Category Archives: Genetic medicine

"These guidelines are as inclusive as possible, wherever there's strong, unbiased evidence to back up our recommendations," said Mary B. Daly, MD, PhD, FACP, Fox Chase Cancer Center, Chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "The guidelines include genes that have been found to increase cancer-susceptibility. These NCCN Guidelines still have a strong focus on BRCA1 and 2 mutations, but also now include other high and moderate penetrance genes associated with breast, ovarian, and pancreatic cancer. We continuously review any new data on genes that might increase a person's risk of getting cancer or impact the effectiveness of their treatment."

The updated guidelines are concentrated around simplified criteria to clarify the genetic testing process. For example, in a newly-added guide for individuals of Ashkenazi Jewish ancestry who have not been diagnosed with cancer, genetic testing may be offered for the three Ashkenazi Jewish founder mutations in the context of a long-term research study, regardless of family history. These individuals should be encouraged to consult with a cancer genetics professional.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment are organized by both disease and syndrome type, and also now include streamlined information on appropriate subsequent steps for persons who meet criteria for genetic testing. The panel acknowledges that genetic mutations can impact the approach to cancer treatment, and the guidelines now state that testing may be clinically indicated if it will aid in systemic therapy decision-making.

"Genetic testing is becoming increasingly utilized in oncology because of its potential to impact surgical decisions and chemotherapy," explained Robert Pilarski, MS, LGC; MSW, Licensed Genetic Counselor, Professor, Clinical Internal Medicine, The Ohio State University Comprehensive Cancer Center, Vice-Chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "At the same time, the complexity of this testing is increasing, with a growing number of genes and tests available,a limited understanding of the management implications of some of the newer genes, and even uncertainty over the implications of mutations in well-established genes in some situations (for example in a condition known as 'mosaicism,' in which the mutation is not present in all of the cells of the body). Because of this, the NCCN Guidelines continue to highlight the critical importance of genetic counseling for patients prior to undergoing genetic testing to ensure that patients are fully informed of the test implications."

Pilarski also offered an important word of caution about the potential risks from direct-to-consumer genetic testing: "More and more patients are presenting to clinic having already had themselves tested through direct-to-consumer labs. Providers need to be aware that the tests offered by many of these labs are not equivalent to traditional genetic testing, and the results may need to be confirmed in another laboratory before being used for clinical care."

The guidelines recommend all pancreatic cancer patients get genetic testing, and the recent update now includes more information about which genes are associated with pancreatic cancer recommendations. Genetic testing in pancreatic cancer can help determine which treatments would be most effective (e.g. PARP inhibitors) and if family members would benefit from screening and preventive action.

"There's been an explosion of recent data showing that roughly 4-10% of individuals with pancreatic cancer harbor inherited genetic mutations, including BRCA1, BRCA2, ATM, the Lynch syndrome genes, and others," said Matthew B. Yurgelun, MD, Dana-Farber/Brigham and Women's Cancer Center, Member of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "Such data have, surprisingly, shown that classic 'high-risk' features of inherited cancer risk (e.g. young age at diagnosis, strong family histories of cancer) are often absent in individuals with pancreatic cancer who carry these mutations. Based off of these data, there is now a compelling reason for all individuals with pancreatic cancer to be offered genetic counseling and germline testing for such variantsparticularly given the possibility that their at-risk family members could greatly benefit from known, effective cancer risk-reducing interventions (e.g. surgical removal of the ovaries for female BRCA1/2 mutation carriers). Emerging data have also begun to suggest possible benefits to pancreatic cancer screening in select high-risk individuals who harbor such mutations. These new guidelines address many of the important nuances and limitations of this exciting and rapidly evolving body of literature."

The NCCN Guidelines for Genetic/Familial High-Risk Assessment are created and maintained by an interdisciplinary panel of experts from the alliance of 28 leading cancer centers that comprise NCCN. NCCN panels also include patients and advocates to make sure treatment recommendations meet the needs of people with cancer and their caregivers.

"Participating on the NCCN panel allows FORCE to share the real-world experiences of patients making complex, and often agonizing medical decisions about hereditary cancer treatment and risk management," said Sue Friedman, DVM, Executive Director, Facing Our Risk of Cancer Empowered (FORCE), Member of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. "As an advocacy organization for people and families affected by hereditary cancer, we see the importance of having standardized guidelines. These guidelines are a critical piece of informed decision-making; we frequently direct our community to NCCN for up-to-date, clear, and credible information developed by experts in the field."

NCCN Guidelines are the recognized standard for clinical policy in cancer care and are the most thorough and frequently updated clinical practice guidelines available in any area of medicine. The intent of the NCCN Guidelines is to assist in the decision-making process of individuals involved in cancer careincluding physicians, nurses, pharmacists, payers, patients and their familieswith the ultimate goal of improving patient care and outcomes. In addition to covering at least 97 percent of cancers affecting patients in the United States, there are also NCCN Guidelines for detection, prevention, risk-reduction (including smoking cessation), supportive care (including the management of pain, distress, and fatigue), and guidelines for specific populations (including children and young adults).

NCCN Guidelines are available free-of-charge for non-commercial use at NCCN.org, or via the Virtual Library of NCCN Guidelines App.

About the National Comprehensive Cancer NetworkThe National Comprehensive Cancer Network (NCCN) is a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, efficient, and accessible cancer care so patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. By defining and advancing high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers around the world.

The NCCN Member Institutions are: Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA; Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope National Medical Center, Duarte, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; O'Neal Comprehensive Cancer Center at UAB, Birmingham, AL; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Rogel Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT.

Clinicians, visit NCCN.org. Patients and caregivers, visit NCCN.org/patients. Media, visit NCCN.org/news. Follow NCCN on Twitter @NCCN, Facebook @NCCNorg, and Instagram @NCCNorg.

Media Contact: Rachel Darwin267-622-6624darwin@nccn.org

SOURCE National Comprehensive Cancer Network

http://www.nccn.org

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Updated Genetic Screening Guidelines Published by National Comprehensive Cancer Network Feature Emerging Evidence on Personalized Medicine -...

BETHESDA, Md., Dec. 4, 2019 /PRNewswire/ --The American College of Medical Genetics and Genomics (ACMG) heads to a new destination in sunny San Antonio, Texas in 2020. Named one of the fastest growing meetings in the USA by Trade Show Executive Magazine, the ACMG Annual Clinical Genetics Meeting continues to provide groundbreaking research and news about the latest advances in genetics, genomics and personalized medicine. To be held March 17-21, the 2020 ACMG Annual Meeting will feature more than 40 scientific sessions, 3 Short Courses, workshops, TED-Style talks and satellite symposia, and over 800 poster presentations on emerging areas of genetic and genomic medicine.

