Diamorphine Hydrochloride

As the first-ever U.S. Food and Drug Administration (FDA) approved over-the-counter (OTC) naloxone in 2023, Emergent is working to expand access with NARCAN® Nasal Spray and build on its longstanding efforts with public interest entities across the country Hundreds of thousands of NARCAN® Nasal Spray cartons are available in over 32,000 retail locations in the U.S., and Emergent is working to increase reach into workplaces, businesses and other locationsApproximately 22 million doses of NARCAN® Nasal Spray were distributed in the U.S. and Canada in 2023, and Emergent is committed to meeting any increase in demand driven by the evolving and worsening epidemicThe recently announced ‘White House Challenge to Save Lives from Overdose’ is a nationwide call-to-action that includes increasing access to life-saving opioid overdose reversal medications, a program with direct alignment to Emergent’s strategy and efforts since the launch of NARCAN® Nasal Spray in 2016Naloxone, the active ingredient in NARCAN® Nasal Spray, is a life-saving medication that can reverse an overdose from opioids, including heroin, fentanyl, and prescription opioid medications, when given in time GAITHERSBURG, Md., March 28, 2024 (GLOBE NEWSWIRE) -- Emergent BioSolutions Inc. (NYSE: EBS) remains committed to fighting the ongoing opioid crisis by broadening access to, and awareness of, NARCAN® Nasal Spray to help save lives in opioid overdose emergencies. In 2022, the U.S. Centers for Disease Control and Prevention (CDC) reported over 107,000 overdose deaths – a number that has risen almost every year and which has continued to break annual records.1 This includes a rise in synthetic opioid overdoses mainly driven by fentanyl.1 There is an inherent risk of potential overdose, wherever opioids are present, which has tragically become the leading cause of accidental death in the U.S.2 These statistics only further underscore the need for multi-sectoral action to address and prevent opioid overdose deaths. One year after Emergent obtained the historic OTC U.S. FDA approval in March 2023 and seven months since retail launch in August 2023, the availability of NARCAN® Nasal Spray in pharmacies, grocery stores and online retailers has helped more people gain access to this life-saving product. Emergent and other stakeholders in the fight must continue raising awareness about the availability of products like NARCAN® Nasal Spray, reducing stigma and further improving access for all Americans. Since the OTC launch, NARCAN® Nasal Spray can be purchased at more than 32,000 mass drug, grocery, online retailers and e-commerce sites. Emergent is working with retail partners to make it easy to find and access, however each retailer ultimately determines in-store product placement. In 2023, Emergent distributed approximately 22 million doses (~11 million two-dose cartons) in the U.S. and Canada through public interest organizations like state and harm reduction groups and retail locations. Emergent also announced a shelf-life extension from 36 to 48 months for NARCAN® Nasal Spray in the U.S., further demonstrating its commitment to ensuring more medicine is available for the public to access. “We’re living in a time when one person dies approximately every six minutes from an accidental opioid overdose – prevention and response efforts require an all-hands on deck approach toward lessening this devastating public health crisis,” said Joseph Papa, president and CEO of Emergent. “In my first month leading Emergent, and alongside our dedicated colleagues, we continue to advance our mission to protect the public from threats such as the opioid epidemic and am proud of our efforts to help save lives.” Emergent is now engaging with partners who are aligned with its mission to expand access, awareness and availability, such as the National Safety Council (NSC*), working together to educate and reach businesses and employers. Specifically, Emergent sees brick and mortar stores, airlines, restaurants, hotels and schools as critical locations where NARCAN® Nasal Spray should be made available in case of an emergency, alongside AED kits. “We know that NARCAN® Nasal Spray alone can’t solve the opioid crisis – and that opioid overdose reversal medication can only be useful if present and administered when a person is experiencing an overdose. When bystanders are unable to provide life-saving measures such as naloxone in nearly half of fatal overdoses, our role to help expand the reach of this medication has never been more important,” said Paul Williams, senior vice president, products business, Emergent. “That’s why we remain committed to increasing awareness of NARCAN® Nasal Spray availability. We also applaud the Biden Administration for their recently announced plan to address the opioid crisis, and Emergent remains prepared to support efforts to our fullest capacity and help save more lives.” Emergent is also maintaining affordability of NARCAN® Nasal Spray and is ready to meet public need as necessary and arm individuals