Fatigue

ST. GALLEN, SWITZERLAND, March 19, 2024 /PRNewswire/ -- CSL Vifor today announced that Health Canada has authorized Ferinject (ferric carboxymaltose) for the intravenous (IV) treatment of iron deficiency anemia in adult and pediatric patients one year of age and older when oral iron preparations are not tolerated or are ineffective, as well as for the treatment of iron deficiency in adult patients with heart failure and New York Heart Association (NYHA) class II/III* 1 to improve exercise capacity.2 Ferinject has now received marketing authorization in 87 countries worldwide. Research shows that rates of iron deficiency are even higher than previously reported in Canada, with the condition particularly prevalent in women of reproductive age3 and children4. "While iron deficiency and associated anemia are some of the most prevalent medical conditions on a global scale, it is easily diagnosed and treatable," said Prof. Dr. Justin Ezekowitz, Director of Cardiovascular Research and Cardiologist at the University of Alberta, Canada. "The news of a new treatment option tested in clinical trials is welcomed, given that oral irons may not be able to adequately deliver the desired outcomes for Canadian patients with heart failure impacted by iron deficiency." Iron deficiency affects one in every two hospitalized patients with heart failure5. Iron deficiency is often accompanied by reduced exercise tolerance and untreated iron deficiency may result in anemia and worsening NYHA class, with reduced quality of life and eventually increased risk of hospitalization 6,7,8 "The approval by Health Canada marks an important step forward for the treatment of iron deficiency anemia as well as iron deficiency in heart failure and supports our promise to patients and public health," said Dr. Vinicius Gomes de Lima, Head of Global Medical Affairs, CSL Vifor. "We are confident that our now approved IV iron therapy can make a meaningful contribution to achieve key therapeutic goals in the treatment of these patients." Marketing authorization in Canada is based on a comprehensive clinical data package and totality of evidence from CSL Vifor's cardiology studies. In Canada, Ferinject® is commercialized through CSL Behring Canada, Inc., with availability expected in the second half of 2024. * The New York Heart Association Functional Classification is used by Healthcare Professionals to classify patients' heart failure based on the severity of their symptoms. Patients who have a slight or marked limitation of their physical activity due to fatigue, palpitation and/or dyspnea are considered to have class II or class III heart failure, respectively.9 About CSL Vifor CSL Vifor is a global partner of choice for pharmaceuticals and innovative, leading therapies in iron deficiency and nephrology. We specialize in strategic global partnering, in-licensing and developing, manufacturing and marketing pharmaceutical products for precision healthcare, aiming to help patients around the world lead better, healthier lives. Headquartered in St. Gallen, Switzerland, CSL Vifor also includes the joint company Vifor Fresenius Medical Care Renal Pharma (with Fresenius Medical Care). The parent company, CSL (ASX: CSL; USOTC: CSLLY), headquartered in Melbourne, Australia, employs 32,000 people and delivers its lifesaving therapies to people in more than 100 countries. For more information about CSL Vifor, visit . About Ferinject Ferinject (ferric carboxymaltose) is an IV iron therapy with marketing authorization in 87 countries as of March 2024. Ferinject has historically delivered significant value to patients and healthcare systems which is based on extensive clinical data and more than 25 million patient years of exposure10. In Canada, Ferinject is indicated for the treatment of iron deficiency anemia in adult and pediatric patients one year of age and older when oral iron preparations are not tolerated or are ineffective, as well as for the treatment of iron deficiency in adult patients with heart failure and NYHA class II/III to improve exercise capacity. The diagnosis of iron deficiency must be based on laboratory tests.2 Important Information for Canada For more information and a complete risk/benefit profile, please refer to the Product Monograph available here. About iron deficiency and associated anemia Iron plays a vital role in many bodily processes, including the production of red blood cells, effective heart and brain function, and the prevention of infection and illness. Without enough iron, the body is unable to function properly. Common symptoms include fatigue, dizziness, and shortness of breath. Iron deficiency and iron deficiency anemia are estimated to affect one in three people worldwide11, yet despite the serious consequences and high prevalence12, the conditions remain under-recognized. The effects of iron deficiency differ from person to person but can be linked to an overall decline in general health and well-being13. Iron deficiency and iron deficiency anemia can be debilitating, exacerbate an underlying chronic disease and lead to increased morbidity and mortality13. Common symptoms include fatigue 13,14,15 pale skin14, brittle nails14, 16, craving non-food items such as dirt, clay and ice17, and an inability to concentrate13, 18. In children, iron deficiency anemia can significantly impair cognitive and motor development19,20,21. Multiple organizations, including the World Health Organization (WHO), UNICEF and the U.S. Agency for International Development (USAID) have called for a comprehensive anemia monitoring framework. Find more information on the global burden of anemia in the report published in the Lancet in July 2023: . References Fox AC, Gorlin R, Levin RI, New York Heart Association. Criteria Committee. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Lippincott Williams and Wilkins; March 1, 1994. Ferinject Product Monograph. CSL Vifor, St. Gallen, Switzerland. Chang V et al. J Nutr 2022 ; 153 : 781–797. doi.org/10.1016/j.tjnut.2022.10.011; Cochrane K et al. J Nutr 2022;152:2238–2244. Tahir E et al. 2020 Can J Public Health 111, 682–693 (2020). doi.org/10.17269/s41997-020-00304-7; Abdullah K et al Canadian Paediatric Surveillance program, 2011 . Del Pinto et al. Eur Heart J Suppl. 2022 Nov; 24(Suppl I): I96–I99). Ebner N, von Haehling S. Iron deficiency in heart failure: a practical guide. Nutrients. 2013;5(9):3730-9. doi:10.3390/nu5093730. Klip IT, Comin-Colet J, Voors A a, et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J. 2013;165(4):575-582.e3. doi:10.1016/j.ahj.2013.01.017. Guedes M NDT 2021. doi: 10.1093/ndt/gfab050; Enjuanes C, et al. Int J Cardiol. 2014;174(2):268–275. Classes of Heart Failure. American Heart Association. May 2017. Data on file. PSUR report. CSL Vifor, St. Gallen, Switzerland. Peyrin-Biroulet L, et al. Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review. Am J Clin Nutr. 2015;102(6):1585-94. World Health Organization. Worldwide prevalence of anaemia 1993-2005. 2008. Available at URL: E0C7?sequence=1. Last accessed: November 2023. Fernando B, et al. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol. 2009 Oct 7; 15(37): 4638-4643. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol. 2016;91(1):31-38. Favrat, B., et al. (2014). Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled study. PLoS One 9(4): e94217. eCollection 2014. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol. 2010;28(4):420-5. Barton JC, et al. Pica associated with iron deficiency or depletion: clinical and laboratory correlates in 262 non-pregnant adult outpatients. BMC Blood Disord. 2010;10:9. doi:10.1186/1471-2326-10-9. Patterson A et al. Iron deficiency, general health and fatigue: Results from the Australian Longitudinal Study on Women's Health. Qual Life Res. 2000;9:491-497. World Health Organization. Nutritional anaemias: tools for effective prevention and control. 2017. Available at URL: . Last accessed: November 2023. Sant-Rayn S, et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 2010; 193 (9): 525-532. doi: 10.5694/j.1326-5377.2010.tb04038.x. Özdemir N. Iron deficiency anemia from diagnosis to treatment in children. Turk Pediatri Ars. 2015 Mar 1;50(1):11-9. doi: 10.5152/tpa.2015.2337. PMID: 26078692; PMCID: PMC4462328. CSL Vifor Media Contact Thomas Hutter +41 79 957 96 73 [email protected] SOURCE Vifor International AG (CSL Vifor)

Zembrace® SymTouch® and Tosymra® will be marketed by Tonix Medicines, Tonix’s wholly-owned commercial subsidiary Commercial capabilities prepare Tonix for the potential launch in 2025 of Tonmya™ for the management of fibromyalgia, assuming FDA approval CHATHAM, N.J., March 19, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals, Inc. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that it will achieve its goal of transitioning to a fully integrated pharmaceutical company on April 1, 2024. Since the acquisition of Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg on June 30, 2023, Tonix Pharmaceuticals has been putting in place the personnel, systems and contracts required to support a commercial organization. Both products are indicated for the treatment of acute migraine with or without aura in adults. “Tonix will become a fully integrated biopharmaceutical company with a mission of developing and marketing innovative, high-value therapeutics,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Tonix will assume responsibility for the distribution, selling and marketing of Zembrace SymTouch and Tosymra, as well as supply chain, regulatory and quality control of the two products.” Dr. Lederman added, “The assumption of commercial activities by Tonix represents an important milestone in the evolution of Tonix as we continue to build and strengthen our commercial organization for the potential launch of Tonmya™ (cyclobenzaprine HCl sublingual tablets) for fibromyalgia in 2025, assuming approval by the U.S. Food and Drug Administration (FDA).” About Zembrace® SymTouch® and Tosymra® Zembrace SymTouch is the only actively promoted brand of sumatriptan autoinjector