Efforts at coronavirus vaccines and treatments abound in the Bay Area – San Francisco Chronicle

The frenetic search for the miracle that will rid the world of COVID-19 is branching out in a thousand directions, and a large part of the microbial treasure hunt is going on in the Bay Area, where major progress has been made in the 100 days since residents were ordered to shelter in place.

Scientists at universities, laboratories, biotechnology companies and drug manufacturers are combing through blood plasma taken from infected patients for secrets that will help them fight the disease.

The key is likely a super-strength antibody found in some patients. But researchers must first figure out how those antibodies work and how they can be harnessed and used to stop the many health problems associated with COVID-19, particularly acute respiratory distress syndrome, or ARDS, which has killed more people than any other complication connected to the disease.

Other developments showing promise include injections of mesenchymal stem cells, found in bone marrow and umbilical cords, that doctors are studying to battle inflammation caused by ARDS. And a steroid called dexamethasone reduced the number of deaths by halting the overreactive immune responses in seriously ill patients in the United Kingdom.

In all, more than 130 vaccines and 220 treatments are being tested worldwide.

What follows is a list of some of the most promising elixirs, medications and vaccines with ties to the Bay Area:

Monoclonal antibodies / Vir Biotechnology, San Francisco: Scientists at Vir and several institutions, including Stanford and UCSF, are studying monoclonal antibodies, which are clones of coronavirus-fighting antibodies produced by COVID-19 patients.

The idea is to utilize these neutralizing antibodies which bind to the virus crown-like spikes and prevent them from entering and hijacking human cells.

Only about 5% of coronavirus patients have these super-strength antibodies, and those people are believed to be immune to a second attack.

The trick for scientists at Vir is to identify these neutralizing antibodies, harvest, purify and clone them. If they succeed, the resulting monoclones could then be used to inoculate people and it is hoped give them long-term immunity against the coronavirus. The company recently signed a deal with Samsung Biologics, in South Korea, to scale up production of a temporary vaccine in the fall after clinical trials are complete.

Another monoclonal antibody, leronlimab, is being studied in coronavirus clinical trials by its Washington state drugmaker, CytoDyn. The companys chief medical officer is in San Francisco, and the company that does laboratory tests of leronlimab is in San Carlos.

Interferon-lambda / Stanford University: Doctors at Stanford are running a trial to see if interferon-lambda, which is administered by injection, helps patients in the early stages of COVID-19. Interferon-lambda is a manufactured version of a naturally occurring protein that has been used to treat hepatitis. Stanford doctors hope it will boost the immune system response to coronavirus infections.

Dr. Upinder Singh, a Stanford infectious-disease expert, said the trial has enrolled more than 50 patients and is halfway finished. We have noted that patients tolerate the drug very well, she said.

Mesenchymal stem cells / UCSF and UC Davis Medical Center: UCSF Dr. Michael Matthay is leading a study about whether a kind of stem cell found in bone marrow can help patients with ARDS. Matthay hopes that the stem cells can help reduce the inflammation associated with some of ARDS most dire respiratory symptoms, and help patients lungs to recover.

Matthay is aiming to enroll 120 patients in San Francisco, the UC Davis Medical Center in Sacramento and hospitals in a handful of other states. He said the trial, which includes a small number ARDS patients who dont have COVID-19, should have results within a year. So far 17 patients are enrolled in the trial, most of them in San Francisco.

Remdesivir / Gilead Sciences (Foster City): Remdesivir, once conceived as a potential treatment for ebola, was the first drug to show some promise in treating COVID-19 patients. The drug interferes with the process through which the virus replicates itself. A large study led by the federal government generated excitement in late April when officials said hospitalized patients who received remdesivir intravenously recovered faster than those who received a placebo.

A later study looking at dosage showed some benefit for moderately ill COVID-19 patients who received remdesivir for five days, but improvement among those who got it for 10 days was not statistically significant. Gilead, a drug company, recently announced that it will soon launch another clinical trial to see how remdesivir works on 50 pediatric patients, from newborns to teenagers, with moderate to severe COVID-19 symptoms. More than 30 locations in the U.S. and Europe will be involved in the trial, the company said.

Coronavirus crisis: 100 days

Editors note: Its been 100 days since the Bay Area sheltered in place, protecting itself from the coronavirus pandemic. What have we learned in that time? And what does the future hold for the region and its fight against COVID-19? The Chronicle explores the past 100 days and looks to the future in this exclusive report.

Favipiravir / Fujifilm Toyama Chemical (Stanford University): This antiviral drug, developed in 2014 by a subsidiary of the Japanese film company to treat influenza, is undergoing numerous clinical studies worldwide, including a Stanford University trial that began this month. Unlike remdesivir, it can be administered orally, so it can be used to treat patients early in the disease, before hospitalization is necessary.

Stanford epidemiologists want to see if favipiravir, which has shown promising results in other trials, prevents the coronavirus from replicating in human cells, halts the shedding of the virus and reduces the severity of infection. The Stanford study, the only outpatient trial for this drug in the nation, is enrolling 120 people who have been diagnosed with COVID-19 within the past 72 hours. Half of them will get a placebo. People can enroll by emailing treatcovid@stanford.edu.

Colchicine / UCSF (San Francisco and New York): The anti-inflammatory drug commonly used to treat gout flare-ups is being studied in the U.S. by scientists at UCSF and New York University. The drug short-circuits inflammation by decreasing the bodys production of certain proteins, and researchers hope that it will reduce lung complications and prevent deaths from COVID-19. About 6,000 patients are receiving colchicine or a placebo during the clinical trial, dubbed Colcorona, which began in March and is expected to be completed in September.

