Chronic Pain

Results from 68-week study of 407 adults with obesity and moderate knee osteoarthritis showed semaglutide 2.4 mg significantly reduced body weight, knee osteoarthritis-related pain, and improved physical function1 Obesity is a major risk factor of knee osteoarthritis development and disease progression2-4 Semaglutide is not approved in the U.S. for the treatment of knee osteoarthritis PLAINSBORO, N.J., Oct. 30, 2024 /PRNewswire/ -- Today, The New England Journal of Medicine published results from Novo Nordisk's STEP 9 phase 3 clinical trial that studied semaglutide 2.4 mg compared to placebo as an adjunct to lifestyle modifications in reducing body weight and knee osteoarthritis-related pain in adults with obesity, and a clinical and radiologic diagnosis of moderate knee osteoarthritis, and pain that is at least moderately severe.1 According to the published trial, semaglutide met the study's primary endpoints and was superior to placebo in significantly reducing body weight and knee osteoarthritis-related pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. In addition, the trial met a key confirmatory secondary endpoint of improving patients' physical function.1 In patients with a mean baseline body weight of 239.5 pounds, semaglutide led to a –13.7% mean change from baseline in body weight at week 68 versus –3.2% with placebo ([95% confidence interval (CI) –12.3, –8.6]; P<0.001). Semaglutide also led to a mean change from baseline (70.9) in the WOMAC pain score of –41.7 at week 68 versus –27.5 with placebo ([95% CI –20.0, –8.3]; P<0.001). WOMAC is a 24-item patient-reported questionnaire that assesses clinically important symptoms of pain, stiffness, and physical function in patients with hip and/or knee osteoarthritis (OA).1,5 A greater improvement in physical functioning scores was also observed from baseline at week 68 among trial participants taking semaglutide versus placebo (mean change: 12.0 versus 6.5 points [95% CI 3.1, 8.0], P<0.001]) as measured by the 36-Item Short Form Survey (SF-36v2).1 Obesity is considered a major risk factor for the development and progression of knee osteoarthritis, a common type of osteoarthritis that can lead to chronic pain and reduced mobility.2-4 Obesity contributes to the development of knee osteoarthritis through increased mechanical stress on weight-bearing joints, metabolic factors, and obesity-related inflammation.2,3 "Obesity-related knee osteoarthritis is a progressive condition that can lead to pain and stiffness of the knee and impair critical daily functions such as walking or moving around. The risk of developing the condition is more than four times higher in people with obesity. Weight reduction along with physical activity is often a recommended approach to managing painful symptoms, but adherence can be challenging," said lead study author Henning Bliddal, MD, M.Sci., The Parker Institute, Copenhagen University Hospital, Denmark. "There is a significant need for non-surgical and sustainable treatment options for those living with obesity-related osteoarthritis. The STEP 9 trial aimed to provide rigorous evidence as to how semaglutide may help these people." The study implemented a targeted approach to safety data collection, with investigators recording only serious adverse events (SAEs), adverse events (AEs) leading to treatment discontinuation, AEs requiring invasive knee procedures, medication error, acute pancreatitis, COVID-19, and pregnancy or pregnancy-related AEs.1 AEs leading to treatment discontinuation occurred in 6.7% of patients in the semaglutide group and 3.0% of patients in the placebo group. The most common AEs leading to treatment discontinuation were gastrointestinal disorders (2.2% of patients in the semaglutide group and 0% of patients in the placebo group) and neoplasms (benign, malignant, and unspecified) (semaglutide, 1.9%; placebo, 1.5%). The incidence of SAEs was similar in both groups (semaglutide, 10.0%; placebo, 8.1%).1 STEP 9 was a randomized, double-blind, placebo-controlled multicenter trial of 407 adults aged ≥18 years with obesity (BMI ≥30 kg/m2) and a clinical diagnosis of knee osteoarthritis per American College of Rheumatology criteria with moderate radiographic changes (Kellgren–Lawrence grade 2 or 3) in the target knee. Participants also had pain due to knee osteoarthritis, with a WOMAC pain score ≥40 out of 100 at randomization.1 "Obesity is a complex metabolic disease associated with multiple co-morbid conditions, including knee osteoarthritis," said Anna Windle, PhD, Senior Vice President, Clinical Development, Medical and Regulatory Affairs, Novo Nordisk. "The STEP 9 results are encouraging and provide important information about the effect of semaglutide, a glucagon-like peptide-1 receptor agonist, on knee osteoarthritis outcomes in people with obesity. We look forward to working with regulatory authorities on next steps based on these findings." About obesity Obesity is a serious chronic, progressive, and misunderstood disease that requires long-term management.6-8 One key misunderstanding is that this is a disease of just lack of willpower, when in fact there is underlying biology that may impede people with obesity from losing weight and keeping it off.6,7 Obesity is