Interview those at the forefront in medical genetics and genomics, connect in person with new sources and get story ideas on the clinical practice of genetics and genomics in healthcare today and for the future. Learn how genetics and genomics research is being integrated and applied into medical practice.

Topics include gene editing, cancer genetics, molecular genomics, exome sequencing, pre- and perinatal genetics, biochemical/metabolic genetics, genetic counseling, health services and implementation, legal and ethical issues, therapeutics and more.

Credentialed media representatives on assignment are invited to attend and cover the ACMG Annual Meeting on a complimentary basis. Contact Kathy Moran, MBA at kmoran@acmg.net for the Press Registration Invitation Code, which will be needed to register at http://www.acmgmeeting.net.

Abstracts of presentations will be available online in January 2020. A few 2020 ACMG Annual Meeting highlights include:

Program Highlights:

Cutting Edge Scientific Concurrent Sessions:

Three half-day Genetics Short Courses on Monday, March 16 and Tuesday, March 17:

Photo/TV Opportunity: The ACMG Foundation for Genetic and Genomic Medicine will present bicycles to local children with rare genetic diseases at the Annual ACMG Foundation Day of Caring on Friday, March 20 from 10:30 AM 11:00 AM at the Henry B. Gonzlez Convention Center.

Social Media for the 2020 ACMG Annual Meeting: As the ACMG Annual Meeting approaches, journalists can stay up to date on new sessions and information by following the ACMG social media pages on Facebook,Twitter and Instagram and by usingthe hashtag #ACMGMtg20 for meeting-related tweets and posts.

Note be sure to book your hotel reservations early.

The ACMG Annual Meeting website has extensive information at http://www.acmgmeeting.net.

About the American College of Medical Genetics and Genomics (ACMG) and the ACMG Foundation for Genetic and Genomic Medicine (ACMGF)

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics and the only medical specialty society in the US that represents the full spectrum of medical genetics disciplines in a single organization. The ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice for more than 2,300 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. ACMG's mission is to improve health through the clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics into all of medicine and healthcare, resulting in improved personal and public health. Four overarching strategies guide ACMG's work: 1) to reinforce and expand ACMG's position as the leader and prominent authority in the field of medical genetics and genomics, including clinical research, while educating the medical community on the significant role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) to secure and expand the professional workforce for medical genetics and genomics; 3) to advocate for the specialty; and 4) to provide best-in-class education to members and nonmembers. Genetics in Medicine, published monthly, is the official ACMG peer-reviewed journal. ACMG's website (www.acmg.net) offers resources including policy statements, practice guidelines, educational programs and a 'Find a Genetic Service' tool. The educational and public health programs of the ACMG are dependent upon charitable gifts from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Kathy Moran, MBAkmoran@acmg.net

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SOURCE American College of Medical Genetics and Genomics

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Press Registration for the 2020 ACMG Annual Clinical Genetics Meeting Is Now Open - P&T Community

The GenomeAsia 100K consortium analyzed the genomes of 1,739 people, which represents the widest coverage of genetic diversity in Asia to date.

The study covers 64 different countries and provides what the authors call the first comprehensive genetic map for Asia that will guide scientists in studying diseases unique to Asians, improve precision medicine and identify drugs that may carry higher risk of adverse reactions for certain ethnic groups.

Despite forming over 40 per cent of the worlds population, Asian people have previously accounted for only six per cent of the worlds recorded genome sequences.

The goal of GenomeAsia 100K, which launched in 2016, is to better understand the genome diversity of Asian ethnicities by sequencing 100,000 genomes of people living in Asia. It is a non-profit consortium hosted by Nanyang Technological University, Singapore (NTU Singapore), the only academic member. Its three other members are Macrogen based in South Korea, Genentech, a member of the Roche Group in United States, and MedGenome from India/US.

NTU Professor Stephan C. Schuster, the consortiums scientific chairman and a co-leader of the study, explained the significance of GenomeAsia 100Ks initial findings on the vast genomic diversity in Asia: To put it into context, imagine we looked at all people of European and based on the level of their genetic diversity, observed that they could all be grouped into just one ancestral lineage or population. Now, if we took that same approach with our new data from people of Asian, then based on the much higher levels of genetic diversity observed we would say that there are 10 different ancestral groups or lineages in Asia.

Schuster added, GenomeAsia 100K is a significant and far-reaching project that will affect the well-being and health of Asians worldwide, and it is a great honour for Singapore and NTU to be hosting it.

Executive Chairman of GenomeAsia 100K, Mahesh Pratapneni said, The publication of this pilot study is a first milestone for GenomeAsia 100K, which is an unprecedented collaboration between academia and industry leaders in the field of genomics. We are certain more partners will join GenomeAsia 100K to accelerate medical breakthroughs for people of Asian heritage.

Chairman and CEO of MedGenome, the largest genomics and molecular diagnostics provider in South Asia with facilities in the US, Singapore and across India, Sam Santhosh, said, "We are excited that over 1000 whole genome sequence data from the Indian sub-continent will now be available to researchers; this is an initial step in covering the underrepresented geographies."

Prof Jeong-Sun Seo, at Seoul National University Bundang Hospital Consortium scientific co-chair and Chairman of Macrogen, said, I hope this Asian-focused study serves as a stepping stone for the democratization of health care and precision medicine in Asia.

How the database of Asian genomes was formed

Over the course of the last three decades prior to the pilot project, thousands of blood and saliva samples have already been collected by scientists and anthropologists from donors across Asia in hopes that one day, a deeper analysis to gain insights into the Asian community can be done.

Of particular interest were participants from remote and isolated communities, who have long been the subjects of study by anthropologists but have not yet undergone genomic analysis, until the GenomeAsia 100K project was kickstarted.

The pilot study included 598 genomes from India, 156 from Malaysia, 152 from South Korea, 113 from Pakistan, 100 from Mongolia, 70 from China, 70 from Papua New Guinea, 68 from Indonesia, 52 from the Philippines, 35 from Japan, and 32 from Russia.

Genomic DNA extracted from the blood and saliva samples was then sequenced in laboratories of the four consortium members in the US, India, South Korea and Singapore. The digital sequencing data were subsequently sent to Singapore for processing and storage.

Singapore was selected by the consortium as the host, as the country offered good travel connections for collaborating scientists, strong supercomputing facilities to crunch the data, and the required cybersecurity standards in its data centre for handling sensitive genetic data.

The combined data was compiled and analyzed by NTU scientists, including Assistant Professor Hie Lim Kim, a population genomics expert at the Asian School of The Environment, with the help of the National Supercomputing Centre Singapore (NSCC) and international collaborators.