Selinexor / Kaiser Permanente: Kaiser hospitals in San Francisco, Oakland and Sacramento are studying selinexor, an anticancer drug that blocks a key protein in the cellular machinery for DNA processing, as a potential COVID-19 treatment. The drug has both antiviral and anti-inflammatory properties, and its administered orally, according to Kaisers Dr. Jacek Skarbinski. The trial aims to enroll 250 patients with severe symptoms at Kaiser and other hospitals that are participating nationwide.

VXA-COV2-1 / Vaxart, South San Francisco: The biotechnology company Vaxart is testing this drug to see if it is as effective at controlling COVID-19 as trials have shown it to be against influenza. VXA-COV2-1, the only potential vaccine in pill form, uses the genetic code of the coronavirus to trigger a defensive response in mucous membranes. The hope is that the newly fortified membranes will prevent the virus from entering the body.

Its the only vaccine (candidate) that activates the first line of defense, which is the mucosa, said Andrei Floroiu, Vaxarts chief executive, noting that intravenous vaccines kill the virus after it is inside the body. Our vaccine may prevent you from getting infected at all.

The drug was effective against influenza and norovirus in trials and appears to work on laboratory animals, Floroiu said. He expects trials of VXA-COV2-1 on humans to begin later this summer.

VaxiPatch / Verndari (Napa and UC Davis Medical Center): Napa vaccine company Verndari makes a patented adhesive patch that can deliver a vaccine instead of a shot. Now, the company is trying to make a vaccine for COVID-19 that they can administer through that patch. At UC Davis Medical Center in Sacramento, Verndari researchers are developing a potential vaccine that relies on the coronavirus spike-shaped protein. When injected into a person, the substance would ideally train their body to recognize the virus and fight it off without becoming ill.

A spokeswoman told The Chronicle that the companys preclinical tests have shown early, positive data in developing an immune response. Verndari hopes to move into the next phase of testing in the coming weeks and start clinical trials in humans this year.

If the vaccine is proved effective and safe, patients could receive it through the mail, according to company CEO Dr. Daniel Henderson. The patch would leave a temporary mark on the skin that patients could photograph and send to their doctor as proof they have taken the vaccine, Henderson has said.

Peter Fimrite and J.D. Morris are San Francisco Chronicle staff writers. Email: pfimrite@sfchronicle.com, jd.morris@sfchronicle.com Twitter: @pfimrite, @thejdmorris

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Efforts at coronavirus vaccines and treatments abound in the Bay Area - San Francisco Chronicle

New Preclinical Data Demonstrates Immune-Enhancing Effects of Triple I/O Combination Therapy with BeyondSpring’s Plinabulin – GlobeNewswire

June 23, 2020 08:00 ET | Source: BeyondSpring, Inc.

Research Presented at 2020 AACR Virtual Annual Meeting

The Triple I/O Combination of Plinabulin, Anti-PD-1 and Radiation Achieved a 100 Percent Complete Response in Anti-PD-1 Non-responsive Animal Model

Triple I/O Combination to Be Administered to Patients Who Failed I/O in Second Half of 2020

NEW YORK, June 23, 2020 (GLOBE NEWSWIRE) -- BeyondSpring (the Company or BeyondSpring) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative immuno-oncology (I/O) therapies, today announced new preclinical research findings that indicate BeyondSprings lead asset, Plinabulin, enhances immuno-radiotherapy for cancer patients. The results of this preclinical study was highlighted in a poster presentation titled, Plinabulin, a microtubule destabilizing agent, improves tumor control by enhancing dendritic cell maturation and CD8 T cell infiltration in combination with immunoradiotherapy, at this years American Association for Cancer Research (AACR) Virtual Annual Meeting on June 22, 2020.

Based on these preclinical findings, including a 100% complete response of the triple I/O combination of Plinabulin, anti-PD-1, and radiation in a PD-1 antibody non-responsive model, the compound is being advanced toward a Phase 1 clinical trial in patients who failed or progressed on PD-1 / PD-L1 antibody treatments. Principal investigator Steven H. Lin,M.D., Ph.D., associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center, presented the research data.

The experiments from my lab demonstrated that Plinabulin treatment in murine cancer models leads to activation of antigen-presenting dendritic cells, said Dr. Lin. The combination therapy with Plinabulin, anti-PD-1 therapy and radiation therapy further activated the immune system, resulting in increased T-cell activation, which is associated with increased tumor regressions.

Additional data highlights include:

The above data presentation is available on the Posters page of BeyondSprings website at: https://www.beyondspringpharma.com/conferences/list.aspx?lcid=3.

Peer-reviewed 2019 publications in Chem and Cell Reports demonstrated that Plinabulin is differentiated from all other tubulin-targeted agents through its binding site and kinetics and is among the most potent agents that induce dendritic cell maturation. Dendritic cells are key immune cell types in the activation of the immune system against cancer cells, but currently approved immuno-oncology agents, such as antibodies to PD-1, only take the brakes off of T-cells without activating antigen-presenting cells that stimulate T-cells to attack foreign proteins expressed by cancer cells.

We believe that the activation of dendritic cells is a key to unlocking the next boost to the efficacy of immuno-oncology agents, said Dr. James Tonra, BeyondSprings Chief Scientific Officer. Activated dendritic cells present foreign tumor antigens to T-cells to induce cancer-directed immune attacks. Thus, adding this critical step of dendritic cell activation in the immune cascade to the established effects of immune checkpoint inhibition therapies is expected to increase overall anti-cancer efficacy in the clinic. Our anti-cancer strategy was to activate dendritic cells and T-cells, in combination with checkpoint inhibition and to add onto the benefits of neoantigen generation and immune activation from radiotherapy, as Plinabulin serves as the key to reverse the tumor non-response to PD-1/PD-L1 antibodies. The data strongly indicates that this triple combination has enough potential to move into clinical testing to help patients who failed or had progressed on anti-PD-1/PD-L1 targeted therapy, a severely unmet medical need.