influenced by a variety of factors, including genetics, social determinants of health, and the environment.9 The prevalence of overweight and obesity is a public health issue that has severe cost implications to healthcare systems.10,11 In the U.S., about 40% of adults live with obesity.12 About the STEP 9 trial (semaglutide 2.4 mg) STEP 9 was a randomized, double-blind, placebo-controlled multicenter trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to lifestyle modifications (counseling on a reduced-calorie diet and physical activity) in reducing body weight and knee osteoarthritis-related pain in patients with obesity and a clinical and radiologic diagnosis of moderate knee osteoarthritis, and pain that is at least moderately severe.1 Participants were randomized 2:1 to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, followed by 7 weeks' off-treatment follow-up. There was a 16-week dose escalation to allow for adjustment to therapy (gastrointestinal adverse reactions). The study randomized participants between October 2021 and March 2022.1 All endpoints were measured from baseline to week 68. The primary endpoints were the percentage change in body weight and change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.1 The trial enrolled 407 adults and was conducted in 11 countries at 61 investigator sites.1 Semaglutide is not approved for the treatment of knee osteoarthritis. Safety and efficacy are not established, and there is no guarantee that semaglutide will become commercially available for this use under clinical investigation. About Novo Nordisk Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With U.S. headquarters in New Jersey and commercial, production, and research facilities in seven states plus Washington DC, Novo Nordisk employs approximately 8,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, X, LinkedIn, and YouTube. References Bliddal H, Bays H, Czernichow S, et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med. 2024; 391:1573-83. Centers for Disease Control and Prevention. Arthritis risk factors. Last accessed: September 2024. Available at . World Health Organization. Osteoarthritis. Last accessed: October 2024. Available at: . Nedunchezhiyan U, Varughese I, Sun AR, et al. Obesity, inflammation, and immune system in osteoarthritis. Front Immunol. 2022;13:907750. doi:10.3389/fimmu.2022.907750. ClinicalTrials.gov. Research study looking at how well semaglutide works in people suffering from obesity and knee osteoarthritis. Last accessed: October 2024. Available at: . Kaplan LM, Golden A, Jinnett K, et al. Perceptions of barriers to effective obesity care: results from the national action study. Obesity. 2018;26(1):61-69. Bray GA, Kim KK, Wilding JPH; World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-723. Garvey WT, Mechanick JI, Brett EM, et al. American association of clinical endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 (Suppl 3):1-203. Centers for Disease Control and Prevention. Causes of obesity. Last accessed: October 2024. Available at: . World Obesity Federation. World Obesity Atlas 2023. Last accessed: October 2024. Available at: . Centers for Disease Control and Prevention. Why it matters. Last accessed: October 2024. Available at: . Centers for Disease Control and Prevention. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021–August 2023. Last accessed October 2024. Available at: . © 2024 Novo Nordisk All rights reserved. US24SEMO01198 October 2024 SOURCE NOVO NORDISK INC. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Analysis Marks the First Study of Spinal Cord Stimulation to Demonstrate Long-term, Significant, and Clinically Meaningful Reductions in HbA1c and Weight in Study Participants with Painful Diabetic Neuropathy and Type 2 Diabetes REDWOOD CITY, Calif., Oct. 29, 2024 /PRNewswire/ -- Nevro Corp. (NYSE: NVRO), a global medical device company that is delivering comprehensive, life-changing solutions for the treatment of chronic pain, today announced the publication of new data in the Journal of Pain Research demonstrating significant, durable pain relief and long-term and clinically meaningful reductions in hemoglobin A1c (HbA1c) and weight in study participants with painful diabetic neuropathy (PDN) and Type 2 diabetes who received 10 kHz high-frequency spinal cord stimulation (SCS) therapy.1 Globally, the number of people with diabetes has quadrupled in the last two decades2, and PDN impacts up to 25% of all people with diabetes.3 PDN can have significant impacts on the quality of life for people living with this condition, with symptoms like numbness, tingling/paresthesia, loss of protective sensation, impaired balance, and reduced response to sensory stimuli.4 Patients typically manage PDN with oral pain medications, but the efficacy of these medications is relatively low and can result in intolerable side effects.5 As a result, people with PDN suffer from significantly reduced health-related quality of life (HRQoL), impaired functionality and other comorbidities like sleep disorders, depression, and anxiety.6 The analysis evaluated 144 patients with Type 2 diabetes and refractory PDN who received 10 kHz SCS therapy during the SENZA-PDN randomized controlled trial (RCT), the largest RCT to evaluate