Paraplegia

5-Year Data from the AMDS DARTS Trial Demonstrates Positive Aortic Remodeling with 94% of Patients Free from Unanticipated Reoperation 30-Day Data from the AMDS PERSEVERE Trial Shows Cerebral Malperfusion Resolution in 90% of Affected Subjects Post-AMDS Implantation 1-Year Data from the NEOS Study Indicate E-vita Open Neo is Safe and Effective in the Treatment of Aortic Arch Pathologies with Low Combined Major Adverse Events Rate ATLANTA, Oct. 10, 2024 /PRNewswire/ -- Artivion, Inc. (NYSE: AORT), a leading cardiac and vascular surgery company focused on aortic disease, today announced data from its AMDS DARTS and PERSEVERE trials and E-vita Open Neo study presented in Late-Breaking Science presentations at the 38th European Association for Cardio-Thoracic Surgery (EACTS) Annual Meeting in Lisbon, Portugal. The presentation regarding the AMDS DARTS trial highlighted 5-year aortic remodeling data that demonstrate positive, durable patient outcomes following AMDS implantation. The presentation on the 30-day AMDS PERSEVERE trial data showed cerebral malperfusion resolution for 90% of affected subjects at 30-days post-AMDS implantation. Additionally, the presentation on the 1-year data from the NEOS study showed E-vita Open Neo is safe and effective for the treatment of acute and chronic aortic arch pathologies with a lower combined major adverse event rate compared to the market leading alternative. "We were thrilled to command such a strong presence at EACTS, with data from our AMDS and E-vita Open Neo clinical trials dominating the aortic focused late-breaking science session," said Pat Mackin, Chairman, President, and Chief Executive Officer of Artivion. "Artivion remains committed to driving continued innovation in treating aortic disease, and these data further validate our best-in-class portfolio." Late-Breaking 5-Year Data from AMDS DARTS Trial: The abstract titled 5-Year Results on Aortic Remodeling in the Dissected Aorta Repair Through Stent (DARTS) Implantation Trial reports five years of clinical follow-up on the remaining 25 of 46 study participants with acute DeBakey Type I dissection who were treated with a proximal aortic repair and AMDS. The results demonstrate durable benefits out to at least 5 years over the baseline: 94% of patients were free from aortic reoperation compared to existing literature on hemiarch-only outcomes which report freedom from late aortic arch reoperation as low as 76%, 95% of patients were free from total aortic diameter (TAD) growth >5 mm between the 3-year and 5-year follow up periods at aortic zones 2 and 4; and In contrast, existing literature on hemiarch-only outcomes suggest a majority of patients have early TAD growth in the proximal descending aorta. Aortic growth can lead to increased risk of rupture or dissection, and reoperation. Principal investigator Dr. Michael Moon, Division of Cardiac Surgery, University of Alberta, Edmonton, Canada said, "Significant dilation of the ascending aorta, measured by changes to the TAD, increases the risk of spontaneous rupture or dissection of the aorta, a serious medical emergency. These long-term results from the DARTS study demonstrate a large majority of patients experience a stable or decreased TAD following treatment with AMDS, meaning these patients were successfully treated with AMDS and are at decreased risk for further aortic dissection and reoperation as far out as 5-years post implantation." Late-Breaking 30-Day Data from AMDS PERSEVERE Trial: The abstract titled AMDS Hybrid Prosthesis Improves Cerebral Malperfusion in Acute DeBakey Type I Dissection- Early Results of the PERSEVERE Study focuses on cerebral blood flow across the full 93 study participant IDE cohort at 30-days following AMDS implantation. 20% of patients (19 of 93 patients) presented with symptomatic pre-operative cerebral malperfusion including stroke, transient ischemic attack, delirium or other mental status changes. The 30-day data showed resolution of cerebral malperfusion in the vast majority of patients treated with AMDS. More specifically: 90% of patients experienced resolution of their cerebral malperfusion; and 63% of those who presented with cerebral malperfusion had complete resolution, while another 26% had no worsening of stroke symptoms The data compare favorably to hemiarch alone based on data from five articles in the literature, which showed a stroke occurrence rate of 20.9% compared to 10.8% (10 of 93 patients) in the PERSEVERE trial. Senior author, Dr. William Brinkman, Baylor Scott & White, The Heart Hospital Plano, Plano, Texas said, "Cerebral malperfusion, which often leads to stroke, is a devasting complication of Acute DeBakey Type I aortic dissection. The data from the PERSEVERE trial indicating that AMDS markedly reduces 30-day malperfusion and new disabling stroke compared