Category Archives: Genetic medicine

Assaf Halevy, Founder and CEO of 2bPrecise

Electronic medical records (EMRs) are widely expected to serve as a cornerstone technology that drives the delivery of modern patient care.

But can the EMR alone support all the informatics capabilities required by an ever-evolving healthcare industry? The rapid growth of precision medicine, particularly the use of genetic and genomic information during clinical decision making, is a compelling example that functionality beyond the EMR is required. Not only does genomic data represent a category of information used differently than traditional clinical knowledge, but the volume of data generated through molecular testing alone also requires informatics and management of a higher magnitude than previously required.

The EMR is designed to reflect a snapshot (or collection of snapshots) in time: clinical summaries, annotated lab and test results, operation notes, etc. These are mostly stored as isolated documents, loosely coupled with the rest of the patient chart. They need to remain available for reference over time, in some instances, so providers can chart and contextualize ongoing trends and chronic conditions. However, these views are anchored in time and represent limited actionable value during clinical decision-making months, years, and decades later.

Genomic information, on the other hand, represents a patients life signature. DNA rarely changes over the course of an individuals lifetime. This means the results from germline testing a patients molecular profile conducted early in life are relevant, meaningful, and actionable during clinical decision making far into the future. They can also deliver insights exposing heritable proclivities that may be life-changing or life-saving for family members as well.

This recognition in and of itself alerts healthcare leaders that they need to adopt an advanced, more sophisticated strategy for data governance, management, and sharing than the approach traditionally applied to other clinical information systems, such as EMRs.

To be successful, healthcare organizations need an accelerator external to the EMR that is built on a data model unique to the management of molecular knowledge so test results and genomic insights can be used and shared across clinical specialties and care settings, as well as overtime. In addition, the rise of precision medicine requires an agile informatics platform that enables the cross-pollination of genomic data with clinical insights and ever-advancing discoveries in genomic science.

Consider these examples of how EMRs fall short of expectations for optimal use of genomic intelligence:

1. Studies have found that, despite ubiquitous availability of molecular tests, providers consistently fail to identify patients most at risk for heritable diseases. The Journal of the American Medical Informatics Association (JAMIA) recently released research showing that half the women meeting national guidelines for genetic screening are not getting the tests they need to determine their breast and ovarian cancer risk.

The reason? The full story of a patients risk for heritable cancer within their record often does not exist in a single location, says the JAMIA article. It is fragmented across entries created by many authors, over many years, in many locations and formats, and commonly from many different institutions in which women have received care over their lifetimes. In other words, no matter which EMRs they use, health systems routinely miss opportunities to improve care for patients they see. To achieve greater success, providers need tools that exceed EMR functionality and span multiple clinical systems.

2. Shortly after birth, Alexander develops a seizure disorder. The neonatologist orders a germline test to help her arrive at a precise diagnosis and begin targeted treatment. This approach is successful and Alexander thrives. In addition to genomic variants identifying the cause of his seizure disorder, the test results also contain information about other heritable risk factors, including cardiovascular disease.

Decades later, in the 70s, Alexander sees his primary care provider (PCP) with a rapid heartbeat and shortness of breath. After doing routine lab work, the PCP diagnoses congestive heart failure (CHF). If, however, the PCP had access to Alexanders genomic test results which remain as relevant and accurate as when he was an infant the PCP would have noted a variation that indicated the CHF was due to dilated cardiomyopathy, requiring a different treatment regime.

It is vital that health leaders immediately begin to plan an informatics strategy that accommodates genetic and genomic data while empowering providers to leverage these insights at the point of care as they make routine, yet critical, clinical decisions. As they evaluate their approach, they would do well to ask the following questions:

Which providers in my organization are already ordering genomic tests on their patients? How are test results being stored and managed and can they be easily shared with and accessed by others in the health system?

As the volume of genetic and genomic testing accelerates and it will how will we manage the volume of data generated? How will we apply consistent governance to the ordering process? How can we ensure results will be consumed as discrete data so our organization can optimize its value now and in the future?

What steps do we need to take so our precision medicine strategy remains current with changing science? Which informatics tools deliver access to up-to-date knowledge bases and clinical guidelines to ensure optimal medical decisions are made?

The advent of precision medicine represents a new standard of care for healthcare providers from coast to coast. Genetic and genomic information supplies a new data set that can be used to arrive at more accurate diagnoses sooner and more effective treatment faster. This, in turn, supports better outcomes, higher patient (and provider) satisfaction, and competitive differentiation for the health system adopting precision medicine first in its market.

But to capture this value, healthcare leaders must look beyond their legacy EMRs, recognizing that they were not developed nor do they have the capacity to properly handle the upcoming data revolution. Instead, industry innovators are looking for platforms agnostic to individual EMRs and integrated with molecular labs to address the next-generation demands of precision medicine.

About Assaf Halevy

Assaf Halevy is the founder and CEO of 2bPrecise, LLC, leading an international team dedicated to bridging the final mile between the science of genomics and making that data useful at the point of care. He joined Allscripts as senior vice president of products and business development in 2013 when the company acquired Israel-based dbMotion. An initial inventor and co-founder of dbMotion, Halevy helped develop the leading clinical integration and population health management platforms in the industry today.

With 13 patents pending in the areas of actionable clinical integration, interoperability, and precision medicine, Halevy leverages his industry expertise by evaluating strategic alliances and partnerships for U.S. and international markets. Halevy was invited to participate in several U.S. government activities and contribute to an HHS privacy committee task force. In 2016, he was part of a small selective group of executives invited to the White House by Vice President Joe Biden to discuss the future of interoperability.