SCS to treat PDN. Changes in pain intensity, HbA1c, weight, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c. At 24 months, the following benefits were noted1: Significant, durable pain relief: Study participants had a mean pain reduction of 79.8% and the mean visual analog scale (VAS) score for lower limb pain decreased from 7.5 ± 0.1 cm at preimplantation to 1.5 ± 0.2 cm (p < 0.001). Clinically meaningful, statistically significant mean reductions in HbA1c: Participants with preimplantation HbA1c >7% and >8% achieved mean reductions of 0.5% (p = 0.031) and 1.1% (p = 0.004), respectively. Significant mean weight loss: Across all study participants, patients achieved a significant mean weight loss of 3.1 kg (p = 0.003). In participant subgroups with body mass indices (BMI) of ≥ 30 and ≥ 35 kg/m2, mean weight reductions were 4.1 kg (p = 0.001) and 5.4 kg (p = 0.005), respectively. Significant, durable reductions in pain interference with sleep: Study participants experienced a highly significant improvement in sleep quality, with pain and sleep questionnaire three-item (PSQ-3) scores decreasing by a mean of 65.2%, corresponding to a mean value of 1.9 ± 0.2 cm (p < 0.001). "People with PDN know that this condition can extend well beyond pain – impacting sleep, sensory functions, and overall quality of life," said Dr. David Klonoff, Medical Director, Diabetes Research Institute at Mills-Peninsula Medical Center. "This is the first study of SCS to demonstrate long-term, significant and clinically meaningful reductions in HbA1c and weight in people with PDN and Type 2 diabetes – suggesting possible metabolic benefits with 10 kHz SCS for these patients." "The SENZA-PDN RCT has already demonstrated the significant pain relief benefit when using Nevro's HFX device for the millions of people suffering from PDN around the world," said Dr. David Caraway, Nevro's Chief Medical Officer. "Now, for the first time, we've observed secondary benefits like improved HbA1c and weight loss, which exhibit potentially disease-modifying effects for people with Type 2 diabetes. I'm grateful for the dedication of the clinical investigators who supported this latest analysis and the broader SENZA-PDN RCT as we continue gathering data to support market access for more patients." The 24-month data from the SENZA-PDN RCT were originally published in Diabetes Research and Clinical Practice in 2023. These data showed that patients who received a high-frequency 10 kHz SCS implant and conventional medical management (CMM), compared to CMM alone, experienced durable pain relief and improvements in HRQoL, neurological function, and sleep at 24 months post-implantation. To learn more about Nevro's 10 kHz Therapy™ for PDN, visit . References Nevro's high-frequency, 10 kHz spinal cord stimulation (SCS) device has not been approved or evaluated by the U.S. Food and Drug Administration (FDA) for the treatment of HbA1c and/or weight loss. World Health Organization. (‎2016)‎. Global report on diabetes. World Health Organization. Shillo P, et al. Painful and Painless Diabetic Neuropathies: What Is the Difference? Curr Diab Rep. 2019 May 7;19(6):32. doi: 10.1007/s11892-019-1150-5. PMID: 31065863; PMCID: PMC6505492. Pop-Busui R, Ang L, Boulton AJM, Feldman EL, Marcus RL, Mizokami-Stout K, et al. Diagnosis and Treatment of Painful Diabetic Peripheral Neuropathy. Arlington (VA): American Diabetes Association; 2022. Yang, M., Qian, C., & Liu, Y. (2015). Suboptimal Treatment of Diabetic Peripheral Neuropathic Pain in the United States. Pain medicine (Malden, Mass.), 16(11), 2075–2083. Alleman, C. J., Westerhout, K. Y., Hensen, M., Chambers, C., Stoker, M., Long, S., & van Nooten, F. E. (2015). Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature. Diabetes research and clinical practice, 109(2), 215–225. Internet Posting of Information Nevro routinely posts information that may be important to investors in the "Investors" section of its website at . The company encourages investors and potential investors to consult the Nevro website regularly for important information about Nevro. About Nevro Headquartered in Redwood City, California, Nevro is a global medical device company focused on delivering comprehensive, life-changing solutions that continue to set the standard for enduring patient outcomes in chronic pain treatment. The company started with a simple mission to help more patients suffering from debilitating pain and developed its proprietary 10 kHz Therapy™, an evidence-based, non-pharmacologic innovation that has impacted the lives of more than 115,000 patients globally. Nevro's comprehensive HFX™ spinal cord stimulation (SCS) platform includes the Senza® SCS system and support services for the treatment of chronic pain of the trunk and limb and painful diabetic neuropathy. Nevro recently added a minimally invasive treatment option for patients suffering from chronic sacroiliac joint ("SI joint") pain and now provides the most comprehensive portfolio of products in the SI joint fusion space, designed to meet the preferences of physicians and varying patient needs in order to improve outcomes and quality of life for patients. Senza®, Senza II®, Senza Omnia™, and HFX iQ are the only SCS systems that deliver Nevro's proprietary 