to the baseline, is very encouraging." Late-Breaking 1-Year Data from E-vita Open Neo NEOS Study: The abstract titled E-vita Open Neo in the treatment of acute or chronic aortic pathologies: 1-year results of the European multicenter NEOS study and sub-group analysis includes 161 participants treated with E-vita Open Neo in Europe. The 1-year data suggests E-vita Open Neo is safe and effective in the treatment of aortic arch pathologies and compares favorably to the IDE study results of the current market leading device: The 1-year mortality rate observed for E-vita Open Neo (9.9%) compared favorably to current market leading device (10.8%); and Lower 1 year combined major adverse events rate of mortality, stroke, and paraplegia/ paraparesis occurring after treatment with E-vita Open Neo (17% vs 23.1% for current market leading device). Professor Martin Grabenwöger, Head, Department of Cardiovascular Surgery, Hietzing Hospital, Vienna, Austria said, "These exciting results from the NEOS study demonstrate the clinical benefits of E-vita Open Neo compare favorably to currently available options for treatment of aortic arch pathologies. This study is a major step forward in improving care for patients suffering from this life-threatening disease." About the AMDS DARTS Trial The AMDS DARTS (Dissected Aorta Repair Through Stent Implantation) trial is a prospective, multicenter, nonrandomized, single-arm trial of 47 patients evaluating the safety and efficacy of the AMDS Hybrid Prosthesis for the treatment of Acute DeBakey Type I (ADTI) dissection. Trial results supported regulatory approvals for AMDS in Canada, Europe, and other countries around the world. About the AMDS PERSEVERE Trial The AMDS PERSEVERE trial is a prospective, multicenter, non-randomized clinical trial to determine if patients with ADTI dissection can be treated safely and effectively using the AMDS Hybrid Prosthesis. The trial is designed to support the company's forthcoming application to the U.S. Food and Drug Administration (FDA) for premarket approval of the AMDS. The trial consists of 93 participants in the U.S., who have experienced an ADTI dissection. Each participant will be followed for up to 5 years. The combined 30-day safety and primary efficacy endpoints were used to determine the impact of the AMDS Hybrid Prosthesis on DANE prevention, reducing mortality, new disabling stroke, new onset renal failure requiring dialysis, and myocardial infarction, as well as remodeling of the aorta. Full 30-day IDE data from the PERSEVERE trial presented at the Society of Thoracic Surgeons in January 2024, demonstrated statistically significant reduction in all-cause mortality and primary major adverse events (MAEs) at 30 days with use of AMDS in ADTI dissections complicated by malperfusion. Data from the trial also demonstrated a 72% reduction in all-cause mortality and 54% reduction in primary major MAEs when compared to the current standard of care hemiarch procedure. Data presented from the PERSEVERE trial at the 104th American Association for Thoracic Surgery (AATS) Annual Meeting April 2024, showed positive aortic remodeling at 30-days after treatment with AMDS, as well as no occurrence of distal anastomotic new entry (DANE) tears. More specifically, at 30 days, the majority of patients demonstrated favorable remodeling with over 80% showing either stable or decreased total aortic diameter (TAD). About the E-vita Open Neo NEOS Study The E-vita Open Neo NEOS study is an observational, multicenter study to determine the safety and clinical performance of E-vita Open Neo Stent Graft System in the treatment of acute and chronic aneurysm and dissection in the ascending aorta, aortic arch and descending thoracic aorta. The observational study consists of 161 patients with acute or subacute type A aortic dissection, chronic type A aortic dissection or thoracic aortic aneurysm enrolled at 12 centers in Europe and Asia December 2020 to March 2022. The primary end point was the rate of all-cause mortality at 30 days. The secondary end points included further clinical and safety data that are reported up to 3–6 months postoperatively. About Artivion, Inc. Headquartered in suburban Atlanta, Georgia, Artivion, Inc. is a medical device company focused on developing simple, elegant solutions that address cardiac and vascular surgeons' most difficult challenges in treating patients with aortic diseases. Artivion's four major groups of products include: aortic stent grafts, surgical sealants, On-X mechanical heart valves, and implantable cardiac and vascular human tissues. Artivion markets and sells products in more than 100 countries worldwide. For additional information about Artivion, visit our website, . Contacts: SOURCE Artivion, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

