Isoniazid

LOS ANGELES, Nov. 14, 2024 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, announced two oral presentations on tuberculosis (TB) therapy that took place at The Union Conference on Lung Health 2024, in Bali, Indonesia. The oral presentation “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was presented by Faith Mugodhi, M.Sc., H.S.W., University of Zimbabwe-Clinical Trials Research Centre (UZ-CTRC). The oral presentation High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial was presented by Soyeon Kim, Sc.D., IMPAACT Senior Statistician, Frontier Science Foundation. “ACTG is honored to share these important findings with the many global stakeholders who are gathered in Indonesia at the Union Conference,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “TB is one of ACTG’s key research priorities, as the disease remains a leading killer worldwide. The knowledge gained from the research presented today has the potential to inform our approach to TB treatment and ultimately improve the experiences of people with TB.” “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was a sub-study that investigated experiences around disclosure and treatment preferences among participants in ACTG 5362. Also known as CLO-FAST, this multi-center treatment-shortening trial for drug-susceptible TB randomized individuals to receive either a three-month regimen containing clofazimine (which can be associated with skin hyperpigmentation) or the six-month standard of care. The sub-study consisted of exploratory, qualitative in-depth interviews with 23 participants undergoing treatment in CLO-FAST from India, Malawi, and Zimbabwe. This presentation reported that all sub-study participants with TB had voluntarily disclosed their TB status to at least one other person. Nearly half of participants (43.5 percent) feared inadvertent disclosure of their status due to their treatment and attendance at the TB clinic; 80 percent (n=8) of these were taking clofazimine. One in five participants reported experiencing stigma or discrimination as a result of inadvertent disclosure, including being treated badly by their families or communities. Today’s presentation also found that participants had different preferences around the kind of treatment they received. Two-thirds (n=15) of participants reported that they would prefer the shortened regimen even if one of the medications led to a change in their skin color, while one-third (n=8) reported a preference for the longer regimen. That preference was associated with anticipation of stigma and beliefs that a longer regimen is more potent against TB. These data suggest that anticipated stigma and pre-existing beliefs may be important in understanding treatment preferences. High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial is an analysis from the PHOENIx study, an ongoing clinical trial evaluating the efficacy and safety of preventive treatment for multi-drug resistant TB (MDR-TB) with delamanid compared to isoniazid, conducted jointly by the ACTG and IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) networks. (IMPAACT is a global collaboration of investigators, institutions, community representatives, and other partners, with a mission to improve health outcomes for infants, children, and adolescents as well as pregnant and postpartum people who are impacted by or living with HIV by evaluating novel treatments and interventions for HIV and its complications for tuberculosis and other related complications, through the conduct of high-quality clinical trials.) Knowledge of drug susceptibility in people with active TB is important for the provision of both efficacious treatment for their TB disease and TB preventive treatment for their contacts. This presentation sought to describe drug resistance patterns in adults with MDR-TB whose household members were approached to participate in PHOENIx. Between June 2019 and October 2023, 1,353 adults with documented MDR-TB were enrolled from 28 sites and 13 countries in Africa, Asia, and Central and South America. Among those for whom isoniazid mutation data were available, 73 percent (n=783 of 1078) had high-level resistance (katG mutations). Among the 699 participants who had fluoroquinolone drug-susceptibility testing available, 20 percent (n=139) had fluoroquinolone resistance. These results suggest that it is important to have non-fluoroquinolone options for TB preventive treatment. They also support the relevance of the PHOENIx trial’s evaluation of delamanid vs. isoniazid for TB preventive treatment in high-risk household contacts of adults with MDR-TB. Primary results of the clinical trial are anticipated in 2027. CLO-FAST is led by John Metcalfe, M.D., Ph.D., M.P.H., University of California San Francisco; Samuel Pierre, M.D., Les Centres Gheskio, Haiti; and Kimberly Scarsi, Pharm.D., M.S., University of Nebraska Medical Center and study drugs were supplied by the Global Drug Facility. PHOENIx is jointly conducted by ACTG and IMPAACT and led by Gavin Churchyard M.B.Ch.B., M.Med., Ph.D., The Aurum Institute NPC; Amita Gupta, M.D., M.H.S., Johns Hopkins University; Anneke Hesseling, M.B.Ch.B., M.Sc., Ph.D., Desmond Tutu TB Centre - Stellenbosch University; and Susan Swindells, M.B.B.S., University of Colorado. Delamanid is supplied for PHOENIx by Otsuka Pharmaceutical Company, Ltd. ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair). The studies are sponsored by the National Institute of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. IMPAACT is also funded by NIAID with support and co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH). About ACTGACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at hundreds of locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH. Media Contact:Jenna Conley, ACTGjenna@conleycommunications.net

NORTH CHICAGO, IL, USA I October 17, 2024 I AbbVie (NYSE: ABBV ) today announced that the U.S. Food and Drug Administration (FDA) has approved VYALEV™ (foscarbidopa and foslevodopa) as the first and only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced Parkinson’s disease (PD). “For too long, the Parkinson’s community has had limited treatment options for advanced disease. Due to the progressive nature of the disease, oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required,” said Robert A. Hauser, M.D., MBA, Professor of Neurology and Director of the Parkinson’s and Movement Disorder Center at the University of South Florida. “This new, non-surgical regimen provides continuous delivery of levodopa morning, day and night.” The approval was supported by the pivotal Phase 3, 12-week study evaluating the efficacy of continuous subcutaneous infusion of VYALEV in adult patients with advanced PD compared to oral immediate-release carbidopa/levodopa (CD/LD IR) 1 , along with a 52-week, open-label study which evaluated the long-term safety and efficacy of VYALEV. 2 Findings from the pivotal study showed patients receiving VYALEV demonstrated superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with oral CD/LD IR. 1 “On” time refers to the periods of time when patients are experiencing optimal motor symptom control while “off” time is when symptoms return. 3,4 The majority of adverse reactions (ARs) with VYALEV were non-serious and mild or moderate in severity. The most frequent ARs (greater than or equal to 10 percent and greater than CD/LD IR incidence) were infusion site events, hallucinations, and dyskinesia. 1,2 “People living with advanced Parkinson’s disease experience daily challenges as a result of uncertainty in managing motor fluctuations, especially as their disease progresses,” said Roopal Thakkar, M.D., executive vice president, research & development, and chief scientific officer, AbbVie. “We are proud to bring this innovation to patients who may benefit from motor symptom control through continuous 24-hour administration of VYALEV.” PD is a progressive and chronic movement disorder resulting in tremor, muscle rigidity, slowness of movement and difficulty with balance resulting from the loss of dopamine-producing brain cells. 5 Timing for a patient’s access to VYALEV is dependent on their individual insurance plan. Coverage for Medicare patients is expected in the second half of 2025. To learn more about this treatment, people should speak with their prescribing healthcare provider. About Parkinson’s Disease More than 10 million people worldwide are living with Parkinson’s disease (PD) 6 , a progressive and chronic neurological disorder characterized by tremor, muscle rigidity, slowness of movement, and difficulty with balance. 5 The motor symptoms of Parkinson’s disease begin when approximately 60-80 percent of the dopamine-producing cells in the brain are lost and symptoms continue to worsen slowly over the course of time. 7 While there is no known cure for the disease, there are treatments available to help reduce symptoms. 7 As PD progresses, patients experience complications, including motor and non-motor fluctuations and dyskinesia. Patients report switching from an “on” state (when symptoms are generally well controlled) to an “off” state, during which symptoms such as tremor and stiffness may reappear and patients have more difficulty moving. 4 Patients with advanced PD may also experience dyskinesia (involuntary movements) which can significantly hinder daily activities. 4 Neuronal degeneration and fluctuating plasma levodopa levels are responsible for the onset of these motor complications, with 50 percent of patients reporting them two to five years after diagnosis and approximately 80-100 percent of patients presenting with them after 10 years. 