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Meaningful Use of Genomics Requires Informatics Beyond EMRs - HIT Consultant

DURBAN, South Africa Doctors and nurses at a South African hospital group noticed an odd spike in the number of Covid-19 patients in their wards in late October. The government had slackened its lockdown grip, and springtime had brought more parties. But the numbers were growing too quickly to easily explain, prompting a distressing question.

Is this a different strain? one hospital official asked in a group email in early November, raising the possibility that the virus had developed a dangerous mutation.

That question touched off a high-stakes genetic investigation that began here in Durban on the Indian Ocean, tipped off researchers in Britain and is now taking place around the world. Scientists have discovered worrisome new variants of the virus, leading to border closures, quarantines and lockdowns, and dousing some of the enthusiasm that arrived with the vaccines.

Britain has been particularly overwhelmed. Infections and hospitalizations have skyrocketed in recent weeks since that country discovered its own variant of the virus, which is more contagious than previous forms. By one estimate, the mutated virus is already responsible for more than 60 percent of new infections in London and surrounding areas.

The coronavirus has evolved as it made its way across the world, as any virus is expected to do. But experts have been startled by the pace at which significant new variants have emerged, adding new urgency to the race between the worlds best defenses vaccinations, lockdowns and social distancing and an aggressive, ever-changing foe.

The new variant pummeling Britain has already been found in about 45 countries, from Singapore to Oman to Jamaica, but many countries are effectively flying blind, with little sense of how bad the problem may be.

Long before the pandemic emerged, public health officials were calling for routine genetic surveillance of outbreaks. But despite years of warnings, many countries including the United States are conducting only a fraction of the genomic studies needed to determine how prevalent mutations of the virus are.

Denmark, which has invested in genetic surveillance, discovered the variant afflicting Britain in multiple Danish regions and recently tightened restrictions. The health minister compared it to a storm surge, predicting that it would dominate other variants by mid-February.

And as countries go looking, they are discovering other variants, too.

With the world stumbling in its vaccination rollout and the number of cases steeply rising to peaks that exceed those seen last spring, scientists see a pressing need to immunize as many people as possible before the virus evolves enough to render the vaccines impotent.

Its a race against time, said Marion Koopmans, a Dutch virologist and a member of a World Health Organization working group on coronavirus adaptations.

The vaccine alone will not be enough to get ahead of the virus: It will take years to inoculate enough people to limit its evolution. In the meantime, social distancing, mask-wearing and hand-washing coupled with aggressive testing, tracking and tracing might buy some time and avert devastating spikes in hospitalizations and deaths along the way. These strategies could still turn the tide against the virus, experts said.

We do know how to dial down the transmission of the virus by a lot with our behavior, said Carl T. Bergstrom, an evolutionary biologist at the University of Washington in Seattle. Weve got a lot of agency there.

Yet in the course of the pandemic, governments have often proven reluctant or unable to galvanize support for those basic defenses. Many countries have all but given up on tracking and tracing. Mask-wearing remains politically charged in the United States, despite clear evidence of its efficacy. Cities like Los Angeles have been gripped by a spike in cases linked to Christmas festivities, and national public health officials are bracing for surges elsewhere, driven by people who ignored advice and traveled during the holidays.

Much remains unknown about the new variants, or even how many are sprouting worldwide. Scientists are racing to sequence enough of the virus to know, but only a handful of countries have the wherewithal or commitment to do so with any regularity.

The rapid spread of the new variants is a reminder of the failings and missteps of major countries to contain the virus earlier. Just as China failed to stop travelers from spreading the virus before the Lunar New Year last year, Britain has failed to move fast enough ahead of the new variants spread. Britain lowered its guard during the holidays, despite a rise in cases now known to be linked to a variant. And just as China became a pariah early on in the pandemic, Britain now has the unfortunate distinction of being called Plague Island.

The spread of the variant lashing Britain has left some countries vulnerable at a time when they seemed on the brink of scientific salvation.

A case in point: Israel. The country, which had launched a remarkably successful vaccine rollout, tightened its lockdown on Friday after having discovered cases of the variant. About 8,000 new infections have been detected daily in recent days, and the rate of spread in ultra-Orthodox communities has increased drastically.

The variant discovered in Britain, known as B.1.1.7, has 23 mutations that differ from the earliest known version of the virus in Wuhan, China, including one or more that make it more contagious, and at least one that slightly weakens the vaccines potency. Some experiments suggest that the variant spreads more easily because mutations enable it to latch more successfully onto a persons airway.

Dr. Bergstrom and other scientists were surprised to see this more transmissible variant emerge, given that the coronavirus was already quite adept at infecting people.

While the exact order of vaccine recipients may vary by state, most will likely put medical workers and residents of long-term care facilities first. If you want to understand how this decision is getting made, this article will help.

Life will return to normal only when society as a wholegains enough protection against the coronavirus. Once countries authorize a vaccine, theyll only be able to vaccinate a few percent of their citizens at most in the first couple months. The unvaccinated majority will still remain vulnerable to getting infected. A growing number of coronavirus vaccines are showing robust protection against becoming sick. But its also possible for people to spread the virus without even knowing theyre infected because they experience only mild symptoms or none at all. Scientists dont yet know if the vaccines also block the transmission of the coronavirus. So for the time being, even vaccinated people will need to wear masks, avoid indoor crowds, and so on. Once enough people get vaccinated, it will become very difficult for the coronavirus to find vulnerable people to infect. Depending on how quickly we as a society achieve that goal, life might start approaching something like normal by the fall 2021.

