Category Archives: Molecular Genetics

Watch here: https://www.youtube.com/watch?feature=youtu.be&v=VVkQU91KbEs

press release: The UW has a long history of pioneering medical advancements that have transformed the world. From performing the first bone marrow transplant in the United States to cultivating the first laboratory-derived human embryonic stem cells. Now, where will UW medical research go next?

On the next Wisconsin Medicine Livestream, meet trailblazing doctors, researchers, and medical leaders who are charting a bold course to completely alter the health care landscape. During this insightful panel discussion, well explore how gene therapy and cell replacements could hold the keys to treating inherited and acquired blindness. Youll also discover the remarkable potential in xenotransplantation where nonhuman animal source organs are transplanted into human recipients. In addition, you will learn about UW Healths journey to build a multidisciplinary program to serve the community. These, and other, fascinating developments in treatment and care are happening right now at the UW and are the future of medicine. The presentation will be moderated by Robert Golden, the dean of the University of WisconsinMadisons School of Medicine and Public Health.

Our Guests:

David Gamm, professor, Department of Ophthalmology and Visual Sciences; Emmett A. Humble Distinguished Director, McPherson Eye Research Institute; Sandra Lemke Trout Chair in Eye Research

Dr. Gamms lab is at the forefront in developing cell-based therapies to combat retinal degenerative diseases (RDDs). As the director of the McPherson Eye Research Institute and a member of the Waisman Center Stem Cell Research Program, the UW Stem Cell and Regenerative Medicine Center, and the American Society for Clinical Investigation, his efforts are directed toward basic and translational retinal stem cell research. The Gamm Lab uses induced pluripotent stem cells to create retinal tissues composed of authentic human photoreceptor cells rods and cones that can detect light and initiate visual signals in a dish. The aims of his laboratory are to investigate the cellular and molecular events that occur during human retinal development and to generate cells for use in retinal disease modeling and cell replacement therapies. In collaboration with other researchers at UWMadison and around the world, the lab is developing methods to produce and transplant photoreceptors and/or retinal pigment epithelium (RPE) in preparation for future clinical trials. At the same time, the Gamm Lab uses lab-grown photoreceptor and RPE cells to test and advance a host of other experimental treatments, including gene therapies. In so doing, the lab seeks to delay or reverse the effects of blinding disorders, such as retinitis pigmentosa and age-related macular degeneration, and to develop or codevelop effective interventions for these RDDs at all stages of disease.

Dhanansayan Shanmuganayagam, assistant professor, Department of Surgery, School of Medicine and Public Health; Department of Animal and Dairy Sciences, UWMadison; director, Biomedical, and Genomic Research Group

Dr. Shanmuganayagams research focuses on the development and utilization of pigs as homologous models to close the translational gap in human disease research, taking advantage of the overwhelming similarities between pigs and humans in terms of genetics, anatomy, physiology, and immunology. He and his colleagues created the human-sized Wisconsin Miniature Swine breed that is unique to the university. The breed exhibits greater physiological similarity to humans, particularly in vascular biology and in modeling metabolic disorders and obesity. He currently leads genetic engineering of swine at the UW. His team has created more than 15 genetic porcine models including several of pediatric genetic cancer-predisposition disorders such as neurofibromatosis type 1 (NF1). In the context of NF1, his lab is studying the role of alternative splicing of the nf1 gene on the tissue-specific function of neurofibromin and whether gene therapy to modulate the regulation of this splicing can be used as a viable treatment strategy for children with the disorder.

Dr. Shanmuganayagam is also currently leading the efforts to establish the University of Wisconsin Center for Biomedical Swine Research and Innovation (CBSRI) that will leverage the translatability of research in pig models and UWMadisons unique swine and biomedical research infrastructure, resources, and expertise to conduct innovative basic and translational research on human diseases. The central mission of CBSRI is to innovate and accelerate the discovery and development of clinically relevant therapies and technologies. The center will also serve to innovate graduate and medical training. As the only center of its kind in the United States, CBSRI will make UWMadison a hub of translational research and industry-partnered biomedical innovation.

Petros Anagnostopoulos, surgeon in chief, American Family Childrens Hospital; chief, Section of Pediatric Cardiothoracic Surgery; professor, Department of Surgery, Division of Cardiothoracic Surgery

Dr. Anagnostopoulos is certified by the American Board of Thoracic Surgery and the American Board of Surgery. He completed two fellowships, one in cardiothoracic surgery at the University of Pittsburgh School of Medicine and a second in pediatric cardiac surgery at the University of California, San Francisco School of Medicine. He completed his general surgery residency at Henry Ford Hospital in Detroit. Dr. Anagnostopoulos received his MD from the University of Athens Medical School, Greece. His clinical interests include pediatric congenital heart surgery and minimally invasive heart surgery.

Dr. Anagnostopoulos specializes in complex neonatal and infant cardiac reconstructive surgery, pediatric heart surgery, adult congenital cardiac surgery, single ventricle palliation, extracorporeal life support, extracorporeal membrane oxygenation, ventricular assist devices, minimally invasive cardiac surgery, hybrid surgical-catheterization cardiac surgery, off-pump cardiac surgery, complex mitral and tricuspid valve repair, aortic root surgery, tetralogy of Fallot, coronary artery anomalies, Ross operations, obstructive cardiomyopathy, and heart transplantation.

When: Tuesday, Sept. 29, at 7 p.m. CDT

Where: Wisconsin Medicine Livestream: wiscmedicine.org/programs/ending-alzheimers

Excerpt from:
ONLINE: The Future of Medicine - Isthmus

LA JOLLA, Calif., Sept. 23, 2020 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that its intranasal SARS-CoV-2 vaccine prototype for COVID-19, using BC-PIV technology, successfully induced systemic serum IgG and mucosal IgA neutralizing antibodies against the S1 antigen (Ag) of SARS-CoV-2 in mice.

A mouse model study was conducted to assess systemic IgG and mucosal IgA antibody production against S1 Ag after intranasal vaccination with MediciNova’s BC-PIV SARS-CoV-2 vaccine prototype. We confirmed a high IgA antibody titer against S1 Ag in the nasal lavage fluid from mice given intranasal BC-PIV SARS-CoV-2 vaccine. We also confirmed that a high IgG antibody titer against S1 Ag was induced in mice serum.

Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc., commented, "We are very encouraged that our intranasal BC-PIV SARS-CoV-2 vaccine induced high titers of systemic serum IgG and mucosal IgA neutralizing antibodies in a mouse model study. These successful results support the scientific and technical rationale of our intranasal vaccine in addition to similar success with BioComo’s BC-PIV RSV vaccine prototype. We look forward to reporting additional progress on our intranasal COVID-19 vaccine in the near future.”