Different Asian ethnic groups respond differently to mainstream drugs

Every person has approximately 3.2 billion different nucleotides, or building blocks, in their genome, which form their DNA code.

Its estimated that for the genomes of any two people, 99.9 per cent of this code is the same and on average, 0.1 per cent or three million nucleotides, are different between them.

This genetic variance help humankind colonize the most diverse environments on the planet and make it resilient to disease, but it also results in differential response to many medicines.

Genetic variance is the reason we are distinctively different from each other including differences in the diseases that each of us suffer from during our lifetimes. Understanding these differences is the most important source of clues that we have for driving the discovery of innovative new medicines, said Dr Andrew Peterson, an author of the paper and an expert in the use of genetics to drive drug discovery.

Peterson was head of Molecular Biology at Genentech while this work was being carried out, is now Chief Scientific Officer at MedGenome, where he leads drug discovery efforts at MedGenomes Seven Rivers Genomic Medicines division.

The frequencies of known genetic variants related to adverse drug response were analyzed for the genomes collected in this study.

For example, warfarin, a common anticoagulant drug prescribed to treat cardiovascular diseases, likely has a higher than usual risk of adverse drug response for people carrying a certain genetic variant. This particular genetic variant has a higher frequency to appear in those with North Asian ancestry, such as Japanese, Korean, Mongolian or Chinese.

Using data analysis, scientists can now screen populations to identify groups that are more likely to have a negative predisposition to a specific drug.

Knowing a persons population group and their predisposition to drugs is extremely important if personalized medicine is to work, stressed Prof Schuster: For precision medicine to be precise, you need to know precisely who you are.

Hie Lim Kim, who leads the projects efforts in population genetics, added: Only by sequencing the entire genome of an individual can a persons ancestry and genetic background be known. Their genome explains why some people are afflicted by certain diseases while others arent. Scientists know that there is no single drug that works well for everybody and our latest findings not only reinforce this, but suggest how specific groups could be harmed by specific medicines.

Moving forward, the GenomeAsia 100K will continue to collect and analyze up to 100,000 genomes from all of Asias geographic regions, in order to fill in the gaps on the worlds genetic map and to account for Asias unexpected genetic diversity.

Reference

GenomeAsia100K Consortium. (2019) The GenomeAsia 100K Project enables genetic discoveries across Asia. Nature. DOI: https://doi.org/10.1038/s41586-019-1793-z

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Insights into Asian Ancestry and Genetic Diversity - Technology Networks

Rapid advances in telomere biology are paving the way to new clinical applications that promise better diagnosis and treatment options in select patients. Scientists understanding about the role of telomerescaps at the ends of chromosomes that prevent attrition of DNAhas progressed to the point that telomere measurements are being used in diagnostic workups at some medical centers. Broader dissemination of this type of analysis will go hand-in-hand not only with a deeper understanding of the link between telomere length and health and disease but also more standardized testing methods and parameters. Expanding the use of telomere testing also will depend on better coordinated care among clinical disciplines that have not traditionally worked together, according to Mary Armanios, MD, professor of oncology, genetic medicine, molecular biology and genetics, and pathology at Johns Hopkins University in Baltimore.

The causal role telomeres play in aging and age-related diseases has been known for decades. However, new studies now reveal that extreme short or long telomere lengths are associated with specific heritable diseases and cancers. This knowledge, a pivotal advance, has added urgency to the quest to accurately measure telomere length and define clinically relevant short and long thresholds. With the advent of precision genomics, we have the opportunity to identify and manage these disorders for the benefit of patients, said Mrinal Patnaik, MBBS, an associate professor of medicine and oncology and a consultant hematologist at the Mayo Clinic in Rochester, Minnesota.

Telomeres shorten every time a cell divides, naturally shortening with age and at a certain point signaling cells to stop dividing and become senescent. However, when genes responsible for telomere synthesis, trafficking, maintenance, and for telomerase function are perturbed, accelerated telomere shortening leads to a group of genetic disorders called short telomere syndromes (STS). Notably, although 13 causative genes have been identified, these account for only about 40% of STS cases. The fact that more than half of our patients with short telomeres do not have detectable gene mutations on sequencing panels indicates that we havent yet discovered all the mutations that affect telomere length, said Patnaik.

STS encompass disparate clinical manifestations across multiple organ systems including immunodeficiency, idiopathic pulmonary fibrosis and emphysema, esophageal stenosis and enterocolitis, hepatic fibrosis and cirrhosis, and bone marrow failure. Anytime you see a triad of symptoms that include premature greying of hair, fibrotic involvement of lung and liver, and bone marrow failure, it should raise flags as a potential STS, said Patnaik.

In contrast, mutations that lengthen telomeres cause long telomere syndromes. These are associated with a high cancer risk: glioma and familial melanoma, in particular. Insights from genome-wide association studies have identified genetic variants in telomere-related genes concurrent with these cancers, further strengthening the telomere-cancer link.

Diagnosing patients with telomere length disorders is challenging, especially STS, given their broad clinical spectrum. The Telomere Clinic at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, which Armanios leads, offers a telomere measurement service to clinicians and provides multidisciplinary care to patients with telomere-related disorders. Our goal was to establish a clinically reliable tool for telomere length measurement in a hospital setting and make it available to physicians and their patients for precise diagnosis and treatment recommendations, she said.

Patients with severe STS often need organ transplants as a result of end-organ failure. Telomere-related testing can offer these patients a more tailored approach to managing their disease, especially in pre-transplant settings. For example, most patients with STS cant tolerate standard doses of radiation and cytotoxic therapies; recognizing this enables physicians to choose a different conditioning regimen. Also, dysfunctional telomere-related gene(s) are passed through autosomal or X-linked transmission; physicians can therefore screen potential donorsoften patients close relativesto make sure they do not carry these same faulty gene(s).

Armanios and her team recently reported using telomere length as a diagnostic tool to identify patients with STS (Proc Natl Acad Sci U S A 2018;115:E235865). After establishing normal telomere ranges from a healthy control population and determining that telomere measurements have tight concordance and reproducible upper and lower boundaries across populations, they also found that most patients with variants in telomere-related genes had short telomere lengths. In addition, they observed a correlation between the severity of the disease phenotype and the age at diagnosis. We saw different clinical presentations depending on when telomeres reached a critical threshold, said lead author Jonathan Alder, PhD, now an assistant professor of medicine at the University of Pittsburgh. Crucially, the Johns Hopkins team reported that telomere measurements led to treatment changes in one-quarter of 38 pediatric and adult patients with idiopathic bone marrow failure as physicians changed to less harsh therapies like reduced doses of chemotherapy and less use of immunosuppressant drugs.

