tPA

Courtesy of John Tlumacki/The Boston Globe via Getty Images One day ahead of a data presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference, Science reported a second patient death has been linked to Eisai and Biogen’s lecanemab. The death occurred in a clinical trial for early Alzheimer’s disease and was described in an unpublished case report obtained by Science. The two companies originally announced positive data for the drug in late September. In the Phase III Clarity AD trial, lecanemab demonstrated a “highly statistically significant” slowing in disease progression and decreased clinical decline by 27% compared to placebo after 18 months based on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) assessment. A "One-Two Punch" Due to privacy protections, Eisai "cannot provide any information about specific patients or comment on information that was provided by other sources," a company spokesperson told BioSpace. "It can be difficult to determine what contributed to the death in any given patient, in particular when they are elderly, have multiple medical problems and may have recently received a concomitant treatment or intervention for an acute condition," the spokesperson said. The independent Data Safety Monitoring Board completed a review of all ARIA-related safety data from the Phase III trial. This “indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause," the spokesperson added. When approached for comment, Biogen deferred to Eisai. An earlier death possibly associated with lecanemab was reported in late October. The death occurred in June and, as in this case, was due to bleeding in the brain. Rudolph Castellani, M.D., a neuropathologist at Northwestern University Medical Center in Chicago who co-authored the case report, performed an autopsy on the patient per her husband's request. He described the case as “very dramatic.” “It was a one-two punch,” Castellani told Science. “There’s zero doubt in my mind that this is a treatment-caused illness and death. If the patient hadn’t been on lecanemab, she would be alive today.” The one-two punch is a reference to first, lecanemab, and second, a blood thinner used to treat a stroke the patient had suffered earlier. Castellani and his co-authors noted that tissue plasminogen activator (tPA), a common blood-clot treatment given to the patient in the emergency room, and possibly other less potent blood thinners, may pose safety considerations for Alzheimer’s patients when combined with treatments like lecanemab. The patient, a 65-year-old woman, reportedly died from a brain hemorrhage. She suffered a stroke and amyloid-related imaging abnormalities (ARIA), which included both swelling and brain bleeds. According to Science, the autopsy results indicate the woman had a pre-existing condition that contributed to her death - widespread cerebral amyloid angiopathy (CAA). CAA occurs when amyloid deposits replace the smooth muscle of blood vessel walls. Several experts who reviewed the autopsy report, including Castellani, believe CAA made the woman’s blood vessels susceptible to weakening when lecanemab cleared amyloid from the brain. The tPA then likely ruptured the weakened blood vessels, causing serious ARIA and a fatal brain bleed, the experts noted. A Familiar Tune Biogen’s Aduhelm (aducanumab), which was approved by the FDA in June 2021, is also an antibody targeting beta-amyloid. ARIA and brain bleeds have also been reported in patients taking Aduhelm. The FDA issued a warning on the drug's label directing doctors to monitor for ARIA-E, which ncludes cerebral edema. It is linked to headache, confusion, nausea and gait disturbances. In an August 2021 analysis of Aduhelm and ARIA by Clinical Trials Arena, the organization noted that ARIA is a “known class side effect of antibodies like Aduhelm that target amyloid plaque in the brain. Data from Clarity AD will be presented Tuesday at CTAD. The study enrolled approximately 1,800 people with indications of early Alzheimer’s disease. Biogen and Eisai have submitted a Biologics License Application for lecanemab to the FDA under an accelerated approval pathway with a target action date of early 2023.