About the BC-PIV SARS-CoV-2 V accine for COVID-19

BC-PIV, an innovative non-transmissible viral vector co-developed by BioComo and Mie University, is derived from the recombinant human parainfluenza virus type 2 (hPIV2). It is highly efficient in its ability to transfer multiple foreign proteins to recipients and has a strong safety profile as no secondary infectious virus is produced. BC-PIV is designed to display not only the gene but also the foreign protein itself on the surface and inside of the viral membrane. Therefore, it can carry the large membrane proteins of viruses and signal transduction receptors/ligand proteins on the viral surface. BC-PIV is able to carry the proteins that require a proper three-dimensional structure or multimeric structure while maintaining the structure. BC-PIV elicits good immunogenicity against antigen proteins without adjuvants. The BC-PIV SARS-CoV-2 vaccine prototype has been developed to include the specific SARS-CoV-2 antigen protein in order to express maximum antigenicity. The BC-PIV SARS-COV-2 vaccine can be developed as an intranasal vaccine in addition to an intramuscular injection because of its high affinity to nasal and upper respiratory tract mucosa, which is the same route of the natural infection of SARS-CoV-2. An intranasal vaccine is expected to induce local mucosal immunity. To date, BioComo has succeeded in producing a recombinant Ebola virus vaccine ( https://www.nature.com/articles/s41598-019-49579-y ) and a Respiratory Syncytial virus prefusion F vaccine (unpublished data) using this BC-PIV platform technology.

About BioComo

BioComo, a biotech company founded at Mie Prefecture Japan in May 2008, is developing cutting-edge technology platforms for creating the novel and predominant vaccine carriers and adjuvants to enhance immunity in collaboration with the Microbiology and Molecular Genetics Department of Mie University. They have already succeeded in the development of a highly efficacious and state-of-the art vaccine carrier and novel adjuvant candidates. Their technology will be applied to the production of the next generation vaccines for the prevention of infections such as RS virus, Ebola virus, Influenza virus, and SARS-CoV-2. It will also enable faster and more cost-effective production of those vaccines. BC-PIV is the core platform technology which carries the corporate namesake, BioComo, and the leading vaccine carrier that is derived from the recombinant human parainfluenza virus 2 (hPIV2) vectors. BioComo is dedicated to inventing new vaccines for both global infection threats as well as malignant tumors.

About MediciNova MediciNova, Inc. is a publicly traded biopharmaceutical company founded upon acquiring and developing novel, small-molecule therapeutics for the treatment of diseases with unmet medical needs with a primary commercial focus on the U.S. market. MediciNova's current strategy is to focus on BC-PIV SARS-COV-2 vaccine for COVID-19, MN-166 (ibudilast) for neurological disorders such as progressive multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and substance dependence (e.g., alcohol use disorder, methamphetamine dependence, opioid dependence) and glioblastoma, as well as prevention of acute respiratory distress syndrome (ARDS) caused by COVID-19, and MN-001 (tipelukast) for fibrotic diseases such as nonalcoholic steatohepatitis (NASH) and idiopathic pulmonary fibrosis (IPF). MediciNova’s pipeline also includes MN-221 (bedoradrine) for the treatment of acute exacerbations of asthma and MN-029 (denibulin) for solid tumor cancers. MediciNova is engaged in strategic partnering and other potential funding discussions to support further development of its programs. For more information on MediciNova, Inc., please visit http://www.medicinova.com .

Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of BC-PIV SARS-COV-2 vaccine , MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," considering,” planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of BC-PIV SARS-COV-2 vaccine , MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2019 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements.

INVESTOR CONTACT: Geoff O'Brien Vice President MediciNova, Inc. info@medicinova.com

Originally posted here:
MediciNova Announces that its Intranasal COVID-19 Vaccine Successfully Induced Systemic IgG and Mucosal IgA Neutralizing Antibodies Against SARS-CoV-2...

WASHINGTON, Aug. 20, 2020 /PRNewswire/ --Since COVID-19 emerged late last year, there's been an enormous amount of research produced on this novel coronavirus disease. But the content publicly available for this data and the format in which it's presented lack consistency across different countries' national public health institutes, greatly limiting its usefulness, Children's National Hospital scientists report in a new study. Their findings and suggestions, published online August 19 in Science & Diplomacy, could eventually help countries optimize their COVID-19-related data and data for future outbreaks of other diseases to help further new research, clinical decisions and policy-making around the world.

Recently, explains study senior author Emmanule Dlot, Ph.D., research faculty at Children's National Research Institute, she and her colleagues sought data on sex differences between COVID-19 patients around the world for a new study. However, she says, when they checked the information available about different countries, they found a startling lack of consistency, not only for sex-disaggregated data, but also for any type of clinical or demographic information.

"The prospects of finding the same types of formats that would allow us to aggregate information, or even the same types of information across different sites, was pretty dismal," says Dr. Dlot.

To determine how deep this problem ran, she and colleagues at Children's National, including Eric Vilain, M.D., Ph.D., the James A. Clark Distinguished Professor of Molecular Genetics and the director of the Center for Genetic Medicine Research at Children's National, and Jonathan LoTempio, a doctoral candidate in a joint program with Children's National and George Washington University, surveyed and analyzed the data on COVID-19.

The research spanned data reported by public health agencies from highly COVID-19 burdened countries, viral genome sequence data sharing efforts, and data presented in publications and preprints.

At the time of study, the 15 countries with the highest COVID-19 burden at the time included the US, Spain, Italy, France, Germany, the United Kingdom, Turkey, Iran, China, Russia, Brazil, Belgium, Canada, the Netherlands and Switzerland. Together, these countries represented more than 75% of the reported global cases. The research team combed through COVID-19 data presented on each country's public health institute website, looking first at the dashboards many provided for a quick glimpse into key data, then did a deeper dive into other data on this disease presented in other ways.

The data content they found, says LoTempio, was extremely heterogenous. For example, while most countries kept running totals on confirmed cases and deaths, the availability of other types of data such as the number of tests run, clinical aspects of the disease such as comorbidities, symptoms, or admission to intensive care, or demographic information on patients, such as age or sex differed widely among countries.

Similarly, the format in which data was presented lacked any consistency among these institutes. Among the 15 countries, data was presented in plain text, HTML or PDF. Eleven offered an interactive web-based data dashboard, and seven had comma-separated data available for download. These formats aren't compatible with each other, LoTempio explains, and there was little to no documentation about where the data that supplies some formats such as continually updated web-based dashboards was archived.

