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Scientists explore using CAR-T and other engineered immune cells to target COVID-19 – FierceBiotech

CAR-T and TCR-T therapies that involve engineering a patients own immune cells with antigen-specific receptors have revolutionized blood cancer treatment. Nowscientists at Duke-NUS Medical School are exploring the possibility of turning the approach against COVID-19.

The idea of using CAR/TCR-T cell therapy has already been proposed for treating chronic viral infections such as HIV and hepatitis B. Based on previous research, Antonio Bertoletti from Duke-NUS emerging infectious diseases research program suggest these immunotherapies might also be useful in treating SARS-CoV-2, the virus causing the current pandemic.

We demonstrated that T cells can be redirected to target the coronavirus responsible for SARS. Our team has now begun exploring the potential of CAR/TCR T cell immunotherapy for controlling the COVID-19-causing virus, SARS-CoV-2, and protecting patients from its symptomatic effects, Bertoletti said in a statement.

Virtual Clinical Trials Online

This virtual event will bring together industry experts to discuss the increasing pace of pharmaceutical innovation, the need to maintain data quality and integrity as new technologies are implemented and understand regulatory challenges to ensure compliance.

These types of therapies involve modifying patients' own T cells with either a chimeric antigen receptor (CAR) or a T-cell receptor (TCR) that can recognize specific antigens associated with cancer,and then guiding the immune cells to eradicate the targets when infused back into the patients.

In a 2011 article published in the Journal of Virology, Bertoletti led a team that generated TCR-T cells that can go after SARS, another coronavirus that caused a deadly outbreak in China and other countries in late 2002 and early 2003.

The team showed that those TCR-redirected T cells displayed a functional profile similar to that of SARS-specific memory CD8 T cells from people who recovered from SARS-CoV infection. Based on the findings, the researchers suggested that TCR-T cells represent a promising prophylactic or therapeutic treatment for SARS.

RELATED:How 'duoCAR-T' cells could clear HIV and prevent resurgence of virus reservoirs

CAR-T cells have been explored in other viruses. A research team from the Albert Einstein College of Medicine and the University of Pittsburgh, for example,designed duoCAR-T cells that target three sites on the HIV envelope glycoprotein. In the lab, the cell therapy eliminated up to 99% of immune cells infected with different strains of HIV.

Despite thepromise of T-cell therapies, however, Bertoletti and colleague Anthony Tanoto Tan cautioned about potential safety concerns of using them to treat viral infections affecting vital organs. For one thing, CAR-T treatments havebeen linked to the dangerous side effect called cytokine release syndrome, in which overreactive immune cells launch an inflammatory response that can destroy organs, they said in a recent Journal of Experimental Medicine commentary. Similar cytokine storm effects have been reported in somesevere COVID-19 patients, leading to potentially life-threatening lung inflammations.

[T]he infusion ofT cells stably expressingpathogen-specific CAR/TCR poses therisk that these T cells might proliferate and wipe out all the infected cells that might be the majority of the infected organ, Bertoletti and Tanoto Tan wrote in their article.

To addressthat problem, Bertoletti and colleagues are using mRNA electroporation to engineer CAR/TCR T cells, which they say can limit their inflammatory capability and shorten the functional activity. That may offer a safer way to use engineered immune cells to treat viral diseases.

Several organizations are also working on cell therapies for COVID-19. AlloVir and Baylor College of Medicine have teamed up to develop an off-the-shelf therapy that entails exposing donor T cells to cytokines combined with viral fragments so the new cells can target the novel coronavirus. Celgene spinoff Celularity just started clinical trial of its cancer treatment CYNK-001 for COVID-19. The drugturns placental stem cells into one-size-fits-all natural killer cells.

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Scientists explore using CAR-T and other engineered immune cells to target COVID-19 - FierceBiotech

Researchers use cell therapy to recover damaged brain areas in mice that suffered – Mirage News

Dispositiu per a realitzar registres electrofisiolgics amb les llums LED incorporades per lus doptogentica.

Equip investigador.

Researchers from Lund University (Sweeden) and the Institute of Neurosciences of the University of Barcelona (UBNeuro) have recovered, through cell therapy, the mobility and sensibility of mice that suffered a cardiovascular accident. The results of this study were published in the journal Proceedings of the National Academy of Sciences (PNAS).

Researchers used an ischemic model of ictus in mice to which they transferred stem cells obtained from the skin of a healthy human donor. The cells were reprogramed to become neuronal progenitors of the damaged area of the brain, specifically the brain cortex. Six months after the transplant, researchers could observe how the new cells had repaired the damage that was caused by the cerebrovascular injury. In addition, the sensor and motor problems resulting from the stroke had been reversed as well.

We observed that the fibers of the cells that were put in the cortical area grew and created connections in brain areas that are far from the transplant area, notes Daniel Tornero, researcher in the Laboratory of Stem Cells and Regenerative Medicine in UBNeuro. To identify the transplanted cells, researches used different techniques that enable the monitoring so as to prove the connection in damaged circuits is right. Although there is a lot of work to do -the researcher adds-, the study sheds light on the possibility of replacing the damaged cells for new healthy cells in patients with ictus.

This is the last study of a series of three articles in which the researchers used cell therapy to work on brain healing. Previous studies showed it is possible to transplant nervous cells derived from human stem cells or reprogrammed cells in the brain of mice affected by cardiovascular injuries. However, researchers did not know whether the transformed cells could create new connections in the mice brains and restore the movement and feelings of touch.

The next step is to understand how the transplant affects intellectual functions such as memory, and the potential adverse effects, concludes Tornero.

Article reference:

S. Palma-Tortosa, D. l Tornero, M. Grnning Hansen, E. Monni, M. Hajy, S. Kartsivadze, S. Aktay, O. Tsupykov, M. Parmar, K. Deisseroth, G. Skibo, O. Lindvall, y Z. Kokaia. Activity in grafted human iPS cellderived corticalneurons integrated in stroke-injured rat brain regulatesmotor behavior. Proceedings of the National Academy of Sciences (PNAS). Doi: doi: 10.1073/pnas.2000690117

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Researchers use cell therapy to recover damaged brain areas in mice that suffered - Mirage News

Scientists from IKBFU, Moscow and Kiev conducted research on treating obesity – Science Codex

In the 21st century, the search for methods of treating noncommunicable diseases, such as obesity, metabolic syndrome, and diabetes are among the top priorities. Prevention and treatment of these diseases include changing and controlling lifestyle, diet, and the use of pharmaceuticals.