About BeyondSpring BeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies. BeyondSprings lead asset, first-in-class agent Plinabulin as an immune and stem cell modulator, is in a Phase 3 global clinical trial as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and two Phase 3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has strong R&D capabilities with a robust pipeline in addition to Plinabulin, including three immuno-oncology assets and a drug discovery platform using the ubiquitination degradation pathway. The Company also has a seasoned management team with many years of experience bringing drugs to the global market.

About Plinabulin Plinabulin, BeyondSprings lead asset, is a differentiated immune and stem cell modulator. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The durable anticancer benefits of Plinabulin have been associated with its effect as a potent antigen-presenting cell (APC) inducer (through dendritic cell maturation) and T-cell activation (Chem and Cell Reports, 2019). Plinabulins CIN data highlights the ability to boost the number of hematopoietic stem / progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin to not only treat CIN but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements that are not historical facts. Words such as "will," "expect," "anticipate," "plan," "believe," "design," "may," "future," "estimate," "predict," "objective," "goal," or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring's current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company's future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSprings most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.

Media Contacts Caitlin Kasunich / Raquel Cona KCSA Strategic Communications 212.896.1241 / 212.896.1276 ckasunich@kcsa.com / rcona@kcsa.com

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New Preclinical Data Demonstrates Immune-Enhancing Effects of Triple I/O Combination Therapy with BeyondSpring's Plinabulin - GlobeNewswire

[Herald Interview] Spinning cord blood into stem cell therapies – The Korea Herald

Medipost CEO Yang Yoon-sun (Lim Jeong-yeo/The Korea Herald)

Her journey as a professor of pathology at Samsung Medical Center to head of a cord blood stem cell research company at the age of 37 came with prejudices, challenges and pitfalls, but also with encouragement, conviction and immense potential.

Cord blood is that inside the umbilical cord that connects the baby and mother, and can be ethically, and legally, procured after a babys birth. Despite containing one of the most potent types of stem cell and possibilities for vast medicinal repurposing, cord blood has often been discarded due to a lack of technology to refine it, Yang said.

In 2000, the concept of processing raw cord blood for stem cell therapies was still in a nascent stage across the world.

Soon Yang came to realize that research on cord blood should be approached commercially rather than academically to fast-track the development of consequential treatments.

The conviction was supported by her colleagues, and further fostered by a nationwide boom in startups.

Yang met obstetricians and gynecologists nationwide to help persuade laboring mothers to donate the otherwise unusable blood.

Medipost humbly started out in a rented laboratory of a Doosan Group research facility in Yongin, Gyeonggi Province, on June 26, 2000.

The company soon got listed on Koreas tech-heavy secondary bourse Kosdaq in 2005. In 2019, the company posted roughly 45.8 billion won ($37.9 million) in revenue with a net loss of over 14.1 billion won.

Medipost now operates from a self-owned building with 14 levels in the biocluster of Pangyo, Seongnam in Gyeonggi Province. Some 200 full-time employees work for Medipost, with entities strewn in global locations such as the US, China and Japan.

It has seven subsidiaries, three of which are Medipost America, Shandong Orlife Pharmaceutical and Evastem Corp., located overseas in the US, China and Japan, respectively.

Medipost, the embodiment of Yangs visions, has three business pillars: its cord blood bank, cell therapy developments and health supplements.

The companys main revenue source is the cord blood bank, where over 259,000 children have their cord blood stored, with more being added. It roughly costs around 1.4 million won to store a vial containing cord blood for 15 years, and 4 million won to store it for a lifetime.

Celltree cord blood bank (Medipost)

Most recently, Winter Sonata actor Choi Ji-woo decided to store the cord blood of her first daughter, whom she gave birth to at age 45.

It was not always a smooth ride, as soon after the companys initial public offering, there broke out the ethical scandal of embryonic stem cell research that clouded the general perception of stem cell research in the public eye. More than once the companys revenue has taken a dive of 50 percent.

However, Yang has no regrets.

As for me, every step was an unexpected challenge and overcoming each hardship taught me to be prepared for anything to maintain business stability, Yang said in an interview with The Korea Herald.

Cord blood, Yang said, is an immune response-safe therapeutic insurance in case the children and their families face incurable diseases such as leukemia, refractory anemia, immune disorders, cerebral palsy, developmental disorders or various forms of cancer.

If the babys cord blood is used to treat the same baby, it would be called an autologous therapy. If used for another family member, that is an allogenic therapy.

Cartistem, an allogenic osteoarthritis treatment that was approved by the local Drug Ministry in 2012, is the next biggest contributor to Mediposts business growth, as well as a balm to the knee problems of seniors.

Celltree cord blood bank (Medipost)

Cartistem is a stem cell therapeutic agent for cartilage regeneration crafted from Mediposts pool of research-purpose cord blood. Once surgically applied to the affected region, the drug has been successful in triggering regrowth of knee cartilage in 98 percent of the 103 patients treated in clinical phase 3 trials.

Medipost counts over 16,000 patients who have so far benefited from the use of Cartistem in the eight years the drug has been in service. It is prescribed at some 550 hospitals here.

The therapy has currently finished clinical phase 1 and 2a trials in the US to launch there, and is pending phase 2 clinical trials in Japan with aims to start tests in July. As it would require a great volume of funding to carry out wide-scale clinical phase 3 trials in the US, it might be Japan where Cartistem launches first, Yang said.