Dr. Vilain says that a robust system is already in place to allow uniform sharing of data on flu genomes the World Health Organization's (WHO) Global Initiative on Sharing All Influenza Data (GISAID) which has been readily adapted for the virus that causes COVID-19 and has already helped advance some types of research. However, he says, countries need to work together to develop a similar system for harmonized sharing other types of data for COVID-19. The study authors recommend that COVID-19 data should be shared among countries using a standardized format and standardized content, informed by the success of GISAID and under the backing of the WHO.

In addition, the authors say, the explosion of research on COVID-19 should be curated by experts who can wade through the thousands of papers published on this disease since the pandemic began to identify research of merit and help merge clinical and basic science.

"Identifying the most useful science and sharing it in a way that's usable to most researchers, clinicians and policymakers, will not only help us emerge from COVID-19 but could help us prepare for the next pandemic," Dr. Vilain says.

Other researchers who contributed to this study include D'Andre Spencer, MPH, Rebecca Yarvitz, BA, and Arthur Delot-Vilain.

About Children's National HospitalChildren's National Hospital, based in Washington, D.C., celebrates150yearsof pediatric care, research and commitment to community. Volunteers opened the hospital in 1870 with 12 beds for children displaced after the Civil War. Today, 150 years stronger, it is among the nation's top 10 children's hospitals. It is ranked No. 1 fornewborn carefor the fourth straight year and ranked in all specialties evaluated by U.S. News & World Report. Children's National is transforming pediatric medicine for all children. In 2020, construction will be complete on the Children's National Research & Innovation Campus, the first in the nation dedicated to pediatric research. Children's National has been designated twice as a Magnethospital, demonstrating the highest standards of nursing and patient care delivery. This pediatric academic health system offers expert care through a convenient, community-based primary care network and specialty outpatient centers in the D.C., metropolitan area, including the Maryland and Northern Virginia suburbs. Children's National is home to theChildren's National Research InstituteandSheikh Zayed Institute for Pediatric Surgical Innovationand is the nation's seventh-highest NIH-funded children's hospital. It is recognized for its expertise and innovation in pediatric care and as a strong voice for children through advocacy at the local, regional and national levels.

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SOURCE Childrens National Hospital

See more here:
Inconsistencies in data presentation could harm efforts against COVID-19 and future outbreak preparedness - PRNewswire

- Own developed SARS-CoV-2 Kit with PULB for COVID-19 uses real-time PCR (RT-PCR) technology on open PCR platforms, designed to provide results in approximately one hour

- 100% Sensitivity and 97.3% Specificity demonstrated in isolated RNA

- Inclusion of PCR-Compatible Universal Lysis Buffer (PULB) in the kit as a workflow option allows labs to circumvent the need for extraction equipment and reagents

GAITHERSBURG, Md., and HOLZGERLINGEN, Germany, Aug. 20, 2020 (GLOBE NEWSWIRE) -- OpGen, Inc. (Nasdaq: OPGN, OpGen), a precision medicine company harnessing the power of molecular diagnostics and bioinformatics to help combat infectious disease, announced today that its subsidiary Curetis GmbH has obtained the CE mark certification in the European Union for its own SARS-CoV-2 Kit with PULB for the detection of SARS-CoV-2, the virus that causes COVID-19.

Developed and manufactured by Curetis team in Germany, the SARS-CoV-2 Kit with PULB uses real-time reverse transcription polymerase chain reaction (RT-PCR) technology for qualitative detection of the SARS-CoV-2 virus isolated from oropharyngeal and nasopharyngeal swab specimens from individuals suspected of COVID-19 by their healthcare provider or for screening of asymptomatic individuals. This kit can be used with RNA isolated by performing standard RNA isolation processes, as well as with oropharyngeal or nasopharyngeal swabs collected in PCR compatible viral transport medium treated with PCR-Compatible Universal Lysis Buffer (PULB) provided in the kit. Including PULB in the kit as a workflow option allows labs to circumvent the need for extraction equipment and extraction kits/reagents, thereby providing operational and workflow efficiencies, time and cost savings. The kit is designed to provide time to results in approximately one hour, and it runs on open real-time PCR instruments such as the QuantStudio 5 Real-Time PCR System and the Bio-Rad CFX96 Real-Time PCR Detection System.

The CE-IVD Marking is an important step in advancing our efforts to support critical COVID-19 testing; the Curetis SARS-CoV-2 Kit with PULB provides additional testing capacity in countries that recognize the CE Mark to test patients, said Johannes Bacher, COO of OpGen.

By launching this new product in Europe, we are committed to helping our distributors and customers to expand the availability of SARS-CoV-2 diagnostic testing, and our own-developed CE-IVD marked SARS-CoV-2 Kit with PULB is expected to help increase availability of these much-needed tests," said Oliver Schacht, PhD, CEO of OpGen. Our customers will benefit from an optimized workflow and a test that delivers great performance and significantly shorter time-to-result at favorable economics compared to many of the commercially available open PCR platform COVID-19 tests including the BGI SARS-CoV-2 kit. Having access to our own SARS-CoV-2 kit allows us to have that product distributed rather than the BGI test kit which we will cease distributing effective immediately.

About OpGen, Inc.OpGen, Inc. (Gaithersburg, MD, USA) is a precision medicine company harnessing the power of molecular diagnostics and bioinformatics to help combat infectious disease. Along with subsidiaries, Curetis GmbH and Ares Genetics GmbH, we are developing and commercializing molecular microbiology solutions helping to guide clinicians with more rapid and actionable information about life threatening infections to improve patient outcomes, and decrease the spread of infections caused by multidrug-resistant microorganisms, or MDROs. OpGens product portfolio includes Unyvero, Acuitas AMR Gene Panel and Acuitas Lighthouse, and the ARES Technology Platform including ARESdb, using NGS technology and AI-powered bioinformatics solutions for antibiotic response prediction.

For more information, please visit http://www.opgen.com.

Forward-Looking Statements by OpGenThis press release includes statements regarding the commercial launch of a SARS-CoV-2 Kit by OpGens subsidiary, Curetis GmbH. These statements and other statements regarding OpGens SARS-CoV-2 test kits, their commercialization and launch, future plans and goals constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties that are often difficult to predict, are beyond our control, and which may cause results to differ materially from expectations. Factors that could cause our results to differ materially from those described include, but are not limited to, our ability to successfully, timely and cost-effectively develop, seek and obtain regulatory clearance for and commercialize our product and services offerings, the rate of adoption of our products and services by hospitals and other healthcare providers, the success of our commercialization efforts, the impact of COVID-19 on the Companys operations, financial results, and commercialization efforts as well as on capital markets and general economic conditions, the realization of expected benefits of our business combination transaction with Curetis GmbH, the effect on our business of existing and new regulatory requirements, and other economic and competitive factors. For a discussion of the most significant risks and uncertainties associated with OpGen's business, please review our filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which are based on our expectations as of the date of this press release and speak only as of the date of this press release. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

OpGen Contact:Oliver SchachtCEOInvestorRelations@opgen.com

Press Contact:Matthew BretziusFischTank Marketing and PRmatt@fischtankpr.com

Investor Contact:Megan PaulEdison Groupmpaul@edisongroup.com

Source: OpGen, Inc.