Despite the progress in medicine and pharmacology (developing new solutions for correcting metabolism) and biotechnologies, new effective approaches are still on demand in treating obesity, metabolic syndrome, and diabetes.

Researchers note that adipose tissue is one of the key players in the development of obesity and diabetes. Adipose tissue is classified both by anatomical location and by function (white and brown fat). So, the main functions of white adipose tissue are to save energy in the form of lipids, and it also has an endocrine function - the secretion of hormones, growth factors, cytokines, chemokines, etc.

The function of brown adipose tissue is to generate heat during adaptive thermogenesis (the process of generating heat in response to cold stimulation). In humans, unlike rodents (laboratory animals most widely used in medical experiments, including modeling of obesity, metabolic syndrome and diabetes), brown adipose tissue is present in significant numbers only in newborns and infants. Recently, the existence of active thermogenic adipose tissue in adults has been shown, but this adipose tissue differs from classical brown adipose tissue in several aspects (development, morphology, gene expression, adipokine production, etc.). This adipose tissue is called "brown".

All types of adipocytes (cells that make up adipose tissue mainly) arise from adipose stem cells during differentiation. Currently, the question of the origin of brown adipocytes (from the same stem cell as white adipocytes, or from the same stem cell as brown adipocytes, or from its own stem cell), as well as the ability of white adipose tissue to differentiate into brown adipose tissue.

The ability to control the formation of new adipose tissue, turn white adipose tissue into brown one, or determine the direction of adipocyte stem cell differentiation into a specific subtype is an attractive goal for the development of new pharmacological substances for the treatment of obesity, metabolic syndrome and diabetes.

In addition to the search for new pharmacological substances designed to control the functions of adipose tissue or various other biochemical aspects of energy homeostasis, it is also important to study the role of water in human health, metabolism and the pathogenesis of various diseases. Water is the most abundant chemical substance on Earth and makes up the largest mass fraction in living organisms as a percentage. Water is also a universal solvent in which the basic biochemical processes of living organisms occur.

An important component of a healthy diet is drinking water instead of sugar and soda. So, the modulation of the biological and physico-chemical properties of water is also a promising opportunity to increase the effectiveness of the treatment of said diseases.

Dr. Larisa Litvinova, Ph.D. in Medicine, Head of the Immunology and Cell Biotechnologies Laboratory^

"One of the focuses of modern medicine is the development of deuterium-containing drugs. Another direction relates to the role of the D/H ratio of isotopology and its change in water, which will be used as

an adjuvant in the treatment of cancer. A different D/H ratio manifests itself in the form of a kinetic isotope effect, which is characterized by a change in the rates of biotransformation and excretion of drugs. Moreover, methodological approaches to the quality control of medicines based on isotopology of water could reduce the toxic load on the body".

IKBFU Scientists Larisa Litvinova and Maria Wulf were conducting the research in cooperation with colleagues from Moscow and Kiev and the goal of the research was to find out whether deuterium is engaged in differentiation of adipose tissue stem cells regulation. Adipogenic differentiation of mesenchymal stem cells was chosen as an in vitro model, where the efficiency of the formation of mature fat cells from precursor cells in media with different deuterium contents was evaluated.

The data on the effect of various concentrations of deuterium on the efficiency and direction (formation of brown/beige or white adipocytes) of differentiation of mesenchymal stem cells in an in vitro model system were obtained in the study. Naturally for the possible practical application of these results, additional studies are needed that would allow a more detailed description of the molecular mechanisms of the influence of various concentrations of deuterium at the cellular level, as well as studies at the body level.

The results of the study are published in the article "The influence of deuterium on the effectiveness and type of adipogenic differentiation of stem cells of human adipose tissue in vitro" in the Scientific Reports journal.

The results can serve as the basis for the development of new approaches in the treatment of obesity, metabolic syndrome and diabetes, by regulating the differentiation of fat stem cells and adipocyte functions.

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Scientists from IKBFU, Moscow and Kiev conducted research on treating obesity - Science Codex

Lessons for medical profession during management of covid-19 pandemic: Is there a silver lining? – Elets

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Covid 19 pandemic caused by corona virus has become a sort of global showstopper with apparently huge negative impact on human life as well as economy worldwide. It has, undeniably, emerged as a daunting challenge for medical profession in 21st century. Despite its glorious victories over the past pandemics of plague, cholera, polio and smallpox, medical profession is bracing itself to take on Covid 19 juggernaut. Currently, every person, layman or medical, is dismayed by ferocity of its spread and rapidity of its killing, particularly among high-risk persons. In various hotspots of this pandemic, healthcare systems are severely overwhelmed by clinical load of patients requiring hospitalization as well as intensive care. This is first time that medical professionals have a dual responsibility- to treat the patient as well as to prevent themselves from succumbing to same illness. While healthcare professionals all over the world are showing exemplary fortitude and gusto in dealing with this uphill task, it is time to decipher few lessons which can be usher in new era of healthcare following covid pandemic.Advantages of recent rationing of routine specialized medical services

Undeniably the patient load at various hospitals (both public as well as private) over last few weeks has hit the rock bottom due to peoples reluctance and doctors hesitance in engaging with medical care. Even suggesting going to hospital is sending shivers down the spine of a person with simple fever or cough. This sudden aversion to hospital visits clearly echoes the scenario 150 years back when hospitals were first established in western world. The hospitals in early America were primarily used as alms-houses for homeless poor and getting hospitalized was a stigma for the society (Health, Illness, and Society: An Introduction to Medical Sociology By Steven E. Barkan). Same stigma has resurfaced now during covid 19 pandemic, though in a different social and medical context.

