Impact of Baseline Dyskinesia on Safety and Efficacy of NOUR
BEDMINSTER, N.J., May 26, 2020 /PRNewswire/ -- Kyowa Kirin, Inc., an affiliate of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151) a global specialty pharmaceutical company, today announces the presentation of results from a post hoc pooled analysis assessing the impact of baseline dyskinesia (pre-existing dyskinesia before istradefylline treatment) on the safety and efficacy of NOURIANZ® (istradefylline) in patients with Parkinson's disease (PD) experiencing "OFF" episodes or "OFF" time. Dyskinesia is recognized as the most frequent adverse reaction in istradefylline treatment.1 The findings showed patients had reductions in "OFF" time and increases in "ON" time without troublesome dyskinesia regardless of the presence of dyskinesia at baseline. Patients with baseline dyskinesia before starting NOURIANZ were more likely to experience dyskinesia as an adverse event (AE) during treatment than those who did not have dyskinesia at baseline, but both groups on NOURIANZ experienced a reduction in "OFF" time and an increase in "ON" time without troublesome dyskinesia. These findings were presented during the 6th Congress of the European Academy of Neurology (EAN).
The pooled analysis examined subgroup data from 2,719 patients with PD taking levodopa-containing products with or without other anti-PD medications who experienced "OFF" episodes, either with baseline dyskinesia (+BL-dyskinesia) or without baseline dyskinesia (–BL-dyskinesia) prior to the addition of istradefylline or placebo to their treatment regimen. Data were pooled from eight randomized, placebo-controlled, double-blind clinical studies. In the studies, patients received a daily 20mg or 40mg dose of istradefylline or a placebo for 12 or 16 weeks. The primary endpoint for these trials was change in "OFF" time as reported in patient-completed diaries, with AEs recorded throughout.2 Primary analyses from these studies showed that the use of istradefylline as an adjunctive treatment to levodopa/carbidopa in adult patients with PD experiencing "OFF" episodes was associated with a decrease in "OFF" time and an increase in "ON" time without troublesome dyskinesia.1
Results from the post hoc subanalysis of the eight pooled studies demonstrated that dyskinesia was reported by more patients as an AE during the trials by patients with baseline dyskinesia versus patients without baseline dyskinesia, regardless of whether they received istradefylline or placebo. Dyskinesia as an AE during the studies was reported by 14.1%, 24.7% and 25.9% of patients with baseline dyskinesia (+BL-dyskinesia) receiving a placebo or 20 mg/day or 40 mg/day of istradefylline, respectively, versus 3.5%, 4.4% and 8.4% of patients without baseline dyskinesia, respectively. Reduction in "OFF" time and increase in "ON" time without troublesome dyskinesia were greater with istradefylline than with placebo, which was consistent with previous studies.2
"Uncontrolled, involuntary movements commonly known as dyskinesia can be very troublesome in patients with PD, especially those patients who experience 'OFF' episodes," said Dr. Stuart Isaacson, MD, Parkinson's Disease and Movement Disorders Center of Boca Raton, Florida. "The results being presented at EAN suggest that dyskinesia is observed more often in patients with baseline dyskinesia before istradefylline was added to the treatment regimen and that the overall efficacy of istradefylline was not affected by patients' baseline status. We believe these data can be helpful to physicians as they make treatment decisions and may provide insight into the appropriate use of NOURIANZ in the treatment of 'OFF' time in patients with PD."
While these data provide further information, physicians should continue to monitor patients for dyskinesia or exacerbation of existing dyskinesia during NOURIANZ treatment. The most common adverse reactions with an incidence ≥5% and occurring more frequently than with placebo were dyskinesia (15%, 17%, and 8%), dizziness (3%, 6%, and 4%), constipation (5%, 6%, and 3%), nausea (4%, 6%, and 5%), hallucination (2%, 6%, and 3%), and insomnia (1%, 6%, and 4%) for NOURIANZ 20 mg, 40 mg, and placebo, respectively.
NOURIANZ is the first and only adenosine A2A receptor antagonist approved in the U.S. as an adjunctive or "add on" treatment to levodopa/carbidopa in adult patients with PD experiencing "OFF" episodes.3
Parkinson's disease is a progressive nervous system disorder that affects movement and occurs when cells in the brain, which produce the chemical dopamine, become damaged or die. Dopamine signaling is an important component of the pathways in the brain that control movement.4 In patients with PD, dopamine loss is often treated with levodopa/carbidopa or other medicines that help regulate dopamine.5 Over time and as the disease progresses, these treatments may become less effective, and symptoms return before it's time for the next dose of medicine. These periods when symptoms return are known as "OFF" episodes or "OFF" time.6
Please see NOURIANZ indication and Important Safety Information below.
NOURIANZ® (istradefylline) is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "OFF" episodes.