Read more here:
OpGen Announces CE-IVD Marking and Commercial Launch in Europe of its Own Developed Molecular Diagnostic SARS-CoV-2 Kit with PULB for Detection of the...

Photo Courtesy Jeff Fitlow

By Rishab Ramapriyan 8/18/20 9:18pm

On Tuesday, Will Rice College announced that the remainder of Orientation Week activities will be conducted fully online. The announcement came after a second Will Rice O-Week advisor tested positive for COVID-19 this morning.

According to the Dean of Undergraduates Bridget Gorman, this decision was not mandated by the Rice University administration, but rather reached locally by the Will Rice magisters and O-Week coordinator team. In their email to the Will Rice advising team and new student cohort, the coordinators said that this decision was made out of an abundance of caution.

We take this action to minimize the risk to your own health and to limit further spread of the virus, the coordinators wrote.

Advisors and new students living on-campus are restricted to their floors as mandated campus-wide, but they are still able to use outdoor spaces, according to Rahul Popat, the Will Rice College President. As long as students follow the guidelines set by the Culture of Care Agreement, they are free to exit their rooms.

Vice President of Administration Kevin Kirby, who chairs the Crisis Management Advisory Committee, said that Rices team of 17 contact tracers promptly responded to both Will Rice cases. Any individuals who met the Centers for Disease Control and Prevention criteria for close contact (within 6 feet for more than 15 minutes) were quarantined and tested using a molecular test (polymerase chain reaction test). A few additional advisors who believed that they had been in contact with the COVID-19-positive students voluntarily quarantined themselves, according to Kirby. All of the quarantined students have tested negative and there have been no additional cases in the Will Rice community as of this morning.

New students and advisors had all received an antigen rapid test from CVS on move-in day, but antigen tests have a lower sensitivity and specificity than molecular tests. As such, all O-Week participants will undergo a follow-up molecular test by the end of this week. However, the entire Will Rice advising team and new student cohort will be tested via the molecular test either today or tomorrow as a precaution, according to Kirby. Results from Rices molecular tests, which are provided by Houston Methodist and Baylor Genetics, are returned within 48 hours, but Kirby said that the tests are often being returned in 24 hours.

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We'll go through the whole college and test everybody, Kirby said. We'll see if there are any [COVID-19 positive students] that have been missed or any new infections and sort of sweep through and get everybody today or tomorrow. And these tests are very accurate.

According to Kirby, there was an additional Will Rice advisor who tested positive for COVID-19, however this student had fully recovered from a previous COVID-19 infection and Student Health Services determined that they did not pose any risk for transmission, according to Kirby. The CDC notes this possibility in their guidance on discontinuing isolation measures.

Recovered persons can continue to shed detectable SARS-CoV-2 RNA in upper respiratory specimens for up to 3 months after illness onset, albeit at concentrations considerably lower than during illness, in ranges where replication-competent virus has not been reliably recovered and infectiousness is unlikely, the CDC writes. Studies have not found evidence that clinically recovered persons with persistence of viral RNA have transmitted SARS-CoV-2 to others.

Following this guidance, Kirby said that this additional Will Rice advisor was not isolated, but continues to be monitored.

Kirby said that 833 new students were given rapid tests on Saturday and Sunday, and three students tested positive. Those who tested positive could either move in to Sid Richardson College, the designated isolation housing, or return home. No more than two students have occupied Sid Rich at any point thus far, Kirby noted.

Campuswide, there have been 4,595 tests administered between August 1 and August 17, and 11 people (3 staff, 7 undergraduates, 1 graduate student) have tested positive, based on a recent update from Crisis Management. Kirby said that Rice will be administering 4,500 tests per week by the first week of classes.

Gorman said that two restrictions have been added to the campuswide O-Week program as precautionary measures. First, all remaining cross-college events have been canceled for the week. Second, students will not be allowed to eat meals together in the college commons, and must eat meals in their dorm rooms or outdoors in a physically-distanced manner.

We're testing everybody this week, as we're doing every week, Gorman said. So we're going to know in the next couple of days whether we're seeing any more spread or whether it's just these two cases at Will Rice.

Gorman said that she hopes to remove the restriction on college commons dining after O-Week, but will decide after more test results are returned.

I think by the weekend after we've gone through and gotten the test results back on everybody on campus and we get a sense about where we're at, we will make a decision at that point, Gorman said. But in preparation, just in case, we are going to ramp up our outside furniture.

Kirby said that while the COVID-19 positivity rate is substantially lower on campus than in Houston, it is important to continue all safety precautions and adapt to changing conditions.

We have to be very careful and wary right about that and we need to not have a false sense of optimism here, Kirby said. That's why it's important that we continue to do all the safety precautions ... and we continue to do our testing rigorously and often. We're prepared to make changes like we already have. I'm sure we'll continue to make changes over the course of the fall semester.

[8/18/2020 at 11:15 p.m.] The story was updated with correct information about the movement of on-campus students. Will Rice President Rahul Popat clarified that on-campus students are not restricted to their rooms.

[8/18/2020 at 11:45 p.m.] The story was updated with information about an additional Will Rice advisor who tested positive for COVID-19, but was determined to not pose any risk for transmission.

[8/19/2020 at 3:10 p.m.] The story was updated with statistics from on-campus COVID-19 testing.

Go here to read the rest:
Will Rice College O-Week moves online after two advisors test positive for COVID-19 - The Rice Thresher

A-level student Kilian Robinson.

Kilian Robinson, 18, of Egton, consistently achieved the highest possible grades for his subjects Biology, Chemistry and Maths over the past two years.

But he was horrified on Thursday to discover that his centre assessment grades had been reduced from A*A*A* to ABB by the controversial Government algorithm, despite him not once attaining anything lower than an A.

He said today (Tues) that Imperial College London had indicated they would keep his place on a Biological Scienes course open to him if he successfully appealed.

Yesterday's Governments U-turn means Kilian has attained his grades and fulfilled his side of the bargain.

He is now waiting to hear back from Imperial College London, having emailed them after the dramatic climbdown was announced.

They said they would honour my offer if I got the grades now Ive got them," he said.

The fight isnt over. Everyone is anxious about it and what if the course is full?

Its a massive problem, yes Ive got my grades but its still to be resolved.

Kilian was offered a place on a Molecular Genetics course in Edinburgh, despite not his results being initially downgraded, but he declined as he has set his heart on a place at Imperial College London.

