XADAGO clinical
efficacy & safety

XADAGO clinical efficacy & safety

More daily ON time—without troublesome dyskinesia

XADAGO patients reported significant improvements in their health status at 6 months

XADAGO significantly reduced daily OFF time at 6 months

XADAGO improved motor function at 6 months based on UPDRS III scores

18-month extension to Study 1

ON time and OFF time improvement maintained over 2 years

XADAGO 6-month study designs^1-3

Two pivotal, 6-month studies: Study 1 (016) and Study 2 (SETTLE)

In 2 randomized, 24-week, multicenter, double-blind, placebo-controlled trials, the efficacy and safety of XADAGO as add-on therapy to a stable dose of levodopa in patients with Parkinson’s disease (PD) experiencing motor fluctuations were evaluated. After a levodopa stabilization phase, patients were randomized to receive XADAGO 50 mg/day or 100 mg/day or placebo.

Study 1 (016) and Study 2 (SETTLE) efficacy outcomes

Primary endpoints

The primary endpoints were mean daily ON time (ON time without dyskinesia plus ON time with nontroublesome dyskinesia) at 6 months

Secondary endpoints

Secondary outcomes of Study 1 and Study 2 included:
- Decrease in total daily OFF time, as measured by Hauser diary
- Unified Parkinson’s Disease Rating Scale (UPDRS) Part III during ON phase—mean change from baseline to end of study
- Parkinson’s Disease Questionnaire 39 (PDQ-39): mean change from baseline to end of study

Secondary outcomes of Study 1 and Study 2 included:

Decrease in total daily OFF time, as measured by Hauser diary
Unified Parkinson’s Disease Rating Scale (UPDRS) Part III during ON phase—mean change from baseline to end of study
Parkinson’s Disease Questionnaire 39 (PDQ-39): mean change from baseline to end of study

In Study 2, if there were no tolerability issues by day 14, the starting dosage was increased to 100 mg/day³

More daily ON time—without troublesome dyskinesia^1-3

At 6 months, XADAGO significantly increased daily ON time without troublesome dyskinesia when used as an adjunct to levodopa^1-3

Study 1 (016)^1,2

Graph of Study 1 comparing daily on time for patients taking XADAGO 50 mg, XADAGO 100 mg, and a placebo over a 6-month period.

Study 2 (SETTLE)^2,3

Graph of Study 2 showing improvements in daily on time with XADAGO 100 mg/day versus placebo.

XADAGO patients reported significant improvements in their health status at 6 months^1-3

XADAGO 100-mg dose group showed significant improvements based on PDQ-39 total scores^1-3

PDQ-39 is a PD-specific health status questionnaire comprising 39 items. Items are grouped into 8 subscales (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, bodily discomfort) that are scored by expressing summed item scores as a percentage score ranging between 0 and 100.⁴

Study 1 (016) and Study 2 (SETTLE)^1-3

Graph showing the PDQ-39 scores for Study 1 and Study 2.

XADAGO significantly reduced daily OFF time at 6 months^1-3

Study 1 (016)

Graph showing the change from baseline in daily off time at 24 weeks from Study 1.

Study 2 (SETTLE)

Graph from Study 2 showing the change from baseline in daily off time at 24 weeks for XADAGO 100 mg and a placebo.

XADAGO improved motor function at 6 months based on UPDRS III scores^1-3

Change from baseline in UPDRS III score during ON time^1-3

Table showing UPDRS III scores from Study 1 and Study 2.

18-Month extension to Study 1 (016)^1,2,6

Study 018 was a double-blind, placebo-controlled, 18-month extension to Study 1 (016), aimed at assessing the long-term efficacy and safety of XADAGO as add-on therapy to levodopa in patients with PD and motor fluctuations

Chart comparing outcomes of Study 1 and Study 018.

The primary efficacy endpoint in Study 018 was the Dyskinesia Rating Scale (DRS) score and was not statistically significant

Secondary outcomes of Study 018 included:

Mean change from baseline to end of study in diary ON time without troublesome dyskinesia
UPDRS Part III (motor) scores
Mean change from baseline to end of study in diary OFF time

Data from Study 018 do not appear in the XADAGO Prescribing Information

66% of patients in Study 016 completed the entire 2-year treatment period
81% of patients in Study 018 completed the 18-month extension period

Changes and/or adjustments to subjects’ other concomitant PD medications were allowed throughout the study at the discretion of the site investigators

ON time and OFF time improvement maintained over 2 years^1,2,6

Two graphs showing the improvements in daily on time and reductions in daily off time over a 2 year period for patients taking XADAGO 50 mg, XADAGO 100 mg, and a placebo.