Patnaik and his colleagues also use telomere testing to assess patients with bone marrow failure, as part of Mayo Clinics Center for Individualized Medicine. We found very quickly that the most common referrals to the Center were people with short telomere syndromes that extended beyond bone marrow failure into conditions like lung and liver fibrosis, he said. In recent reports, he and his team have described their diagnostic workups for patients with suspected inherited STS and with unexplained cytopenias. In the case of inherited STS, they defined this population as having telomere lengths in either granulocytes or lymphocytes less than the first centile of normal controls (Mayo Clin Proc 2018;93:834-9). They perform this screening in concert with an in-house next-generation-sequencing (NGS) panel that consists of telomere-associated genes. Patients who test negative for the NGS panel proceed to research-based whole-exome sequencing to identify other potential mutations.

The options for measuring telomere length are broadand complicated. We are measuring a population of cells, and each cell has between 92 and 184 telomeres, so we are really measuring a population of telomere lengths in an individual, said Alder. Some methods measure individual telomere length, some measure the average, some measure the average of many cells together, and still others measure the average of individual cells.

These methodologies encompass quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH)-based techniquesincluding flow cytometry combined with FISH (flow-FISH) and quantitative FISHtelomere restriction fragment length analysis, optical techniques, and hybridization protection assays. In hospital settings, the preferred method is flow-FISH, which both Johns Hopkins and Mayo Clinic use. Both favor this approach because of its accuracy, reproducibility, ability to define normal telomere length range, and ability to test large numbers of samples. Flow-FISH is standardized, clinically validated, cost-effective, commercially available, and can be implemented anywhere to screen patients with suboptimal telomere length, said Patnaik. Flow-FISH reports also provide data on telomere lengths relative to age, which is important because telomere attrition is part of the normal aging process.

Although an estimated 5,000 to 10,000 individuals in the U.S. have STS, the place for telomere testing remains unclear in diagnosing and predicting long telomere-associated cancers. In cancers where telomere length is elongated, the role of telomere-related testing is still ongoing and not quite ready for clinical prime time, said Patnaik. He added that more research into understanding why shorter telomeres negatively impact outcomes in the management of bone marrow failure syndromes and blood cancers will be quite useful, potentially informing future clinical interventions.

Others remain skeptical about how broadly telomere testing might disseminate. Telomere length testing makes complete sense for rare diseases like STS where you have a specific genetic cause. But I dont think it has any clinical relevance as yet for identifying risk factors for more common diseases like cancer, cardiovascular disease, diabetes, chronic lung disease, Alzheimers disease, and infectious diseases, said Brge Nordestgaard, MD, professor of clinical medicine at the University of Copenhagen and chief physician in the department of clinical biochemistry at Herlev and Gentofte Hospital and Copenhagen University Hospital Denmark. Nordestgaard has conducted genetic epidemiology studies exploring long telomere length and cancer risk and short telomere length and ischemic heart disease risk.

Alder agreed that work remains in identifying the best diagnostic niches for this emerging field. Telomere testing is definitely not a standard part of every clinical work-up in the nation. In the future, it is important to define clinical scenarios where it makes sense for telomeres to be measured, he said. The next step would be to define what the critical thresholds are for making a diagnosis that can lead to an actionable intervention.

Even as the science and practice of telomere testing remains in flux, Armanios, speaking at a Pulmonary Fibrosis Foundation meeting, laid out a future in which genetic evaluation with telomere length might replace lung biopsies in affected patients. She also envisions a time when identifying patients with telomere-mediated lung disease could aid in managing lung transplants, both for anticipating and averting complications.

One catch in advancing the field is that there are no specific treatments for telomere biology disorders. Patnaik echoed Armanios call for specialty-crossing care to plot next steps for newly diagnosed patients. More centers of excellence are needed that can integrate different clinical fields and provide a unique multidisciplinary skill set to manage and counsel these patients, he stressed.

Pranali P. Pathare, PhD, is a medical writer and editor in St. Louis. +Email: ppranali@gmail.com

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On the Trail of Telomeres - American Association for Clinical Chemistry (AACC)

A coalition that includes major drugmakers like Pfizer and Johnson & Johnson is running ads featuring workers in hard hats and hiring former labor officials and well-known union lobbyists to deliver their message. Many see the pairing between pharma and the unions as an odd one, because members often struggle with the high costs of drugs. Meanwhile, the White House contends that House Speaker Nancy Pelosi's drug plan will hurt innovation.

The New York Times:Labor Unions Team Up With Drug Makers To Defeat Drug-Price ProposalsHouse Speaker Nancy Pelosis bill to lower drug prices has the backing of many of the nations biggest labor groups, including the United Auto Workers, the A.F.L.-C.I.O., and unions representing teachers and other government workers. But a wave of Facebook ads that ran this fall appeared to suggest otherwise. The ads, featuring a dejected-looking man in a hard hat, warned that the bill threatens thousands of good-paying jobs and restricts access to lifesaving medication. (Thomas, 12/3)

CNBC:White House: Pelosi's Drug-Pricing Bill Would Result In 100 Fewer DrugsDemocratic House Speaker Nancy Pelosis sweeping drug-pricing bill would result in as many as 100 fewer drugs hitting the U.S. market over the next decade, the White House claimed in a report Tuesday. The White House, citing an analysis from the Council of Economic Advisers, an agency within the executive office, also said Pelosis bill would lead to worse health outcomes and cost the U.S. economy $1 trillion per year over that time period. The report from the administration, which has some health policy analysts scratching their heads, suggests far greater consequences than other estimates for both the drug industry and American consumers if the bill is enacted. (Lovelace, 12/3)

And in other pharmaceutical news

Stat:Huntington's Clinical Trial Opens A Door To Hope But Only If Patients Get In[Perry Stewart] is one of about 800 patients around the world enrolled in a final-stage clinical trial of a drug designed to slow maybe even stop the progression of the disease. Though it wouldnt be a cure, its the first time a therapy aimed at the actual root of Huntingtons has reached this far in its development odyssey. And it is one of a wave of therapies to rely on advances in genetic medicine to combat previously untreatable inherited diseases. (Joseph, 12/4)

Stat:4 Questions Key To Making Sense Of New Data On Biogens Alzheimers DrugThe annual Alzheimers research meeting known as CTAD was supposed to be a snoozefest this year. That all changed six weeks ago, when Biogen (BIIB) stunned the medical world by bringing an Alzheimers drug back from the dead and vowed to make a detailed scientific case for the decision at the gathering this week. On Thursday morning, Biogen will give that highly anticipated presentation livestreamed here detailing data from two late-stage clinical trials of its drug, known as aducanumab. (Robbins, 12/4)

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Low-Profile Pharma Group Taps Into Fears That Pelosi's Drug Pricing Bill Will Threaten 'Thousands Of Good-Paying Jobs' - Kaiser Health News

IRVING, Texas and ALISO VIEJO, Calif., Dec. 4, 2019 /PRNewswire/ --Caris Life Sciences, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, and Ambry Genetics(Ambry), a leading clinical genetic testing company, today announced that Caris will begin offering Ambry's 67-gene CancerNext-Expanded panel to evaluate the hereditary risks for cancer. Combined with Caris' somatic (tumor) tests that analyze a cancer's detailed molecular makeup, Caris will provide patients and their healthcare providers unparalleled information to more accurately diagnose and treat cancer. This will be the most comprehensive, clinically relevant molecular and genetic offering on the market today to guide treatment and management of cancer.