Elective procedures are almost at standstill for following two reasons: First, as an austerity measure to preserve potential resources for covid patients and second, to protect the vulnerable from exposure to virus. Even, emergency facilities are also witnessing load shedding with recent reports of 40-70% decrease in STEMI (ST Elevated Myocardial Infarction) patients all over the world (https: //www. tctmd. com/ news/ mystery-missing-stemis-during-covid-19-pandemic). In a study published in Spain (by Rodrguez-Leor O et al), interventional cardiology is almost in a state of lockdown and surprisingly corresponding increase in medical management of heart disease patients is still slight. Published reports of activation of cardiac catheterization labs for STEMI patients also showed a decline of 38% (Garcia S, et al. J Am Coll Cardiol. 2020; Accepted Date: 7 April 2020). This should not be alone attributed to serious patients failing to reach hospitals due to fear of corona virus. Literature search easily reveals that false activation rate of catheterization labs ranges from 12.5-40% (by Degheim G et al JRSM Cardiovascular Disease 2019, Vol 8;1-5). Therefore, recent decline of 38% during Covid pandemic is concordance with previously reported false activation rate and thereby reflects avoidable or unnecessary therapeutic demand.

One potential upside of this recent drop in healthcare utilization is the reduction in too much medicine- a term gaining prominence in recent medical lexicon. This is wide ranging concept which encompasses processes like over-detection (diagnosing harmless, static or incidental conditions which will either resolve spontaneously or do not progress), over-definition (where thresholds for diagnosing illnesses are gradually lowered leading to quasi-indications for treatment) and over-selling (by alarming patients with insidious symptoms mirroring serious pathology, carpet testing for some vague symptoms till patient is medically labelled)(BMJ Evidence-Based Medicine February 2018 | volume 23 | number 1). These terms assume importance when we look at the previously published data for out-of-pocket medical expenditure by patients with medical care. A recent study revealed that healthcare spending pushes 3.5 to 6.2% of Indian population below poverty line every year (BMC Public Health19, 1020; 2019). In another study using National Sample Survey Organization (NSSO) data, odds of falling below poverty line were 38% higher for persons hospitalized with cardiovascular disease as compared to communicable disease (Engelgau MM, Karan A, Mahal A. The Economic impact of Noncommunicable Diseases on households in India. Global Health 2012; 8: 9). Importantly, spread of covid 19 is already forcing every hospital or healthcare institute for rationing of medical care and many hospital-based practices including tests and procedures routinely performed before covid 19 catastrophe have suddenly become redundant and avoidable( by Wang X & Bhatt DL in J of Invasive Cardiology 2020; 32 (4): E81-E84).

Since most hospitals are not currently teaming up with non covid patients, the burden of pervasive hospital acquired antibiotic resistance pathogens is also likely to ebb. Past data had shown that 7% of patients from developed countries and 10% from developing countries suffer from hospital acquired nosocomial infections at any given time totaling hundreds of millions worldwide every year (https://www.who.int/gpsc/country_ work/gpsc_ccisc_fact_sheet_en.pdf). This unintended break in continuum of hospital care is a valuable opportunity to sanitize all those hospitals which are not involved in active patient care of covid patients. In addition, medical research (mostly repetitive or redundant) in tertiary institutes has also come to standstill which will save patients from avoidable investigations and additional visits just for the sake of data collection. Finally, it is a rare medical touch point where patients are not being reprimanded by medical healthcare providers for delayed health care seeking and mutually participative healthcare actively guided by doctors on phones has become a new buzzword.

Advantages of emerging public health practices

With widespread practice of hand washing which has now emerged as a globally cherished pastime of human race, it can play a protective role against surge of bacterial infections during ongoing summer season. Also, if this forced ritual becomes a habit (very likely due to so many weeks of rigorous daily practice), the trend for community acquired bacterial infections is likely to be further blunted for longer duration. Food borne illnesses like typhoid, shigellosis and bacterial infections like staphylococcus are going to see notable fall in coming peak season. Worm infestations of children where dirty hands are the key culprit are also likely to recess as well. Recent emphasis on use of warm/hot water for repeated drinking as a guard against covid 19 will certainly play key role in stonewalling common waterborne illness like cholera and hepatitis A or E. Stringent guidelines for not coughing or sneezing in public with widespread use of masks will further stymie the spread of viral infections like measles, mumps, rubella as well as other flu viruses including H1N1.

Advantages of accompanying lockdown

Orthopaedic, neurosurgery and trauma wards are no more brimming with injured patients. It is quite apparent that trauma due to road traffic accidents and criminal acts is almost negligible during the lockdown.

With the rapidly accumulating evidence of fall in pollution levels of air, most medical professionals are going to see far a smaller number of acute exacerbations of asthma in children as well as adults. The impact of improving air quality on the incidence of other respiratory illnesses, cardiovascular disorders as well as lung cancer will be very interesting to monitor in near future.

Earlier most of the urban population was spending time indoors in the air-conditioned offices, cabs, metros or even homes. This lifestyle had morphed almost whole human race into vitamin D endemic species. Fortunately, with strictly imposed lockdown, people are forced to spend good amount of their daytime in the lawns, rooftops, balconies or corridors. Though there may be many who still are not fortunate to have enough sunlight exposure, yet overall lockdown has come as a blessing in disguise for the health of urban population. Availability of ample opportunities for exposure to sun will replenish the chronically depleted vitamin D stores, again a known immune booster which may be crucial during this time of crisis. Most mothers, wives as well as daughters are rediscovering the time tested and traditional recipes with rich repertoire of macro as well as micro nutrients which will further uplift and fortify the nutritional milieu of families. The typical middle-class penchant for enjoying fried, oily and refined sugar laced foods is also likely to be subdued due to limited availability of raw materials at homes during ongoing lockdown. This will further safeguard their health from risk of obesity and its subsequent health consequences. Renewed interest in intake of seasonal and local fruits available easily is another take-away of lockdown.

Party culture with access to unhealthy food as well as substances of abuse is certainly a nonstarter now. College students compelled to be at home are enjoying freshly prepared healthy home food. Most hostel messes providing nutritionally sub optimal meals are closed.

