neenan M, Facheris MF. J Parkinsons Dis. 2021;11(4):1695-1702.
Rosebraugh M, Stodtmann S, Liu W, Facheris M. Parkinsonism Relat Disord. 2022,97:68-72.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Vyalev™ (foslevodopa and foscarbidopa solution for infusion) Indication and Summary of Important Treatment Considerations

Indication
Treatment of advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results.

Contraindications
VYALEV™ is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients, narrow‑angle glaucoma, severe heart failure, acute stroke, severe cardiac arrhythmia, comedication with selective MAO type A inhibitors and nonselective MAO inhibitors, conditions contraindicated for adrenergics (e.g. pheochromocytoma, hyperthyroidism, and Cushing’s syndrome), and suspicious undiagnosed skin lesions or history of melanoma.

Select special warnings and precautions for Vyalev™
Special warnings and precautions for Vyalev™

Several warnings and precautions below are generic for levodopa and, therefore, also for Vyalev™

Not recommended for the treatment of drug-induced extrapyramidal reactions.

Caution use in patients with: severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions. History of myocardial infarction with residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored during the initial dosage adjustments. Monitor all patients for the development of mental changes, depression with suicidal tendencies, and other serious mental changes. Caution with past or current psychosis and antipsychotics used concomitantly with dopamine receptor-blocking properties (observe for loss of antiparkinsonian effect). Higher frequency of hallucinations may occur with dopamine agonists and/or other dopaminergic treatments including Vyalev™. Monitor patients regularly for the development of impulse control disorders, for example Dopamine Dysregulation Syndrome (DDS). Before initiation of treatment, warn patients and caregivers of the potential risk of developing DDS. The dose of Vyalev™ may need to be adjusted downwards in order to avoid levodopa induced dyskinesias. Caution in chronic wide-angle glaucoma; monitor for intra-ocular pressure changes. Vyalev™ may induce orthostatic hypotension and should be given cautiously in patients taking other medicinal products that may cause orthostatic hypotension. Concomitant use of selegiline and levodopa/carbidopa has been associated with serious orthostatic hypotension. Levodopa may induce somnolence and sudden sleep: caution should be exercised when driving and operating machines. Risk of symptoms resembling Neuroleptic Malignant Syndrome following abrupt dose reduction or discontinuation.

Infusion site events (see section 4.8) have been reported in patients receiving Vyalev™. Follow aseptic techniques and frequently rotate the infusion site to reduce the risk. In clinical studies, few patients who reported infusion site reactions also experienced infusion site infections. Therefore, monitor for serious infusion site reactions and infusion site infections.

Patients with Parkinson’s disease have a higher risk of developing melanoma. Monitor patients for melanomas on a regular basis when using Vyalev™.

Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with Vyalev™.

Vyalev™ contains hydrazine (foscarbidopa degradation product), that can be genotoxic and probably carcinogenic. The approximately median exposure of hydrazine is 0.2 mg/day, with a maximum of 0.5 mg/day. The clinical significance of this hydrazine exposure is not known.

Reduced ability to handle the delivery system can lead to complications. In such patients a caregiver should assist the patient.

A sudden or gradual worsening of bradykinesia may indicate an obstruction in the device for whatever reason and needs to be explored.

Polyneuropathy has been reported; evaluate for history/signs of and known risk factors before starting therapy.

Vyalev™ is high in sodium; considered especially in patients on a low salt diet.

Caution is needed in concomitant administration of Vyalev™ with the following medicinal products: Antihypertensives, antidepressants, COMT inhibitors, dopamine antagonists, MAO inhibitors, amantadine. Sympathomimetics may increase cardiovascular adverse events related to levodopa. Foscarbidopa is a potential inducer of CYP1A2 in vitro. Care should be taken when prescribing Vyalev™ in combination with sensitive CYP1A2 substrates (e.g. caffeine). Review section of interactions with other medicinal products in SmPC for further details about these and a complete list of interactions.

Fertility, pregnancy and lactation
Vyalev™ is not recommended during pregnancy. Breast-feeding should be discontinued during treatment with Vyalev™.