CD8+ regulatory-like T cells reach the brain within 24 hours after stroke onset, where they release molecules that provide direct neuroprotective effects, as well as limit inflammation and secondary brain damage. A unique subset of white blood cells confers fast-acting and lasting protection against ischemic stroke in mice, University of Pittsburgh neurologists and immunologists reported in the Journal of Clinical Investigation today. This study identified a novel subset of CD8+ regulatory-like T cells, or CD8+TRLs, as "first responders" to stroke. Attracted to the site of ischemic injury by a unique "homing" signal released by dying brain cells, CD8+TRLs reach the brain within 24 hours after stroke onset, where they release molecules that provide direct neuroprotective effects, as well as limit inflammation and secondary brain damage. "The beauty of CD8+TRLs is in their fast response. They confer very potent protection to the brain, which can last a long time," said co-corresponding author Xiaoming Hu, M.D., Ph.D., associate professor of neurology at Pitt and a U.S. Department of Veterans Affairs (VA) investigator. "Most importantly, these cells are easily accessible because they circulate in the blood before they enter the injured brain." "Creating shelf-stable and ready-to-use CD8+TRLs or developing a cocktail of neuroprotective signaling molecules released by those cells once they reach the brain could present effective future therapies against stroke and offer hope to hundreds of thousands of patients who are ineligible for treatments available to them currently," said co-senior author Jun Chen, M.D., Ph.D., professor of neurology at Pitt and a U.S. Department of VA investigator. Stroke affects 800,000 Americans yearly, but only a quarter of those patients will be eligible to receive one of only two Food and Drug Administration-approved treatments: An injection of a blood clot-busting enzyme called tPA or mechanical thrombectomy, a surgical procedure that removes the blood clot in the brain with a stent retriever. Because those treatments must be administered very early after the stroke, many people, especially those living in remote areas, are ineligible for those therapies. The remaining 600,000 people are left with symptoms-based treatments and are at high risk of developing long-term health complications, including mobility challenges and, in some cases, speech and cognitive pathologies. In addition, the blood clot-busting therapy, in particular, has drawbacks that further limit the number of people benefiting from such therapy. Immune response plays an important role in stroke. As soon as a blood clot wedges itself in a blood vessel, the brain sends an "SOS" signal to activate the immune system. This rapid immune response aims to clear out the cell debris, limit brain damage and kick-start brain repair processes. However, the function of the immune system is diverse and complex, and different types of immune cells may play distinct beneficial or detrimental roles in a damaged brain. As Chen, Hu, and their colleagues showed for the first time, the CD8+TRLs enter the brain much faster than any other regulatory immune cells. Within 24 hours after researchers depleted these special CD8+TRLs from the bloodstream of stroke mice, the size of the brain region affected by ischemia expanded by 50% compared to animals whose CD8+TRL levels remained intact. Even more reassuringly, mice who received a transfusion of purified CD8+TRLs prepared in the lab fared better and recovered faster than those who were untreated for over five weeks. These unique CD8+TRLs, therefore, serve as early responders to rally defenses after stroke and may collaborate with other immune cells to safeguard the brain for a long time. "Despite the efforts of thousands of people devoting their careers to finding treatments that could benefit stroke patients, therapy options are minimal," said Chen. "I have been working in this field for more than 30 years, and this is the first time I feel that I am seeing the light at the end of the tunnel, promising future clinical translation that will benefit patients." Additional authors of this study are Wei Cai, M.D., Ph.D., Ligen Shi, M.D., Ph.D., Jingyan Zhao, M.D., Ph.D., Fei Xu, B.S., Connor Dufort, B.S., Qing Ye, M.D., Tuo Yang, M.D., Ph.D., Xuejiao Dai, M.D., Ph.D., Junxuan Lyu, M.D., Chenghao Jin, M.D., Hongjian Pu, Ph.D., Fang Yu, M.D., Ph.D., Sulaiman Hassan, B.S., Zeyu Sun, M.D., Ph.D., Wenting Zhang, M.D., Ph.D., T. Kevin Hitchens, Ph.D., Yejie Shi, M.D., Ph.D., and Angus Thomson, Ph.D., all of Pitt; and Rehana Leak, Ph.D., of Duquesne University. This research was supported by the NIH/NINDS (grants NS105430 and NS094573), the University of Pittsburgh School of Medicine and the UPMC Endowed Chair for stroke research.