What will be the fate of NCDs-noncommunicable diseases due to lockdown following covid 19 pandemic? The patients with poor control of diabetes and hypertension are at risk of higher covid 19 morbidity as well as mortality. On the positive side, the fear of contagion itself may provide these high-risk patients further incentive to optimize their compliance with the treatment as well as other lifestyle measures like diet and exercise. Lockdown restrictions will certainly block the easy access of diabetic and hypertensive patients to less healthy outdoor food served at popular restaurants or eating joints- usually a rite of passage for urban population. Moreover, limited accessibility to cold drinks, snacks like chips, burgers, pizzas either directly in the market or through online food delivery services will further play a protective role in controlling the needless intake of sugar and salt in such patients. Additional risk factor increasing the human vulnerability to NCDs is trans fats (mainly embedded in food items available from market). Trans fats are the major offender for worsening metabolic as well as vascular health and during lockdown, they are likely to be replaced by healthy polyunsaturated fats and oils routinely available in the kitchens of most homes.

Substance abuse is one more niche area which is likely to see substantial change in coming weeks. Accessibility to regular supply of substances of abuse especially recreational drugs as well as alcohol are in serious jeopardy due to lockdown. Reports of addicts reporting major withdrawal symptoms are already getting media attention. High risk sexual behaviours as well as free access to red light areas have been restrained to large extent, hence expecting fall in STIs as well as HIV incidence.

Hospital driven care for various psycho social needs have also plummeted considerably. Except for major psychiatric illnesses, patients with common mental or psycho social health issues are clearly opting for either self-management or various alternative modes of care to safeguard their mental or psycho social health. Occupational injuries including those due to noise and light pollution have declined due to industrial shutdown and on long term, hazards of occupational exposure to toxins or poisonous substances will show beneficial trend. In addition, palpable decline in crime rate all over the world will have indirect impacts on the health of people in those high-risk localities, especially the children and women.

Emergence of cost-effective models of healthcare with participatory patient doctor relationship

Role of mobile or e-healthcare has skyrocketed in last few weeks as a surrogate for actual care at hospitals or clinics. The need for digitized medical care cannot be overemphasized in the backdrop of the fact that hospitals and their medical staff are emerging as hotspots of covid infection and are likely to act as super-spreaders. Hence, hospitals or medical care centres are no longer the safest niche for persons with routine sickness and people are, instead, voluntarily opting for tele care through their mobile phones. Also, family doctors as well as local health volunteers are efficiently filling the recent void in medical care. Frankly speaking, the covid pandemic lockdown has catalysed the redux of long-forgotten art of medical practice through either family doctors or local health volunteers in the present heavily institutionalized medical ecosystem. The current phase of covid turmoil is, indeed, a salvageable touch point for public health. Covid 19 has clearly proven that more than 80% of our population just needs a sound public health advice (hand washing, cough hygiene and social distancing), another 10-15% of population needs minimal medical support (like paracetamol) while remaining 5-10% population is salvageable with basic medical support (with oxygen, IV fluids and antibiotics/antimalarials). Importantly, none of them require massive public or private health institutes and well-trained health workers or volunteers are competent enough to deal with it. It is only 1% extreme outlier or even lower percentage of population who will be eligible for intensive healthcare with significant chunk of them unlikely to be salvageable. This model of pyramidal approach where only top 1% will require technically advanced medical care is uniformly applicable to rest of the diseases as well. Given the hierarchical needs of healthcare, a highly cost-effective framework of public health needs to be urgently prioritized over overbearingly technocratic medical science, both among lay public as well as policy makers.

The covid 19 pandemic is probably first instance where doctors are clearly finding themselves as or even more susceptible than their patients whom they treat. Reflecting thoughtfully, covid 19 is showing medical fraternity a mirror to judge their much-vaunted prowess as demigods. Never ever a situation has arrived in modern medicine where doctors find themselves at receiving end in treating patients as currently happening with covid pandemic. There is almost a role reversal where instead of patients fearing their doctor, doctors are fearing their patients. Honestly, this is the greatest humbling moment in the history of modern medicine. Have you ever seen doctors repeatedly and pleadingly begging each and every person for such mundane household chores of washing their hands and keeping social distancing? In the era of robotic surgeries, organ transplantations, stem cell therapies and genomic medicine, isnt it an antithesis to the currently hyped medical armamentarium capable of potentially decimating any disease present in the world? On the other hand, almost every grandmother or nanny has been offering this time-tested household wisdom of regular hand washing (the current front line strategy to prevent covid spread) to the kids since time immemorial.

Surely once the crisis settles, there will be serious contemplation about the heavily distorted medical care pyramid which stands exposed by covid like threats looming over the whole humanity. The heavily institutionalized framework of healthcare has proven to be a limitation both for treating increasing burden of covid patients as well as preventing the further spread of infection. The weakened public health foundation of healthcare landscape is a serious caveat which needs urgent makeover. Importantly, people have this rare opportunity to reboot their demagogy of overarching importance of hospital driven medical realm. Most of our health issues are self-limiting, benign or non-threatening or stress precipitated. Let us reclaim the control of such problems from the hands of medical professionals and set up our own roadmap with active participation of public health institutions. Over-reliance on medicines and treatments is self-defeating and preventive measures need to take centre stage in our daily lives. Luckily, there is a golden opportunity for people to allow natural healing of their bodies as well as minds unconfounded by medical care. Analysis of such data will motivate people to rediscover their self confidence in natural healing of body as well as other alternative sciences of healthcare.

Natures Experiment with Covid Intervention

Looking from natures perspective, it seems that a prospective controlled trial has been implemented in the world? It is not a multi-centric or multi-country, but it is a multi-continental research trial. And the intervention being tested is primum non nocere a Hippocratic oath first, do no harm. The data are being sequentially collected from precovid world (baseline or control phase) and covid affected world (study intervention phase). The precovid world which had been heavily dependent upon modernized medical care for last many decades will provide data for control or baseline phase. For the intervention phase, fresh data are being generated from all major hospitals where non-covid medical care has almost completely halted (a constrained form of primum non nocere). The data of baseline phase are already widely available in literature. The results have shown that nearly one in every 10 patients in developed countries is harmed due to hospital care, 50% of which is preventable (www.who.int features fact files patient_safety). The baseline scenario is more alarming in low- and middle-income countries (LMICs) where hazardous hospital care causes 134 million adverse events leading to 2.6 million deaths every year. Now with a global lockdown due to corona virus pandemic, routine hospital care has almost ceased. Only limited cases are being treated and all resources are diverted towards management of patients with Covid 19 illness. In this scenario, it would be quite revealing to know the magnitude of harm inflicted every year due to medical care. If such data are collated from all over the world throughout the covid pandemic, it would provide a unique and valuable comparative insight about the magnitude of harm posed simply by failure of Hippocratic principle of first do no harm.