"We are committed to providing clinicians with high-quality information they can use to inform treatment decisions," said David D. Halbert, Caris Life Sciences Chairman, Chief Executive Officer and Founder. "By partnering with Ambry Genetics to better inform patient care, we are able to provide clinicians a greater ability to learn about a cancer's molecular composition."

Caris currently offers clinicians Caris Molecular Intelligence, a proprietary, comprehensive tumor profiling approach that assesses DNA, RNA, and proteins unique to an individual's cancer to reveal a molecular blueprint in order to guide more precise and individualized treatment decisions.

Through the partnership, Caris will now offer Ambry's CancerNext-Expanded hereditary cancer panel. This panel analyzes 67 genes associated with an increased hereditary risk of cancer, including brain, breast, colon, ovarian, pancreatic, prostate, renal, uterine, and many other cancers. Its comprehensive testing identifies inherited risks for cancer in order for clinicians to accurately diagnose, treat, and manage cancer risks for each patient's needs.

"To best diagnose and treat cancer, clinicians must understand whether patients have mutations in genes associated with an increased risk for hereditary cancer," said Aaron Elliott, Chief Executive Officer of Ambry. "Caris' molecular tests combined with Ambry's germline genetic testing, give clinicians the most comprehensive, clinically relevant molecular profile on the market to guide treatment and management."

The combined Caris and Ambry testing is now available nationwide.

"Being able to simultaneously conduct comprehensive tumor genomic testing and multi-gene germline sequencing is invaluable, especially for sick patients at the beginning of their cancer journey," said Michael J. Hall, M.D., M.S., Chair, Department of Clinical Genetics at Fox Chase Cancer Center. "This is information I can immediately begin using for my patients to more accurately diagnose them and to better individualize their treatments."

About Caris Life Sciences Caris Life Sciences is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation. The company's suite of market-leading molecular profiling offerings assesses DNA, RNA and proteins to reveal a molecular blueprint that helps physicians and cancer patients make more precise and personalized treatment decisions.

Caris is also advancing precision medicine with Next Generation Profiling that combines its innovative service offerings, Caris Molecular Intelligence and ADAPT Biotargeting System, with its proprietary artificial intelligence analytics engine, DEAN, to analyze the whole exome, whole transcriptome and complete cancer proteome. This information, coupled with mature clinical outcomes on thousands of patients, provides unmatched molecular solutions for patients, physicians, payers and biopharmaceutical organizations.

Whole transcriptome sequencing with MI Transcriptome provides the most comprehensive and unique RNA analysis available on the market and covers all 22,000 genes, with an average of 60 million reads per patient, to deliver extremely broad coverage and high resolution into the dynamic nature of the transcriptome. Assessing the whole transcriptome allows us to dig deeper into the RNA universe to uncover and detect fusions, splice variants, and expression changes that provide oncologists with more insight and actionable information when determining treatment plans for patients.

Caris Pharmatech, a pioneer of the original Just-In-Time research system with the largest research-ready oncology network, is changing the paradigm from the traditional physician outreach model to a real-time approach where patient identification is completed at the lab and the physician is informed so that the patient can be enrolled days earlier, and remain in the local physician's care, without having to travel to a large central trial site. This fundamentally redefines how pharmaceutical and biotechnology companies identify and rapidly enroll patients in precision oncology trials by combining Caris' highest quality industry leading large-scale molecular profiling services with Pharmatech's on-demand site activation and patient enrollment system.

Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets. To learn more, please visitwww.CarisLifeSciences.comor follow us on Twitter (@CarisLS).

About Ambry GeneticsAmbry Genetics, as part of Konica Minolta Precision Medicine, excels at translating scientific research into clinically actionable test results based upon a deep understanding of the human genome and the biology behind genetic disease. Our unparalleled track record of discoveries over 20 years, and growing database that continues to expand in collaboration with academic, corporate and pharmaceutical partners, means we are first to market with innovative products and comprehensive analysis that enable clinicians to confidently inform patient health decisions. We care about what happens to real people, their families, and the people they love, and remain dedicated to providing them and their clinicians with deeper knowledge and fresh insights, so together they can make informed, potentially life-altering healthcare decisions. For more information, please visitambrygen.com.

Caris Company Contact & Media:Srikant RamaswamiVice President, Chief Communications Officersramaswami@carisls.com +1-214-769-5510

Ambry Genetics Media Contact:Liz Squirepress@ambrygen.com (202) 617-4662

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Caris Life Sciences and Ambry Genetics Partner to Advance Cancer Care - P&T Community

Country doctor James DeLine talks about his work with the Amish

In 33 years at the La Farge clinic, Dr. James DeLine has gained the trust of many Amish. He understands their beliefs and their financial limitations, and he leaves the medical decisions to the families.

Mark Hoffman, Milwaukee Journal Sentinel

MILWAUKEE, Wis.It is 5 degrees below zeroand a light powdering ofsnow swirls across the roads of Vernon County.Afew horses and buggies clop through the chillmorningair, but Perry Hochstetler leaves his buggy at the family farmand has a driver take him to his doctors appointment.

TheHochstetlersare Amish. With no health insuranceanda modest income, they cannot afford most doctors.

They can afford James DeLine, once the lone doctor in the western Wisconsin village of LaFarge. Population 750.

When he became the village doctor in 1983, DeLine had no experience treating the Amish and no idea the crucial role they would play in his work. Today, about 20% of the doctors patients are Amish or Old Order Mennonite, part of a Christian population called Plain People. They are known for their separation from the modern world and adherence to a simple lifestyle and unadorned dress.

Something of a throwback himself,DeLine, 65, is a short,bespectacledman with a walrus mustache, a doctor who carries a brown medical bag to house calls. For years, he carried his equipment in a fishing tackle box.