The Phase 3 study results are being published in PAIN® Journal, which is the leading journal devoted to pain medicine and research. PAIN is the official journal of the International Association for the Study of Pain, and features original research on the nature, mechanisms and treatment of pain.This Phase 3 study met primary and important key secondary endpoints, with SP-102 (SEMDEXA™) treatment, decreasing pain intensity for over a month in sciatica patients and resulting in statistically significant and clinically meaningful improvement in the disability index score while maintaining safety comparable to placebo.This Phase 3 topline data result was presented at the American Society of Interventional Pain (ASIPP) conference in Las Vegas in May 2022 in an oral presentation by Dr. Nebojsa Nick Knezevic, M.D., Ph.D., Professor of Anesthesiology and Surgery, College of Medicine, University of Illinois at Chicago, President of the Illinois Society of Interventional Pain Physicians, Director-at-Large of the North American Society of Neuromodulation, Vice-Chair for Research and Education, Advocate Illinois Masonic Medical Center, Department of Anesthesiology and Pain Management.This Phase 3 study represents a potential significant improvement in treatment of adult patients with lumbosacral radicular pain (sciatica), who struggle with the clinical consequences of no currently FDA approved therapies, suboptimal formulations of corticosteroids used off-label and/or excess pain and disability.SP-102 (SEMDEXA™) was granted Fast Track status from the FDA in 2017. PALO ALTO, Calif., June 14, 2024 (GLOBE NEWSWIRE) -- Scilex Holding Company (Nasdaq: SCLX, “Scilex” or the “Company”), an innovative revenue-generating company focused on acquiring, developing and commercializing non-opioid pain management products for the treatment of acute and chronic pain, today announced the publication of results of the pivotal registration trial of SP-102 (SEMDEXA™) in PAIN, the official journal of the International Association for the Study of Pain, which features original research on the nature, mechanisms and treatment of pain. SP-102 (SEMDEXA™) is a novel injectable corticosteroid gel formulation product in development for the treatment of lumbosacral radicular pain, which contains no preservatives, surfactants, solvents, or particulates. The C.L.E.A.R. Trial (Corticosteroid Lumbosacral Epidural Analgesia for Radiculopathy) was designed to investigate safety and analgesic effects of a single and repeat transforaminal injections of SP-102 (SEMDEXA™) compared to placebo (saline injection). The trial enrolled 401 low back pain subjects with unilateral intervertebral lumbar disc herniation, resulting in radicular pain symptoms of moderate to severe leg pain. It is the largest known randomized well-controlled trial in sciatica using epidural steroid injections. The trial met its primary and important key secondary endpoints with statistical significance, demonstrating clinically meaningful reduction of pain, improvement in disability and functional outcomes. Safety analysis demonstrated a clean safety profile with no identified safety risks. There were no serious adverse events related to the drug or injection procedure, and no adverse events of special interest reported, such as hematoma and infection at the injection site, or paraplegia. By contrast, these events are associated with the off-label use of non-approved steroid preparations. The C.L.E.A.R trial also established safety of repeat injections, as patients who experienced moderate-to-severe radicular pain between 4 and 23 weeks following initial injection were allowed to receive an open-label additional SP-102 (SEMDEXA™) injection. The safety analysis was comparable between treatment groups through 4, 12 and 24 weeks of the study period. “I am very glad to be involved in the C.L.E.A.R. trial, having first-hand experience with SP-102 (SEMDEXA™), pain management medication with extended local effect. Currently, we have to use steroid formulations developed for other uses, which are unapproved for epidural administration. If SP-102 (SEMDEXA™) is approved by the FDA, it would be the first corticosteroid ever approved for epidural injections, addressing safety issues with current formulations. This could be an important addition to treatment options for patients with lumbosacral radicular pain,” said Alan Miller, M.D., Principal Investigator from Coastal Clinical Research Specialists, Jacksonville, Florida, primary author of the publication. A copy of the publication can be downloaded here. For more information on Scilex Holding Company, refer to www.scilexholding.com For more information on ZTlido® including Full Prescribing Information, refer to www.ztlido.com. For more information on ELYXYB®, including Full Prescribing Information, refer to www.elyxyb.com. For more information