DUBLIN, June 8, 2022 /PRNewswire/ -- The "Stroke Management Market by Type and Application: Global Opportunity Analysis and Industry Forecast, 2021-2030" report has been added to ResearchAndMarkets.com's offering. The global stroke management market was valued at $31,702.20 million in 2020, and is projected to reach $67,771.95 million by 2030, registering a CAGR of 7.8% from 2021 to 2030. Stroke is caused by lack of blood flow to the brain which can be caused either due to the blockage of the blood supply or a blood vessel within the brain. Such blood insufficiency causes the brain tissue to die, owing to lack of oxygen for the functioning of the brain, eventually resulting into stroke. Stroke is a medical emergency that requires urgent diagnosis and treatment to minimize brain damage. According to the Centers for Disease Control and Prevention, in 2018, stroke was responsible for one out of every six fatalities caused by cardiovascular disease. Stroke is a leading cause of serious long-term disability. Ischemic stroke, hemorrhagic stroke, and transient ischemic stroke are the three main types of strokes. The main symptoms of stroke are difficulty in speaking, understanding, and walking; headache; numbness or inability to move parts of face, arm, or leg; gradual loss of vision; and others. Increase in healthcare awareness, rise in incidence of diabetes, surge in number of tobacco users, and growth in geriatric population drive the growth of the market. Moreover, technological advancements for the diagnosis and treatment of stroke also contribute toward the growth of the market. However, high cost of diagnosis and treatment and lack of reimbursement policies are the major barriers for the growth of the market. Ongoing R&D activities in the field of stroke management are expected to offer lucrative opportunities for market expansion during the forecast period. The stroke management market is segmented on the basis of type, application, and region. On the basis of type, the market is segmented into diagnostics and therapeutics. The diagnostics segment is classified into computed tomography scan (CT scan), magnetic resonance imaging (MRI), carotid ultrasound, cerebral angiography, electrocardiography, echocardiography, and others. The therapeutics segment is classified into tissue plasminogen activator, anticoagulant, antiplatelet, and antihypertensive. By application, it is segmented into ischemic stroke and hemorrhagic stroke. Region wise, the market is analyzed across North America, Europe, Asia-Pacific, and LAMEA. Key Benefits This report provides a detailed quantitative analysis of the current market trends and future estimations from 2020 to 2030, which assists to identify the prevailing market opportunities An in-depth analysis of various regions is anticipated to provide a detailed understanding of the current trends to enable stakeholders to formulate region-specific plans A comprehensive analysis of the factors that drive and restrain the growth of the stroke management market is provided An extensive analysis of various regions provides insights that allow companies to strategically plan their business moves Key market players and their strategies have been analyzed to understand the competitive outlook of the market Key Topics Covered: Chapter 1: Introduction Chapter 2: Executive Summary Chapter 3: Market Landscape 3.1. Market Definition and Scope 3.2. Key Findings 3.2.1. Top Investment Pockets 3.2.2. Top Winning Strategies 3.3. Porter's Five Forces Analysis 3.3.1. Bargaining Power of Suppliers 3.3.2. Threat of New Entrants 3.3.3. Threat of Substitutes 3.3.4. Competitive Rivalry 3.3.5. Bargaining Power Among Buyers 3.4. Market Share Analysis/Top Player Positioning 3.4.1. Market Share Analysis/Top Player Positioning 2020 3.5. Market Dynamics 3.5.1. Drivers 3.5.2. Restraints 3.5.3. Opportunities 3.6. Covid-19 Impact Analysis 3.7. Market Volume and Forecast Chapter 4: Stroke Management Market, by Type 4.1. Market Overview 4.1.1Market Size and Forecast, by Type 4.2. Diagnostics 4.2.1. Key Market Trends, Growth Factors and Opportunities 4.2.2. Market