SK Bioland, an SK Group subsidiary, in-licensed Cartistems indication for ankle joint inflammation at end-2019 to carry out clinical phase 3 trials and have full domestic rights to the drugs use for ankle therapy.

Other than Cartistem, Medipost has Pneumostem, Neurostem and SMUP-Cell injections under developments.

Pneumostem is a stem cell therapy for prematurely born babies lung fibrosis. Unlike adult lung fibrosis, which has numerous causes and is sometimes isolated, newborn babies lung problems have a singular cause and therefore a clearer path of tackling it.

Pneumostem is undergoing clinical phase 2 trials in Korea and has completed phase 1 and 2 clinical trials in the US. It has been designated by the US Food and Drug Administration and the European Medicines Agency as an orphan drug, granting it government assistance as it would otherwise prove unprofitable due to its limited scope, and it has the FDAs fast track designation. Once its efficacy is proved, it may attempt to expand Penumostems indications to other forms of lung inflammation, including COVID-19, Yang said.

Neurostem is a proposed Alzheimers disease stem cell therapy. It is believed to promote the degradation of beta-amyloid, and accumulation in the brain is believed to cause Alzheimers-type dementia. The pipeline has completed phase 1 and 2a clinical trials in Korea, and has been cleared for the FDAs phase 1 and 2 investigational new drug application.

SMUP-Cell, an injectable type innovative knee joint treatment, saves patients the trouble of undergoing intrusive surgery. Medipost has finished administrating the cell therapy to the first round of clinical phase 1 trials and has begun the five-year tracking of patients progress. If the drug makes it to commercial stage, it would be a groundbreaking solution for patients of joint inflammation who are in pain, but not at the stage yet to go under the knife.

At its basement in Pangyo, Medipost has enough space to install more cord blood tanks to last the next 20 years.

Our only goal should be to provide stem cell regenerative therapy to patients whose predicament previously had no life-extending solution. If we save one patient -- while to us it may just be one person, it is 100 percent to the patient themselves. That is our step-by-step approach, said Yang.

By Lim Jeong-yeo (kaylalim@heraldcorp.com)

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[Herald Interview] Spinning cord blood into stem cell therapies - The Korea Herald

Children’s Hospital Los Angeles Ranked No. 1 Children’s Hospital in the Western U.S., No. 5 Nationally for Second Straight Year – Business Wire

LOS ANGELES--(BUSINESS WIRE)--Children's Hospital Los Angeles (CHLA) ranks again among the nations premier destinations for pediatric care, according to the U.S. News & World Report Best Children's Hospitals annual list released today.

CHLA not only retained its national No. 5 ranking in U.S. News Honor Roll of Best Childrens Hospitalswhich recognizes institutions with the most outstanding pediatric clinical careit continued its four-year streak of being the highest-scoring childrens hospital in the entire Western United States.

To make U.S. News & World Reports prestigious Best Childrens Hospitals Honor Roll, one must demonstrate the strongest achievements in clinical excellence, with a matchless team of expert, compassionate specialists committed to research and education as well as protocols that drive safety and quality and consistently lead to the best health outcomes for patients, says CHLA President and Chief Executive Officer Paul S. Viviano. "This honor affirms the work of every CHLA team member and our belief that when parents choose Childrens Hospital Los Angeles, they are choosing the best care for kids."

Every year, U.S. News scores nearly every major hospital and health system in the country and ranks them according to performance benchmarks, peer review, certifications, and other data provided by the hospital and third-party measurements of excellence. Children's hospitals are ranked separately from other facilities due to the specialized expertise, equipment and facilities required to care for infants, children and youth.

This year, U.S. News surveyed 118 pediatric medical centers, including hospitals that are freestanding or part of a larger institution. CHLA improved its ranking over last year in seven of the 10 pediatric specialty categories the survey considers, including a number two ranking for Neonatal Care. In all, the hospital earned top-10 recognition in seven of those categories:

CHLA has an organization-wide commitment to providing our patients the care they need no matter their circumstances, says CHLA Chief Medical Officer James Stein, M.D., MSc. "Our clinical teams often treat the most acute cases that are outside the scope or expertise of other childrens hospitals in California, and being named a Top-5 childrens hospital in the U.S. is a testament to the clinicians and staff who work every day to make sure each child receives the best care and experience possible.

Founded in 1901, Children's Hospital Los Angeles is a pediatric academic medical center built around its mission of creating hope and building healthier futures for children. Renowned for its world-class clinical care, leading-edge research and one of the largest and most successful pediatric training programs in the countryall while being the pediatric safety net hospital for the entire regionCHLA now sees more than 600,000 patient visits annually between its main hospital and five neighborhood care clinics.

CHLA physicians, nurses and clinical staff provide compassionate and lifesaving pediatric care for patients ranging from infants to young adults, hailing from all 50 states and more than 75 countries. Clinical care is led by physicians who are faculty members of the Keck School of Medicine of USC. Many of the hospital's achievements in care are made possible through a cohesive relationship between clinical experts at the bedside and the basic, translational, and clinical research conducted in The Saban Research Institute of CHLA.

In the past year, CHLA has had several notable achievements, including:

U.S. News & World Report works with research firm RTI International to develop its annual Best Children's Hospitals list, a collaboration between hospitals and the magazine to benchmark the performance of childrens hospitals for the benefit of parents and their children. The survey evaluates hundreds of data points, including patient survival and surgical complication rates; staffing, technology and special services; infection prevention and delivery of care; reputation among peer physicians nationwide (i.e. Where would the best pediatric specialists send their kids?); how involved parents are in their childrens care; and many other measurements of excellence.

U.S. News Media Group, parent of U.S. News & World Report, announced the 2020-21 hospital rankings online at 12:01 a.m. EDT on Tuesday, June 16. For additional information, please visit the Best Childrens Hospitals Honor Roll and specialty rankings page at usnews.com/childrenshospitals.