with an essential tool to combat against opioid overdose. As announced at the OTC retail launch last year, the Manufacturer’s Suggested Retail Price of NARCAN® Nasal Spray is $44.99 per two-dose carton, which is equivalent to roughly $22.50 per dose. While Emergent works with partners to help maintain access and affordability, the price of the product is set by individual retailers. Emergent set the public interest price at $41.00 per two-dose carton, building on its long-standing engagement with public interest groups to ensure naloxone is readily available to at-risk communities. In addition, Emergent continues to prioritize efforts to reduce the barriers to access, including addressing stigma, encouraging businesses and school districts to carry naloxone, supporting policy to ensure Health Spending Account (HSA) and Flexible Saving Account (FSA) eligibility for naloxone and working with state Medicaid agencies to provide coverage. NARCAN® Nasal Spray is an appropriate choice for a known or suspected opioid overdose as immediate administration, however it is not a substitute for emergency assistance. To learn more about this life-saving medicine and access resources, education and advocacy tools, visit NARCAN.com. *As a contracted commercial partner of Emergent, NSC will receive a fee for service. About NARCAN® Nasal Spray NARCAN® Naloxone HCl Nasal Spray 4 mg is the first FDA-approved, over-the-counter (OTC) 4 mg naloxone product for the emergency treatment of opioid overdose. NARCAN® Nasal Spray is not a substitute for emergency medical care. Repeat dosing may be necessary. Use as directed. About Emergent BioSolutions At Emergent, our mission is to protect and enhance life. For 25 years, we’ve been at work defending people from things we hope will never happen—so we are prepared just in case they ever do. We provide solutions for complex and urgent public health threats through a portfolio of vaccines and therapeutics that we develop and manufacture for governments and consumers. We also offer a range of integrated contract development and manufacturing services for pharmaceutical and biotechnology customers. To learn more about how we plan to protect or enhance 1 billion lives by 2030, visit our website and follow us on LinkedIn, X, Instagram, Apple Podcasts and Spotify. Safe Harbor Statement This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, are forward-looking statements. We generally identify forward-looking statements by using words like “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “forecast,” “future,” “goal,” “intend,” “may,” “plan,” “position,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” and similar expressions or variations thereof, or the negative thereof, but these terms are not the exclusive means of identifying such statements. Forward-looking statements are based on our current intentions, beliefs and expectations regarding future events based on information that is currently available. We cannot guarantee that any forward-looking statements will be accurate. Readers should realize that if underlying assumptions prove inaccurate or if known or unknown risks or uncertainties materialize, actual results could differ materially from our expectations. Readers are, therefore, cautioned not to place undue reliance on any forward-looking statements. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, we do not undertake any obligation to update any forward-looking statement to reflect new information, events or circumstances. There are a number of important factors that could cause the company’s actual results to differ materially from those indicated by any forward-looking statements. Readers should consider this cautionary statement, as well as the risk factors and other disclosures included in our periodic reports filed with the U.S. Securities and Exchange Commission, when evaluating our forward-looking statements. Investor Contact:Richard S. LindahlExecutive Vice President, CFOlindahlr@ebsi.com Media Contact:Assal HellmerVice President, Communicationsmediarelations@ebsi.com 1 Centers for Disease Control and Prevention. (March 21, 2024). Drug Overdose Deaths in the United States, 2002–2022. https://www.cdc.gov/nchs/products/databriefs/db491.htm 2 Centers for Disease Control and Prevention. (February 14, 2022). Understanding Drug Overdoses and Deaths. https://www.cdc.gov/drugoverdose/epidemic/index.html