Yes, but not forever. The two vaccines that will potentially get authorized this month clearly protect people from getting sick with Covid-19. But the clinical trials that delivered these results were not designed to determine whether vaccinated people could still spread the coronavirus without developing symptoms. That remains a possibility. We know that people who are naturally infected by the coronavirus can spread it while theyre not experiencing any cough or other symptoms. Researcherswill be intensely studying this question as the vaccines roll out. In the meantime, even vaccinated people will need to think of themselves as possible spreaders.

The Pfizer and BioNTech vaccine is delivered as a shot in the arm, like other typical vaccines. The injection wont be any different from ones youve gotten before. Tens of thousands of people have already received the vaccines, and none of them have reported any serious health problems. But some of them have felt short-lived discomfort, including aches and flu-like symptoms that typically last a day. Its possible that people may need to plan to take a day off work or school after the second shot. While these experiences arent pleasant, they are a good sign: they are the result of your own immune system encountering the vaccine and mounting a potent response that will provide long-lasting immunity.

No. The vaccines from Moderna and Pfizer use a genetic molecule to prime the immune system. That molecule, known as mRNA, is eventually destroyed by the body. The mRNA is packaged in an oily bubble that can fuse to a cell, allowing the molecule to slip in. The cell uses the mRNA to make proteins from the coronavirus, which can stimulate the immune system. At any moment, each of our cells may contain hundreds of thousands of mRNA molecules, which they produce in order to make proteins of their own. Once those proteins are made, our cells then shred the mRNA with special enzymes. The mRNA molecules our cells make can only survive a matter of minutes. The mRNA in vaccines is engineered to withstand the cell's enzymes a bit longer, so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.

But other experts had warned from the start that it would only be a matter of time before the virus became an even more formidable adversary.

Every situation we have studied in depth, where a virus has jumped into a new species, it has become more contagious over time, said Andrew Read, an evolutionary microbiologist at Penn State University. It evolves because of natural selection to get better, and thats whats happening here.

Much of the global response has focused on shutting out Britain, with a hodgepodge of national restrictions that harken back to the early reactions to the epidemic.

China has banned flights and travelers from Britain. Japan took an even harsher measure, banning entry to nonresident foreigners from more than 150 countries.

Others like India and New Zealand are allowing some flights from Britain but require passengers to have two negative tests one before departure and another after arrival. Australia is sticking with its policy of requiring hotel quarantines and testing for international travelers.

Experts say that countries should focus instead on ramping up vaccinations, particularly among essential workers who face a high risk with few resources to protect themselves. The longer the virus spreads among the unvaccinated, the more mutations it might collect that can undercut the vaccines effectiveness.

That is why, when the World Health Organization working group saw the first data on the variant circulating in South Africa on Dec. 4, everyone took notice.

Your next question immediately is: Can the vaccines still protect us if we get viruses with these mutations? said Dr. Koopmans, who was in the meeting.

For now, the answer seems to be yes, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle. Dr. Koopmans agrees.

The variants that have emerged in South Africa and Brazil are a particular threat to immunization efforts, because both contain a mutation associated with a drop in the efficacy of vaccines. In one experiment, designed to identify the worst-case scenario, Dr. Blooms team analyzed 4,000 mutations, looking for those that would render vaccines useless. The mutation present in the variants from both Brazil and South Africa proved to have the biggest impact.

Still, every sample of serum in the study neutralized the virus, regardless of its mutations, Dr. Bloom said, adding that it would take a few more years before the vaccines need to be tweaked.

There should be plenty of time where we can be prospective, identify these mutations, and probably update the vaccines in time.

That sort of surveillance is precisely what led to the discovery of the new variants.

Liza Sitharam, a nurse and infectious disease specialist in coastal South Africa, was among those who first noticed a small cluster that was quickly bulging.

Wed have five cases and then itd double really quickly, she recalled. The raw numbers werent alarming, she said, but there was something just not looking right.

Her boss at the Netcare hospital group, Dr. Caroline Maslo, figured that with the countrys borders open, business travelers from German auto companies had perhaps brought in a European variant of the virus. She sought help from Tulio de Oliveira, a professor and geneticist at the Nelson Mandela School of Medicine in Durban who had studied viral variants during the first Covid-19 wave.

Soon, his lab was analyzing swabs, shipped on ice by courier overnight. On Dec. 1, he emailed a British scientist, Andrew Rambaut, and asked him to review some of his early findings: a series of strange mutations on the viruss outer surface.

Dr. de Oliveira, a Brazilian-South African scientist who sports long hair and a surfer vibe, shared his findings at a Dec. 4 meeting of the World Health Organization working group. All took notice because of the variants potential to disrupt the vaccines effectiveness.

Days later, Dr. de Oliveira recalled, Dr. Rambaut emailed him with a discovery of his own: British scientists had scoured their databases and found a similar but unrelated mutation that appeared linked to a cluster of infections in the county of Kent.

Coming two weeks before Christmas, Dr. de Oliveira immediately thought of the Lunar New Year early in the pandemic, when millions of people in China traveled far and wide for the holiday, some carrying the virus.

It was crystal clear, Dr. de Oliveira said in an interview. These variants will spread nationally, regionally and globally.

Dr. Rambaut and colleagues released a paper on the variant discovered in Britain on Dec. 19 the same day that British officials announced new measures. The variant had apparently been circulating undetected as early as September. Dr. Rambaut has since credited the South Africa team with the tip that led to the discovery of the variant surging in Britain.

Public health officials have formally recommended that type of swift genetic surveillance and information-sharing as one of the keys to staying on top of the ever-changing virus. But they have been calling for such routine surveillance for years, with mixed results.