Undesirable effects
Summary of the safety profile

The most frequent adverse reactions (≥10%) reported in all Phase 3 studies in patients exposed to Vyalev™ were infusion site events (infusion site erythema, infusion site cellulitis, infusion site nodule, infusion site pain, infusion site oedema, infusion site reaction, and infusion site infection), hallucination, fall, and anxiety.

This is not a complete summary of all safety information. Please refer to your country specific product labeling for complete product prescribing and safety information.

AE-VYAL-240018

VYALEV™ 12-Week Efficacy and Safety Study Endpoints³

Primary

• Change from baseline to Week 12 in “On” time without troublesome dyskinesia (hours/day)^a,b

Key Secondary

Change from baseline to Week 12 in:

• “Off” time (hours/day)^b

• Motor aspects of experiences of daily living (MDS-UPDRS)^c

• Morning akinesia (%)^d

Other Secondary

Change from baseline to Week 12 in:

• “On” time without dyskinesia (hours/day)

• Sleep symptoms (PDSS-2)

• Quality of life (PDQ-39)

• Quality of life (EQ-5D-5L)^e

• PD symptoms (median/IQR PKG bradykinesia and dyskinesia score)

^a“On” time without troublesome dyskinesia is the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia.

^bBased on PD diary (normalized to a 16-hour waking day and averaged over 3 consecutive days).

^cMDS-UPDRS Part II score.

^dMorning akinesia is defined as reporting “Off” status as the first morning symptom on waking.

^eEQ-5D-5L summary index is based on the weighted scoring algorithm for the United States.

EQ-5D-5L=EuroQol 5-Dimension Questionnaire; IQR=InterQuartile Range; MDS-UPDRS=Movement Disorder Society—Unified Parkinson’s Disease Rating Scale; PDSS-2=Parkinson’s Disease Sleep Scale-2; PDQ-39=39-item Parkinson’s Disease Questionnaire; PKG=Parkinson’s KinetiGraph or Personal KinetiGraph (Global Kinetics, MN, USA); SE=standard error.

VYALEV™ 52-Week Safety Study Endpoints²

Primary

• Adverse events (%)^a

• Percentage of patients with adverse events of special interest^a

• Percentage of patients with numeric grade ≥5 and with letter grade ≥D on the Infusion Site Evaluation Scale^b

Change from baseline to end of study in:

• Clinical laboratory test data

• Vital sign measurements

• Electrocardiograms (ECGs)

Secondary

Change from baseline to end of study in:

• Average normalized daily “Off” time and “On” time^c

• Parkinson’s disease clinical status^d

• Sleep symptoms^e

• Quality of life^f

• Health-related quality of life^g

• Morning akinesia (%)^h

^aFrom initiation of continuous subcutaneous infusion (CSCI) through 30 days after last infusion device was removed (up to 56 weeks).

^bThe Infusion Site Evaluation Scale, a two-part numeric (0-7) and letter (A-G) grade scale, where 7 and G indicated the worst outcomes, was used to assess skin tolerability.⁴

^cPD diary.

^dMovement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I-IV (with Part III measured in the patients’ best “On” state) score.

^eParkinson’s Disease Sleep Scale-2 (PDSS-2) total score.

^fPD Questionnaire-39 items (PDQ-39).

^gEuroQol 5-dimensions questionnaire (EQ-5D-5L).

^hPercentage of subjects with early morning “Off” status based on the first morning symptom upon awakening derived from PD diary.

PD=Parkinson’s disease.

Subcutaneous VYALEV™ and enteral DUODOPA^® (levodopa/carbidopa intestinal gel) were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, supporting a comparable efficacy profile.¹

Levodopa exposure following 24-hour VYALEV™ infusion and 16-hour DUODOPA infusion followed by nighttime oral LD/CD doses⁵

Formulation

VYALEV™

DUODOPA + Nighttime Oral LD/CD

DUODOPA^® Provides Less “Off” Time and More “On” Time Without Troublesome Dyskinesia^2,4

DUODOPA demonstrated significant improvements in “Off” time (baseline to endpoint) and “On” time without troublesome dyskinesia (baseline to endpoint) compared to oral levodopa/carbidopa (LS mean difference). Analysis of other secondary efficacy endpoints are not presented here. Please refer to the VYALEV™ SmPC for further information about these endpoints.