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Whitby student welcomes A-level U-turn - but still left in limbo over his future - Whitby Gazette

SALT LAKE CITY, Aug. 13, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN, Myriad or the Company), a global leader in molecular diagnostics and precision medicine, today announced the appointment ofPaul J. Diazas President and Chief Executive Officer, effective August 13, 2020. He will also serve on the Companys Board of Directors. Mr. Diaz brings toMyriad Geneticsmore than three decades of executive leadership and business transformation experience in healthcare across a variety of healthcare segments.

Paul is an exceptional leader and executive with extraordinary passion, vision, experience, and operational skills, saidS. Louise Phanstiel, Chair of Myriads Board of Directors. His focus on building high performing teams, and instilling a culture that empowers people to deliver high quality patient care, distinctive customer service and innovation, will be important to supporting Myriads mission and growth. We are excited to have Paul assume the leadership of Myriad Genetics and chart the course to realize the Companys full potential. We look forward to officially introducing Paul during our fourth quarter earnings call. Myriad is dedicated to providing vital information to physicians, patients and their families that enables them to make better decisions about their health and treatment planning. Pauls personal dedication, throughout his career, to patients and their care will be critical in advancing Myriads vision of being a trusted advisor transforming patients lives worldwide with pioneering molecular diagnostics.

I am very excited to join the talented management team and Board of Directors of Myriad Genetics, an organization dedicated to helping patients and physicians identify the risk of developing disease and accurately diagnosing disease and disease progression, commented Paul. Our goal is to empower patients, as consumers, and their physicians and our payer partners with the information and data to help guide their treatment decisions, to improve clinical outcomes and lower healthcare costs.I am equally excited about Myriads potential for innovation and growth.The Company has a tremendous opportunity to transform its business, and strategically position itself for sustainable, profitable growth. We will look to leverage the companys culture of innovation and revitalize our approach to the commercializing of its products and customer service levels.

Mr. Diaz served as the President and Chief Executive Officer and Executive Director and Director of Kindred Healthcare, Inc. for over ten years, where he led the growth, revitalization and diversification of the business that positioned Kindred as the largest provider of post-acute health care services in the United States. Most recently, Mr. Diaz was a Partner at Cressey & Company LP, a private equity firm focusing on healthcare services and HCIT companies. Mr. Diaz is an experienced director and operating executive, having served as an executive and board member of multiple public and private companies. He currently serves on the board of DaVita, Inc. (NYSE: DVA) and is a member of the Board of Trustees of Johns Hopkins Medicine. Mr. Diaz graduated from The American University with a B.S. in Business Administration and with a J.D. from The Georgetown University Law Center.

Heidrick & Struggles led the search process for Myriad.

About Myriad GeneticsMyriad Genetics Inc., is a leading personalized medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on three strategic imperatives: transitioning and expanding its hereditary cancer testing markets, diversifying its product portfolio through the introduction of new products and increasing the revenue contribution from international markets. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, Vectra, Prequel, Foresight, GeneSight, riskScore and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to realizing the Companys full potential; officially introducing Paul during the Companys fourth quarter earnings call; advancing Myriads vision of being a trusted advisor transforming patients lives worldwide with pioneering molecular diagnostics; the Companys potential for innovation and growth; the Companys tremendous opportunity to transform its business, and strategically position itself for sustainable, profitable growth; and the Companys strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties associated with COVID-19, including its possible effects on our operations and the demand for our products and services; our ability to efficiently and flexibly manage our business amid uncertainties related to COVID-19; the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions in Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2020, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

Excerpt from:
Myriad Genetics Appoints Paul J. Diaz as President and Chief Executive Officer and a Member of the Board of Directors - GlobeNewswire

Whats the news: Continuing shortages of reagents, viral transport media, pipettes and other supplies means 2020 will continue to negatively affect the nations COVID-19 polymerase chain reaction (PCR) testing capacity. Given that sobering fact, the AMA and other organizations with expertise in medical testing are urging Health and Human Services Secretary Alex Azar to ensure the nations limited testing resources go to patients with medically identified needs or to public health surveillance efforts.

Its not just the surge of COVID-19 cases that is straining the nations testing capacity, but also a big jump in demand for testing of asymptomatic individuals with no medically indicated need for testing services. These include tests for employees going back to work, students returning to colleges and universities, and individuals wishing to engage in nonessential travel, says the letter sent to Azar by the AMA, American College of Medical Genetics and Genomics, American Society for Clinical Pathology, Association for Molecular Pathology, Association of Pathology Chairs, College of American Pathologists, and Infectious Diseases Society of America.

Given that laboratories already face significant issues in providing access to medically indicated tests and timely return of results, we urge the administration to consider the utility of new testing prioritization guidelines, says the letter. Without improvement in available supplies, we simply do not have the resources to meet the huge demand for testing by asymptomatic individuals without exposure to COVID-19.

HHS testing priorization guidelines should ensure that patients with a medically indicated need for SARS-CoV-2 diagnostic testing can get it. That includes patients with:

Why its important: In public health emergencies such as the COVID-19 pandemic, limited testing resources must first be directed towards those who need them mostthose at immediate risk of infection and serious illness, says the letter to Azar from the AMA and the other organizations.

Outside of necessary public health surveillance strategies, limited resources should not be utilized by those with no symptoms or known exposure and whose needs could be equally served by following quarantine measures, the letter adds. Without adequate testing capacity to rapidly serve those with a medically indicated need for testing, we risk continued widespread transmission of this disease. We also threaten the ability of health care facilities to continue to offer critical medical services to those in need of care.

As long-postponed procedures ramp up, laboratories are struggling to accommodate demand for pre-procedure COVID-19 testing, which further jeopardizes clinical care for millions of Americans, the letter says, noting that the supply-chain problems also are taking a toll on the nations capacity to perform other diagnostic tests.

Testing for other infectious diseases are at risk, and our colleagues report that many molecular tests are being delayed as they simply cannot all be offered while attempting to meet the demands for COVID-19 testing.

The AMA and the other organizations advised that rapid screening tests, designed to be administered at home or at the point of care, could play a significant role in asymptomatic screening and surveillance efforts, as well as reopening efforts, without placing additional strain on the PCR diagnostic test market.

The administration should prioritize support for development of such rapid testing tools.

Learn more: Physicians can stay up to date on all of theAMAs COVID-19 advocacy effortsand track the pandemic with theAMA's COVID-19 resource center, which offers a library of current resources from theJAMA Network, the Centers for Disease Control and Prevention, and the World Health Organization.

See the original post:
With supplies short, COVID-19 tests should go where most needed - American Medical Association

A UO-led team of researchers spanning physics, neuroscience, molecular biology, ecology and evolution will use a new $325,000 grant to examine aquatic symbioses the interactions between different animal species living together.