The message was very clear, that this is the way surveillance has to go, said Dr. Josep M. Jansa, a senior epidemiologist at the European Centre for Disease Prevention and Control. Just as Covid-19 exposed flaws in the worlds pandemic plans a year ago, the hunt for new variants is exposing gaps in surveillance. Were learning, he said. Slowly.

Britain has one of the most aggressive surveillance regimens, analyzing up to 10 percent of samples that test positive for the virus. But few countries have such robust systems in place. The United States sequences less than 1 percent of its positive samples. And others cannot hope to afford the equipment or build such networks in time for this pandemic.

In Brazil, labs that had redirected their attention from Zika to the coronavirus had discovered a worrisome mutation there as early as this spring. But little is known about the variants circulating in the country, or how quickly they are spreading.

We just dont know because no one is either sequencing or sharing the data, said Dr. Nuno Faria at Imperial College and Oxford University who coordinates genomic sequencing projects with colleagues in Brazil. Genomic surveillance is expensive.

As the virus continues to mutate, other significant variants will almost certainly emerge. And those that make the virus hardier, or more contagious, will be more likely to spread, Dr. Read said.

The faster we can get the vaccines out, the faster we can get on top of these variants, he said. Theres no room for complacency here.

Matt Apuzzo reported from Durban, South Africa, and Brussels, Selam Gebrekidan from London, and Apoorva Mandavilli from New York. Reporting was contributed by Thomas Erdbrink; Melissa Eddy from Berlin; Isabel Kershner from Jerusalem; Manuela Andreoni from Rio de Janeiro; Christina Anderson from Stockholm; Amy Chang Chien and Amy Qin from Taipei, Taiwan; and Jennifer Jett and Tiffany May from Hong Kong.

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As Coronavirus Mutates, the World Stumbles Again to Respond - The New York Times

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Verve Therapeutics, a biotech company pioneering gene editing medicines to treat cardiovascular disease, today announced that Sekar Kathiresan, M.D., co-founder and chief executive officer, will present a company overview during the 39th Annual J.P. Morgan Healthcare Conference on Tuesday, January 12, 2021 at 9:15 a.m. ET. Dr. Kathiresans presentation will include an overview of Verves strategy to create once-and-done gene editing medicines for coronary heart disease and an update on the companys preclinical progress.

Gene editing is a promising new treatment approach for coronary heart disease, the leading cause of death worldwide. Genetic studies have revealed gene variants that naturally turn off a disease-causing gene in the liver and dramatically lower some individuals lifetime risk of coronary heart disease. These individuals have low levels of LDL cholesterol or triglycerides lifelong, are protected against heart attack, and are otherwise healthy. Verve is developing gene editing medicines to safely turn off a target gene in the liver and mimic naturally-protective variants to permanently lower LDL cholesterol and triglyceride levels and thereby treat coronary heart disease.

About Verve Therapeutics

Verve Therapeutics is a biotechnology company created with a singular focus: to protect the world from heart disease. The company brings together human genetics analysis and gene editing two of the biggest breakthroughs in 21st century biomedicine to develop transformative therapies for coronary heart disease. Verve is developing medicines, administered once in life, to safely edit the genome of adults and mimic naturally occurring gene variants to permanently lower LDL cholesterol and triglyceride levels and thereby treat coronary heart disease. Founded by world-leading experts in cardiovascular medicine, human genetics and gene editing, Verve is backed by a top-tier syndicate of investors, including GV (formerly Google Ventures), ARCH Venture Partners, F-Prime Capital, Biomatics Capital, Wellington Management, Casdin Capital, and Partners Innovation Fund. Verve is headquartered in Cambridge, Massachusetts. For more information, visit http://www.VerveTx.com.

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Verve Therapeutics to Present at the 39th Annual J.P. Morgan Healthcare Conference - Business Wire

BOSTON--(BUSINESS WIRE)--Jnana Therapeutics, a biotechnology company targeting the solute carrier (SLC) family of metabolite transporters to treat underserved diseases, today announced the appointment of two experienced scientific and clinical leaders to the companys boards. Annie C. Chen, MD, MPH, Chief Medical Officer of Nimbus Therapeutics, joins the companys Board of Directors. Katalin Susztak, MD, PhD, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, joins the companys Scientific Advisory Board.

We are delighted to welcome Annie to our Board. Her experience leading the clinical development of drug candidates at biotech and pharmaceutical companies will be tremendously valuable as we move our pipeline of novel SLC therapeutics toward the clinic, said Joanne Kotz, PhD, Co-founder, Chief Executive Officer and President of Jnana.

Jnanas small molecule approach to targeting SLC transporters represents a promising avenue for discovering new medicines for patients across a range of diseases, said Dr. Annie Chen. I look forward to serving on the Board as the company evolves to its next stage of growth and builds an early clinical pipeline.

Dr. Annie Chen is an expert in clinical development strategy with an extensive background in immunology, where she has brought multiple therapies forward to regulatory approval. In addition to her role as CMO at Nimbus, she is President of the companys Tyk2 subsidiary, Nimbus Lakshmi, Inc. Prior to joining Nimbus, she was Executive Director of Clinical Research, Section Head of Vaccines for Merck, where she oversaw clinical research activities for a broad portfolio of vaccines from discovery through registration and life cycle management. Dr. Chen also held the role of Section Head of Immunology, where she oversaw clinical research for small molecule and protein therapeutics. Prior to Merck, she held roles of increasing responsibility at Genentech and began her industry career at Celera Genomics. She was formerly Assistant Clinical Professor of Medicine at the University of California San Francisco, where she completed her fellowship training in rheumatology. She received her MD from Cornell University, her MPH in epidemiology from the University of California Berkeley and her AB in biological sciences from Harvard University.

