CYP1A2

sNDA intended to satisfy post-marketing requirements to confirm a clinical benefit in patients with PBC Precedent-setting submission includes data from post-marketing studies COBALT and Study 401 as well as real-world evidence from a claims database and patient registries FDA has assigned a PDUFA target action date of October 15, 2024 MORRISTOWN, N.J., Feb. 29, 2024 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc., a biopharmaceutical company and wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) for Ocaliva for the treatment of individuals with primary biliary cholangitis (PBC). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 15, 2024. In this communication, the agency informed Intercept that they are planning to hold an Advisory Committee meeting to discuss the application. “The sNDA data submission asserted that, with more than seven years on the market and more than 40,000 patient-years of post-marketing experience in PBC, Ocaliva is the only second-line therapy that has multiple published analyses of registry data and real-world evidence showing significant effect on transplant-free and decompensation-free survival in people living with PBC,” said Paul Nitschmann, M.D., Senior Vice President of Regulatory Affairs at Intercept. “We are pleased that the FDA has filed the submission and look forward to continued, constructive interactions with the agency, including discussing our precedent-setting application during the forthcoming Advisory Committee meeting.” Ocaliva received accelerated approval in 2016 and is indicated for the treatment of adult patients living with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The precedent-setting sNDA for Ocaliva is intended to satisfy the post-marketing requirements to confirm a clinical benefit in patients with PBC. The sNDA is supported by data from the Company’s post-marketing requirement studies COBALT and Study 401 as well as real-world evidence from a U.S. claims database and international PBC patient registries. Intercept and Alfasigma remain committed to supporting people living with PBC and look forward to advancing discussions with the agency. About Primary Biliary Cholangitis Primary biliary cholangitis (PBC) is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant, or death. About Ocaliva® (obeticholic acid) OCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis. OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment. Contraindications OCALIVA is contraindicated in patients with: decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event compensated cirrhosis who have evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) complete biliary obstruction Warnings and Precautions Hepatic Decompensation and Failure in PBC Patients with Cirrhosis Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Among post-marketing cases reporting it, median time to hepatic decompensation (e.g., new onset ascites) was 4 months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage. Hepatotoxicity was observed in the OCALIVA clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of OCALIVA of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with OCALIVA in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC. Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time to determine whether drug discontinuation is needed. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment. Severe Pruritus Severe pruritus was reported in 23% of patients in the OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arm in a 12-month double-blind randomized controlled clinical trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. Consider clinical evaluation of patients with new onset or worsening severe pruritus. Management strategies include the addition of bile acid binding resins or antihistamines, OCALIVA dosage reduction, and/or temporary interruption of OCALIVA dosing. Reduction in HDL-C Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). Dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to OCALIVA after 1 year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. Adverse Reactions The most common adverse reactions (≥5%) are: pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. Drug Interactions Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of OCALIVA. If taking a bile acid binding resin, take OCALIVA at least 4 hours before or 4 hours after taking the bile acid binding resin, or at as great an interval as possible. Warfarin The International Normalized Ratio (INR) decreased following coadministration of warfarin and OCALIVA. Monitor INR and adjust the dose of warfarin, as needed, to maintain the target INR range when co-administering OCALIVA and warfarin. CYP1A2 Substrates with Narrow Therapeutic Index Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with OCALIVA. Inhibitors of Bile Salt Efflux Pump Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of obeticholic acid in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitor serum transaminases and bilirubin. Please click here for Full Prescribing Information, including Boxed WARNING. To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or . About Intercept Intercept is a biopharmaceutical company and a wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, including primary biliary cholangitis (PBC) and severe alcohol-associated hepatitis (sAH). Intercept owns the commercial rights to Ocaliva in the U.S. market. For more information, please visit or connect with the Company on LinkedIn, Threads, and X (formerly Twitter). Contact For more information about Intercept, please contact: For media: media@interceptpharma.com

