Overactive bladder syndrome

STAMFORD, CT, USA I August 05, 2024 I Imbrium Therapeutics L.P. (“Imbrium”), a subsidiary of Purdue Pharma L.P. (“Purdue”), has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) to evaluate sunobinop for the potential treatment of moderate to severe alcohol use disorder (AUD)*. Sunobinop is an investigational, novel and potential first-in-class oral compound discovered by our scientists that is currently in clinical development. Sunobinop is designed to bind to and activate the nociceptin/orphanin-FQ peptide receptor (NOP), a protein that is widely expressed in the central and peripheral nervous system 1 and involved in a range of biological functions. 2 “Over the past several years, the data collected to date in our sunobinop development program has supported this potent, partial and selective agonist 3 as a potential treatment approach for AUD and other serious conditions,” said Dr. Julie Ducharme, Vice President, Chief Scientific Officer. “As part of our ongoing commitment to improve public health as an R&D driven pharmaceutical company, we look forward to learning more about sunobinop and the role of NOP receptors in AUD,” said Craig Landau, MD, President and CEO, Purdue. Sunobinop Development Program Imbrium is evaluating sunobinop as a potential treatment option for AUD, as well as for overactive bladder syndrome (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). This IND submission is informed from data that suggest NOP agonists, like sunobinop, have potential for the treatment of AUD. 4,5 Preclinical studies have shown activation of NOP in AUD models reduces the reinforcing and motivating effects of ethanol (alcohol). 6,7 In humans, NOP activity has been associated with relapse risk in patients with AUD. 8 The National Institute of Drug Abuse has identified NOP receptor agonists in the ten most wanted pharmacological mechanisms for rapid development of therapeutics to treat substance use disorder. 9 Sunobinop studies have suggested improvements in various sleep measurements. Building on these data, Imbrium intends to conduct a two-part, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the impact of sunobinop given at bedtime on alcohol consumption, as well as alcohol craving. In this Phase 2 study, a total of 240 subjects with moderate to severe AUD who are seeking treatment will be recruited. *This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that sunobinop will successfully complete development or gain FDA approval. About Imbrium Therapeutics L.P. Imbrium is a clinical-stage biopharmaceutical company dedicated to advancing medical science through the development of important new therapeutics. We are pursuing treatments for genitourinary disorders, disorders of the central nervous system, oncology chemotherapeutics, and non-opioid approaches to the management of pain. As a subsidiary of Purdue Pharma L.P., Imbrium strives to develop new medicines that serve the unmet needs of patients, physicians, and health systems worldwide. We have built a robust and diversified pipeline of investigational drug candidates, and we seek to actively collaborate with industry and academic partners to identify and advance future impactful medicines. For more information, please visit www.imbriumthera.com . References: 1. Zaveri N. The nociceptin opioid receptor (NOP) as a therapeutic target: Progress in translation from preclinical research to clinical utility. J Med Chem . 2016;59(15):7011-7028. 2. Lambert D. The nociceptin/orphanin FQ receptor: a target with broad therapeutic potential. Nat Rev Drug Discov . 2008;7:694–710. 3. Whiteside G, Kyle D, Kapil R, et al. The nociceptin/orphanin FQ receptor partial agonist sunobinop promotes non-REM sleep in rodents and patients with insomnia. J Clin Invest . 2024; 134(1):e171172 4. Kuzmin A, Sandin J, Terenius L, Ogren SO. Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of opioid receptor-like 1 receptor agonists and naloxone. J Pharmacol Exp Ther. 2003;304(1):310-8. 5. Kuzmin A, Kreek MJ, Bakalkin G, Liljequist S. The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reducesalcohol self-administration and prevents relapse-like alcohol drinking. Neuropsychopharmacology 2007;32(4):902-10. 6. Ciccocioppo R, Panocka I, Polidori C, Regoli D, Massi M. Effect of nociceptin on alcohol intake in alcohol-preferring rats. Psychopharmacology . 1999;141(2):220-4. 7. Kuzmin A, Sandin J, Terenius L, Ogren SO. Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of opioid receptor-like 1 receptor agonists and naloxone. J Pharmacol Exp Ther . 2003;304(1):310-8. 8. Tollefson S, Stoughton C, Himes ML, et al. Imaging nociceptin opioid peptide receptors in alcohol use disorder with [11C]NOP-1A and positron emission tomography: Findings from a second cohort. Biol Psychiatry . 2023;94(5):416-423. 9. Rasmussen K, White DA, and Aci JB. NIDA’s medication development priorities in response to the Opioid Crisis: ten most wanted. Neuropsychopharmacology 2019; 44(4):657-659. SOURCE: Imbrium Therapeutics