About Children's Hospital Los Angeles

Founded in 1901, Children's Hospital Los Angeles is ranked the top childrens hospital in California and fifth in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll of childrens hospitals. Clinical care is led by physicians who are faculty members of the Keck School of Medicine of USC through an affiliation dating from 1932. The hospital also leads the largest pediatric residency training program at a freestanding childrens hospital of its kind in the western United States. The Saban Research Institute of Childrens Hospital Los Angeles encompasses basic, translational and clinical research conducted at CHLA. The hospitals Center for Global Health facilitates services for international patients from more than 75 countries. To learn more, follow us on Facebook, Instagram, LinkedIn and Twitter, and visit our blog for families (CHLA.org/blog) and our research blog (ResearCHLABlog.org).

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Children's Hospital Los Angeles Ranked No. 1 Children's Hospital in the Western U.S., No. 5 Nationally for Second Straight Year - Business Wire

The BCG a Tuberculosis Vaccine Boosts Immune Cells and Reduces Risk of Other Infections – Gilmore Health News

According to a new study published in Cell Host & Microbe, a vaccine against tuberculosis (TB) that has been around for about a century can offer protection against other infections as well.

BCG Vaccine

Researchers from the University of Bonn and the Radboud University Medical Center, Nijmegen, in collaboration with counterparts from Australia and Denmark, have found that the BCG vaccine bolsters the immune system. BCG is an abbreviation for Bacillus Calmette-Guerin, the bacterium responsible for tuberculosis.

Read Also: Tuberculosis Vaccine (BCG) Could Help the Immune System Fight COVID 19

The BCG vaccine was first used medically in 1921. A hundred years after, it offers the only effective vaccination against the microbe causing TB.

Evidence suggests that the TB vaccine seems to enhance the immunity of patients. Scientists have only been unable to explain why this is the case before now.

People vaccinated with this biological preparation were found to have fewer infection issues. For instance, evidence from a West African country shows that newborns that were vaccinated died less often compared to those that were not.

Read Also: Coronavirus Mutations May Render Search for Vaccine Futile, Researchers Find

This new study explains to an extent why the effects of vaccination may persist for years, reducing vulnerability to other infections.

There is what medical experts call trained immunity. This may be described as the immunological memory of the innate immune system. It enables improved innate immune response to different types of infections.

There is insufficient research to explain why trained immunity could be effective for years. Its efficacy remains long after the immune cells present in the blood when a vaccine was used have died off. Scientists wanted to learn more about this in the new research.

Read Also: Can the World Produce Enough Vaccine For Coronavirus?

The team administered the BCG vaccine to 15 volunteers. It gave a placebo to five other subjects to enable assessment of vaccination effects.

Blood and bone marrow samples of these subjects were obtained three months after the vaccination. The researchers observed notable differences between persons in the two groups.

Immune cells in the blood of participants that got the vaccine produced considerably more cytokines. These inflammatory, intercellular messengers help to mediate and regulate immunity. They bolster the immune system.

Vaccination also promoted the activity of entirely different genes. These, in particular, included those involved in the production of cytokines.

Read Also: COVID-19: All the Essential Vitamins and Minerals for a Strong Immune System

Immune cells are of diverse types, but they all originate from the bone marrow. The hematopoietic stem cells, which give birth to all immune cells, come from the bone marrow.

Like other human cells, these cells contain in their nuclei numerous thousands of genes. These hereditary units may be compared to books containing instructions. Cells access these books for instructions whenever they want to produce a molecule.

However, it is not always possible or easy for cells to access the genes. The BCG vaccine changes the narrative in such cases when access is denied.

Read Also: Measles Temporarily Wipes Out The Immune System According To Study

We have found that after vaccination, certain genetic material becomes more accessible, which means that it can be read by the cells more frequently, said Prof. Dr. Andreas Schlitzer, a Life and Medical Sciences (LIMES) researcher at the University of Bonn.

Vaccination makes genes accessible for many months or even years. This is helpful for the increased production of cytokines, leading to stronger immune systems.

Prof. Dr. Mihai G. Netea of Radboud University Medical Center, Nijmegen said their findings explain how long-term, improved immune response results from vaccination. It possibly explains the persistent training effect on immunity.

Researchers are currently trying to develop vaccines to check the incidence of COVID-19 and other critical diseases among at-risk groups. This new study may contribute to that endeavor the scientists are hopeful that BCG vaccination could prove helpful.

Read Also: Bexsero, Meningococcal B Vaccine, May Protect Against Gonorrhea, Study Finds

According to the team, the vaccine may not entirely keep the coronavirus at bay. But it could reduce the risk of severe infections, especially among health workers.

Another interesting finding in the study was that vaccination made cells more efficient in fighting pathogens. A molecule referred to as hepatic nuclear factor (HNF) causes the cells to release cytokines only when there is a real threat.

However, this is not a recommendation of the BCG vaccine for protection against other infections. The World Health Organization (WHO) has yet to approve it for that purpose.

BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment

https://www.radboudumc.nl/en/news/2020/study-on-effect-of-bcg-vaccine-on-coronavirus-infection-in-the-elderly

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The BCG a Tuberculosis Vaccine Boosts Immune Cells and Reduces Risk of Other Infections - Gilmore Health News

FDA Approves Second Biomarker-Based Indication for Merck’s KEYTRUDA (pembrolizumab), Regardless of Tumor Type – The Baytown Sun

KENILWORTH, N.J.--(BUSINESS WIRE)--Jun 17, 2020--

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

For the second time, KEYTRUDA monotherapy is now approved based on a biomarker rather than the location in the body where the tumor originated, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. TMB-H, defined as 10 mutations per megabase or more, can help identify patients most likely to benefit from KEYTRUDA. Were pleased that our collaborative efforts to advance biomarker research have resulted in our ability to provide a new treatment option that addresses a high unmet medical need for these patients with cancer.