Astellas is returning to the Super Bowl to help educate game viewers about VEOZAH and vasomotor symptoms (VMS), the most commonly reported menopause symptoms1 The "Fewer Hot Flashes, More Not Flashes" ad features women experiencing common moderate to severe hot flash and night sweat moments that impact their daily lives NORTHBROOK, Ill., Feb. 1, 2024 /PRNewswire/ -- Astellas Pharma US, Inc. (President: Mark Reisenauer, "Astellas") today announced that it will air a new version of its commercial for VEOZAH® (fezolinetant) just before Super Bowl kickoff on Sunday, February 11, 2024. VEOZAH is a nonhormonal treatment option approved by the U.S. Food and Drug Administration (FDA) to reduce the frequency and severity of moderate to severe vasomotor symptoms (VMS), also known as hot flashes and night sweats, due to menopause.1,2 The "Fewer Hot Flashes, More Not Flashes" TV spot is expected to reach millions of women in the U.S. tuning in who may be experiencing VMS due to menopause, as well as their partners, friends, and family.3,4 Jill Jaroch, Senior Director, Women's Health, Astellas "Approximately half of the audience are women, making the Super Bowl an incredible platform to showcase the different types of hot flash moments women in midlife may experience.4 At Astellas, we want all women to feel heard and their unique needs to be validated, which is why we are continuing to elevate this conversation. After all, nearly half of women in the U.S. going through menopause may experience moderate to severe VMS.3 We want to empower them to talk openly about their experiences and to have more informed discussions with their healthcare providers about VEOZAH." The TV spot showcases relatable hot flash moments, emphasizing that fewer interruptions from moderate to severe VMS due to menopause can be possible.2 When women with VMS are not having a hot flash, that's a not flash. The ad, as part of a larger consumer campaign, aims to encourage women to speak up and seek appropriate treatment options with their healthcare providers. To find more information about moderate to severe VMS due to menopause and this nonhormonal treatment option, visit VEOZAH.com. About VEOZAH® (fezolinetant) VEOZAH ® (fezolinetant) is a neurokinin 3 (NK3) receptor antagonist approved in the U.S. for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause.2 VEOZAH is not a hormone.2 VMS are the feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating ("hot flashes" or "hot flushes").1 VEOZAH works by blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center of the brain (the hypothalamus) to reduce the frequency and severity of moderate to severe VMS due to menopause.1,2 About VMS due to Menopause VMS, characterized by hot flashes (also called hot flushes) and/or night sweats, are common symptoms of menopause.1 In the U.S., nearly half of women going through menopause may experience moderate to severe VMS.3 VMS can have a disruptive impact on women's daily activities and overall quality of life.5 U.S. Important Safety Information Do not use VEOZAH if you: have cirrhosis. have severe kidney problems or kidney failure. are taking certain medicines called CYP1A2 inhibitors. Ask your healthcare provider if you are not sure. Before you use VEOZAH, tell your healthcare provider about all of your medical conditions, including if you: have liver disease or problems. have kidney problems. have any medical conditions that may become worse while you are using VEOZAH. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VEOZAH may affect the way other medicines work, and other medicines may affect how VEOZAH works. What are the possible side effects of VEOZAH? VEOZAH can cause serious side effects, including: increased liver blood test values. Your healthcare provider will do a blood test to check your liver before you start taking VEOZAH. Your healthcare provider will also do this blood test at month 3, month 6, and month 9 after you start taking VEOZAH. Call your healthcare provider right away if you have the following signs and symptoms of liver problems: nausea vomiting yellowing of the eyes or skin (jaundice) pain in the right upper stomach (abdomen) The most common side effects of VEOZAH include: stomach (abdominal) pain diarrhea difficulty sleeping (insomnia) back pain hot flashes or hot flushes These are not all the possible side effects of VEOZAH. Tell your healthcare provider if you have any side effect that bothers you or does not go away. Call your healthcare provider for medical advice about side effects. You may report side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. For more information, please see the full Prescribing Information and Patient Product Information for VEOZAH (fezolinetant). About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at . Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. References 1 Thurston RC. Vasomotor symptoms. In: Crandall CJ, Bachman GA, Faubion SS, et al., eds. Menopause Practice: A Clinician's Guide. 6th ed. Pepper Pike, OH: The North American Menopause Society, 2019:43-55. 2 Veozah [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 3 Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause 2014;21(9):924-32. 4 Men, Women and the Super Bowl: The Science Marketers Should Note, Martec Group. 5 English M, Stoykova B, Slota C, et al. Qualitative study: burden of menopause-associated vasomotor symptoms (VMS) and validation of PROMIS sleep disturbance and sleep-related impairment measures for assessment of VMS impact on sleep. J Patient Rep Outcomes 2021;5(37):1-13. SOURCE ASTELLAS PHARMA INC.