The project is funded by a 30-month award from the Gordon and Betty Moore Foundation and involves the study of zebrafish in controlled ecosystems.

The team will leverage decades worth of pioneering research at the UO involving zebrafish and explorations of the gut microbiome, in which vast numbers of microbes contribute to both health and disease in their hosts. UO has been a leader in zebrafish research since the 1960s, when the late biologist George Streisinger established zebrafish as an ideal model for studying human development and disease.

We aim to develop new tools for studying these symbioses throughout the entire lifespan of zebrafish, which serves as a model aquatic animal and a model for phenomena relevant to all vertebrates, including humans, said Raghuveer Parthasarathy, an Alec and Kay Keith Professor in the Department of Physics, a member of the UOs Institute of Molecular Biology and Materials Science Institute, and the principal investigator on the award.

The project builds on the successes of the zebrafish group here at the UO and it pushes it to the next frontier of trying to capture the whole lifespan of the animal and its ecosystem, Parthasarathy said.

Along with Parthasarathy, the team includes Karen Guillemin, Judith Eisen and Brendan Bohannan, all professors in the Department of Biology. Guillemin is a Philip H. Knight Chair and a member of the Institute of Molecular Biology. Eisen is a member of the Institute of Neuroscience. Bohannan, the James F. and Shirley K. Rippey Chair in Liberal Arts and Sciences, is a member of the Institute of Ecology and Evolution.

The team also includes John Rawls, a professor of molecular genetics and microbiology at Duke University and the director of the Duke Microbiome Center.

Part of the Moore Foundations Symbiosis in Aquatic Systems Initiative, the project will contribute to a larger effort to equip the scientific community with new genetic tools, cultivation methods and other infrastructure to improve experimental capabilities in aquatic symbiosis research over the coming decade. Increasingly, researchers are recognizing that symbiotic bacteria are critical components in the processes that sculpt the evolution, ecology, development and physiology of animals, yet remarkably little is known about exactly how those processes play out.

The four UO researchers have worked together on previous projects as part of the UOs interdisciplinary Microbial Ecology and Theory of Animals, a National Institutes of Health-funded Center of Excellence in Systems Biology. The center is funded by a $7.6 million grant and seeks to better understand the bacteria and other microorganisms that reside in the animal gut and influence many biological functions.

Building on their earlier work studying individual biological processes, the new research will explore the entire ecosystem and lifespan of zebrafish and consider food chains, population densities and other attributes. The project will serve as a bridge between more traditional model system research and field studies, opening up new frontiers in zebrafish research, Parthasarathy said.

The project involves three main areas. Investigators will:

Were hoping to learn how can we both predict and control ecosystem constituents, things like food and bacteria and how can that give us healthy organisms throughout their lifespan, Parthasarathy said. Our approach focuses especially on better understanding nutrition and on engineering new aquatic habitats that allow controlled investigation of symbiotic interactions. We want to watch and learn from the entire process.

The UO team will be building on a strong foundation of zebrafish research. That includes groundbreaking work by Eisen examining interactions between the nervous system, immune system and bacteria in the gut, and Guillemins innovative development of specialized sterile zebrafish that allow scientists to better determine the role microbes play as animals grow.

Bohannan has conducted important research on zebrafish, tracking them throughout their life cycle to see how diet, genetics and immune response affect their microbial diversity. And Parthasarathy has employed physics to better understand how gut microbes move and interact with each other, producing stunning, high-resolution, three-dimensional images and videos of gut bacteria in zebrafish using a technique known as light sheet microscopy.

Rawls, the biologist from Duke University, studies gut bacteria in zebrafish and their role in regulating digestive physiology, innate immunity and gut-brain communication.

I think (this research) may open up a lot of ecological questions, Parthasarathy said. If we succeed, we can expand our methods to other species such as plants and algae and explore their interactions. I think there is lots of potential for growth.

The project is the latest in a string of awards to UO researchers from the Moore Foundation. Earlier this year Eisen received a $2 million grant through the same symbiosis initiative to probe the relationship between symbiotic bacteria and neural development, using zebrafish as a model organism. In January, UO biologist Kelly Sutherland received a $1.1 million grant from the foundation funding her research examining the swimming mechanisms of gelatinous marine organisms.

These awards are a testament to the exceptional research being conducted at the University of Oregon, said Provost and Senior Vice President Patrick Phillips. We are grateful to the Gordon and Betty Moore Foundation for their generous support of our researchers and their investment in these innovative and impactful projects, which support the foundations critical mission of fostering pathbreaking scientific discovery and further the UOs commitment to enriching the human condition through creative inquiry and scientific discovery.

By Lewis Taylor, University Communications

Read this article:
UO team will use zebrafish in new study of aquatic symbioses - AroundtheO

Once known as a paradigm changing class of precision oncology, or targeted, drugs,1 Bruton tyrosine kinase (BTK) inhibitors are now well established as treatment for several hematological malignancies. They are named for Lt Col Ogden C. Bruton, MD, chief of pediatrics at Walter Reed Army Medical Center in the 1950s, who in 1951 discovered the first host immunodeficiency in humans, X-linked agammaglobulinemia.2,3

The BTK protein is essential to helping B cells develop and mature into functional and specialized white blood cells; these are part of the adaptive immune response in producing antibodies, or immunoglobulins.4 But mutations in the BTK gene, more than 600 of which have been identified, can lead to a sizeable reduction in the number of circulating B cells, along with reduced ability to fight infection, absence of the BTK protein, production of abnormal BTK protein, or cancer cell growth.5,6

Mutated immunoglobulins essentially malfunction in their roles as antigen receptors on the surfaces of B cells, especially in the cancer space, by not recognizing antigens as damaging or by not sending the correct signals to destroy the malignant cells.

This is where BTK inhibitors come in: They help to trigger cell death by blocking the B-cell receptor signaling that leukemias and lymphomas use to grow and survive.7 The first-generation BTK inhibitor ibrutinib (Imbruvica) came to market in 2013, when it was approved by the FDA to treat adult patients with mantle cell lymphoma. A targeted treatment, it stops cancer cells from surviving and multiplying by blocking abnormal protein signaling.8 Other indications, as monotherapy or in combination, have been approved for chronic lymphocytic leukemia, Waldenstrm macroglobulinemia, small lymphocytic lymphoma, relapsed/refractory marginal zone lymphoma, and chronic graft-versus-host disease.9 Ibrutinib is a once-daily oral agent and can be used in the frontline and relapsed settings.10

Despite its many benefits and indications, however, ibrutinib as BTK inhibition is also associated with numerous adverse effects (AEs) on nonmalignant cells, which range from common to uncommon and from mild to severe, making ibrutinibs toxicity profile notorious.7

Among the most severe AEs are hemorrhage; high blood pressure; heart rhythm irregularities, including ventricular arrhythmias, atrial fibrillation, and atrial flutter; second primary cancers (eg, skin, other organs); and tumor lysis syndrome.11 Some of the most common AEs, occurring in more than 30% of patients, are hematological (eg, decreased platelets, neutrophils, and hemoglobin), musculoskeletal, and respiratory in nature.