on Gloperba®, including Full Prescribing Information, refer to www.gloperba.com. https://www.facebook.com/scilex.pharm https://www.linkedin.com/company/scilex-holding-company/ info@scilexholding.com About Scilex Holding Company Scilex Holding Company is an innovative revenue-generating company focused on acquiring, developing and commercializing non-opioid pain management products for the treatment of acute and chronic pain. Scilex targets indications with high unmet needs and large market opportunities with non-opioid therapies for the treatment of patients with acute and chronic pain and are dedicated to advancing and improving patient outcomes. Scilex’s commercial products include: (i) ZTlido® (lidocaine topical system) 1.8%, a prescription lidocaine topical product approved by the U.S. Food and Drug Administration (the “FDA”) for the relief of neuropathic pain associated with postherpetic neuralgia, which is a form of post-shingles nerve pain; (ii) ELYXYB®, a potential first-line treatment and the only FDA-approved, ready-to-use oral solution for the acute treatment of migraine, with or without aura, in adults; and (iii) Gloperba®, the first and only liquid oral version of the anti-gout medicine colchicine indicated for the prophylaxis of painful gout flares in adults and will be launched on June 10, 2024. In addition, Scilex has three product candidates: (i) SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (“SEMDEXA™” or “SP-102”), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, for which Scilex has completed a Phase 3 study and has granted Fast Track status from the FDA in 2017; (ii) SP-103 (lidocaine topical system) 5.4%, (“SP-103”), a next-generation, triple-strength formulation of ZTlido, for the treatment of chronic neck pain and for which Scilex has recently completed a Phase 2 trial in low back pain. SP-103 has granted Fast Track status from the FDA in low back pain; and (iii) SP-104 (4.5 mg, low-dose naltrexone hydrochloride delayed-release capsules) (“SP-104”), a novel low-dose delayed-release naltrexone hydrochloride being developed for the treatment of fibromyalgia, for which Phase 1 trials were completed in the second quarter of 2022. Scilex Holding Company is headquartered in Palo Alto, California. Forward-Looking Statements This press release and any statements made for and during any presentation or meeting concerning the matters discussed in this press release contain forward-looking statements related to Scilex and its subsidiaries under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding Scilex’s expectation that SP-102’s Phase 3 study represents a potential paradigm shift in treatment for adult patients with lumbar radicular pain (sciatica) over many years, statements regarding SP-102 (SEMDEXA™), if approved by the FDA, including that SP-102 (SEMDEXA™) would be the first FDA-approved corticosteroid for epidural injections addressing safety issues with steroid medications that have been used off-label in the past few decades, Scilex’s expectation that SP-102 (SEMDEXA™) would be an important addition to treatment options for patients with lumbosacral radicular pain, Scilex’s development and commercialization plans, and the expected launch of Gloperba®. Risks and uncertainties that could cause Scilex’s actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks associated with the unpredictability of trading markets and whether a market will be established for Scilex’s common stock; general economic, political and business conditions; risks related to COVID-19 (and other similar disruptions); the risk that the potential product candidates that Scilex develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Scilex’s product candidates; the risk that Scilex will be unable to successfully market or gain market acceptance of its product candidates; the risk that Scilex’s product candidates may not be beneficial to patients or successfully commercialized; the risk that Scilex has overestimated the size of the target patient population, their willingness to try new therapies and the willingness of physicians to prescribe these therapies; risks that the outcome of the trials and studies for SP-102, SP-103 or SP-104 may not be successful or reflect positive outcomes; risks that the prior results of the clinical and investigator-initiated trials of SP-102 (SEMDEXA™), SP-103 or SP-104 may not be replicated; regulatory and intellectual property risks; and other risks and uncertainties indicated from time to time and other risks described in Scilex’s most recent periodic reports filed with the Securities and Exchange Commission, including Scilex’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent Quarterly Reports on Form 10-Q that the Company has filed or may file, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and Scilex undertakes