- PRODUODOPA® (foslevodopa/foscarbidopa) is the first-and-only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of advanced Parkinson's disease - PRODUODOPA demonstrated sustained improvements in "Off" time (when symptoms return between medication doses), "On" time (when symptoms are controlled) without dyskinesia (involuntary movement), and morning akinesia ("Off" time upon waking) NORTH CHICAGO, Ill., Jan. 9, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the launch of PRODUODOPA® (foslevodopa/foscarbidopa) in the European Union for the treatment of advanced Parkinson's disease with severe motor fluctuations and hyperkinesia (excessive movement) or dyskinesia (involuntary movement), and when available combinations of Parkinson's medicinal products have not given satisfactory results.1 PRODUODOPA is the first-and-only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of severe motor fluctuations in people living with advanced Parkinson's disease whose symptoms are inadequately controlled by other therapies. The continuous delivery of PRODUODOPA provides levodopa 24-hours a day which may help patients by extending the period when symptoms are well-controlled, often referred to as "On" time.2 AbbVie was granted marketing authorization of PRODUODOPA through the Decentralized Procedure in the third quarter of 2022. The VYAFUSER™ pump for the subcutaneous delivery of PRODUODOPA received Conformité Européenne (CE) Mark in November of 2023. Parkinson's disease is a chronic, progressive neurodegenerative disorder affecting approximately 6.1 million people globally3 and is expected to double by 2040. Parkinson's disease is characterized by tremor, muscle rigidity, slowness of movement and difficulty with balance.4 As the disease progresses, the severity of symptoms increases5, and patients tend to experience greater disability and an impaired ability to perform activities of daily living6, as well as the reemergence of symptoms as standard treatment wears off.7 Characteristics of advanced Parkinson's disease may include needing help with performing daily activities, increased motor fluctuations (changes in the ability to move referred to as "On-Off" times), difficulty swallowing, recurrent falls, dementia, dyskinesia (involuntary movements) and other symptoms.5 "People living with Parkinson's disease experience daily challenges and uncertainty, especially as their disease progresses and symptoms are no longer adequately controlled," said Roopal Thakkar, Senior Vice President, Development and Regulatory Affairs and Chief Medical Officer, AbbVie. "This approval is an example of our unwavering commitment to this community by developing new, transformative therapeutic options for people experiencing advanced Parkinson's disease, their families, and care partners." The launch was supported by three studies: the Phase 3, 12-month open label study (M15-741 study) which evaluated the long-term safety, tolerability, and efficacy of continuous subcutaneous infusion of PRODUODOPA8, the Phase 3, 12-week study (M15-736 study) which compared the efficacy and safety of PRODUODOPA to oral levodopa/carbidopa2, and a Phase 1 pharmacokinetic comparability study.9 Findings from the M15-741 safety and tolerability study showed a favorable benefit/risk profile and demonstrated sustained improvements in "Off" time and "On" time without dyskinesia, and morning akinesia as measured by the percentage of patients in early morning "Off" time as recorded by PD diary.8 The majority of adverse events (AEs) with PRODUODOPA were non-serious and mild or moderate in severity. The most frequent AEs (greater than or equal to 10 percent) 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.1 "This approval represents a significant advancement for those with Parkinson's disease who have historically had limited treatment options for advanced stages," said Angelo Antonini, MD, PhD, Professor of Neurology at the Department of Neuroscience, University of Padua, Italy. "When oral treatment no longer sufficiently helps with improvement in motor fluctuations, patients need alternative options. PRODUODOPA's around-the-clock infusion allows for continuous delivery of levodopa, the gold standard of treatment." "As Parkinson's progresses, it can take a significant physical and emotional toll not only on the person but also on their family and care partners, who often play a critical role in their daily lives," said Josefa Domingos, President, Parkinson's Europe. "It is vital that the Parkinson's community have more options that can help them manage their symptoms." About the Phase 3 M15-741 Study8 The Phase 3, single arm, open-label study evaluated the safety and tolerability, and efficacy of 24-hour daily exposure of continuous subcutaneous infusion of PRODUODOPA in people with advanced Parkinson's disease whose motor symptoms were inadequately controlled by their current treatment. The primary endpoint was to evaluate the safety and tolerability of PRODUODOPA. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, and total scores from quality-of-life surveys. The study was conducted at 58 sites across 13 countries (Australia, Belgium, Canada, Denmark, Germany, Italy, Japan, Netherlands, Russia, Spain, Sweden, United Kingdom, and United States). Eligible patients included adults 30 years or older diagnosed with levodopa-responsive idiopathic Parkinson's disease experiencing an average of greater than or equal to 2.5 hours of "Off" time per day, as assessed by patient's Parkinson's disease diaries. Reduction in motor fluctuations was observed as early as one week and persisted through week 52. The percentage of patients experiencing morning akinesia dropped from 77.7 percent at baseline to 27.8 percent at week 52. Indicators of sleep and quality of life were assessed from baseline through week 52 as published in the Journal of Neurology & Therapy (). More information on the study can be found on (NCT03781167). About the Phase 3 M15-736 Study2 The Phase 3 randomized, double-blind, double-dummy, active-controlled study compared the efficacy, safety and tolerability of PRODUODOPA to oral immediate-release levodopa/carbidopa (LD/CD) in patients with advanced Parkinson's disease. Participants were provided with a home diary (the PD Diary) to assess their motor state during the day. The primary endpoint was "On" time without troublesome dyskinesia. The study included 141 participants who were randomly assigned and received treatment at 65 centers in the U.S. and Australia. Participants were randomized one to one to receive either the PRODUODOPA solution as a continuous delivery under the skin (subcutaneous) plus oral placebo capsules for LD/CD or oral capsules containing immediate-release LD/CD plus continuous subcutaneous delivery of placebo solution for PRODUODOPA. The treatment duration was 12 weeks. The increase in "On" time without troublesome dyskinesia at week 12 was an average of 2.72 hours for PRODUODOPA versus 0.97 hours for oral LD/CD (p= 0.0083). Improvements in "On" time were observed as early as the first week and persisted throughout the 12 weeks. This study also assessed changes from baseline to week 12 in motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, however results did not achieve statistical significance. More information on the study can be found on (NCT04380142) and in The Lancet Neurology ((22)00400-8). About the Phase 1 Pharmacokinetic study9 A Phase 1, open label, randomized, two period cross over study was conducted to compare the pharmacokinetics (PK) of levodopa from 24-hour continuous subcutaneous infusion of PRODUODOPA (foslevodopa/foscarbidopa) to the PK of levodopa from 16-hour levodopa-carbidopa intestinal gel (LCIG), followed by two night-time oral levodopa/carbidopa (LD/CD) doses. The levodopa exposures following subcutaneous infusion of PRODUODOPA over 24 hours were similar (less than 8 percent difference) to those of LCIG mg LD/CD administered over 16 hours, followed by two oral doses at 18 and 21 hours after the start of LCIG delivery. The study concluded that 24-hour continuous subcutaneous infusion of PRODUODOPA provides levodopa exposures comparable to LCIG throughout the day. More information on the study can be found on (35339102) and in Science Direct (). About PRODUODOPA® (foslevodopa/foscarbidopa) PRODUODOPA® (foslevodopa/foscarbidopa) is a solution of levodopa and carbidopa prodrugs for 24-hour continuous subcutaneous infusion for the 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. PRODUODOPA® (foslevodopa and foscarbidopa solution for infusion) Indication and Summary of Important Treatment Considerations1 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 PRODUODOPA 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, co-medication 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 PRODUODOPA Special warnings and precautions for PRODUODOPA Several warnings and precautions below are generic for levodopa and, therefore, also for PRODUODOPA. 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 PRODUODOPA. 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 PRODUODOPA 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. PRODUODOPA 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 PRODUODOPA. 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 PRODUODOPA. Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with PRODUODOPA. PRODUODOPA 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. PRODUODOPA is high in sodium; considered especially in patients on a low salt diet. Caution is needed in concomitant administration of PRODUODOPA 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 PRODUODOPA 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 PRODUODOPA is not recommended during pregnancy. Breast-feeding should be discontinued during treatment with PRODUODOPA. Undesirable effects Summary of the safety profile The most frequent adverse reactions (≥10%) reported in all Phase 3 studies in patients exposed to PRODUODOPA 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. Globally, prescribing information varies; please refer to your country specific product labeling for complete product prescribing and safety information. About AbbVie in Neuroscience At AbbVie, our commitment to preserving personhood of people around the world living with neurological and psychiatric disorders is unwavering. With more than three decades of experience in neuroscience, we are providing meaningful treatment options today and advancing innovation for the future. AbbVie's Neuroscience portfolio consists of approved treatments in neurological conditions, including migraine, movement disorders, and psychiatric disorders, along with a robust pipeline of transformative therapies. We have made a strong investment in research and are committed to building a deeper understanding of neurological and psychiatric disorders. Every challenge makes us more determined and drives us to discover and deliver advancements for those impacted by these conditions, their care partners, and clinicians. For more information, visit . About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @AbbVie on X (formerly Twitter), Facebook, Instagram, YouTube, and LinkedIn Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. References 1 PRODUODOPA® (foslevodopa/foscarbidopa solution for infusion) Summary of Product Characteristics. November 2023. 2 Soileau, M., et al. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. The Lancet Neurology. December 2022. 3 Armstrong, MJ. and Okun, MS. (2020). Diagnosis and Treatment of Parkinson Disease. A Review. JAMA 2020; 323(6): 548-560. 4 "What is Parkinson's?" Parkinson's Foundation. Available at: . Accessed: August 29, 2023. 5 Luquin M-R et al. Parkinson's Dis. 2018; 4047392. 6 Malaty IA et al. (2022). Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries. Gainsville: BCM Neurology. 7 "Wearing off and motor fluctuations". Parkinson's Europe. Available at . Accessed November 6, 2023. 8 Aldred, J., et al. Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study. Journal of Neurology & Therapy. August 2023. 9 Rosebraugh, M., et al. Foslevodopa/foscarbidopa subcutaneous infusion maintains equivalent levodopa exposure to levodopa-carbidopa intestinal gel delivered to the jejunum. Science Direct. April 2022. SOURCE AbbVie