in the United States (other sumatriptan autoinjector products on the market are Imitrex® and generics to Imitrex®). It has a unique low dose and has demonstrated onset of migraine pain relief in as few as 10 minutes (17% of patients vs. 5% for placebo).1 Zembrace SymTouch also demonstrated migraine pain freedom for 46% of patients (vs 27% for placebo) at 2 hours in a single-attack, double-blind study (N=230).1 Zembrace SymTouch currently has patent protection to 2036. Tosymra employs Intravail® permeation enhancer technology and is pharmacokinetically equivalent to 4 mg subcutaneous sumatriptan.2 Tosymra delivers migraine pain relief in as little as 10 minutes with just one spray for some patients (13% vs. 5% for placebo).2 Tosymra currently has patent protection to 2031. About Migraine Nearly 40 million people in the United States suffer from migraine3 and it has been recognized as the second leading cause of disability in the world.4 Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity often associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).3 References: Zembrace SymTouch [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: February 2021. Tosymra [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: Feb 2021. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17(11):954-976. About Tonmya* (also known as TNX-102 SL) Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints. *Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication. Tonix Pharmaceuticals Holding Corp.* Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults. *Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners. This press release and further information about Tonix can be found at . Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Investor Contact Jessica Morris Tonix Pharmaceuticals investor.relations@tonixpharma.com (862) 904-8182 Peter Vozzo ICR Westwicke peter.vozzo@westwicke.com (443) 213-0505 Media Contact Ben Shannon ICR Westwicke ben.shannon@westwicke.com (919) 360-3039 Zembrace® SymTouch® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION Zembrace SymTouch (Zembrace) can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency help if you have any signs of a heart attack: discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded Zembrace is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam shows no problem. Do not use Zembrace if you have: history of heart problems narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease) uncontrolled high blood pressure hemiplegic or basilar migraines. If you are not sure if you have these, ask your provider. had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation severe liver problems taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, dihydroergotamine. are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure. an allergy to sumatriptan or any of the components of Zembrace Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements. Zembrace can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert. Zembrace may cause serious side effects including: changes in color or sensation in your fingers and toes sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever cramping and pain in your legs or hips; feeling of heaviness or tightness in your leg muscles; burning or aching pain in your feet or toes while resting; numbness, tingling, or weakness in your legs; cold feeling or color changes in one or both legs or feet increased blood pressure including a sudden severe increase even if you have no history of high blood pressure medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider. serotonin syndrome, a rare but serious problem that can happen in people using Zembrace, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking. hives (itchy bumps); swelling of your tongue, mouth, or throat seizures even in people who have never had seizures before The most common side effects of Zembrace include: pain and redness at injection site; tingling or numbness in your fingers or toes; dizziness; warm, hot, burning feeling to your face (flushing); discomfort or stiffness in your neck; feeling weak, drowsy, or tired. Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Zembrace. For more information, ask your provider. This is the most important information to know about Zembrace but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit or call 1-888-869-7633. You are encouraged to report adverse effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. INDICATION AND USAGE Zembrace is a prescription medicine used to treat acute migraine headaches with or without aura in adults who have been diagnosed with migraine. Zembrace is not used to prevent migraines. It is not known if it is safe and effective in children under 18 years of age. Tosymra® (sumatriptan nasal spray): IMPORTANTSAFETYINFORMATION Tosymra can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop Tosymra and get emergency medical help if you have any signs of heart attack: discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw, or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded Tosymra is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam is done and shows no problem. Do not use Tosymra if you have: history of heart problems narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease) uncontrolled high blood pressure severe liver problems hemiplegic or basilar migraines. If you are not sure if you have these, ask your healthcare provider. had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, or dihydroergotamine. Ask your provider if you are not sure if your medicine is listed above. are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure. an allergy to sumatriptan or any ingredient in Tosymra Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements. Tosymra can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert. Tosymra may cause serious side effects including: changes in color or sensation in your fingers and toes sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever cramping and pain in your legs or hips, feeling of heaviness or tightness in your leg muscles, burning or aching pain in your feet or toes while resting, numbness, tingling, or weakness in your legs, cold feeling or color changes in one or both legs or feet increased blood pressure including a sudden severe increase even if you have no history of high blood pressure medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider. serotonin syndrome, a rare but serious problem that can happen in people using Tosymra, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking. hives (itchy bumps); swelling of your tongue, mouth, or throat seizures even in people who have never had seizures before The most common side effects of Tosymra include: tingling, dizziness, feeling warm or hot, burning feeling, feeling of heaviness, feeling of pressure, flushing, feeling of tightness, numbness, application site (nasal) reactions, abnormal taste, and throat irritation. Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Tosymra. For more information, ask your provider. This is the most important information to know about Tosymra but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit or call 1-888-869-7633. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. INDICATION AND USAGE Tosymra is a prescription medicine used to treat acute migraine headaches with or without aura in adults. Tosymra is not used to treat other types of headaches such as hemiplegic or basilar migraines or cluster headaches. Tosymra is not used to prevent migraines. It is not known if Tosymra is safe and effective in children under 18 years of age.

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogenous neutrophilic inflammatory disease associated with skin and systemic symptoms, such as fever, pain, and fatigue1,2,3,4 In China, SPEVIGO®’s expanded approval adds the reduction of occurrences of GPP in pediatric patients aged 12 and above weighing ≥40 kg, and adults5 The US FDA’s approval expands the use of SPEVIGO® to include the treatment of GPP in adults and pediatric patients aged 12 and above weighing ≥40 kg, making it the first targeted therapy that addresses the need for acute and chronic treatment for GPP patients6 SPEVIGO® is currently approved in 48 countries7 Boehringer Ingelheim today announced that the US Food and Drug Administration (FDA) has approved SPEVIGO® (spesolimab-sbzo) injection for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients aged 12 and above weighing ≥40 kg.5 This approval follows the Chinese National Medical Products Administration’s (NMPA) recent approval of SPEVIGO® for the reduction of occurrence of generalized pustular psoriasis (GPP) in adolescents from 12 years of age with a body weight ≥40 kg and adults. SPEVIGO® is a novel, humanized selective IgG1 antibody that binds to interleukin-36 receptor (IL-36R), a key part of a signaling pathway within the immune system shown to be involved in the cause of GPP.8,9,10,11,12 The regulatory authorities’ decisions are majorly based on the positive results of the EFFISAYIL® 2 clinical trial, a 48-week clinical trial that showed that SPEVIGO® significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of SPEVIGO® subcutaneous treatment in the high-dose group (n=30).13,14,15,16 In the Effisayil® 2 trial, SPEVIGO® was associated with an increased incidence (≥9 cases per 100 patient-years) of injection site reaction, urinary tract infection, arthralgia, and pruritus compared to placebo. “Until now, people living with GPP have not had any approved options to treat their disease,” said Bruce Strober, MD, PhD, Clinical Professor, Dermatology, Yale University and Central Connecticut Dermatology. “SPEVIGO® has the potential to redefine the treatment options for the patients we serve.” Distinct from plaque psoriasis, GPP is a rare, chronic, heterogenous, inflammatory neutrophilic disease associated with painful skin manifestations and systemic symptoms, such as fever, pain, and fatigue.1-4 GPP varies widely between individuals living with the condition, with