As physicians, we are always looking to find new options for patients, especially in the second-line or higher treatment setting, said Roy S. Herbst, M.D., Ph.D., ensign professor of medicine (medical oncology) and professor of pharmacology, Yale School of Medicine; chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital; and associate cancer center director for translational research, Yale Cancer Center. Its great to see the use of innovative biomarkers and immunotherapy come together with this approval and encouraging that we now have an option for patients with TMB-H tumors across cancer types, including rare cancers.

The FDA also approved FoundationOne CDx test as the companion diagnostic to identify patients with solid tumors that are TMB-H (10 mutations/ megabase) who may benefit from immunotherapy treatment with KEYTRUDA monotherapy.

These approvals stem from years of research into how TMB levels may influence a patients response to immunotherapy, said Brian Alexander, M.D., M.P.H., chief medical officer, Foundation Medicine. Its critical that healthcare professionals have access to a validated genomic test to measure TMB in clinical tumor assessments and pinpoint those who are more likely to respond. Were proud to be collaborating with Merck to help match appropriate patients to this important treatment.

Data Supporting the Approval

The accelerated approval was based on data from a prospectively-planned retrospective analysis of 10 cohorts (A through J) of patients with various previously treated unresectable or metastatic solid tumors with TMB-H, who were enrolled in KEYNOTE-158 (NCT02628067), a multicenter, non-randomized, open-label trial evaluating KEYTRUDA (200 mg every three weeks). The trial excluded patients who previously received an anti-PD-1 or other immune-modulating monoclonal antibody, or who had an autoimmune disease, or a medical condition that required immunosuppression. TMB status was assessed using the FoundationOne CDx assay and pre-specified cutpoints of 10 and 13 mut/Mb, and testing was blinded with respect to clinical outcomes. Tumor response was assessed every nine weeks for the first 12 months and every 12 weeks thereafter. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) in the patients who received at least one dose of KEYTRUDA as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

In KEYNOTE-158, 1,050 patients were included in the efficacy analysis population. TMB was analyzed in the subset of 790 patients with sufficient tissue for testing based on protocol-specified testing requirements. Of the 790 patients, 102 (13%) had tumors identified as TMB-H, defined as TMB 10 mut/Mb. The study population characteristics of these 102 patients were: median age of 61 years (range, 27 to 80); 34% age 65 or older; 34% male; 81% White; and 41% Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 and 58% ECOG PS of 1. Fifty-six percent of patients had at least two prior lines of therapy.

In the 102 patients whose tumors were TMB-H, KEYTRUDA demonstrated an ORR of 29% (95% CI, 21-39), with a complete response rate of 4% and a partial response rate of 25%. After a median follow-up time of 11.1 months, the median DOR had not been reached (range, 2.2+ to 34.8+ months). Among the 30 responding patients, 57% had ongoing responses of 12 months or longer, and 50% had ongoing responses of 24 months or longer.

In a pre-specified analysis of patients with TMB 13 mut/Mb (n=70), KEYTRUDA demonstrated an ORR of 37% (95% CI, 26-50), with a complete response rate of 3% and a partial response rate of 34%. After a median follow-up time of 11.1 months, the median DOR had not been reached (range, 2.2+ to 34.8+ months). Among the 26 responding patients, 58% had ongoing responses of 12 months or longer, and 50% had ongoing responses of 24 months or longer. In an exploratory analysis in 32 patients whose cancer had TMB 10 mut/Mb and <13 mut/Mb, the ORR was 13% (95% CI, 4-29), including two complete responses and two partial responses.

The median duration of exposure to KEYTRUDA was 4.9 months (range, 0.03 to 35.2 months). The most common adverse reactions for KEYTRUDA (reported in 20% of patients) were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain and abdominal pain.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

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FDA Approves Second Biomarker-Based Indication for Merck's KEYTRUDA (pembrolizumab), Regardless of Tumor Type - The Baytown Sun

Orca Bio Emerges With Nearly $300 Million to Transform Allogeneic Cell Therapy – Stockhouse

Company aims to safely and effectively regenerate a healthy blood and immune system for patients with hematological malignancies, genetic diseases and autoimmune disorders

High precision cell therapies manufactured by Orca Bio have the potential to replace conventional bone marrow transplants and expand the eligible patient population

$192 million Series D financing strengthens the company with resources to propel lead product candidate to completion of clinical development

MENLO PARK, Calif. , June 17, 2020 (GLOBE NEWSWIRE) -- Orca Bio, a clinical-stage biotechnology company developing high precision allogeneic cell therapies, today announced a Series D financing that brings its total capital raised since its 2016 launch to nearly $300 million. The company creates precisely controlled cell therapies by building each dose cell-by-cell from another person’s blood. Each therapy is constructed by formulating a proprietary mixture of cells that aims to cure the patient’s disease and eliminate dangerous side effects.

Orca Bio’s $192 million Series D financing was co-led by Lightspeed Venture Partners and an undisclosed investor. Other new and existing blue-chip investors also participated in the latest round, including 8VC, DCVC Bio, ND Capital, Mubadala Investment Company, Kaiser Foundation Hospitals, Kaiser Permanente Group Trust and IMRF.

The financing will support the continued advancement of Orca Bio’s cell therapy pipeline and its novel manufacturing platform, which sorts blood with single-cell precision and a high level of purity and speed to create optimal therapeutic mixtures of immune and stem cells. These proprietary mixtures have the potential to revolutionize allogeneic cell therapy for hematological and other cancers, as well as many other diseases and disorders.