Additional possible AEs include diarrhea, constipation, vomiting, skin infections, dizziness, dehydration, petechiae, arthralgia, stomatitis, rash, and fatigue.12 Ibrutinib carries warnings for use among those with bleeding problems, liver problems, and for those who are planning surgery or recently had surgery; women who are pregnant or thinking of becoming pregnant; women who breastfeed or plan to do so; and men with female partners capable of pregnancy.

Second-generation BTK inhibitors seek to improve upon first-generation agents like ibrutinib by having less cardiotoxicity, fewer AEs that result in stopping treatment, and fewer off-target effects. For example, ibrutinib inhibits the activity of 3 major off-targets: epidermal growth factor, which can result in severe skin toxicities13; interleukin-2 inducible kinase, which impairs natural killer cells cytotoxic abilities14; and the Tec family of kinases, decreasing their ability to aid in phosphorylation.15

In updated results of the ASPEN trial presented at this years virtual American Society of Clinical Oncology (ASCO) 2020 Annual Meeting, zanubrutinib (Brukinsa), the most recent second-generation BTK inhibitor to hit the US market, was shown to have a survival advantage over ibrutinib in patients with Waldenstrm macroglobulinemia who lacked the MYD88 mutation typically associated with successful treatment.16

ASPEN first compared zanubrutinib with ibrutinib in patients with Waldenstrm macroglobulinemia who have the MYD88 mutation, and zanubrutinib was shown in December 2019 to increase the incidence of complete response (CR) or very good partial response (VGPR) by close to 46% compared with ibrutinib28.9% vs 19.8%, respectivelyin patients with relapsed or refractory disease.17

The updated results, from 5 additional months of data, widened this gap, showing a 30.4% CR plus VGPR rate for zanubrutinib compared with 18.2% for ibrutinib, as well as less occurrence of atrial fibrillation/flutter of any grade, bleeding of any grade, major hemorrhage, diarrhea, and hypertension. In addition, patients without the MYD88 mutation had an overall response rate of 80.8%, which included a 50.0% major response ratewhich itself included a VGPR rate of 26.9%and 12-month progression-free survival of 72.4%.18

Lead investigator, Constantine Tam, MBBS, MD, a clinical hematologist and professor at the Peter MacCallum Cancer Centre in Victoria, Australia, noted of zanubrutinib, Those patients who potentially have a history of hypertension or have a history of atrial fibrillationor have an abnormal ECG or abnormal echocardiogrammaybe theyre the ones who would be better off on [zanubrutinib] compared with ibrutinib. We think its how clean the targeting is.19

Zanubrutinib is associated with less incidence of muscle spasm, peripheral edema, pneumonitis, and pneumonia. In essence, fewer overall AEs with second-generation BTK inhibitors means less of a need to reduce dosing and a greater likelihood of being able to stay on treatment longer. Tam noted that most AEs happen with zanubrutinib during the first year on treatment, before their incidence plateaus, whereas prolonged treatment with ibrutinib has a greater chance of inflicting cumulative damage to the vascular system.20 Compared with first-generation BTK inhibitors, the second-generation drugs are associated with fewer concerns about primary and acquired drug resistance. For example, ibrutinib use among patients with relapsed/refractory mantle cell lymphoma has been shown to both have no effect on the disease and have a negative impact on additional therapies.21

These resistance mechanisms of action are 2-fold. They are molecular, in that they involve sustained distal B-cell receptor signaling through PIK3-AKT (protein kinase B) pathway activation, NFkB pathway activation, and cell cycle progression. They also are therapeutic, in that lines of therapy administered after BTK inhibitors do not produce prolonged responses or exceptional overall survival.21

Less Cardiotoxicity in Second Generation

Some of the strongest gains in this newer generation of BTK inhibitors, however, can be seen in the cardiovascular space, when compared with the toxicities of the first-generation inhibitors

that often lead to treatment discontinuation, especially among older, sicker patients who have a history of cardiac disease. In fact, most BTK inhibitors are prescribed for older patients, because the class of drugs is used primarily to treat chronic lymphocytic leukemia, for which the average age of onset is older than 60 years.22

I think its that a lot of the toxicities are related to off-target effects, meaning the binding of the BTK inhibitor drug to receptors or molecules that are not the ones that that theyre supposed to be treating the cancer for, said Michael Kolodziej, MD, FACP, vice president and chief innovation officer, ADVI Health, in an interview with Evidence-Based Oncology.

The big ones that were identified with the first-generation inhibitors were cardiovascular, or hypertension and atrial arrhythmias, atrial fibrillation. And they were not rare side effects.

Kolodziej explained that the second-generation drugs have fewer off-target effectsless cardiovascular toxicity, atrial arrhythmias, and hypertensionbecause of their improved toxicity profile, largely because the drugs are just better at being BTK inhibitors. Its not any more complicated than that.

The chief challenge of the first-generation BTK inhibitors is that the AEs cause clinicians and patients to stop treatment with them, Kolodziej noted. The cancer does not become resistant, but the toxicities become unbearable and the patients become intolerant, he emphasized.

The thinking is that the reduced cardiovascular side effects, the reduced bleeding, are going to allow a better persistence on the second-generation drugs, he explained.

Tolerability and Payers

Indeed, in a pooled analysis of clinical trials of the second-generation BTK inhibitor acalabrutinib (Calquence), also presented in May at ASCO, lead author Richard R. Furman, MD, of Weill Cornell Medicine in New York, found that at a median follow-up of 26.4 months, 65% of patients were still on treatment. Of the 34% of patients who stopped acalabrutinib, half (17%) did so because their disease progressed; only 9% stopped due to treatment-related AEs.23

Tolerability, especially as patients define it, is increasingly important to payers, starting with Medicare. The Center for Medicare and Medicaid Innovation has announced that it will incorporate patient-reported outcomes (PROs) into the Oncology Care First model, the proposed successor to the Oncology Care Model.24 Advocates for including PROs in payment models are encouraging drug developers to broaden definitions of tolerability, to include quality-of-life data in trial designs.25

Its a straightforward idea: When patients can tolerate treatment, it improves their chances of survival. This is important, Tam said during ASCO. The longer you take the drug, the better your responses become.19

Author Information

Maggie L. Shaw is associate editor, The American Journal of Managed Care.