Actionable Metrics for future roadmap

Few statistical indicators will certainly offer deep insight into the real need of medical care in our modern society. The sales of medicines, the hospital admission as well as readmission rates, number of diagnostic and therapeutic procedures as well as surgeries performed, healthcare spending, baseline rates of commonly reported hospital illness before and during covid 19 pandemic and final mortality data (both non covid as well as covid related deaths) stratified by age, gender, socioeconomic strata as well as severity of underlying illness will be immensely discerning metrics for policy makers and planners. Interestingly, experts with institutionalized mindset of health care model are attributing recent decline in healthcare demands for non covid illnesses as lull before storm. So far, the post covid Wuhan scenario seems to contradict the lull before storm theory of missing non covid illnesses and there are no alarming media reports that non covid mortality has spiked due to shutdown of most hospitals or clinic based medical centres. However, if things do not show the expected resurgence as fore casted by many experts, then it is high time to reboot the mindset of policy makers as well as public for better, safer, cheaper and simpler healthcare paradigms as well as models of care.

Take home message

It is high time that our highly institutionalized medical profession must cross the Rubicon and commit to Home Based Medical Care (HBMC) and Self-Monitoring (SM) as new paradigms of healthcare. Hopefully, the post covid zeitgeist is going to be marked with patient centric as well as patient driven care aided actively by public health institutions over hospital driven management protocols.

(Disclaimer: The author is Dr Sahul Bharti, MD Pediatrics (PGI, Chandigarh), PDCC Pediatric Endocrinology (SGPGI, Lucknow), Dip Statistics (PU, Chandigarh). He is Sat Pal Mittal National Award winner & founder of research based NGO-Build Healthy India Movement (BHIM). Views expressed are a personal opinion.)

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Lessons for medical profession during management of covid-19 pandemic: Is there a silver lining? - Elets

Outlook on the Worldwide Amniotic Membrane Industry to 2027 – Strategic Recommendations for New Entrants – Yahoo Finance

Dublin, April 24, 2020 (GLOBE NEWSWIRE) -- The "Amniotic Membrane - Global Market Outlook (2018-2027)" report has been added to ResearchAndMarkets.com's offering.

The Global Amniotic Membrane market accounted for $979.07 million in 2018 and is expected to reach $2650.28 million by 2027 growing at a CAGR of 11.7% during the forecast period. Rise in the geriatric population, increase in technological advancements and surge in awareness to reduce healthcare costs are the major factors propelling the market growth. However, factors such as dearth of skilled professionals are hampering the market growth.

Amniotic membrane is a combination of tissues and cells which helps in wound healing by being as a foundation for re-development of soft tissues. These are most widely used in eye surgery as a biological bandage to heal or replace damaged eye tissue.

Based on the end user, the hospitals segment is going to have a lucrative growth during the forecast period due to common visits by patients and its ability to cater to a varied range of surgical interventions. By geography, North America is going to have a lucrative growth during the forecast period owing to increasing the number of ophthalmic surgeries in the United States due to the geriatric population and presence of well-established healthcare infrastructure.

Some of the key players profiled in the Amniotic Membrane Market include Tissue-Tech Inc. (Amniox Medical Inc.), Skye Biologics Inc., MiMedx Group Inc., Katena Products, Inc. (IOP Ophthalmics), Integra Lifesciences Holdings Corporation (Derma Sciences Inc.), Human Regenerative Technologies, LLC, FzioMed Inc., Applied Biologics LLC, Amnio Technology, LLC and AlliquaBioMedical Inc.

What the report offers:

Key Topics Covered:

1 Executive Summary

2 Preface2.1 Abstract2.2 Stake Holders2.3 Research Scope2.4 Research Methodology2.5 Research Sources

3 Market Trend Analysis3.1 Introduction3.2 Drivers3.3 Restraints3.4 Opportunities3.5 Threats3.6 Product Analysis3.7 Application Analysis3.8 End User Analysis3.9 Emerging Markets3.10 Impact of Covid-19

4 Porters Five Force Analysis4.1 Bargaining power of suppliers4.2 Bargaining power of buyers4.3 Threat of substitutes4.4 Threat of new entrants4.5 Competitive rivalry

5 Global Amniotic Membrane Market, By Product5.1 Introduction5.2 Cryopreserved Amniotic Membrane5.3 Lyophilization Amniotic Membrane5.4 Dehydrated Amniotic Membrane

6 Global Amniotic Membrane Market, By Age Group6.1 Introduction6.2 Children6.3 Adults

7 Global Amniotic Membrane Market, By Application7.1 Introduction7.2 Surgical Wounds7.3 Stem Cell Biology7.4 Regenerative Medicine7.5 Prenatal Diagnosis7.6 Ophthalmology

8 Global Amniotic Membrane Market, By End User8.1 Introduction8.2 Specialized Clinics8.3 Hospitals8.4 Ambulatory Surgical Centers8.5 Academic Research Centers & Laboratory

9 Global Amniotic Membrane Market, By Geography9.1 Introduction9.2 North America9.2.1 US9.2.2 Canada9.2.3 Mexico9.3 Europe9.3.1 Germany9.3.2 UK9.3.3 Italy9.3.4 France9.3.5 Spain9.3.6 Rest of Europe9.4 Asia Pacific9.4.1 Japan9.4.2 China9.4.3 India9.4.4 Australia9.4.5 New Zealand9.4.6 South Korea9.4.7 Rest of Asia Pacific9.5 South America9.5.1 Argentina9.5.2 Brazil9.5.3 Chile9.5.4 Rest of South America9.6 Middle East & Africa9.6.1 Saudi Arabia9.6.2 UAE9.6.3 Qatar9.6.4 South Africa9.6.5 Rest of Middle East & Africa