A conventional bone marrow transplant relies on naturally occurring T cells. However, the uncontrolled cellular composition often results in life-threatening complications. The company’s most advanced program, TRGFT-201, is evaluating a highly controlled formulation of T cells that includes subsets of regulatory T cells, in a Phase I/II clinical study in patients with certain blood cancers. The company’s second program, OGFT-001, is evaluating a fully controlled cell product candidate that contains a next-generation formulation of T cells, in a Phase I study, also in patients with blood cancers. Orca Bio’s two ongoing clinical studies are among the largest Phase I cell therapy trials ever conducted. Each product candidate has the potential to deliver curative outcomes for the initial indications Orca Bio is pursuing, as well as the promise to significantly expand the eligible patient population by substantially reducing the severe toxicities associated with conventional bone marrow transplants.

The capital we have raised has formed the launch pad for a world-class, fully integrated allogeneic cell therapy company differentiated from all others,” said Ivan Dimov, PhD, Co-founder and Chief Executive Officer of Orca Bio. Replacing bone marrow transplants is a logical first step in next-generation allogeneic cell therapy. While a conventional bone marrow transplant administers an uncontrolled cell product, Orca Bio has been the first to deliver a high precision cell therapy. We are initially focused on advancing two clinical programs in patients with blood cancers and have successfully treated the largest-ever number of patients with a high precision cell therapy. We believe our approach has the potential to transform allogeneic cell therapy, and thus the treatment of not only blood cancer, but also many other diseases with significant unmet need, such as a variety of genetic diseases and autoimmune disorders.”

With precise reconstitution using highly defined cell preps and a swift reboot of the patient’s immune system, Orca Bio’s product candidates have the potential to eliminate fatal side effects, such as graft-versus-host disease, and infections commonly associated with bone marrow transplants while maintaining or enhancing anti-tumor efficacy,” said Rick Klausner, MD, an investor and member of Orca Bio’s advisory board. The possibility of improving cure rates and minimizing toxicity holds the promise of expanding the eligible patient population for successful bone marrow transplantation in cancer.”

Orca Bio’s visionary leadership team, seasoned advisors, solid financial foundation and novel technology make the company uniquely suited to develop truly differentiated, scalable allogeneic cell therapies,” said Jonathan MacQuitty, PhD, Venture Partner at Lightspeed Venture Partners. I look forward to the Orca Bio team’s continued development and commercialization of revolutionary allogeneic cell therapies.”

Internationally Recognized Experts and Leaders

Orca Bio’s leadership, Ivan Dimov, PhD, Chief Executive Officer, Nate Fernhoff, PhD, Chief Scientific Officer, and Jeroen Bekaert, PhD, Chief Operating Officer, met at Stanford University and launched the company in 2016. Orca Bio’s board of directors and advisory board are comprised of renowned scientific leaders and seasoned biotech executives with extensive experience in drug discovery and cell-based therapeutics, including:

About Orca Bio

Established in 2016, Orca Bio is a clinical-stage biotechnology company developing a pipeline of high precision allogeneic cell therapy products that are designed to safely and effectively replace a patient’s blood and immune system with a healthy one. The company’s proprietary therapeutic and manufacturing platforms are exclusively licensed from Stanford University. The manufacturing platform sorts donor blood with single-cell precision and a high level of purity and speed, enabling the creation of proprietary, optimal therapeutic mixtures of immune and stem cells that have the potential to transform allogeneic cell therapy. The company’s lead product candidate is being evaluated in a multi-center Phase I/II clinical trial in patients with blood cancers. For more information, please visit http://www.orcabio.com.

Media Contact: media@orcabio.com

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Orca Bio Emerges With Nearly $300 Million to Transform Allogeneic Cell Therapy - Stockhouse

UCLA receives nearly $14 million from NIH to investigate gene therapy to combat HIV – Mirage News

NIAID/Flickr

Researchers will focus on an immunotherapy known as CAR T, which uses genetically modified stem cells to target and destroy HIV-infected cells like this one.

UCLA researchers and colleagues have received a $13.65 million grant from the National Institutes of Health to investigate and further develop an immunotherapy known as CAR T, which uses genetically modified stem cells to target and destroy HIV.

The five-year grant, part of an NIH effort to develop gene-engineering technologies to cure HIV/AIDS, will fund a collaboration among UCLA; CSL-Behring, a biotechnology company in the United States and Australia; and the University of WashingtonFred Hutchinson Cancer Research Center.

Scott Kitchen, an associate professor of medicine in the division of hematology and oncology, and Irvin Chen, director of the UCLA AIDS Institute at the David Geffen School of Medicine at UCLA, are leading the effort. The project will build on their previous research using CAR T therapy to combat the virus, which is constantly mutating and difficult to beat.

The overarching goal of our proposed studies is to identify a new gene therapy strategy to safely and effectively modify a patients own stem cells to resist HIV infection and simultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection, said Kitchen, who also directs the humanized mouse core laboratory for UCLAs Center for AIDS Research and Jonsson Comprehensive Cancer Center. It is a huge boost to our efforts at UCLA and elsewhere to find a creative strategy to defeat HIV.

The only known cure of an HIV-infected person was announced in 2008. The famous Berlin patient received a stem cell transplant from a donor whose cells naturally lacked a crucial receptor that HIV binds to in order to kill cells and destroy the immune system. The main problems with this approach, the researchers say, are that the donor and recipient have to be highly matched often a rare event and that it often fails to produce a sufficient amount of HIV-protected cells that can clear the virus from the body.