He knows the families on every local farm and their medical histories. He knows whos beenborn,andcalls on the mothers and infants to make sure they are healthy. He knows whos dying, and looks in on them in their final days, sitting by their bedside, talking in a gentle voice, making sure they have what they need for pain.

Amish farms are clustered together along Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

As a young doctor,DeLine never imagined he would find himselfsomedaywith one foot planted solidly in medicines past, the other in its future.

The doctor who makes housecallsalso collaborates with English and American geneticists studying some of the rarest diseases on Earth. Some occur at much higher levels among the Amish, Mennonites and other closed communities that dont allow marriage to outsiders. This prohibition increases the likelihood that when a rare, disease-causing mutation appears in the community, it will take root and pass from generation to generation.

It has taken DeLine and his staff years to gain the trust of Plain People, some of whom are wary of medicine and technology.Often,theyfear that going to a hospital or clinic will mean surrendering the decision-making to doctors who neither respect their beliefsnor understand their financial limitations.

DeLine, not a religious man himself, accommodates the beliefs of patients and parents; he has always viewed them as the ultimate decision-makers.

At first glance, Hochstetler seems an unlikely candidate for a rare disease or a health problem of any kind. Work at the local sawmill and his family farm has given the 26-year-old father of two a lean muscular frame. Beneath the skin lies another story.

He has the vasculature of an 80-year-old smoker,DeLinesays.

He inherited the genetic mutation that causes an illness most people have never heard of: sitosterolemia. Only 100 cases have been described in the medical literature, but DeLine has 13 patients with the condition, including four of Hochstetlers 10 siblings and their father.

The disease prevents the body from getting rid of lipids from vegetable oils and nuts, causing them to build up and clog the arteries.

Since diagnosing the disease,DeLinehas treated Hochstetler with a cholesterol-lowering drug called Zetia.

Without diagnosis and treatment,Hochstetlercould by now havesuffereda heart attack, a trauma that Zetia should delay, thoughfor how long isuncertain. There is no cure for sitosterolemia.

Im not afraid, he says. If I die young, I guess Im going to die young. I cant do much about it. I cant say I ever get low and have the blues about it.

Saving grace: The story of an Amish community and the fight for their children's lives

A blizzard almost kept the doctor and village from their appointment.

It was February 1983. DeLine drovehis familyover hilly country roads, staring out the windshield into flurries and fearingtheir carmight not makeit to LaFarge.

DeLinehad just completed his residency at the Wausau Hospital Center. Now, a10-membercommitteeof localswas recruiting him to fill LaFargesvacancy for a doctor. Thevillage had beenwithout one for a couple ofyears.

The doctor liked the friendly villagers, a welcome change from the suit-and-tie types hed interviewed with in other places.

He was 28 years oldwith a bad car, a growing family and $30,000 in unpaid student loans. The average salary for a family doctor in America was then around $80,000, enough to settle down and beginpaying offhis debt.

But the people of LaFargewantedDeLine needed him. Their offer: $20,000.

That would have to coverDeLinesannual salary, the salary of an assistant to answer the phones and handle billing, plus all the clinic equipment andexpenses. .

DeLine took the offer.

The photo of country doctor Ernest Guy Ceriani, made famous in a groundbreaking Life Magazine photo essay by W. Eugene Smith, hangs on James DeLine's refrigerator door at his home in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

DeLinegrew up in New Lenox, Illinois, a farming community outside Joliet.

The village of 1,750 was mostly cornfields. DeLine remembers it asthe kind of place where children grew up building forts during the day and watching bonfires at night. DeLine had twin sisters five years younger than him. Their father owned a restaurant.

From an early age, though, itjust seemed like Id be going to medical school. It was meant to be.

DeLineremembers nights when he could hear his mother struggling to breathe. He could hear his father, too, trying to persuade her to go to the hospital.

She had rheumatic heart disease and took blood thinners starting in her 30s. She sometimes joked about needing a valve job.

DeLinewas 17 when his mother went in for the procedure.

He saw her once after surgerybut I didnt like how she looked.About the third day, his mother suffered cardiac arrest. She was resuscitated but had sustained a severe brain injury. Days later, the family shut off life support. She was 42.

One week after her death, JamesDeLineset out to become a doctor,leavinghome for the University of Illinois in Urbana-Champaign.

Physician James DeLine eases into his work day starting at 5 a.m. at his home in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

University life was hard.DeLineremained so miredin grief that when he ate, he suffered terrible abdominal pain and had to lie on his stomach for relief.

Still, he took on a demanding schedule.Driven students tended to enter the more advanced honors program in either chemistry orbiology. DeLine, a physiology major, enrolled in both.

He paid for college through restaurant jobs and financial aid.

He went on to medical school, first in Champaign, then at the University of Illinois campus in Chicago. He lived in the citys Little Italysection on the nearwestside. There he met his future wife, Ann Doherty, who worked in a print shop.

DeLinegraduated from medical school on June 7, 1980. The next day, he and Ann married.

A week later, he started his residency in Wausau.

He would work a 24-hour shift, take 24 hours off, then head back for another 24 hours at the hospital. By the time Id stagger home for some rest, he says, I was sleep-deprived, hungry, with a headache.

The schedule bothered his wife. She missed him.In his next job, she would see even less of him.

Physician James DeLine checks on Dean Pease at Vernon Memorial Healthcare in Viroqua. Pease was admitted to the hospital for breathing difficulties.Mark Hoffman / Milwaukee Journal Sentinel

In LaFarge,DeLineworked harder than he had in his residency.

He was on call 24 hours a day, seven days a week. To make ends meet, both for his family and the clinic,DeLineworked five shifts a month in the emergency room at Vernon Memorial Hospital in Viroqua.

Some days he would work 9 a.m. to 5 p.m. at the clinic, then drive to the hospital and work 6 p.m. to 8 a.m. in the emergency room. He would return to the familys home just in time to shower and get to the clinic by 9.

There were times when he was tired, but it didnt slow him down, Marcia Bader, his now-retired office managersays. It was that deep-seated caring that kept him going.

After a morning of driving around visiting patients, physician James DeLine, right, updates the staff at his clinic.Mark Hoffman / Milwaukee Journal Sentinel

It was his wife,AnnDeLine, too.

The woman who had dreamed of being a mother did everything for the couples four children, all born within a five-year span. She washed cloth diapers and hung them out to dry. Shecooked, cleaned, took the children for walks, helped with school and play, and accepted with grace all the times when her husband was called away from holidays and birthday parties.

"The calendar of holidays does not apply," she says. "He helps people when they need him like the volunteer fireman races off when the alarm sounds; like the farmer plants and harvests when the ground and weather are ready."

"Life is lived by needs, not calendars and time slots."