8 About the Phase 3 M15-736 Study 1 The Phase 3 randomized, double-blind, double-dummy, active-controlled study compared the efficacy, safety and tolerability of VYALEV to oral CD/LD IR in patients with advanced PD. Participants were provided with a home diary (the PD Diary) to assess their motor state during the day. The primary endpoint of good “on” time (defined as “on” time without dyskinesia plus “on” time with non-troublesome dyskinesia), was collected and averaged over three consecutive days and normalized to a typical 16-hour waking period. Baseline values are defined as the average of normalized good “on” time collected over the three PD Diary days before randomization. Approximately 130 adult participants with advanced PD were enrolled in the study across 80 sites in the U.S. and Australia. Participants were randomized 1:1 to receive either the VYALEV solution as a continuous delivery under the skin (subcutaneous) plus oral placebo capsules for CD/LD or oral capsules containing CD/LD IR plus continuous subcutaneous delivery of placebo solution for VYALEV. The treatment duration was 12 weeks. The increase in “on” time without troublesome dyskinesia at week 12 was 2.72 hours for VYALEV versus 0.97 hours for oral CD/LD IR (p=0.0083). Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks. More information on the study can be found on www.clinicaltrials.gov (NCT04380142) and in The Lancet Neurology ( https://doi.org/10.1016/S1474-4422(22)00400-8 ). About VYALEV™ VYALEV (foscarbidopa and foslevodopa) is a solution of carbidopa and levodopa prodrugs for 24-hour continuous subcutaneous infusion for the treatment of motor fluctuations in adults with advanced PD. VYALEV, also known as PRODUODOPA ® , has been approved in 35 countries and over 4,200 patients worldwide have started treatment. AbbVie continues to work with regulatory authorities around the world to bring VYALEV to people living with advanced Parkinson’s disease. IMPORTANT SAFETY INFORMATION What is the most important safety information I should know about VYALEV TM (foscarbidopa/foslevodopa)? Do not take VYALEV if you currently take or have recently taken (within the last 14 days) a medication for depression called a nonselective monoamine oxidase (MAO) inhibitor. Ask your healthcare provider or pharmacist if you are not sure if you take an MAO inhibitor. Tell your healthcare provider about all your medical conditions and the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. When used together, VYALEV and certain other medicines, including medications for high blood pressure, MAO inhibitors, antipsychotics, metoclopramide, and isoniazid, may affect each other and cause serious side effects. VYALEV may cause other serious side effects. Talk to your healthcare provider before starting VYALEV and while on VYALEV if you have had or have any of the following: Do not stop using VYALEV or change your dose unless you are told to do so by your healthcare provider. Tell your healthcare provider if you develop withdrawal symptoms, such as fever, confusion, or severe muscle stiffness. These are not all the possible side effects of VYALEV. For more information, ask your healthcare provider or pharmacist. VYALEV (foscarbidopa and foslevodopa) injection for subcutaneous use is available in a 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL) solution. Please see the full Prescribing Information , including Medication Guide , for additional information about VYALEV. Talk to your healthcare provider if you have questions. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/PatientAccessSupport to learn more. 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 www.abbvie.com . 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 www.abbvie.com . Follow @AbbVie on X (formally Twitter), Facebook , Instagram , YouTube, and LinkedIn References 1 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. Lancet Neurol. 2022 Dec;21(12):P1099-1109. 2 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. Neurol Ther. 2023 Dec;12(6):1937-1958. 3 “Motor fluctuations.” Parkinson’s Foundation. Available at: https://www.parkinson.org/library/fact-sheets/motor-fluctuations#:~:text=As%20levodopa%20begins%20to%20lose,are%20at%20their%20highest%20point . Accessed October 16, 2024. 4 “Off” Time in Parkinson’s Disease.” The Michael J. Fox Foundation for Parkinson’s Research . Available at: https://www.michaeljfox.org/time-parkinsons-disease . Accessed October 16, 2024. 5 “About Parkinson’s: Parkinson’s 101.” The Michael J. Fox Foundation for Parkinson’s Research . Available at: https://www.michaeljfox.org/understanding-parkinsons/i-have-got-what.php#q2 . Accessed October 16, 2024. 6 “Statistics.” Parkinson’s Foundation . Available at: https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=Nearly%2090%2C000%20people%20in%20the,worldwide%20are%20living%20with%20PD . Accessed October 16, 2024. 7 “Parkinson’s Disease: Hope Through Research.” National Institute of Neurological Disorders and Stroke . Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Parkinsons-Disease-Hope-Through-Research#:~:text=Loss%20of%20dopamine%20results%20in,by%20the%20time%20symptoms%20appear . Accessed October 16, 2024. 8 Freitas, ME., et al. Motor Complications of Dopaminergic Medications in Parkinson’s Disease. Semin Neurol. 2017;37(2):147-157. SOURCE: AbbVie