The primary efficacy endpoint in Study 018 was the DRS score and was not statistically significant

Changes and/or adjustments to subjects’ other concomitant PD medications were allowed throughout the study at the discretion of the site investigators

66% of patients in Study 016 completed the entire 2-year treatment period
81% of patients in Study 018 completed the 18-month extension period

Data from Study 018 do not appear in the XADAGO Prescribing Information

Safety profile

Patients with adverse reactions with an incidence ≥2% in the XADAGO 100 mg/day group and greater than placebo in studies 1 and 2⁷

Discontinuation due to adverse reactions⁷

Overall discontinuation rates due to adverse reactions from Study 1 (016) and Study 2 (SETTLE) were 5% for XADAGO 50 mg/day, 6% for XADAGO 100 mg/day, and 4% for placebo⁷

Discontinuation due to dyskinesia^*,7:
for both XADAGO 50 mg/day and 100 mg/day dosages

*Discontinuation due to dyskinesia for placebo was 0%.

Medical inquiries and reporting adverse events

For all medical inquiries, contact Supernus Pharmaceuticals Medical Affairs: 1-888-492-3246 or medinfo.supernus@apcerls.com. To report SUSPECTED ADVERSE REACTIONS or product complaints, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
You may also report SUSPECTED ADVERSE REACTIONS or product complaints to Supernus Pharmaceuticals at 1-888-4XADAGO (1-888-492-3246)
Additional information can be requested using the Supernus Pharmaceuticals Information Request Form

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IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION FOR HEALTHCARE PROVIDERS

CONTRAINDICATIONS

Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid.
Concomitant use of opioid drugs (e.g., meperidine and its derivatives, methadone, propoxyphene, or tramadol); serotonin-norepinephrine reuptake inhibitors (SNRIs), tri- or tetra-cyclic or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; or St. John’s wort. Concomitant use could result in life-threatening serotonin syndrome.
Concomitant use of dextromethorphan.
In patients with a history of a hypersensitivity to safinamide.
In patients with severe hepatic impairment (Child-Pugh C).

WARNINGS & PRECAUTIONS

XADAGO may cause or exacerbate hypertension. In clinical trials, the incidence of hypertension was 7%, 5%, and 4% for XADAGO 50mg, 100mg, and placebo respectively. Patients should be monitored after starting XADAGO for new-onset hypertension or hypertension that is not adequately controlled. Dietary tyramine restriction is not required during treatment with recommended doses of XADAGO. However, patients should be advised to avoid foods containing a very high amount of tyramine because of the potential for severe increases in blood pressure, also referred to as hypertensive urgency, crisis, or emergency.
Patients treated with dopaminergic medications have reported falling asleep while engaged in activities of daily living. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), XADAGO should ordinarily be discontinued, or the patient should be advised to avoid driving and other potentially dangerous activities.
May cause dyskinesia (or exacerbate dyskinesia).
Patients with a major psychotic disorder should ordinarily not be treated with XADAGO because of the risk of exacerbating psychosis with an increase in central dopaminergic tone. Consider dosage reduction or discontinuation if hallucinations or psychotic-like behavior develop.
Patients can experience impulse control/compulsive behaviors while taking XADAGO. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about new or increased abnormal behaviors.
Withdrawal-emergent hyperpyrexia and confusion, a symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone.
Monitor periodically for visual changes in patients with a history of retinal/macular degeneration, uveitis, inherited retinal conditions, family history of hereditary retinal disease, albinism, retinitis pigmentosa, or any active retinopathy (e.g., diabetic retinopathy).

DOSING GUIDELINES & CONSIDERATIONS

The maximum recommended dosage of XADAGO in patients with moderate hepatic impairment is 50 mg once daily. Discontinue XADAGO if patient progresses from moderate to severe hepatic impairment. XADAGO is contraindicated in patients with severe hepatic impairment.

ADVERSE REACTIONS

In placebo-controlled studies, the most common adverse reactions associated with XADAGO treatment in which the incidence for XADAGO 100mg/day was at least 2% greater than the incidence for placebo were dyskinesia, fall, nausea, and insomnia.

INDICATION

XADAGO (safinamide) is indicated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing “off” episodes.

Please see full Prescribing Information and Patient Information.

To report SUSPECTED ADVERSE REACTIONS or product complaints, contact Supernus Pharmaceuticals, Inc. at 1-888-492-3246 (1-888-4XADAGO). You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

1. Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord. 2014;29(2):229-237. 2. Data on file, US WorldMeds. 3. Schapira AHV, Fox SH, Hauser RA, et al. Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74(2):216-224. 4. Jenkinson C, Fitzpatrick R, Peto V, et al. The Parkinson's Disease Questionnaire (PDQ-39): development and validation of a Parkinson's disease summary index score. Age Ageing. 1997;26: 353-357. 5. Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15) 2129-2170. 6. Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of Safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord. 2014;29(10):1273-1280. 7. XADAGO. Package Insert. US WorldMeds, LLC.