This drawing is a gift from an Amish patient. James DeLine keeps it on his desk at home.Mark Hoffman / Milwaukee Journal Sentinel

Villagers embraced their doctor. Patients said they were accustomed to physicians who talked at them most of the time;DeLinelistened.

The clinic struggled financially in the early years. Not everybody paid their bills, Bader recalls. But the doctor wasnt going to send them to collection firms, and he wasnt going to stop caring for them.

The doctor and his wife became fixtures ofcommunitylife. They went to their childrens cross country meets and other school events. They attended the annual Kickapoo Valley Reserve Winter Festival.

But it was his presence in the homes of area residents that endeared him to them.

My father was diagnosed with colon cancer in 1994. The thing that always struck me was that Dr.DeLinestopped in to see my mom and dad one night after a basketball game, recalls Bonnie Howell-Sherman, editor and publisher of the weekly Epitaph-News in nearby Viola.

That was just unheard of. My mom is going through dementia now and out of all of the people shes met since shes been here, hes the one she remembers.

The villagers didnt just likeDeLine. They depended on him.

They worried about him, too.

Theres been two things about Dr.DeLinethat the whole community has been concerned about, Steinmetz said. One was, how do we keep him? The other was that hestayhealthy.

From time to time, rumors spread that the doctor was sick, even dying.

In 2007,DeLinehad noticed a problem. He would urinate, only to discover a short time later that he needed to go again.

It was prostate cancer.

Courtesy of the Viola Epitaph-News

Feeling, as he put it, reflective, maybe anxious too,DeLineapproached the Epitaph-News editor. He asked to write a series of columns for the newspaper describing his illness and treatment. He would counter the rumors with transparency. He called the column, From the Other Side.

I decided early on that I was comfortable sharing my experience with our community, he wrote in the first column. After all many of you have shared your concerns, fears and symptoms with me for nearly 25 years. Each of us knows that our turn must come for illness and eventually death.

He discussed his fears about surgery to remove his prostate Would I be able to jog again?He evensharedthe frustration of phoning to make a doctors appointment and going through endless computer prompts before reaching a live human voice.

His columns took readers through his surgery, recovery andreturn home.

The way the whole village shared the doctors illness and treatment, thats part of small-town life, explains Howell-Sherman, the newspaper editor.

Its been 12 years sinceDeLinessurgery. The cancer hasnot returned.

An Amish teen pulls farm machinery down a road in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

Of all the relationships the doctor built in LaFarge, the most challenging involved his Amish patients.

DeLine found his medical work was affected by a deeply held principle among the Amish, expressed in the German wordgelassenheit, which means yielding oneself to a higher authority. Among the Amish, the word encompasses a calmness and patience, as well as a belief that individualism must take a back seatto the good of the community and the will of God.

A sign warns motorists they may encounter horse-drawn vehicles on Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

While some Amish visit hospitals and accept modern medical techniques, others prefer natural methods and traditional treatments: herbs, vitamins, supplements and home remedies. In the LaFargearea, it is not unusual for an Amish family to turn to these methods beforedecidingto see DeLine.

Such was the case with Abie and Edna Yoder when their 8-year-old daughter, Barbara, first grew sick in spring 2015.

The girl had little appetite and suffered from a terrible stomachache and bloody diarrhea. Barbara weighed 38 pounds 19 pounds below average for an 8-year-old.

The Yoders took her to a so-called non-traditional doctor used by some of the Amish; these tend to be herbalists, specialists in natural medicine and others, all of whom lack medical degrees.He viewed her blood under a microscope and told the family she might have colon cancer.

The parents worried terribly about their daughters survival, but worried too about putting her in the hands of a traditional doctor. The scenario that haunted them had happened to a 3-year-old Amish boy with leukemia. The boy was given chemotherapy, they say, despite the excruciating pain andultimate failureof the treatment.

He begged to be released to go to Jesus, Edna Yoder recalls.

The Yoders approached a midwife, whosent her husband to speak with DeLine. The husband explained to the doctor the circumstances and the familys hesitation. Then the Yoders brought their daughter.

"Dr.DeLinemade it really clear that he would respect our wishes,Edna Yoder recalls.

Their daughter was admitted to American Family Childrens Hospital in Madison.DeLineconsulted with a pediatric cardiologist hed worked with at UW, Amy Peterson.

Dr.DeLinehad noticed that she had interesting looking bumps on her arms and on her legs, Peterson recalls. They were deposits of cholesterol. Dr.DeLineand I started thinking along very similar lines very quickly.

Genetic testing confirmed their hunch. The girl had extremely rare sitosterolemia, the same illness that would later be diagnosed in Perry Hochstetler.

Treatment lowered the girls sitosterol levels and helped her gain weight.

DeLineand Peterson have since foundamong the local Amisha dozen othercases the second largest cluster of the disease in the world.

An Amish farmer makes his way to work on a fence along Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

Almost 200 diseases are found in much higher proportions among Plain People. Scientists have developed a special Amish genetics test that screens the blood for more than 120 of them.

DeLine has seen patients with more than 30of the diseases on the testand has at least two patients with diseases neverdescribed in medicine.

Across the globe, there have beenonly20 to 30 cases of a disease called BRAT1; DeLine has seen six. Babies with the illness are born rigid and are prone to frequent seizures.

When the baby is born you cant straighten the baby, DeLine says. The eyes are jerking, face twitching. Some moms say they have felt things that suggest the babies have been seizing in the womb.

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In a Wisconsin village, the doctor makes house calls and sees the rarest diseases on Earth - USA TODAY

Tokyo-based Astellas Pharma announced plans to acquire San Francisco-based Audentes Therapeutics for $60 per share in cash, a total equity value of about $3 billion.

Under the terms of the deal, which both companies boards have unanimously approved, Astellas will buy Audentes through Asilomar Acquisition Corp., a wholly-owned subsidiary of Astellas US Holding. The offer represents a 110% premium of Audentes closing share price of $27.61 as of December 2.

The merger is an effort on the part of Astellas to strengthen its genetic medicine and gene therapy business. Hidemaru Yamaguchi, an analyst with Citi, wrote in a note for clients that it was a positive move for Astellas because Audentes had cutting-edge gene therapy modalities. We thought it was only a matter of time before Astellas entered the gene therapy market.

As part of the deal, Astellas gains access to Audentes AT132, which is being developed for XLMTM, a life-threatening, rare neuromuscular disease marked by extreme muscle weakness, respiratory failure and early death. It also picks up a pipeline of possible best-in-class genetic therapies for rare neuromuscular diseases with Audentes AAV gene therapy technology platform, in-house large-scale cGMP manufacturing capabilities and expertise in neuromuscular drugs. It expects to file for regulatory approval for AT312 in mid-2020.