10 Key Developments10.1 Agreements, Partnerships, Collaborations and Joint Ventures10.2 Acquisitions & Mergers10.3 New Product Launch10.4 Expansions10.5 Other Key Strategies

11 Company Profiling11.1 Tissue-Tech Inc (Amniox Medical Inc)11.2 Skye Biologics Inc11.3 MiMedx Group Inc11.4 Katena Products Inc (IOP Ophthalmics)11.5 Integra Lifesciences Holdings Corporation (Derma Sciences Inc)11.6 Human Regenerative Technologies LLC11.7 FzioMed Inc11.8 Applied Biologics LLC11.9 Amnio Technology LLC11.10 Alliqua BioMedical Inc

For more information about this report visit https://www.researchandmarkets.com/r/ft58l6

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

CONTACT: ResearchAndMarkets.comLaura Wood, Senior Press Managerpress@researchandmarkets.comFor E.S.T Office Hours Call 1-917-300-0470For U.S./CAN Toll Free Call 1-800-526-8630For GMT Office Hours Call +353-1-416-8900

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Outlook on the Worldwide Amniotic Membrane Industry to 2027 - Strategic Recommendations for New Entrants - Yahoo Finance

What Is The Economic Value of Receiving CAR T-Cell Therapy in an Outpatient Setting? – AJMC.com Managed Markets Network

Chimeric antigen receptor (CAR) T-cell therapy has been shown to improve health-related quality of life in patients with relapsed/refractory diffuse large B-cell lymphoma (LBCL). Currently, CAR T-cell therapies are primarily administered in inpatient settings. In a study published in JAMA Network Open, researchers found CAR T-cell therapy administered to patients with relapsed or refractory LBCL in outpatient settings was associated with lower estimated overall costs.

In a study published in JAMA Network Open, researchers found CAR T-cell therapy administered to patients with relapsed or refractory LBCL in outpatient settings was associated with lower estimated overall costs. CAR-T cell therapies also hold promise for patients with hematologic malignant neoplasms that are unresponsive or resistant to standard treatments, researchers said.

The treatment involves harvesting and reengineering an individuals own cells to attack specific malignant cells. CAR-T cells were initially developed using knowledge gleaned from allogeneic stem cell transplantsthat donor mature immune cells can attack healthy cells in the recipient patient.

In an economic evaluation, researchers used a decision-tree model to document patient clinical outcomes and costs, using only hypothetical patients and facilities. Excluding the CAR T-cell acquisition cost, researchers found hospitalization and office visits comprised 65.3% of the costs in inpatient settings and 48.4% of the costs in outpatient settings. Specifically, outpatient administration of CAR T-cell therapy in nonacademic specialty oncology networks was associated with a $32,987 (40.4%) reduction in total costs. Sensitivity analyses were carried out to address assumptions made to build the model.

Before the approval of CAR T-cell therapy, the available treatments for patients with relapsed or refractory LBCL included high-dose chemotherapy, salvage chemotherapy, and autologous hematopoietic stem cell transplantation (auto-HSCT); however, the prognosis after these treatments is often poor, authors said.

Researchers analyzed a predefined period from lymphodepletion to 30 days after the receipt of CAR T-cell infusion, in order to account for potential incidences of adverse events. Data were collected from several sources including theHealthcare Cost and Utilization Project National Inpatient Sample and the Medicare Hospital Outpatient Prospective Payment System. Investigators used secondary literature to inform model inputs.

Total cost of therapy included any costs associated with lymphodepletion, acquisition and infusion of CAR T-cells and management of acute adverse events.

The model also showed:

In this scenario, the model found patients who received CAR T-cell therapy in a nonacademic specialty oncology network setting would save $27,294 compared with the inpatient setting. In addition, in the scenario analysis the decrease in incremental cost reductions was associated with a lower overall incidence of AEs, which reduced the consequences of associated AE management costs, while the monitoring required at baseline was held constant.

The results indicate CAR T-cell therapy with a better safety profile may be more economical and could further leverage the outpatient site of care, researchers said. They concluded, The potential availability of CAR T-cell therapies with lower AE rates that are suitable for outpatient administration may reduce the total costs of care.

One limit to the study highlighted by the authors is the fact that outpatient administration may not be an option for all patients with LBCL.Eligibility can be contingent on the patients health status, support system, or the availability of housing near hospitals.

However, some specialists predict a gradual shift of all CAR T-cell therapies to the outpatient setting. Part of the reason for that [shift] is the way that it's reimbursed as an outpatient therapy is slightly more favorableso, financially it is better to do that, said John Sweetenham, MD, professor in the Department of Internal Medicine at UT Southwestern Medical Center and the Associate Director for Clinical Affairs at UTSWs Harold C. Simmons Comprehensive Cancer Center.

He continued, The problem is that these are very toxic treatments, and that many of the patients are not going to be manageable in the outpatient setting; but I do see that as one of the factors which is influencing a slow transition to outpatient CAR-Ts.

Expanded access to novel therapies in immune-oncology (IO) like CAR T-cell therapy also remains a priority among community level oncologists. Reimbursement, operational, and medical challenges associated with cellular therapy inhibit widespread uptake of the therapy, explained Lee Schwartzberg, MD, FACP, chief medical officer and board member at OneOncology. Only a small number of patients, frankly, have been treated with the first-generation CAR-T cells. So we need to develop new technologies and new operational models to do this, he said in an interview with The American Journal of Managed Care.

Reference

Lyman GH, Nguyen A, Snyder S, et al. Economic evaluation of chimeric antigen receptor T-cell therapy by site of care among patients with relapsed or refractory large B-cell lymphoma [published online April 6, 2020]. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2020.2072.

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Healing the heart by returning it to its infancy – FierceBiotech

Nearly a decade ago, researchers at UT Southwestern Medical Center discovered that when mouse hearts were damaged in the first seven days of life, they would regenerate. They reasoned that if they could find a way to recreate that regenerative ability later in life, it might provide a new way to treat heart damage.

Now, that same team has discovered that a protein called calcineurin plays a key role in blocking the ability of heart muscle to regenerate after the first week of life. The discovery could be used to develop treatments that reverse this process, in essence returning the heart to its developmental stage, they reported in the journal Nature.