Duration: 12 weeks. Study type: Randomized, double-blind, double-dummy, double-titration trial. Patient population: 71 adult patients with advanced PD and motor complications. Aim: To assess the efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. Primary endpoint: Change from baseline to final visit in motor “Off” time.⁴

LS=least squares; SD=standard deviation; SE=standard error.

^aActive control, oral levodopa/carbidopa 100/25 mg tablets.

Sleep Data From 52-Week Safety Study²

PDSS-2 is a secondary efficacy endpoint of this 52-week, Phase 3, open-label, single-arm, multicenter study

Sleep Data From 52-Week Safety Study²

PDSS-2 is a secondary efficacy endpoint of this 52-week, Phase 3, open-label, single-arm, multicenter study

Change from baseline to Week 52 in PDSS-2 total score^1,2*

*For patients on VYALEV™, the PDSS-2 total score was 20.4 (n=243) at baseline with a change of -7.5 (n=131) at Week 52.

PDSS-2=Parkinson’s Disease Sleep Scale-2.

VYALEV™ Clinical Studies

VYALEV™ Clinical Studies

The efficacy and safety of 24-hour continuous levodopa-based therapy with VYALEV™ were demonstrated in 2 trials.1-3

12-week

52-week

VYALEV™ 12-Week Efficacy and Safety Study Design1,3

VYALEV™ 12‑Week Efficacy and Safety Study Design1,3

What Does 24-Hour Continuous Delivery Without Surgery Mean for Your Patients?

What Does 24-Hour Continuous Delivery Without Surgery Mean for Your Patients?

Reduction in morning “Off” time (morning akinesia)1*

Less “Off” time and more good “On” time during morning, day, and night1,3†‡

Fewer interruptions over 24 hours morning, day, and night3†

More “On” time and less “Off” time over 24 hours means more for patients1‡

VYALEV™ Provided a Superior Improvement in Good “On” Time vs Oral IR Levodopa/Carbidopa1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

VYALEV™ Provided a Superior Improvement in Good “On” Time vs Oral IR Levodopa/Carbidopa1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

VYALEV™ Provided a Superior Improvement in Daily “Off” Time vs Oral IR Levodopa/Carbidopa1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

VYALEV™ Provided a Superior Improvement in Daily “Off” Time vs Oral IR Levodopa/Carbidopa1,3

Key Efficacy Endpoints From the 12-Week Efficacy and Safety Study

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study1,3

Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.

VYALEV™ 52-Week Safety Study Design1,2

VYALEV™ 52‑Week Safety Study Design1,2

VYALEV™ subcutaneous administration and DUODOPA® (levodopa/carbidopa intestinal gel) enteral administration were shown to have comparable levodopa Cmax, AUC, and degree of fluctuation, which support a comparable efficacy profile.1

VYALEV™ subcutaneous administration and DUODOPA® (levodopa/carbidopa intestinal gel) enteral administration were shown to have comparable levodopa Cmax, AUC, and degree of fluctuation, which support a comparable efficacy profile.1

Patients Treated With VYALEV™ Experienced MORE “On” Time Without Troublesome Dyskinesia vs Baseline1,2*

Secondary Efficacy Endpoints From the 52-Week Safety Study

Patients Treated With VYALEV™ Experienced MORE “On” Time Without Troublesome Dyskinesia vs Baseline1,2*

Secondary Efficacy Endpoints From the 52-Week Safety Study

Patients Treated With VYALEV™ Experienced Less “Off” Time1,2

Secondary Efficacy Endpoints From the 52-Week Safety Study

Patients Treated With VYALEV™ Experienced Less “Off” Time1,2

Secondary Efficacy Endpoints From the 52-Week Safety Study

Continue to Safety page

Vyalev™ (foslevodopa and foscarbidopa solution for infusion) Indication and Summary of Important Treatment Considerations

VYALEV™ 12-Week Efficacy and Safety Study Endpoints3

VYALEV™ 12-Week Efficacy and Safety Study Endpoints3

Primary

Key Secondary

Other Secondary

VYALEV™ 52-Week Safety Study Endpoints2

VYALEV™ 52-Week Safety Study Endpoints2

Primary

Secondary

Subcutaneous VYALEV™ and enteral DUODOPA® (levodopa/carbidopa intestinal gel) were shown to have comparable levodopa Cmax, AUC, and degree of fluctuation, supporting a comparable efficacy profile.1