References

1. Erba HP. BTK inhibition in B-cell lymphomas: an overview of Bruton tyrosine kinase inhibition. Targeted Oncology. June 21, 2019. Accessed July 18, 2020. https://www.targetedonc.com/view/btk-lymphoma

2. Wyckoff AS. Dr. Brutons discovery set the stage for modern clinical immunology. American Academy of Pediatrics News. May 31, 2018. Accessed July 18, 2020. https://www.aappublications.org/news/2018/05/31/dyk053118

3. Buckley RH. [Commentary:] agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9:722-728. Pediatrics. 1998;102(suppl 1):213-215. https://pediatrics.aappublications.org/content/102/Supplement_1/213

4. Deane P. B cells: the antibody factories of the immune system. Life Extension Advocacy Foundation. August 22, 2017. Accessed July 18, 2020. https://www.lifespan.io/news/b-cells/

5. BTK gene: Bruton tyrosine kinase. US National Library of Medicine/Genetics Home Reference. Updated July 7, 2020. Accessed July 18, 2020. https://ghr.nlm.nih.gov/gene/BTK#

6. Bruton tyrosine kinase inhibitor. Science Direct. Accessed July 18, 2020. https://www.sciencedirect.com/topics/medicine-and-dentistry/bruton-tyrosine-kinase-inhibitor

7. BTK inhibitors. Drugs.com. Updated January 7, 2020. Accessed July 18, 2020. https://www.drugs.com/drug-class/btk-inhibitors.html

8. Ibrutinib. MedlinePlus. Updated May 15, 2019. Accessed July 19, 2020. https://medlineplus.gov/druginfo/meds/a614007.html

9. Imbruvica approval history. Drugs.com. Updated 2020. Accessed July 19, 2020. https://www.drugs.com/history/imbruvica.html

10. Berger JA. The evolving role of BTK inhibitors in treating chronic lymphocytic leukemia BTK inhibition: disease state effectiveness. Targeted Oncology. April 16, 2020. Accessed July 19, 2020. https://www.targetedonc.com/view/evolving-btk-cll?seriesVid=2

11. How does Imbruvica work? Imbruvica (ibrutinib). April 20, 2020. Accessed July 19, 2020. https://imbruvica.com/cll/how-does-imbruvica-work

12. Imbruvica. Chemocare. Accessed July 19, 2020. chemocare.com/chemotherapy/drug-info/imbruvica.aspx

13. Ghasoub R, Albattah A, Elazzazy S, et al. Ibrutinib-associated sever[e] skin toxicity: a case of multiple inflamed skin lesions and cellulitis in a 68-year-old male patient with relapsed chronic lymphocytic leukemia case report and literature review. J Oncol Pharm Pract. 2020;26(2):487-491. doi:10.1177/1078155219856422

14. Bennett C. Ibrutinib may impair natural killer cell cytotoxic activity, study suggests. Cancer Therapy Advisor. June 19, 2019. Accessed July 19, 2020. https://www.cancertherapyadvisor.com/home/cancer-topics/lymphoma/ibrutinib-for-mantle-lymphoma-mcl-may-impair-naturalcyto-toxic-activity/

15. Patel V, Balakrishnan K, Bibikova E, et al. Comparison of acalabrutinib, a selective Bruton tyrosine kinase inhibitor, with ibrutinib in chronic lymphocytic leukemia cells. Clin Cancer Res. 2017;23(14):3734-3743. doi:10.1158/1078-0432.CCR-16-1446

16. Garcia-Sanz R, Dimopoulos MA, Lee H-P, et al. Updated results of the ASPEN trial from a cohort of patients with MYD88 wild-type (MYD88WT) Waldenstrm macroglobulinemia (WM). J Clin Oncol. 2020;38(15 suppl; abstr e20056). doi:10.1200/JCO.2020.38.15_suppl.e20056

17. Tam CSL, Opat S, DSa S, et al. ASPEN: results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenstrm macroglobulinemia (WM). J Clin Oncol. 2020;38(15 suppl; abstr 8007). doi:10.1200/JCO.2020.38.15_suppl.8007

18. BeiGene presents updated head to head results from phase 3 trial of zanubrutinib vs. ibrutinib in patients with Waldenstrms macroglobulinemia at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. News release. BeiGene; May 29, 2020. Accessed August 3, 2020. https://www.globenewswire.com/news-release/2020/05/29/2040883/0/en/BeiGene-Presents-Updated-Head-to-Head-Results-from-Phase-3-Trial-of-Zanubrutinibvs-Ibrutinib-in-Patients-with-Waldenstrm-s-acroglobulinemiaat-the-2020-American-Society-of-Clini.html

19. Caffrey M. Zanubrutinib pulls away from ibrutinib in update, shows durable responses in Waldenstrom patients lacking key mutation. The American Journal of Managed Care. May 30, 2020. Accessed July 21, 2020. https://www.ajmc.com/conferences/asco-2020/zanubrutinib-pulls-away-from-ibrutinib-in-update-shows-durable-responses-in-waldenstrom-patients-lacking-key-mutation

20. Dr Constantine Tam discusses the benefits of zanubrutinib on cardiac effects. The American Journal of Managed Care. May 31, 2020. Accessed July 22, 2020. https://www.ajmc.com/conferences/asco-2020/dr-constantine-tam-discusses-the-benefits-of-zanubrutinib-on-cardiac-effects

21. Hershkovitz-Rokah O, Pulver D, Lenz G, Shpilberg O. Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects. Br J Haematol. 2018;181(3):306-319. doi:10.1111/bjh.15108

22. Chronic lymphocytic leukemia. CancerWall. Accessed July 24, 2020. https://cancerwall.com/chronic-lymphocytic-leukemia-lifeexpectancy-symptoms/

23. Furman RR, Byrd JC, Own RG, et al. Safety of acalabrutinib (acala) monotherapy in hematologic malignancies: pooled analysis from clinical trials. J Clin Oncol. 2020;38(suppl 15; abstr 8064). doi:10.1200/JCO.2020.38.15_suppl.8064

24. Bekele B, Macher D, Ferguson S, et al. Emerging trends in oncology management. Avalere Health. June 2, 2020. Accessed July 31, 2020. https://avalere.com/insights/emerging-trends-in-oncology-management

25. Basch E, Campbell A, Hudgens S, et al. A Friends of Cancer research white paper: broadening the definition of tolerability in cancer clinical trials to better measure the patient experience. Friends of Cancer Research. October 24, 2018. Accessed July 31, 2020. https://www.focr.org/sites/default/files/Comparative%20Tolerability%20Whitepaper_FINAL.pdf

Excerpt from:
Second-Generation BTK Inhibitors Hit the Treatment Bullseye With Fewer Off-Target Effects - AJMC.com Managed Markets Network