The asset is indicated for the treatment of overactive bladder syndrome symptoms in adult patients. Credit: New Africa / Shutterstock. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved Pierre Fabre’s vibegron (Obgemsa) to treat overactive bladder (OAB) syndrome symptoms in adults. Symptoms include urgency, high urinary frequency and incontinence. A beta 3 adrenergic receptor agonist, vibegron functions as a bladder muscle relaxant to ease the bladder muscle activity. The recommended daily dose is a 75mg film-coated tablet. The approval is backed by data from the Phase III EMPOWUR clinical trial, which assessed it for 12 weeks in 1,515 OAB patients. See Also: Conflict means millions of children are missing vaccinations, UN says Moderna and Mitsubishi Tanabe link on mRNA vaccines in Japan Participants received a daily dose of either placebo, vibegron 75mg or an active control. Vibegron significantly reduced daily urination and incontinence episodes versus placebo, with improvements observed within two weeks and sustained over the treatment period. Patients on vibegron reported side effects such as headaches, diarrhoea, constipation, nausea, urinary tract infections and increased post-void residual urine volume. The MHRA assures ongoing monitoring of vibegron’s safety and efficacy and encourages reporting of any side effects through the Yellow Card scheme. The MHRA has also approved AstraZeneca ’s capivasertib (Truqap) for advanced HR-positive, HER2-negative breast cancer with specific genetic abnormalities unresponsive to other treatments. Capivasertib, an AKT inhibitor, impedes cancer cell proliferation and is administered orally alongside fulvestrant, a hormonal therapy. The approval was supported by a clinical trial involving 708 patients, with a subset of 289 patients exhibiting the targeted genetic mutations. In clinical studies, capivasertib-treated individuals had an average of 7.3 months during which their cancer did not progress, compared to 3.1 months for placebo-treated patients. High blood sugar, diarrhoea, rash and other skin drug responses, urinary tract infection, low blood haemoglobin levels, appetite loss, nausea, vomiting, mouth sores or ulcers with gum inflammation, itching and fatigue are possible side effects of the medication.

STAMFORD, Conn.--(BUSINESS WIRE)-- Imbrium Therapeutics L.P. (“Imbrium”), a subsidiary of Purdue Pharma L.P. (“Purdue”), achieved last patient last visit in its Phase 1b study of the investigational drug sunobinop as a potential treatment for overactive bladder syndrome (OAB)*. Sunobinop is an investigational, novel and potential first-in-class oral compound discovered by Imbrium Therapeutics and that is currently in clinical development. Sunobinop is designed to bind to and activate the nociceptin/orphanin-FQ peptide receptor (NOP), a protein that is widely expressed in the central and peripheral nervous system1 and involved in a range of biological functions, including bladder function.2,3 Fifty-one female patients suffering from OAB were enrolled in this multicenter, randomized, double-blind, placebo-controlled crossover study. The study was designed to test the effects of sunobinop at bedtime on key disease symptoms, such as urinary urgency, frequency, incontinence, and nocturia in subjects with OAB compared to placebo. OAB is a life-long urologic disorder that reduces patients’ quality of life. The condition affects 14% of men and women in the U.S.4 "Millions of patients with overactive bladder are in need of additional treatment options for the disruptive, distressing symptoms. This study will help us learn more about sunobinop’s potential to be a new treatment option,” said Dr. Julie Ducharme, Vice President and Chief Scientific Officer. “We look forward to reviewing and analyzing the results later this year.” “We are pleased to achieve last patient last visit in the sunobinop Phase 1b study,” said Craig Landau, MD, President and CEO of Purdue. “Our continued progress in this work demonstrates our ongoing commitment to innovation through research and development.” In addition to OAB, Imbrium is also evaluating sunobinop as a potential treatment for interstitial cystitis/bladder pain syndrome (IC/BPS) and separately for alcohol use disorder. *This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that sunobinop will successfully complete development or gain FDA approval. About Imbrium Therapeutics L.P. Imbrium is a clinical-stage biopharmaceutical company dedicated to advancing medical science through the development of important new therapeutics. We are pursuing treatments for genitourinary disorders, disorders of the central nervous system, oncology chemotherapeutics, and non-opioid approaches to the management of pain. As a subsidiary of Purdue Pharma L.P., Imbrium strives to develop new medicines that serve the unmet needs of patients, physicians, and health systems worldwide. We have built a robust and diversified pipeline of investigational drug candidates, and we seek to actively collaborate with industry and academic partners to identify and advance future impactful medicines. For more information, please visit . References 1. Zaveri, N. The nociceptin opioid receptor (NOP) as a therapeutic target: Progress in translation from preclinical research to clinical utility. J Med Chem. 2016; 59(15): 7011-7028. 2. Lambert, D. The nociception/orphanin FQ receptor: a target with broad therapeutic potential. Nat. Rev. 2008 Aug;7(8):694-710. 3. Lazzeri, M., Calò, G., Spinelli, M., et al. Daily intravesical instillation of 1 mg nociceptin/orphanin FQ for the control of neurogenic detrusor overactivity: a multicenter, placebo controlled, randomized exploratory study. J Urol. 2006 Nov;176(5):2098-102. 4. Reynolds, W., Fowke, J., & Dmochowski, R. The burden of overactive bladder on US public health. Current Bladder Dysfunct Rep. 2016 Mar;11(1):8-13. MR-08567