Important Safety Information
Warnings and Precautions
Dyskinesia: NOURIANZ in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In controlled clinical trials (Studies 1, 2, 3, and 4), the incidence of dyskinesia was 15% for NOURIANZ 20 mg, 17% for NOURIANZ 40 mg, and 8% for placebo, in combination with levodopa. One percent of patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.
Hallucinations / Psychotic Behavior: Because of the potential risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with NOURIANZ. Consider dosage reduction or discontinuation if a patient develops hallucinations or psychotic behaviors while taking NOURIANZ. In controlled trials (Studies 1, 2, 3, and 4), the incidence of hallucinations was 2% for NOURIANZ 20 mg, 6% for NOURIANZ 40 mg, and 3% for placebo. In patients treated with NOURIANZ 40 mg, 1% discontinued because of hallucinations, compared to 0% for placebo and 0% for patients treated with NOURIANZ 20 mg.
Impulse Control / Compulsive Behaviors: Patients treated with NOURIANZ and one or more medication(s) for the treatment of Parkinson's disease (including levodopa) may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, and the inability to control these urges. In clinical trials, 1 patient treated with NOURIANZ 40 mg was reported to have impulse control disorder, compared to no patient on NOURIANZ 20 mg or placebo.
The maximum recommended dosage in patients taking strong CYP3A4 inhibitors is 20 mg once daily. Avoid use of NOURIANZ with strong CYP3A4 inducers.
Pregnancy: Based on animal data, may cause fetal harm.
Hepatic impairment: The maximum recommended dosage of NOURIANZ in patients with moderate hepatic impairment is 20 mg once daily. Avoid use in patients with severe hepatic impairment.
The most common adverse reactions with an incidence ≥5% and occurring more frequently than with placebo were dyskinesia (15%, 17%, and 8%), dizziness (3%, 6%, and 4%), constipation (5%, 6%, and 3%), nausea (4%, 6%, and 5%), hallucination (2%, 6%, and 3%), and insomnia (1%, 6%, and 4%) for NOURIANZ 20 mg, 40 mg, and placebo, respectively.
You are encouraged to report suspected adverse reactions to Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Nourianz Full Prescribing Information, here.
About Kyowa Kirin
Kyowa Kirin commits to innovative drug discovery driven by state-of-the-art technologies. Kyowa Kirin focuses on creating new value in four therapeutic areas: nephrology, oncology, immunology/allergy and neurology. Under the Kyowa Kirin brand, the employees from 36 group companies across North America, Europe and Asia/Oceania unite to champion the interests of patients and their caregivers in discovering solutions wherever there are unmet medical needs. Since 2018, the company has received approval from the U.S. Food and Drug Administration for three first-in-class medicines. You can learn more about the business of Kyowa Kirin at https://www.kyowakirin.com.
About NOURIANZ® (istradefylline) tablet
NOURIANZ is an orally administered, selective adenosine A2A receptor antagonist approved in the U.S. for adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "OFF" episodes. The product has been marketed in Japan under the brand name NOURIAST® since May 30, 2013. In Japan, NOURIAST® is indicated for the improvement of the "wearing-off" phenomenon in patients with Parkinson's disease on levodopa-containing preparations.
About Parkinson's disease
Parkinson's disease is a progressive, neurodegenerative disease characterized by motor symptoms such as tremors, rigidity, slow movement and postural instability. It is thought to be caused by progressive degeneration associated with decreased levels of dopamine in certain parts of the brain, i.e., the substantia nigra and striatum.
NOURIANZ® and NOURIAST® are trademarks of Kyowa Kirin Co., Ltd.
1 NOURIANZ® (istradefylline) Prescribing Information [Package Insert]. Kyowa Kirin Co., Ltd.; 2019.
2 Isaacson SH, Hattori N, Truong D, et al. Impact of Baseline Dyskinesia on the Safety and Efficacy of Istradefylline, an Adenosine A2A Receptor Antagonist, in Patients with Parkinson's Disease: a Pooled Analysis of 8 Clinical Studies. Data presented at: 6th Congress of the European Academy of Neurology: May 23-26, 2020; Virtual.
3 FDA approves new add-on drug to treat off episodes in adults with Parkinson's disease. U.S. Food and Drug Administration (2019). https://www.fda.gov/news-events/press-announcements/fda-approves-new-add-drug-treat-episodes-adults-parkinsons-disease. Accessed April 2020.
4 Parkinson's Disease. National Institute on Aging. https://www.nia.nih.gov/health/parkinsons-disease. Accessed April 2020.
5 Schapira AH, Emre M, Jenner P, Poewe W. Levodopa in the treatment of Parkinson's disease. Eur J Neurol. 2009;16:982–989. doi: 10.1111/j.1468-1331.2009.02697.x.
6 Hickey P, Stacy M. Available and emerging treatments for Parkinson's disease: a review. Drug Des Devel Ther. 2011;5:241-254. doi: 10.2147/DDDT.S11836
Contact: Lauren Walrath, Senior Director, Public Affairs – North America, [email protected]
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