It is a pleasure to have Katalin serve on Jnanas scientific advisory board. Her deep expertise in renal diseases will be instrumental as we pursue therapeutic opportunities targeting SLC transporters in the kidney, said Joel Barrish, PhD, Co-founder and Chief Scientific Officer of Jnana.

There is substantial untapped potential to target SLC transporters in important disease areas, including renal diseases, where I am keenly aware of the need for new therapeutic approaches, said Dr. Katalin Susztak. I welcome the opportunity to work with Jnanas scientific leaders and SAB to bring new treatments to patients.

Dr. Katalin Susztak is an accomplished physician-scientist, and her laboratory is focused on understanding the pathological mechanisms of chronic kidney disease. Dr. Susztak is a Professor of Nephrology / Medicine and Genetics at the University of Pennsylvania and Director of the Complications Unit at the Institute of Diabetes, Obesity and Metabolism. Dr. Susztak has made fundamental discoveries towards defining critical genes, cell types and mechanisms of chronic kidney disease. She was instrumental in defining genetic, epigenetic and transcriptional changes in diseased human kidneys, has identified novel kidney disease genes, and has demonstrated the contribution of Notch signaling and metabolic dysregulation to kidney disease development. She is Principal Investigator of the Transformative Research in Diabetic Nephropathy (TRIDENT), a public-private observational clinical study to identify novel therapeutic targets and biomarkers for kidney disease development. Dr. Susztak was the recipient of the 2011 Young Investigator Award of the American Society of Nephrology and American Heart Association. She is an elected member of the American Society for Clinical Investigation and the American Association of Physicians.

About Jnana Therapeutics

Jnana Therapeutics is a biotechnology company focused on opening the solute carrier (SLC) family of metabolite transporters as a target class to develop transformational therapeutics. Jnana uses its RAPID platform, a proprietary, cell-based drug discovery approach, to systematically target SLC transporters and develop best-in-class therapies to treat a wide range of diseases, including immune-mediated, neurological and metabolite-dependent diseases. Headquartered in Boston, Jnana is founded by world-renowned scientists and backed by leading life science investors. For more information, please visit http://www.jnanatx.com and follow us on Twitter and on LinkedIn.

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Jnana Therapeutics Appoints Dr. Annie Chen to Board of Directors and Dr. Katalin Susztak to Scientific Advisory Board - Business Wire

(CNN) The US reported moreCOVID-19 cases and deathsin the last week than any previous seven days during the pandemic, data showed Friday morning.

And more than 4,080 US coronavirus deaths were reported on Thursday alone the most ever reported in a single day during the pandemic and the first time the daily tally rose above 4,000, Johns Hopkins University (JHU) data showed.

In other words, even though the US is working to distribute vital COVID-19 vaccines a processcriticized as being too slow the pandemic generally isnt showing signs of slowing down, and the virus is advancing with alarming speed in some areas, the White House coronavirus task force said in its report to states this week.

In Los Angeles County, where some ambulance crews have beenreported to wait for hours with their patientsoutside hospitals because the facilities are overwhelmed, one person is dying of COVID-19 on an average of everyeight minutes, officials said.

Were seeing heroes in our hospitals, were seeing angels in our ambulances, stretched thin to just deal with the onslaught right now, Los Angeles Mayor Eric Garcetti said Thursday.

Hospitals in the county are now preparing to ration care with triage officers who will decided which patients will receive care, with a focus of doing the most good for the most people, according to new guidelines issued by the LA County Department of Public Health.

Texas reported record-high COVID-19 hospitalizations statewide for the fifth day in a row Thursday. Hospitals in Dallas County the states second largest county had just 13 adult ICU beds available on Wednesday, County Judge Clay Jenkins said ina tweet.

The US has averaged about 228,400 COVID-19 cases a day over the last week as of Thursday an all-time high, and more than 3.4 times a summertime peak set in late July, JHU data shows.

And the country has averaged 2,764 deaths a day over the last week the highest figure of the pandemic, according to JHU data.

Hospitalizations also are soaring. Some 131,889 COVID-19 patients were in US hospitals on Friday the third-highest figure recorded, the COVID Tracking Project data show.

In a report this week, the White Housecoronavirus task force speculatedthere may be a USA variant that has evolved here that spreads more easily than the known variant.

This fall/winter surge has been at nearly twice the rate of rise of cases as the spring and summer surges. This acceleration suggests there may be a USA variant that has evolved here, in addition to the UK variant that is already spreading in our communities and may be 50% more transmissible, the report said.

So far, theres no evidence of a US variant, the Centers for Disease Control and Prevention and academic researchers said Friday.

Significant continued deterioration, from California across the Sunbelt and up into the Southeast, Mid-Atlantic and Northeast, despite low testing rates during the holidays, suggests aggressive community spread, the task force report said.

But a CDC spokesman said that researchers have been monitoring US strains since the pandemic began, including 5,700 samples collected in November and December. To date, neither researchers nor analysts at CDC have seen the emergence of a particular variant in the United States like those identified in the UK and in South Africa.

Trevor Bedford of the University of Washington and the Fred Hutchinson Cancer Research Center, who helps maintain a database of genetic mutations in the coronavirus, said he saw no evidence of a homegrown US strain that is spreading more aggressively.

The CDC did say at least 63 cases of a variant first identified in the UK have been recorded in eight US states. This includes at least 32 cases in California, 22 cases in Florida, three cases in Colorado, two cases in Connecticut, and one case each in Georgia, New York, Texas and Pennsylvania.

The agency says this does not represent the total number of cases circulating in the US, but rather just those that have been found by analyzing positive samples.