Subcutaneous VYALEV™ and enteral DUODOPA® (levodopa/carbidopa intestinal gel) were shown to have comparable levodopa Cmax, AUC, and degree of fluctuation, supporting a comparable efficacy profile.1

Levodopa exposure following 24-hour VYALEV™ infusion and 16-hour DUODOPA infusion followed by nighttime oral LD/CD doses5

Formulation

DUODOPA® Provides Less “Off” Time and More “On” Time Without Troublesome Dyskinesia2,4

DUODOPA® Provides Less “Off” Time and More “On” Time Without Troublesome Dyskinesia2,4

Sleep Data From 52-Week Safety Study2

PDSS-2 is a secondary efficacy endpoint of this 52-week, Phase 3, open-label, single-arm, multicenter study

Sleep Data From 52-Week Safety Study2

PDSS-2 is a secondary efficacy endpoint of this 52-week, Phase 3, open-label, single-arm, multicenter study

Our therapy areas

Additional info

The efficacy and safety of 24-hour continuous levodopa-based therapy with VYALEV™ were demonstrated in 2 trials.^1-3

VYALEV™ 12-Week Efficacy and Safety Study Design^1,3

VYALEV™ 12‑Week Efficacy and Safety Study Design^1,3

Reduction in morning “Off” time (morning akinesia)^1*

Less “Off” time and more good “On” time during morning, day, and night^1,3†‡

Fewer interruptions over 24 hours morning, day, and night^3†

More “On” time and less “Off” time over 24 hours means more for patients^1‡

VYALEV™ Provided a Superior Improvement in Good “On” Time vs Oral IR Levodopa/Carbidopa^1,3

VYALEV™ Provided a Superior Improvement in Good “On” Time vs Oral IR Levodopa/Carbidopa^1,3

VYALEV™ Provided a Superior Improvement in Daily “Off” Time vs Oral IR Levodopa/Carbidopa^1,3

VYALEV™ Provided a Superior Improvement in Daily “Off” Time vs Oral IR Levodopa/Carbidopa^1,3

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

Secondary Efficacy Endpoints From the 12-Week Efficacy and Safety Study^1,3

VYALEV™ 52-Week Safety Study Design^1,2

VYALEV™ 52‑Week Safety Study Design^1,2

VYALEV™ subcutaneous administration and DUODOPA^® (levodopa/carbidopa intestinal gel) enteral administration were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, which support a comparable efficacy profile.¹

VYALEV™ subcutaneous administration and DUODOPA^® (levodopa/carbidopa intestinal gel) enteral administration were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, which support a comparable efficacy profile.¹

Patients Treated With VYALEV™ Experienced MORE “On” Time Without Troublesome Dyskinesia vs Baseline^1,2*

Patients Treated With VYALEV™ Experienced MORE “On” Time Without Troublesome Dyskinesia vs Baseline^1,2*

Patients Treated With VYALEV™ Experienced Less “Off” Time^1,2

Patients Treated With VYALEV™ Experienced Less “Off” Time^1,2

VYALEV™ 12-Week Efficacy and Safety Study Endpoints³

VYALEV™ 12-Week Efficacy and Safety Study Endpoints³

VYALEV™ 52-Week Safety Study Endpoints²

VYALEV™ 52-Week Safety Study Endpoints²

Subcutaneous VYALEV™ and enteral DUODOPA^® (levodopa/carbidopa intestinal gel) were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, supporting a comparable efficacy profile.¹

Subcutaneous VYALEV™ and enteral DUODOPA^® (levodopa/carbidopa intestinal gel) were shown to have comparable levodopa C_max, AUC, and degree of fluctuation, supporting a comparable efficacy profile.¹

Levodopa exposure following 24-hour VYALEV™ infusion and 16-hour DUODOPA infusion followed by nighttime oral LD/CD doses⁵

DUODOPA^® Provides Less “Off” Time and More “On” Time Without Troublesome Dyskinesia^2,4

DUODOPA^® Provides Less “Off” Time and More “On” Time Without Troublesome Dyskinesia^2,4

Sleep Data From 52-Week Safety Study²

Sleep Data From 52-Week Safety Study²