The discovery builds on previous work at UT Southwestern that focused on the protein Meis1, a transcription factor that prevents heart cells from dividing. When the researchers deleted the gene in mice that makes that protein, their cardiomyocytes continued to divide after the first week of life. But the effect was transient.

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RELATED: Stem cells don't repair injured hearts, but inflammation might, study finds

Then the researchers discovered that another protein called Hoxb13 was also key, because it shuttles Meis1 into the cell nucleus. So they deleted the genes for both Meis1 and Hoxb13 in adult mice to see what would happen after a heart attack.

It worked. The ability of the animals hearts to pump blood quickly returned to near-normal levels, they said. Even though the mice were adults, their hearts looked much like they would in animals that were still developing.

After a series of further experiments, the UT Southwestern scientists discovered that calcineurin regulates both Hoxb13 and Meis1. Inhibiting calcineurin prolongs the window of cardiomyocyte proliferation, they wrote in the study.

The idea of treating heart damage by turning back the clock isnt new. In fact, several research teams have tried using stem cells to repair damaged heart tissue. But those efforts have been disappointing so far.

Last year, a team from the Cincinnati Children's Hospital Medical Center tracked stem cells injected into the hearts of mice and concluded that it was not the cells themselves, but rather their ability to activate macrophage cells from the immune system that promoted healing. That led the researchers to suggest that efforts to regenerate the heart focus less on stem cells and more on other processes in the body that might promote healing.

The discovery of calcineurins role in regulating the regeneration of the heart is notable due to the fact that there are already drugs on the market that target the protein. Thats because calcineurin plays a role in a variety of diseases, including rheumatoid arthritis and diabetes. Testing these drugs, either individually or in combination, and developing new medicines that target calcineurin directly could offer new strategies for repairing hearts damaged by heart attacks, high blood pressure, viruses and more, suggested co-author Hesham Sadek, M.D., Ph.D., a professor of internal medicine, molecular biology and biophysics at UT Southwestern.

"By building up the story of the fundamental mechanisms of heart cell division and what blocks it, Sadek said in a statement, we are now significantly closer to being able to harness these pathways to save lives.

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Academy adds new members from UW who ‘expand the boundaries of knowledge’ – University of Wisconsin-Madison

Six University of WisconsinMadison faculty have been elected to the American Academy of Arts and Sciences.

Bioethicist R. Alta Charo, psychologist Seth Pollak, philosopher Steven Nadler, historian Louise Young, geographer Lisa Naughton and chemist Martin Zanni are among the 276 new members announced April 23. Election to the academy recognizes distinguished contributions by these scholars to their fields.

Former UWMadison Provost Sarah Mangelsdorf was also elected to the academy this year. Mangelsdorf began her tenure as president of the University of Rochester in July 2019.

Charo

Charo is the Warren P. Knowles Professor of Law and Bioethics and an expert on law and policy related to research ethics, stem cell research and new medical technology. She has served as an adviser and expert to the federal government and multiple presidential administrations on ethical concerns in cutting-edge research. And she recently co-chaired a National Academy of Sciences panel to develop recommendations around human gene editing.

Pollak

Pollak is the College of Letters & Science Distinguished Professor of Psychology. At UWMadisons Waisman Center, he researches the link between childhood stress and well-being. Pollaks team has uncovered the lasting effects of negative experiences in childhood and seeks to use this knowledge to improve the social and emotional experiences of children and the adults they become.

Nadler

Nadler is the William H. Hay II Professor and Evjue-Bascom Professor in Humanities and a philosopher specializing in early modern and Jewish philosophy. He has authored 13 books, including Rembrandts Jews, a Pulitzer Prize finalist, and the graphic book, co-authored with his son Ben Nadler, Heretics!: The Wondrous (and Dangerous) Beginnings of Modern Philosophy. Nadler currently serves as director of UWMadisons Institute for Research in the Humanities.

Young

Young is a professor of Japanese history. Her research has covered Japan in and around the Second World War, and she has authored two books on Japans culture before and during the war. Her current book projects include a history of the countrys transition from feudal systems to a modern class hierarchy and a reexamination of Japans role in creating the modern world from the mid-19th century onward.

Naughton

Naughton is a professor of geography focused on the social and political consequences of biodiversity conservation. Her research has focused on protected areas, wildlife and land use conflicts in South America, and she has studied public attitudes toward wolf recovery in the Upper Midwest. She directed UWMadisons Land Tenure Center from 2009 to 2013 and chaired the Nelson Institutes graduate program in Conservation Biology and Sustainable Development from 2007 to 2010.

Zanni

Zanni is the V.W. Meloche-Bascom Professor of Chemistry. Using an innovative method known as two-dimensional spectroscopy, the Zanni lab studies topics in biophysics and the energy sciences. They have researched carbon nanotube energy transfer, solar cell charge transfer, and the ways in which protein aggregations lead to diseases such as Type 2 diabetes and cataracts. Zanni was elected a fellow of the American Physical Society in 2010.

The news that six colleagues are new members of the American Academy of Arts and Sciences is further evidence for a fact: Faculty at UWMadison are extraordinary, says UWMadison Provost Karl Scholz. We congratulate these six for this wonderful recognition and thank them, and all in the UWMadison community, for relentless efforts to expand the boundaries of knowledge and understanding of the human condition.

The academy was formed in 1780 to honor exceptional individuals and engage them in advancing the public good. Members have included Benjamin Franklin, Alexander Hamilton, Margaret Mead and Martin Luther King Jr. This years new members include former Attorney General Eric Holder, author Ann Patchett and filmmaker Richard Linklater.

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Academy adds new members from UW who 'expand the boundaries of knowledge' - University of Wisconsin-Madison

What Factors Influence Hematological Recovery in Patients Who Receive CAR-T Therapies? – Cancer Therapy Advisor

A few weeks afterreceiving chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, many patientsexperience prolonged reductions in blood cell counts, possibly making them morevulnerable to infections.

Two recent studies characterized the extent and duration of postCAR-T cytopenia among patients receiving CAR-T therapy for hematological malignancies with 1 study offering insights on some of the possible factors that may influence hematological count recovery.