While vaccinations have been happening for several weeks, experts have said it will be months before theyre widespread enough to make a meaningful impact in the pandemics course.

Meanwhile, President-elect Joe Biden aims to release nearly every available dose of the coronavirus vaccine when he takes office, a break with the Trump administrations strategy of holding back half of US vaccine production to ensure second doses are available,CNNs Sara Murray reported Friday.

Releasing nearly all vaccine doses on hand could allow more people access to a first dose during a given time.

It could also be a risky strategy, as the vaccines from both Pfizer/BioNTech and Moderna require two doses, administered 21 days or 28 days apart, respectively, and vaccine manufacturing has not ramped up as rapidly as many experts had hoped.

Thesecond dose is absolutely critical, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases said Friday.

The President-elect believes we must accelerate distribution of the vaccine while continuing to ensure the Americans who need it most get it as soon as possible. He supports releasing available doses immediately, and believes the government should stop holding back vaccine supply so we can get more shots in Americans arms now, said TJ Ducklo, a spokesman for Bidens transition.

A transition official said the Biden team believes that vaccine manufacturers will be able to produce enough second doses in a timely fashion while administering first doses to more Americans.

The Trump administration has said its necessary to hold back doses, to ensure Americans who receive the first course of the two-dose vaccine will be sure to have access to a second dose.

But that had sparked a debate about whether a better strategy would be releasing all available doses as quickly as possible, particularly amid rising death and hospitalization rates.

A study published Monday in the Annals of Internal Medicine found that administering first doses of a COVID-19 vaccine to more people quickly, instead of withholding available supply for use as a second dose, may reduce the number of new cases.

And World Health Organization advisers said Friday that a second dose of Pfizer and BioNTechs vaccine can be delayed as long as six weeks if need be. Thats based on currently available clinical trial data, the WHO guidance document said.

Moderna also believes a second dose of its vaccine can be given effectively 21 to 42 days after the first, a spokesperson for the company told CNN.

Kentucky Gov. Andy Beshear said Friday he agreed with Bidens plan, but wants assurances the second dose will be there.

Nearly 6.7 million people have received their first doses of a vaccine and more than 22 million doses have been distributed,the CDC said Friday.

Federal officials had said 20 million people would have received first dosesby the end of December.

Some health leaders said states need more money and more staff in order to be able to administer the vaccines fast enough.

Pennsylvania Secretary of Health Dr. Rachel Levine said states, cities and territories had been given just $340 million to build the infrastructure for vaccine rollouts up until the end of the year.

That is clearly insufficient to accomplishing what were trying to accomplish, Levine said.

President Donald Trump signed a$900 billion COVID-19 relief packagein December that includes funds for vaccine rollout, something health leaders were absolutely thrilled about, Levine said.

The money will be critical for several aspects of our response, Levine added, including contracting with companies to do community vaccine clinics.

The US Food and Drug Administration has alerted health care providers and labs that genetic variants of the novel coronavirus including an emergingvariant first detected in the United Kingdom could lead to false negative COVID-19 test results.

False negative results can occur with any molecular test for the detection of the virus if a mutation has occurred in the part of the viruss genome that the test examines, the FDA said Friday.

But the risk that these mutations will impact overall testing accuracy is low, the FDA said. If COVID-19 is suspected after a negative test, repeat testing should be done with a different test, the agency recommends.

The agency noted three COVID-19 tests authorized in the United States may be impacted by genetic variants MesaBiotech Accula, TaqPath COVID-19 Combo Kit and Linea COVID-19 Assay Kit but the impact does not appear to be significant.

Since the TaqPath and Linea COVID-19 tests detect multiple genetic targets, the overall test sensitivity should not be impacted, the FDA noted. However, if certain patterns emerge in individual results from those tests, labs might consider further genetic sequencing of specimens.

That may help with early identification of new variants in patients to reduce further spread of infection, the FDA said in its letter to labs and health care providers, noting that the UK variant has been associated with an increased risk of transmission.

The FDA will continue to monitor SARS-CoV-2 genetic viral variants to ensure authorized tests continue to provide accurate results for patients, FDA Commissioner Dr. Stephen Hahn said, referring to the name of the coronavirus that causes COVID-19.

With information from the Indiana Department of Health through Jan. 7, 2021, this timeline reflects updated tallies of deaths and positive tests prior to that date.

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1-week US COVID-19 case and death totals are higher than ever - WISHTV.com

After decades of work and mass vaccination campaigns that have spared millions of children from paralysis, the world is close to wiping out polio.

But a small number of outbreaks that have simmered in areas of low vaccination remain. And some happened after weakened virus in the oral polio vaccine, over time, moved around a community and regained the ability to cause disease. No other vaccines made with weakened live viruses have caused outbreaks of disease.

To stamp out vaccine-derived polio outbreaks, the World Health Organization has granted emergency use for a new polio vaccine. The oral vaccine got the go-ahead on November 13.

We are very, very enthusiastically looking forward to using this new vaccine, says medical epidemiologist Chima Ohuabunwo of Morehouse School of Medicine in Atlanta, who has worked on polio eradication in Africa for more than two decades. Along with continuing the crucial work of improving vaccination coverage in places where it is low, the new vaccine will hopefully take us to the finishing line of polio eradication.

Eight years after the WHOs 1980 declaration that the world was free of smallpox, the Global Polio Eradication Initiative launched to tackle polio. The disease was a promising candidate for eradication. An effective, easily administered and cheap vaccine was available. And poliovirus, which naturally infects only humans, doesnt hang around in other animals in between outbreaks.

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Most people who become infected with poliovirus dont feel sick, while some have flu-like symptoms. But about one in 200 become paralyzed for life. Although not a routine threat in the United States since the early 1950s (SN: 9/12/19), polio has continued to harm people, especially children, around the world.