This head-to-head pharmacodynamic study in healthy volunteers examined the ability of both OPVEE and intranasal naloxone to reverse opioid-induced respiratory depression, which is the shallow and slow breathing associated with an opioid overdose In this model, OPVEE 2.7mg reversed respiratory depression to 95% of pre-opioid baseline within 5 minutes; a similar reversal following a 4 mg dose of intranasal naloxone required 20 minutes RICHMOND, Va., March 11, 2024 /PRNewswire/ -- Indivior PLC (LSE/Nasdaq: INDV) today announced results from a pharmacodynamic study demonstrating that OPVEE® rapidly reverses opioid-induced respiratory depression, which is the major cause of deaths due to opioid overdose. The study, "Reversal of opioid-induced respiratory depression in healthy volunteers: comparison of intranasal nalmefene and intranasal naloxone", was published in the Journal of Clinical Pharmacology (Reversal of Opioid‐Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone - Ellison - The Journal of Clinical Pharmacology - Wiley Online Library) and is the first head-to-head comparison examining the effects of 2.7 mg intranasal (IN) nalmefene (OPVEE) and 4 mg IN naloxone on opioid-induced respiratory depression. This study was a part of the OPVEE development program and reviewed by the FDA as part of the approval process. This study met the primary endpoint by demonstrating that OPVEE reversed the respiratory depression produced by remifentanil, a potent synthetic opioid related to fentanyl, within the first 5 minutes following administration. Both OPVEE and IN naloxone produced a time-dependent reversal of the opioid-induced respiratory depression 2.5 to 20 minutes post administration. Point estimates favored OPVEE, demonstrating non-inferiority and superiority to naloxone. After OPVEE administration, subjects' minute ventilation (a measure of the amount of air that enters the lungs per minute) reached approximately 95% of the pre-opioid baseline within 5 minutes and maintained this robust reversal through the initial 20-minute monitoring period. By contrast, naloxone required 20 minutes to restore respiration to levels equaling those observed 5 minutes after OPVEE. There is an urgent need for rapid acting reversal agents because synthetic opioids, like fentanyl, impair breathing and reduce oxygen levels to vital organs like the brain more rapidly than other opioids such as morphine and heroin. "This study provides the first head-to-head comparison of IN OPVEE and IN naloxone in a clinical model of opioid-induced respiratory depression. While both reverse the effects of remifentanil induced respiratory depression, this pharmacodynamic study provides important insights about the time course of reversal for both drugs," said Christian Heidbreder, Ph.D. and Chief Scientific Officer of Indivior. "The first few minutes following an overdose – particularly with very potent and fast acting synthetic opioids like fentanyl – are critical for a successful rescue. OPVEE reverses the respiratory depression rapidly in this model, making it a valuable tool for combating the synthetic opioid overdose crisis we're facing as a nation." Following administration of OPVEE, subjects' minute ventilation (MV), a measure of how much a person is breathing, increased by an average of 5.75 L/min at 5 minutes, the study's primary endpoint. Intranasal naloxone produced a mean increase of 3.01 L/min at 5 minutes post-administration, and 20 minutes was required to produce an increase in MV similar to that observed 5 minutes after OPVEE. Adverse events (AEs) occurred in 91.8% of subjects following OPVEE and 86.7% of subjects following IN naloxone. The authors conclude that the AEs observed in this study are most likely related to remifentanil and hypercapnic experimental conditions used and not the drugs under investigation. The most common adverse events were headache (59.0% following OPVEE and 58.3% following intranasal naloxone), nausea (39.3% and 41.7%), vomiting (11.5% and 23.3%), and dizziness (18.0% and 21.7%). Adverse events were mild or moderate, with no subjects reporting a serious adverse event. In the United States, the provisional number of reported opioid overdose deaths reached 80,318 in the 12 months ending in September 2023.1 The reported overdose deaths linked to synthetic opioids, such as fentanyl, during the same period was 73,686, representing more than 90% of all opioid overdose fatalities. About the Study This study was an open-label, head-to-head, randomized, 2-period, 2-treatment crossover noninferiority study designed to model the pharmacodynamic effects of intranasal OPVEE® (nalmefene) and intranasal naloxone. A total of 69 opioid-experienced, non -dependent healthy male and female volunteers were randomized to receive study drugs. Subjects breathed a hypercapnic gas mixture containing 7% carbon dioxide and their minute ventilation (MV) was monitored. Minute ventilation is a measure of how deeply and rapidly a patient is breathing and is reduced by opioid exposure.2 Previous work has demonstrated that opioids blunt the increase in MV that normally occurs with hypercapnia (excessive carbon dioxide in the bloodstream) and that opioid antagonists can reverse this effect.3-7 After 10 minutes of breathing the hypercapnic gas mixture, subjects were administered a loading dose of remifentanil followed by a continuous infusion of remifentanil to maintain steady state plasma concentrations. After 25 minutes, the subjects were administered a single dose of either intranasal OPVEE 2.7 mg or intranasal naloxone 4 mg and MV was monitored. The primary objectives were to demonstrate noninferiority at the primary endpoint of 5 minutes after