Transplantation of blood-forming stem cells has been the only treatment strategy that has resulted in a functional cure for HIV infection, Kitchen said. Over 13 years after the first successfully cured HIV-infected patient, there is a substantial need to develop strategies that are capable of being used on everyone with HIV infection.

One of those strategies, CAR T, has been the subject of ongoing research at UCLA by Chen, Kitchen and others. This approach involves genetically engineering a patients own blood-forming stem cells to carry genes for chimeric antigen receptors, or CARs. Once these stem cells are modified and transplanted back into the patient, they form specialized infection-fighting white blood cells known as T cells in this case, CAR T cells that specifically seek out and kill HIV-infected cells. In a recent study, the UCLA scientists found that engineered CAR T cells not only destroyed infected cells but also lived for more than two years the length of the study.

The thinking behind the NIH-funded project, the researchers say, is that a combination of CARs and broadly neutralizing antibodies may be a long-lasting, perhaps permanent, cure for HIV.

Our work under the NIH grant will provide a great deal of insight into ways the immune response can be modified to better fight HIV infection, said Chen, who is a professor of medicine and of microbiology, immunology and molecular genetics at the Geffen School of Medicine. The development of this unique strategy that allows the body to develop multiple ways to attack HIV could have an impact on other diseases as well, including the development of similar approaches targeting other types of chronic viral infections and cancers.

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UCLA receives nearly $14 million from NIH to investigate gene therapy to combat HIV - Mirage News

UChicago working on COVID-19 saliva test Pandemic energizes health care unions Rehab hospital to be built in Libertyville – Crain’s Chicago Business

TRUMP ADMIN TOSSES ANTI-GENDER DISCRIMINATION RULE:TheTrump administration on Friday overturned anObama-era rule that banned discriminationagainst patients based on gender identity.The regulation from the HHS' Office for Civil Rights drops protections based on gender identity from the ACA's chief anti-discrimination provision,Modern Healthcare reports.

Pharmacies, insurers and other covered organizations also won't have to make their healthcare and insurance mailings available in 15 or more languages.

STEM CELL RESEARCHERS GET FDA EMERGENCY APPROVAL FOR COVID-19 TREATMENT:The Global Institute of Stem Cell Therapy and Research, or GIOSTAR,has receiveda compassionate useFDA approval to treathospitalizedCOVID-19patientswith acute inflammation of the lungswith stem cell therapy, the company said in a statement.Researchers with the company, which hasits Midwest headquarters in Glenview, hope the stem cell therapy couldtreatsevere COVID-19 cases and bridge the gap before a vaccine is developed, the statement said.

BEHAVIORAL HEALTH GROUP PARTNERS WITH COMMUNITY REFERRAL NETWORK:Illinois Health Practice Alliance, abehavioral health networkwithmore than 90 providers, is partnering with community service networkNowPowto build a statewide coordinated networkfor social services for peoplebehavioral health needs, the groups said in a statement.

Were seeing a significant rise in the number of Illinoisans experiencing behavioral health issues like mental health and substance abuse in tandem with a rise in social risk factors like housing instability, justice involvement and unemployment, David Berkey,CEO of the practice alliance.IHPA will integrateNowPowinto its population health platform, Health EC, rolling it out at first to 15,000 Medicaid beneficiaries, the statement said.

COMPANIES FORMING ANTI-CYBER ATTACK OPERATIONS CENTER:Evanston Technology Partners andAppGuardInc.are partnering to form a jointHealthcare Asset Operations Center tohelp hospitalssecurecritical medical devices and infrastructure, including ventilators, operational technology and network-connected devices, the companies said in a statement.

HYDROXYCHLOROQUINE SAGA JUST HOW SCIENCE WORKS?:The hydroxychloroquine saga shouldnt erode public trust in science though it should serve as a reminder not to take any individual scientist or study too seriously, according to a Bloomberg opinion piece. Science never finds absolute truth, and it sometimes trips, but it can right itself and move on.READ MORE.

PEOPLE ON THE MOVE:

Kenneth C. Hoffmannhas beenpromotedtopartnerat the law firmBrennanBurtker.Hoffmann has represented individuals, businesses, hospital networks and other healthcareproviders throughall phases of investigation and litigation.

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UChicago working on COVID-19 saliva test Pandemic energizes health care unions Rehab hospital to be built in Libertyville - Crain's Chicago Business

Houston coronavirus updates: What you need to know about June 14 – msnNOW

9:16 a.m.

Texas reported a record high of 2,242 COVID-19 hospitalizations on Saturday, according to Texas Health and Human Services.

Last week, Texas set a new record for COVID-19 hospitalizations in four of the five days, climbing to 2,166 on Friday.

Health officials are concerned that the increase may strain hospital capacity. Dr. James McCarthy, Chief Physician Executive of Memorial Hermann warned about the recent COVID-19 surge and hospital capacity.

"We need to protect hospital capacity for important healthcare needs," McCarthy said, "The one thing we don't want to see is where hospital capacity is strained in a way where the rest of the patients can't be cared for. Important surgeries still need to go on." Read more details of his interview here.

In an in-depth report by Houston Chronicle's Jenny Deam, Houston hospitals are now ramping up the number of beds and ventilators available. There are nearly 18,000 beds available statewide, an increase of about 4,700 from Thursday. Read more of her in-depth report here.

9:05 a.m.

As of Sunday morning, there are now 7,817,064 cases of the novel coronavirus worldwide, according to Johns Hopkins University. The death toll now has climbed to 430,605. The U.S. currently leads the world with 2,074,749 confirmed cases.

According to Texas Health and Human Services, there are now 86,011 cases reported across the state. Harris County leads the state, reporting 16,188 confirmed cases.

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Houston coronavirus updates: What you need to know about June 14 - msnNOW