no obligation to update any forward-looking statement in this press release except as may be required by law. Contacts: Investors and MediaScilex Holding Company 960 San Antonio RoadPalo Alto, CA 94303Office: (650) 516-4310 Email: investorrelations@scilexholding.com Website: www.scilexholding.com SEMDEXA™ (SP-102) is a trademark owned by Semnur Pharmaceuticals, Inc., a wholly-owned subsidiary of Scilex Holding Company. A proprietary name review by the FDA is planned. ZTlido® is a registered trademark owned by Scilex Pharmaceuticals Inc., a wholly-owned subsidiary of Scilex Holding Company. Gloperba® is the subject of an exclusive, transferable license to use the registered trademark by Scilex Holding Company. ELYXYB® is a registered trademark owned by Scilex Holding Company. All other trademarks are the property of their respective owners. © 2024 Scilex Holding Company All Rights Reserved. PDF available: http://ml.globenewswire.com/Resource/Download/f476e2c8-a9c3-40ca-af17-8aeeb214a6d7

Pictured: Rare disease ribbon with cut-outs of people/iStock, nambitomo The Bespoke Gene Therapy Consortium, a public-private collaboration involving the National Institutes of Health, FDA, industry and patient groups intended to help accelerate the delivery of AAV-based gene therapies for rare diseases, is making slow but steady progress, a representative said at the 2024 American Society of Gene & Cell Therapy (ASGCT) annual meeting. Launched in October 2021, the Bespoke Gene Therapy Consortium (BGTC) has more than $100 million in financial and in-kind commitments funded by a public-private entity called the Accelerating Medicines Partnership (AMP), through which the Foundation for the NIH (FNIH) administers funds provided by industry, government and nonprofits. Courtney Silverthorn, vice president of strategic alliances and innovation at FNIH’s AMP, told a Wednesday session that BGTC’s announcement last May at ASGCT 2023 identifying eight rare diseases for its clinical trial portfolio “really kicked things off” for the consortium. “The first year-and-a-half was designed to narrow down and finalize the clinical portfolio that would serve as the proof-of-concept for the goals and aims of the consortium,” Silverthorn said. Based on the early success of BGTC, FNIH is currently developing a similar cell therapy consortium that will be launched in 2025, according to Silverthorn. BGTC’s clinical trial portfolio includes eight diseases: Charcot-Marie-Tooth disease type 4J, congenital hereditary endothelial dystrophy, Morquio syndrome, multiple sulfatase deficiency, NPHP5 retinal degeneration, propionic acidemia, retinitis pigmentosa 45 and spastic paraplegia 50. Silverthorn said all readiness assessments have been completed for the eight assets in the clinical trial portfolio, while progress has also been made on manufacturing agreements. “All of the product for the BGTC is being donated partially or completely in kind to [FINH] as part of the consortium,” she added. BGCT’s private sector partners include 13 life sciences companies such as Biogen, Johnson & Johnson’s Janssen, Novartis, Pfizer, Regenxbio, Spark Therapeutics and Takeda. Last year, REGENEXBIO announced that its preclinical research in Morquio syndrome was selected for inclusion in the consortium’s clinical trial portfolio and that it was donating licenses for its NAV AAV8 and NAV AAV9 assets to the endeavor as a potential treatment for the rare inherited birth defect. In February 2024, BGTC published a “playbook” that lays out the critical steps before the submission of Investigational New Drug (IND) applications for the first human studies and includes regulatory best practices, as well as case studies of existing AAV gene therapies. “This is still a document in progress and we expect to have several more versions published over the next couple of years that will incorporate more of the learnings of the BGTC as we go through our clinical portfolio process,” Silverthorn said. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, in a recorded message at ASGCT 2024, made the case for the importance of BGTC and addressing the challenges faced by gene therapy developers. “This concept of a playbook to try to harmonize manufacturing protocols could really help us,” Marks said. “Automation could really bring us both a reduction in costs and an improvement in quality and consistency of products.” In a previous session at ASGCT, Marks hinted at future guidance from the FDA on other aspects of gene therapy development—namely, accelerated access. “I can’t get into the details,” he said. “But it may be helpful to the community to understand our thinking about how we look at accelerated approval in the gene therapy space.” Greg Slabodkin is the news editor at BioSpace. You can reach him at greg.slabodkin@biospace.com. Follow him on LinkedIn.