antagonist exposure of IN nalmefene to reverse remifentanil-induced reductions in MV and to determine the tolerability of IN nalmefene during remifentanil infusion. Of the 69 subjects who received a single dose of either IN nalmefene or IN naloxone, a total of 52 subjects received both treatments and data was collected at the primary endpoint in 50 subjects. About OPVEE ® OPVEE (nalmefene) nasal spray INDICATION OPVEE nasal spray is an opioid antagonist indicated for the emergency treatment of known or suspected overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression. OPVEE nasal spray is intended for immediate administration as emergency therapy in settings where opioids may be present. OPVEE nasal spray is not a substitute for emergency medical care. HIGHLIGHTED SAFETY INFORMATION CONTRAINDICATIONS Hypersensitivity to nalmefene or to any of the other ingredients. WARNINGS AND PRECAUTIONS Risk of Recurrent Respiratory and Central Nervous System Depression: While the duration of action of nalmefene is as long as most opioids, a recurrence of respiratory depression is possible, therefore, keep patient under continued surveillance and administer repeat doses of OPVEE using a new nasal spray with each dose, as necessary, while awaiting emergency medical assistance. Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists: Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses may be required. Precipitation of Severe Opioid Withdrawal: Use in patients who are opioid dependent may precipitate opioid withdrawal. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated. Monitor for the development of opioid withdrawal. Risk of Cardiovascular (CV) Effects: Abrupt postoperative reversal of opioid depression may result in adverse CV effects. These events have primarily occurred in patients who had preexisting CV disorders or received other drugs that may have similar adverse CV effects. Monitor these patients closely in an appropriate healthcare setting after use of nalmefene hydrochloride. Risk of Opioid Overdose from Attempts to Overcome the Blockade: Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may lead to opioid intoxication and death. ADVERSE REACTIONS Most common adverse reactions (incidence at least 2%) are nasal discomfort, headache, nausea, dizziness, hot flush, vomiting, anxiety, fatigue, nasal congestion, throat irritation, rhinalgia, decreased appetite, dysgeusia, erythema, and hyperhidrosis. For more information about OPVEE and the full Prescribing Information visit . About Indivior Indivior is a global pharmaceutical company working to help change patients' lives by developing medicines to treat substance use disorders (SUD) and serious mental illnesses. Our vision is that all patients around the world will have access to evidence-based treatment for the chronic conditions and co-occurring disorders of SUD. Indivior is dedicated to transforming SUD from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of opioid use disorder treatments, Indivior has a pipeline of product candidates designed to both expand on its heritage in this category and potentially address other chronic conditions and co-occurring disorders of SUD, including alcohol use disorder and cannabis use disorder. Headquartered in the United States in Richmond, VA, Indivior employs more than 1,100 individuals globally and its portfolio of products is available in 37 countries worldwide. Visit to learn more. Connect with Indivior on LinkedIn by visiting . References Ahmad FB, Cisewski JA, Rossen LM, Sutton P. Provisional drug overdose death counts. National Center for Health Statistics. July 2023. Accessed February 8, 2024, from Palkovic B, Marchenko V, Stuth EA, Stucke AG. Multi-level regulation of opioid-induced respiratory depression. Physiology. 2020; 35(6):391-404. Rawat, D., Modi, P., & Sharma, S. (2023). Hypercapnea. In StatPearls. StatPearls Publishing. Accessed February 15, 2024, from Gelberg J, Jonmarker C, Stenqvist O, Werner O. Intravenous boluses of fentanyl, 1 μg kg-1, and remifentanil, 0.5 μg kg-1, give maximum ventilatory depression in awake volunteers. Brit. J. Anaes. 2012; 108(6):1028-34. Webster L, Hansen E, Stoddard G, Rynders A, Ostler D, Lennon H. Ventilatory response to hypercapnia as experimental model to study effects of oxycodone on respiratory depression. Curr. Rev. Clin. Exper. Pharmacol. 2021; 16:1-9. Glass PS, Iselin-Chaves IA, Goodman D, Delong E, Hermann DJ. Determination of the potency of remifentanil compared with alfentail using ventilatory depression as the measure of opioid effect. Anesthesiol. 1999; 90(6):1556-1563. Dahan A, Aarts L, Smith T. Incidence, reversal and prevention of opioid-induced respiratory depression. Anesthes. 2010; 112(1):226-238. Glass, P, Jhaveri, R, Smith, L. Comparison of potency and duration of action of nalmefene and naloxone. Anesth. Analg., 1994; 78(3):536-541. Konieczko K, Jones J, Barrowcliffe M, Jordan C, Altman, D. Antagonism of morphine-induced respiratory depression with nalmefene. Br. J. Anaesth. 1988; 61(3):318-323. SOURCE Indivior PLC