symptoms presenting on a continuum, which means that it can present in either a persistent or a relapsing course.2-4 GPP often requires emergency care and can lead to life-threatening complications, such as multi-organ failure and sepsis.17 GPP’s unpredictable nature can potentially have significant long-term impacts on quality of life for people living with it, and may cause fear and anxiety over the disease course.3,18 “SPEVIGO®’s new approvals constitute a fundamental change for people living with GPP, addressing their huge need for acute and chronic treatment,” said Carinne Brouillon, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “Experiencing GPP can be mentally and physically devastating, leaving those affected with uncertainty and fear of the next episode. Therefore, expanding the treatment of GPP is a critical step towards addressing patients’ needs.” About SPEVIGO® SPEVIGO® is a novel, humanized, selective antibody that specifically blocks the activation of the IL-36R, a signaling pathway within the immune system shown to be involved in the pathogenesis of several autoinflammatory diseases, including GPP.7-11 It is the first targeted therapy for the treatment of GPP and has been evaluated in the largest clinical program specifically for the treatment of patients with GPP.10,19 What is SPEVIGO®? SPEVIGO® is a prescription medicine used to treat generalized pustular psoriasis (GPP) in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg). It is not known if SPEVIGO® is safe and effective in children under 12 years of age or who weigh less than 88 pounds. Important Safety Information Do not receive SPEVIGO® if you or your child have had a severe or life-threatening allergic reaction to spesolimab-sbzo or any of the ingredients in SPEVIGO®. What is the most important information I should know about SPEVIGO®? SPEVIGO® may cause serious side effects, including: Infections. SPEVIGO® may lower the ability of your or your child’s immune system to fight infections and may increase your or your child’s risk of infections. Your healthcare provider should check you or your child for infections and tuberculosis (TB) before starting treatment with SPEVIGO® and may treat you or your child for TB before you begin treatment with SPEVIGO® if you have a history of TB or have active TB. Your healthcare provider should watch you or your child closely for signs and symptoms of TB during or after treatment with SPEVIGO®. Tell your healthcare provider right away if you or your child have an infection or have symptoms of an infection during or after treatment with SPEVIGO®, including: fevers, chills, or sweats muscle aches cough shortness of breath blood in your phlegm (mucus) burning when you urinate urinating more often than normal Allergic reactions and infusion-related reactions. Serious allergic reactions may happen during or after your or your child’s SPEVIGO® injection. If you or your child have a serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO®. If you or your child are given SPEVIGO® in a vein (intravenously) and have an infusion- related reaction, your healthcare provider will stop your or your child’s SPEVIGO® infusion and treat your or your child’s symptoms and may restart SPEVIGO® at a slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you or your child get any of the following symptoms during or after your or your child’s SPEVIGO® injection: feeling faint, dizzy, or lightheaded swelling of your face, eyelids, lips, mouth, tongue, or throat trouble breathing or throat tightness fever mouth sores chest tightness hives or skin rash that is different than the rash from generalized pustular psoriasis (GPP) itching swollen lymph nodes Before you or your child receive SPEVIGO®, tell your healthcare provider about all of your medical conditions, including if you or your child: have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You or your child should not receive live vaccines during and for at least 16 weeks after treatment with SPEVIGO®. You or your child should be brought up to date with all vaccines before starting SPEVIGO®. are pregnant or plan to become pregnant. It is not known if SPEVIGO® can harm your or your child’s unborn baby. are breastfeeding or plan to breastfeed. It is not known if SPEVIGO® passes into your breast milk. Talk to your healthcare provider about the best way to feed your or your child’s baby during treatment with SPEVIGO®. Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of SPEVIGO®? The most common side effects of SPEVIGO® given in a vein (intravenously) for GPP flare treatment include: feeling tired or weak nausea and vomiting headache itching or itchy bumps a collection of blood under the skin at the infusion site or bruising urinary tract infection The most common side effects of SPEVIGO® when given under the skin (subcutaneously) for treatment of GPP when not experiencing a flare include: redness, pain, swelling, hardening, hives, or warmth at the injection site joint pain urinary tract infection itching These are not all of the possible side effects of SPEVIGO®. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1‐800‐FDA‐1088. Please see full Prescribing Information, Medication Guide, and Instructions for Use. CL-SPG-100004 03.18.2024 About the EFFISAYIL® clinical trial program The EFFISAYIL® clinical trial program evaluated the largest and broadest population of GPP patients in trials of a therapy specifically targeting the IL-36 pathway for GPP:10,18 EFFISAYIL® 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of GPP in patients experiencing a flare, including rapid pustular and skin clearance. These results supported the approval of spesolimab as the first specific treatment for GPP flares in adults in major markets10,20 EFFISAYIL® 2: A Phase IIb study that showed spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab SC treatment in the high-dose group (n=30)12–15 EFFISAYIL® ON: An open-label extension study to evaluate the long-term safety and efficacy of spesolimab in patients with GPP who have completed previous spesolimab trials21 About generalized pustular psoriasis (GPP) GPP is a chronic, heterogenous, neutrophilic inflammatory disease associated with skin and systemic symptoms that is distinct from plaque psoriasis. GPP is recognized as a separate clinical entity from other forms of psoriasis, with the IL-36 pathway being a key driver of GPP and triggering response to treatment.1 Prevalence of GPP is low and varies considerably across geographical regions, ranging from 1.76 to 124 patients per million persons in reports from key countries, including France, Japan, Sweden, and South Korea.2 GPP can become life-threatening (mortality rates ranging from 2% to 16%) due to severe complications, such as multisystem organ failure and sepsis requiring urgent hospital care; many GPP patients also suffer from various comorbidities, which contribute to the ongoing burden for the patient and healthcare systems.2,16,17 GPP symptoms appear unpredictable and present on a continuum, which greatly impacts a patient’s quality of life, and may cause fear and anxiety over the disease course, as well as long-term impacts on quality of life related to work/school, emotional health, social activities, and finances.2,3,4 About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units, Human Pharma and Animal Health. Learn more at . March 2024 MPR-CRP-100327, MPR-US-102903 References: 1Marrakchi S, Puig L. Pathophysiology of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:13–19. 2Prinz JC, Choon SE, Griffiths CEM, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. J Eur Acad Dermatol Venereol. 2023;37:256–273. 3Reisner DV, Johnsson FD, Kotowsky N, et al. Impact of generalized pustular psoriasis from the perspective of people living with the condition: Results of an online survey. Am J Clin Dermatol. 2022;23:65–71. 4Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15:907–919. 5National Medical Products Administration. Drug approval document release, March 11 2024. 2024年03月11日药品批准证明文件送达信息发布 (nmpa.gov.cn) (Accessed 14 March 2024) 6Record on file. 7Record on file. 8Bassoy EY, Towne JE, Gabay C. Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281:169–178. 9Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–628. 10Ganesan R, Raymond EL, Mennerich D, et al. Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies. MAbs. 2017;9:1143–1154. 11Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385:2431–2440. 12Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N Engl J Med. 2019;380:981–983. 13Boehringer Ingelheim. Spesolimab prevented generalized pustular psoriasis flares in Effisayil™ 2 trial. 2023. . (Accessed 14 March 2024). 14Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. Lancet. 2023;402:1541–1551. 15Gordon KB, Lebwohl M, Barker J, et al. Effect of spesolimab on achieving sustained disease remission in patients with generalized pustular psoriasis: Results from the Effisayil 2 study. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract P0731. 16Strober B, Augustin M, Tada Y, et al. Effect of high-dose subcutaneous spesolimab on skin manifestations: Results from the pivotal Effisayil 2 trial of flare prevention in generalized pustular psoriasis. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract 1732. 17Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:21–29. 18Burden D, Mrowietz U, Skalicky AM, et al. Symptom experience and content validity of the Psoriasis Symptom Scale (PSS) in patients with generalized pustular psoriasis (GPP). Dermatol Ther (Heidelb). 2022;12:1367–1381. 19Choon SE, Lebwohl MG, Marrakchi S, et al. Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare. BMJ Open. 2021;11:e043666. 20Navarini A, Prinz JC, Morita A, et al. Spesolimab improves patient- reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study. J Eur Acad Dermatol Venereol. 2022; 37:730–736. 21Effisayil™ ON: A study to test long-term treatment with spesolimab in people with generalized pustular psoriasis who took part in a previous study. . (Accessed 14 March 2024).