In the late 1980s, wild poliovirus paralyzed more than 1,000 children each day, according to the Global Polio Eradication Initiative. Since then, thanks to widespread vaccination campaigns, cases have plummeted by more than 99 percent, and two of the three types of wild poliovirus have been eradicated. The last cases from type 2 and type 3 were reported in 1999 and 2012, respectively. Only wild poliovirus type 1 remains, and only in two countries: As of December 30, 56 cases were reported in Afghanistan and 83 in Pakistan caused by type 1, in 2020.

Much of this progress has been possible because of the oral polio vaccine. Its been the workhorse of the eradication campaign, says virologist and infectious disease physician Adam Lauring of the University of Michigan School of Medicine in Ann Arbor. Immunization with the oral vaccine has prevented more than 13 million cases of polio since 2000, according to WHO.

A big advantage of the oral vaccine, which is made of live but weakened poliovirus, is that it not only protects against paralysis it also can stop wild poliovirus from spreading in a community. Poliovirus moves from person to person when someone ingests water or food contaminated with virus-containing stool. The oral vaccine prevents wild poliovirus from multiplying in the gut and being passed on. (There is another, more expensive, injected polio vaccine with killed virus that prevents paralysis but not viral spread.)

While the oral vaccine has nearly wiped out wild poliovirus, it has a vulnerability. Weakened poliovirus in the vaccine has genetic changes that keep it from causing disease. As vaccine virus multiplies in the gut, it can lose key genetic changes, bringing it closer to behaving like wild poliovirus. And altered vaccine virus can be spread to others and establish community transmission, says biologist Raul Andino of the University of California, San Francisco School of Medicine. That can be a problem if not enough people have been immunized against polio.

More than 80 percent of children need to be vaccinated to keep poliovirus from spreading in a community. The first vaccine-derived polio outbreak to be detected occurred in the Dominican Republic and Haiti two decades ago, in areas with low vaccination. That allowed altered vaccine virus, shed in the stool of the immunized, to spread largely unchecked and, over time, return to a form that causes paralysis (SN: 8/10/04). The full process of vaccine virus reverting to disease-causing virus is rare and takes many months of moving around a community.

Today, vaccine-derived outbreaks are primarily found in Afghanistan, Pakistan and countries in Africa. Most of these outbreaks which have been responsible for more polio cases in the last few years than the remaining type of wild poliovirus are linked to vaccine virus type 2. Vaccination campaigns, which had used an oral vaccine containing weakened versions of all three types of poliovirus, switched to using a formulation with just types 1 and 3 in 2016.

However, the way to stop a type 2 vaccine-derived outbreak is with an oral vaccine containing only the weakened type 2 virus. And that has sparked new outbreaks, researchers reported in Science in April. It is this vicious circle, Lauring says. As of December 22, in 2020 there were 854 polio cases linked to the type 2 vaccine virus.

Hence the quest for a new and improved poliovirus type 2 oral vaccine, one that kept the good parts of the original but with tweaks to try to prevent problematic genetic changes. Its a wonderful vaccine, so we didnt want to change the characteristics that induce the bodys immune response, Andino says. The only thing we wanted to do is prevent the reversion to a disease-causing virus.

Andino and colleagues modified the type 2 vaccine virus in several places. The researchers altered a part of the viruss genetic instruction book, or genome, to make the virus less likely to develop a gatekeeper change: a first, critical step along the road to regaining the ability to cause disease.

Poliovirus can swap pieces of its genome with related viruses called enteroviruses. So the researchers moved a string of genetic letters the virus needs to make more copies of itself close to the gatekeeper modification. That way, if the vaccine virus was able to ditch that modification by way of a swap, it would lose this necessary string of genetic letters too, and die out.

Finally, the team tinkered with an enzyme that RNA viruses, including poliovirus, use to help replicate themselves. The enzyme is sloppy and can introduce a lot of genetic changes, Andino says. Thats advantageous for the viruses, which are continuously trying to adapt to a new environment, he says. Andino and colleagues modified this enzyme in the vaccine virus to introduce fewer mistakes, so the virus cannot evolve so quickly. The researchers described their improved oral polio vaccine in a study in Cell Host & Microbe in May.

The new oral polio vaccine was shown to be safe and to produce an immune response similar to that seen with the original vaccine in infants and children, researchers reported online December 9 in the Lancet. The hope is that the modifications will slow the evolution of the new vaccine virus such that it can end the existing outbreaks without creating new ones.

The vaccine-derived outbreaks are a significant, yet surmountable hurdle to polio eradication, says Ohuabunwo, and science is helping. But the key to ending polio is very high vaccination coverage. Obstacles including war, migrating populations, difficult terrain and lack of vaccine acceptance have created pockets of inaccessible children, he says.

Reaching all children requires engaging community leaders, providing culturally sensitive information and finding out how to meet other community needs, says Ohuabunwo. For example, while working in Nigeria, he and his colleagues made progress with nomadic populations. It meant sometimes combining vaccinating their children with vaccinating their animals. The nomads cattle would be immunized against brucellosis and anthrax bacterial infections. Protecting the animals also protected the nomads from these infections, he says, and motivated their cooperation towards having their children receive polio vaccine: a win-win.

Polio eradication has been a long journey, but were getting close, Ohuabunwo says. The new oral polio vaccine is another light in the tunnel.

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A new polio vaccine joins the fight to vanquish the paralyzing disease - Science News Magazine

Advice for healthcare professionals:

Aminoglycosides are broad-spectrum bactericidal antibiotics. The group includes gentamicin, amikacin, tobramycin, and neomycin.