The disease, however, affects only about 40 boys in the U.S. each year. Assuming a maximum price tagconsistent with other approved gene therapiesof about $2 million, that would only generate about $80 million in annual revenue. As such, Stephen Barker, an analyst with Jefferies, notes that, The $3 billion acquisition price is therefore more likely to be mainly predicated on the firms technology platform and manufacturing capabilities.

Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention, said Kenji Yasukawa, president and chief executive officer of Astellas. Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132 for the treatment of X-Linked Myotubular Myopathy (XLMTM). By joining together with Audentes talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases.

This is only the most recent of several deals by Japanese biopharma companies in the last year. Most recently, Asahi Kasei Corp. acquired Denmarks Veloxis Pharmaceuticals A/S for about $1.3 billion. Takeda Pharmaceutical Co. closed on its $62 billion acquisition of Shire Plc.

The deal is the second largest for Astellas after its $3.8 billion acquisition of OSI Pharmaceuticals in 2010.

Astellas currently has four Primary Focus Areas, urology, immunology (transplantation), cardiology, and infectious disease. The company indicates that the fifth, with this acquisition, will be Genetic Regulation, with gene therapy viewed as a key driver of future growth.

We are very pleased to enter into this merger agreement with Astellas, said Matthew R. Patterson, chairman and chief executive officer of Audentes. With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients.

See more here:
Astellas Buys Audentes for $3 Billion to Expand into Gene Therapy - BioSpace

What happened

Shares of Arrowhead Pharmaceuticals (NASDAQ:ARWR) gained as much as 14.4% today after the company announced a public stock offering. It seems counterintuitive, but investors appear to be excited about a snippet of text listing possible uses for the proceeds.

The company made the standard explanation that the cash will be used for general corporate expenses, to fund maturing clinical trials, and the like. But Arrowhead Pharmaceuticals also included a nonstandard detail in the press release for the public offering: "A portion of the net proceeds may also be used for the acquisition of complementary businesses, products and technologies, or for other strategic purposes."

Investors may be getting a little ahead of themselves here, but if Arrowhead Pharmaceuticals pulls the trigger on any strategic investment, then it's likely to be in one (relatively boring) category in particular.

As of 1:55 p.m. EST, the pharma stock had settled to a 10.2% gain.

Image source: Getty Images.

The developer of precision genetic medicines based on RNA interference (RNAi), a technique used to silence disease-driving genes, ended September with $221.8 million in cash and another $37 million in short-term investments. The proposed public offering of up to 4.6 million shares hasn't been priced yet; that information should be announced after market close today. But assuming an offering price of $60 per share, the business would raise up to $275 million in gross proceeds -- not a bad haul.

What could the cash be used for? Well, Arrowhead Pharmaceuticals decided to account for a $252.6 million up-front payment and equity investment, received from Johnson & Johnson subsidiary Janssen in late 2018, using the proportional accounting method. That allowed the business to count chunks of that total each quarter during its fiscal 2019, which resulted in full-year 2019 operating income of $61 million. It reported an operating loss of $55.9 million in fiscal 2018.

The proportional-accounting-method well will run dry in 2020, as there was just $77.8 million remaining against the up-front payment total at the end of September (the end of its fiscal year). In other words, the business is likely to report operating losses again in the near future.

What about a strategic investment, as hinted at in the press release for the public offering? That could happen, too. It may be a little less exciting than investors are imagining, however, because it's likely to be in drug manufacturing.

Arrowhead Pharmaceuticals spent $22 million on drug manufacturing in fiscal 2019, making it the single largest expense in the research and development category -- even more expensive than running clinical trials. The RNAi company has relatively strict manufacturing requirements, and the expense is starting to grow at a significant rate, so it may make sense to bring some of that expertise in-house with its own facility. Others in the precision-medicine space have done the same to reduce costs and operational risks. In fact, there's a manufacturing arms race in gene therapy right now.

The company is wisely taking advantage of a soaring stock price to pad its balance sheet. It will certainly need the cash to develop a maturing pipeline, and to fund operations once a lucrative collaboration revenue stream runs dry in 2020.

Whether Arrowhead Pharmaceuticals makes an acquisition of new technology or boring old manufacturing assets (or none at all), the company is correctly focused on the long term. That said, the company does appear to be a little expensive right now.

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Here's Why Arrowhead Pharmaceuticals Is Soaring Today - The Motley Fool

Sarepta Therapeutics, Inc.'s (NASDAQ:SRPT): Sarepta Therapeutics, Inc. focuses on the discovery and development of RNA-based therapeutics, gene therapy, and other genetic medicine approaches for the treatment of rare diseases. The US$8.4b market-cap posted a loss in its most recent financial year of -US$361.9m and a latest trailing-twelve-month loss of -US$620.3m leading to an even wider gap between loss and breakeven. The most pressing concern for investors is SRPTs path to profitability when will it breakeven? Ive put together a brief outline of industry analyst expectations for SRPT, its year of breakeven and its implied growth rate.

See our latest analysis for Sarepta Therapeutics

According to the 22 industry analysts covering SRPT, the consensus is breakeven is near. They expect the company to post a final loss in 2021, before turning a profit of US$676m in 2022. SRPT is therefore projected to breakeven around 3 years from now. What rate will SRPT have to grow year-on-year in order to breakeven on this date? Using a line of best fit, I calculated an average annual growth rate of 68%, which is rather optimistic! If this rate turns out to be too aggressive, SRPT may become profitable much later than analysts predict.

NasdaqGS:SRPT Past and Future Earnings, December 3rd 2019

Im not going to go through company-specific developments for SRPT given that this is a high-level summary, though, bear in mind that by and large a biotech has lumpy cash flows which are contingent on the product type and stage of development the company is in. This means, large upcoming growth rates are not abnormal as the company is beginning to reap the benefits of earlier investments.

One thing I would like to bring into light with SRPT is its relatively high level of debt. Typically, debt shouldnt exceed 40% of your equity, which in SRPTs case is 44%. Note that a higher debt obligation increases the risk in investing in the loss-making company.

This article is not intended to be a comprehensive analysis on SRPT, so if you are interested in understanding the company at a deeper level, take a look at SRPTs company page on Simply Wall St. Ive also put together a list of relevant aspects you should look at:

If you spot an error that warrants correction, please contact the editor at editorial-team@simplywallst.com. This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. Simply Wall St has no position in the stocks mentioned.

We aim to bring you long-term focused research analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Thank you for reading.

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Breakeven On The Horizon For Sarepta Therapeutics, Inc. (NASDAQ:SRPT) - Yahoo Finance