Whats important to know is that by day 90, mostpatients recover, noted UroosaIbrahim, MD, stemcell transplantation and cellular therapy fellow at the Tisch Cancer Instituteof the Icahn School of Medicine at Mount Sinai,New York, who coauthored 1 of the studies. Were supporting them for [approximately]3 months [with treatment], but then theyll recover, which is good to know.

One study by MemorialSloan Kettering Cancer Center (MSKCC) researchers followed 83 adult patientswho received CAR-T therapy: 40 patients received 1 of 2 Food and DrugAdministration (FDA)-approved therapies, axicabtageneciloleucel (axi-cel; Yescarta) ortisagenlecleucel (tisa-cel; Kymriah), to treat relapsed/refractory B-cell lymphoma.

The remainder comprised 37 patients with relapsed/refractory B-cell acute lymphoblastic leukemia who were currently enrolled in a clinical trial in which they received an experimental CAR-T therapy where cells express the 19-28z CAR construct (ClinicalTrials.gov Identifier: NCT01044069), and 6 multiple myeloma patients who received a different experimental CAR-T construct that targets the B-cell maturation antigen (BCMA) (ClinicalTrials.gov Identifier: NCT03070327). The findings were presented at the annual Transplantation and Cellular Therapy Meetings of ASCT and CIBMTR in February 2020.1

By 1 month, theresearchers observed that 24% of patients experienced a complete recovery ofhemoglobin, platelets, absolute neutrophil count, and white blood cell counts recovery being defined as reaching safe levels, and without requiringtransfusions or treatment with growth factors.

Recovery of hemoglobinwas noted in 61% of patients, platelets in 51% of patients, absolute neutrophilcount in 33% of patients, and white blood cell count in 28% of patients.Examining 41 patients at 3 months, those figures were 93%, 90%, 81%, and 59%,respectively, and overall, 56% saw a complete blood count recovery.

The results werebroadly consistent with recent research by Dr Ibrahim and Keren Osman, MD,associate professor and director of medicine at the Icahn School of Medicine atMount Sinai and director of cellular therapy service in the bone marrow andstem cell transplantation program at the schools Tisch Cancer Institute. Thatstudy comprised 50 patients 41 with multiple myeloma and 9 with diffuse largeB-cell lymphoma who received either axicabtagene ciloleucel, or 1 of 2 experimentalanti-BCMA CAR-T therapies, bb2121 or bb21217.

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FDA Approves New Therapy for Triple Negative Breast Cancer That Has Spread, Not Responded to Other Treatments – FDA.gov

For Immediate Release: April 22, 2020

Today, the U.S. Food and Drug Administration granted accelerated approval to Trodelvy (sacituzumab govitecan-hziy) for the treatment of adult patients with triple-negative breast cancer that has spread to other parts of the body. Patients must have received at least two prior therapies before taking Trodelvy.

Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options. Chemotherapy has been the mainstay of treatment for triple-negative breast cancer. The approval of Trodelvy today represents a new targeted therapy for patients living with this aggressive malignancy, said Richard Pazdur, M.D., director of the FDAs Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDAs Center for Drug Evaluation and Research. There is intense interest in finding new medications to help treat metastatic triple-negative breast cancer. Todays approval provides patients whove already tried two prior therapies with a new option.

Trodelvy is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate, meaning that the drug targets the Trop-2 receptor that helps the cancer grow, divide and spread, and is linked to topoisomerase inhibitor, which is a chemical compound that is toxic to cancer cells. Approximately two of every 10 breast cancer diagnoses worldwide are triple-negative. Triple-negative breast cancer is a type of breast cancer that tests negative for estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2) protein. Therefore, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2.

As part of FDAs ongoing and aggressive commitment to address the novel coronavirus pandemic, we continue to keep a strong focus on patients with cancer who constitute a vulnerable population at risk of contracting the disease, said Pazdur. At this critical time, we continue to expedite oncology product development. This application was approved more than a month ahead of the FDA goal date an example of that commitment. Our staff is continuing to meet with drug developers, academic investigators, and patient advocates to push forward the coordinated review of treatments for cancer.

The FDA approved Trodelvy based on the results of a clinical trial of 108 patients with metastatic triple-negative breast cancer who had received at least two prior treatments for metastatic disease. The efficacy of Trodelvy was based on the overall response rate (ORR) which reflects the percentage of patients that had a certain amount of tumor shrinkage. The ORR was 33.3%, with a median duration of response of 7.7 months. Of the patients with a response to Trodelvy, 55.6% maintained their response for 6 or more months and 16.7% maintained their response for 12 or more months.

The prescribing information for Trodelvy includes a Boxed Warning to advise health care professionals and patients about the risk of severe neutropenia (abnormally low levels of white blood cells) and severe diarrhea. Health care professionals should monitor patients blood cell counts periodically during treatment with Trodelvy and consider treatment with a type of therapy called granulocyte-colony stimulating factor (G-CSF), which stimulates the bone marrow to produce white blood cells called granulocytes and stem cells and releases them into the bloodstream, to help prevent infection, and should initiate anti-infective treatment in patients with febrile neutropenia (development of fever when white blood cell are abnormally low).

Additionally, health care professionals should monitor patients with diarrhea and give fluid, electrolytes, and supportive care medications, as needed. Trodelvy may need to be withheld, dose reduced or permanently discontinued for neutropenia or diarrhea. Trodelvy can cause hypersensitivy reactions including severe anaphylactic (allergic) reactions. Patients should be monitored for infusion-related reactions and health care professionals should discontinue Trodelvy if severe or life-threatening reactions occur. If patients experience nausea or vomiting while taking Trodelvy, health care professionals should use antiemetic preventive treatment, to prevent nausea and vomitting. Patients with reduced uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of Trodelvy treatment.

The most common side effects for patients taking Trodelvy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia (hair loss), constipation, decreased appetite, rash and abdominal pain.

Women who are pregnant should not take Trodelvy because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to inform females of reproductive age to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Male patients with female partners of reproductive potential should also use effective contraception during treatment with Trodelvy and for three months after the last dose.

Trodelvy was granted accelerated approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials are required to verify and describe Trodelvys clinical benefit.

The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Trodelvy was also granted Fast Track designation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need.

The FDA granted approval of Trodelvy to Immunomedics, Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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