10 kHz Therapy. Nevro's unique support services provide every patient with an HFX Coach™ throughout their pain relief journey and every physician with Nevrocloud™ insights for enhanced patient and practice management. SENZA, SENZA II, SENZA OMNIA, OMNIA, HF10, the HF10 logo, 10 kHz Therapy, HFX, the HFX logo, HFX iQ, the HFX iQ logo, HFX Algorithm, HFX CONNECT, the HFX Connect logo, HFX ACCESS, the HFX Access logo, HFX COACH, the HFX Coach logo, Nevrocloud, RELIEF MULTIPLIED, HFX AdaptivAI, the X logo, NEVRO, and the NEVRO logo are trademarks or registered trademarks of Nevro Corp. Patents covering Senza HFX iQ and other Nevro products are listed at Nevro.com/patents. Bluetooth® and the Bluetooth symbol are registered trademarks of their respective owners. To learn more about Nevro, connect with us on LinkedIn, X, Facebook, and Instagram. Investors and Media: Angie McCabe Vice President, Investor Relations & Corporate Communications [email protected] SOURCE Nevro Corp. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

FREEHOLD, N.J., Oct. 29, 2024 (GLOBE NEWSWIRE) -- Chromocell Therapeutics Corporation (“Chromocell”, or the “Company”), (NYSE American: CHRO), a pioneer in the development of non-opioid pain treatment therapeutics, today announced the unveiling of its injectable depot program utilizing peripheral nerve blocks for the treatment of post-operative pain. The depot program is based on the Company’s novel NaV1.7 molecule for treating chronic pain and eye pain. There are approximately 700,000 total knee replacements and 500,000 shoulder arthroplasties performed annually in the Unites States for which this analgesic modality might be applicable, providing a robust potential market for the product. “We are leveraging our existing know-how and intellectual property to target different pain indications and methods of delivery in an efficient and synergistic manner. We are taking advantage of the extensive pre-clinical and Phase I studies performed with CC8464 demonstrating strong efficacy in a wide variety of preclinical models and no dose limiting tolerability concerns in four Phase I trials,” said Frank Knuettel, Chief Executive Officer. Eric Lang, Chief Medical Officer further commented, “Of the various sodium channel targets, NaV1.7 is the most genetically validated for the treatment of pain. The over expression of NaV1.7 activity leads to Erythromelalgia, one of the most severe types of pain described in humans, whereas over expression of NaV1.8 leads to mild-moderate pain. We anticipate that our injectable depot program utilizing peripheral nerve blocks for the treatment of post-operative pain could be an excellent and potent analgesic.” The Company believes there are strong synergies between the programs and is building a suite of related products to address multiple different types of pain and methods of delivery, with a drug that has shown no addictive properties in 4 Phase I trials. With these programs, the Company hopes to reduce usage of opioids and other sub-optimal drugs in various indications and expects to be able to take advantage of certain NOPAIN Act provisions if the drugs are approved by the FDA. About Chromocell Chromocell Therapeutics Corporation is a clinical-stage biotechnology company focused on developing and commercializing novel, non-opioid, non-addictive therapeutics to alleviate pain. The Company’s initial clinical focus is to selectively target the sodium ion-channel known as NaV1.7 for the treatment of various types of chronic neuropathic pain and acute and chronic eye pain. For company updates and to learn more about Chromocell, visit www.chromocell.com or follow us on social media. Forward-Looking Statements This press release contains forward-looking statements regarding the Company’s current expectations. These forward-looking statements include, without limitation, references to the Company’s expectations regarding (i) the amount of shares of Common Stock to be repurchased under the Repurchase Plan, if any, (ii) the Company’s belief that its Common Stock is undervalued, (iii) the Company’s belief that its Common Stock is an attractive investment at its current price, (iv) the Company’s ability to conduct repurchases in accordance with applicable laws and regulations, (v) our ability to enhance stockholder value and (vi) the impact of laws and regulations. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ materially from those set forth in such forward-looking statements include, but are not limited to, risks and uncertainties related to there being no guarantee that the trading price of the Company’s Common Stock will be indicative of the Company’s value or that the Company’s Common Stock will become an attractive investment in the future. These and other risks and uncertainties are described more fully in in our filings with the U.S. Securities and Exchange Commission. The information in this press release is provided only as of the date of this press release, and we undertake no obligation to update any forward-looking statements contained in this press release based on new information, future events, or otherwise, except as required by law. For Investor Inquiries:Mike MoyerManaging Director, LifeSci Advisors, LLCmmoyer@lifesciadvisors.com