Size and Forecast, by Region 4.2.3. Market Share Analysis, by Country 4.2.4. Computed Tomography Scan 4.2.4.1. Market Size and Forecast 4.2.4.2.2. Market Volume and Forecast 4.2.5. Magnetic Resonance Imaging 4.2.5.1. Market Size and Forecast 4.2.5.2.2. Market Volume and Forecast 4.2.6. Carotid Ultrasound 4.2.6.1. Market Size and Forecast 4.2.6.2.2. Market Volume and Forecast 4.2.7. Cerebral Angiography 4.2.7.1. Market Size and Forecast 4.2.7.2.2. Market Volume and Forecast 4.2.8. Electrocardiography 4.2.8.1. Market Size and Forecast 4.2.8.2.2. Market Volume and Forecast 4.2.9. Echocardiography 4.2.9.1. Market Size and Forecast 4.2.9.2.2. Market Volume and Forecast 4.2.10. Others 4.2.10.1. Market Size and Forecast 4.2.10.2.2. Market Volume and Forecast 4.3. Therapeutics 4.3.1. Key Market Trends, Growth Factors and Opportunities 4.3.2. Market Size and Forecast, by Region 4.3.3. Market Share Analysis, by Country 4.3.4. Tissue Plasminogen Activator 4.3.4.1. Market Size and Forecast 4.3.4.2.2. Market Volume and Forecast 4.3.5. Anticoagulant 4.3.5.1. Market Size and Forecast 4.3.5.2.2. Market Volume and Forecast 4.3.6. Antiplatelet 4.3.6.1. Market Size and Forecast 4.3.6.2.2. Market Volume and Forecast 4.3.7. Antihypertensive 4.3.7.1. Market Size and Forecast 4.3.7.2.2. Market Volume and Forecast Chapter 5: Stroke Management Market, by Application 5.1. Market Overview 5.1.1Market Size and Forecast, by Application 5.2. Ischemic Stroke 5.2.1. Market Size and Forecast, by Region 5.2.2. Market Share Analysis, by Country 5.3. Haemorrhagic Stroke 5.3.1. Market Size and Forecast, by Region 5.3.2. Market Share Analysis, by Country Chapter 6: Stroke Management Market, by Region Chapter 7: Company Profiles 7.1. Abbott Laboratories 7.1.1. Company Overview 7.1.2. Key Executives 7.1.3. Company Snapshot 7.1.4. Operating Business Segments 7.1.5. Product Portfolio 7.1.6. Business Performance 7.1.7. Key Strategic Moves and Developments 7.2. B Braun Melsungen AG 7.2.1. Company Overview 7.2.2. Key Executives 7.2.3. Company Snapshot 7.2.4. Operating Business Segments 7.2.5. Product Portfolio 7.2.6. Business Performance 7.2.7. Key Strategic Moves and Developments 7.3. Boston Scientific Corporation 7.3.1. Company Overview 7.3.2. Key Executives 7.3.3. Company Snapshot 7.3.4. Operating Business Segments 7.3.5. Product Portfolio 7.3.6. Business Performance 7.3.7. Key Strategic Moves and Developments 7.4. Bristol Myers Squibb Co. 7.4.1. Company Overview 7.4.2. Key Executives 7.4.3. Company Snapshot 7.4.4. Operating Business Segments 7.4.5. Product Portfolio 7.4.6. Business Performance 7.4.7. Key Strategic Moves and Developments 7.5. Cardinal Health Inc. 7.5.1. Company Overview 7.5.2. Key Executives 7.5.3. Company Snapshot 7.5.4. Operating Business Segments 7.5.5. Product Portfolio 7.5.6. Business Performance 7.5.7. Key Strategic Moves and Developments 7.6. General Electric Company 7.6.1. Company Overview 7.6.2. Key Executives 7.6.3. Company Snapshot 7.6.4. Operating Business Segments 7.6.5. Product Portfolio 7.6.6. Business Performance 7.6.7. Key Strategic Moves and Developments 7.7. GlaxoSmithKline plc 7.7.1. Company Overview 7.7.2. Key Executives 7.7.3. Company Snapshot 7.7.4. Operating Business Segments 7.7.5. Product Portfolio 7.7.6. Business Performance 7.7.7. Key Strategic Moves and Developments 7.8. Medtronic plc 7.8.1. Company Overview 7.8.2. Key Executives 7.8.3. Company Snapshot 7.8.4. Operating Business Segments 7.8.5. Product Portfolio 7.8.6. Business Performance 7.8.7. Key Strategic Moves and Developments 7.9. Merck and Co. Inc. 7.9.1. Company Overview 7.9.2. Key Executives 7.9.3. Company Snapshot 7.9.4. Operating Business Segments 7.9.5. Product Portfolio 7.9.6. Business Performance 7.9.7. Key Strategic Moves and Developments 7.10. Siemens AG 7.10.1. Company Overview 7.10.2. Key Executives 7.10.3. Company Snapshot 7.10.4. Operating Business Segments 7.10.5. Product Portfolio 7.10.6. Business Performance 7.10.7. Key Strategic Moves and Developments For more information about this report visit Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 SOURCE Research and Markets