There is a narrow therapeutic window for aminoglycosides and their use can result in toxicity, including nephrotoxicity and ototoxicity, which can result in permanent hearing loss. This effect is related to the dose and duration of treatment and is exacerbated by renal or hepatic impairment or both and is more likely in elderly people and newborn babies.

To minimise the risk of ototoxicity with systemic aminoglycosides, regular serum concentration monitoring is recommended to maintain aminoglycoside levels below the toxic threshold for the cochleo-vestibular system. The product information for each medicine provides dosing considerations and recommendations for toxicity thresholds.

Assessment of auditory, vestibular, and renal function is particularly necessary in patients with additional risk factors.

In 2020, we conducted a safety review following concerns received about the impact of mitochondrial mutations on the risk of ototoxicity with aminoglycosides. We identified several published epidemiological studies showing an increased risk of deafness in patients with the m.1555A>G mutation who were given aminoglycosides. There have also been reported cases of deafness in m.1555A>G patients with aminoglycoside use within the recommended serum levels. Some cases were associated with a maternal history of deafness or mitochondrial mutations or both.

Although no cases were identified with neomycin or topical preparations of gentamicin, amikacin, or tobramycin, based on a shared mechanism of action there is the potential for a similar effect with neomycin and other aminoglycosides that are administered at the site of toxicity (the ear).

The m.1555A>G mutation is the most common mitochondrial DNA (mtDNA) mutation, with an estimated prevalence of 0.2% in the general population. The mutation is associated with sensorineural deafness and occurs in families with maternally transmitted deafness.

Clinicians should follow local guidelines on mitochondrial mutation screening in patients with a maternal history of deafness or mitochondrial mutations or both and who require aminoglycoside therapy. Genetic screening may be especially appropriate in patients requiring recurrent or long-term aminoglycoside therapy where the risk of ototoxicity is increased.

Our review focused on four key epidemiological studies that reported an association between having mitochondrial mutations and an increased risk of deafness with aminoglycoside use. In addition, 10 case reports were identified from the medical literature indicating this toxicity. This evidence is further supported by a plausible biological mechanism where mutated mitochondrial ribosome more closely resembles the bacterial ribosome and may provide a binding site for aminoglycosides; this effect has been shown in biochemical tests.

While many of the epidemiological studies had weak statistical power due to the rarity of the mitochondrial mutations, the evidence is considered sufficient to update the product information for aminoglycoside products with systemic absorption or that are administered at the site of toxicity (the ear).

The product information will be updated to include warnings of a potentially increased risk of ototoxicity in patients with known mitochondrial mutations. The patient information leaflet will ask patients to talk to their doctor or pharmacist before taking this medicine if they know (or think they have) a mitochondrial disease.

These mitochondrial mutations are rare, and the penetrance of the observed increased ototoxic effect is unknown. For patients known to have susceptible mutations, it is important to consider the need for aminoglycoside treatment and the alternative treatment options available when making prescribing decisions.

Any suspected adverse drug reactions to aminoglycosides should be reported to us on a Yellow Card.

Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset, treatment dates, and product brand name.

Report suspected side effects to medicines, vaccines or medical device and diagnostic adverse incidents used in coronavirus (COVID-19) using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.

Article citation: Drug Safety Update volume 14, issue 6: January 2021: 6.

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Aminoglycosides (gentamicin, amikacin, tobramycin, and neomycin): increased risk of deafness in patients with mitochondrial mutations - GOV.UK

Rare disease and gene therapy industry veterans Steven Altschuler, M.D., R. Nolan Townsend and Jay Barth, M.D., team up with gene therapy pioneer Ronald Crystal, M.D., to launch fully integrated gene therapy company

Financing led, structured and syndicated by Longitude Capital and Omega Funds

Comprehensive pipeline includes three clinical-stage gene therapy programs in monogenic diseases and up to 15 potential additional AAV gene therapy programs in monogenic and acquired diseases primarily developed at Weill Cornell Medicine

NEW YORK, Jan. 07, 2021 (GLOBE NEWSWIRE) -- LEXEO Therapeutics, a clinical-stage gene therapy company, debuted today with an oversubscribed $85 million Series A financing, led by Longitude Capital and Omega Funds, and joined by Lundbeckfonden Ventures, PBM Capital, Janus Henderson Investors, Invus, Woodline Partners LP, the Alzheimers Drug Discovery Foundationiand Alexandria Venture Investments. Proceeds from the financing will help advance the companys three lead investigational programs, including: LX2006, an IV-administered therapy for cardiomyopathy associated with Friedreichs ataxia (Phase 1 start planned for 2021); LX1004, a CNS-administered therapy for CLN2 Batten disease (Phase 1/2 completed); and LX1001, a CNS-administered therapy for APOE4-associated Alzheimers disease (Phase 1 ongoing).

We are thrilled to launch today with a mission to advance LEXEOs promising clinical-stage pipeline of gene therapy treatments for patients diagnosed with some of societys most challenging diseases, said R. Nolan Townsend, Chief Executive Officer of LEXEO Therapeutics. We have the pleasure of collaborating with Dr. Ronald Crystal one of the industrys most accomplished pioneers in the gene therapy space and, drawing on my years of rare disease leadership experience at Pfizer, will together build a world-class gene therapy organization driven by premier science that has the potential to address a range of therapeutic indications.

Founder and Chief Scientific Advisor Dr. Ronald Crystal is Professor and Chairman of Weill Cornells Department of Genetic Medicine and Director of the Belfer Gene Therapy Core Facility. Dr. Crystal has more than 30 years of experience with adenovirus and adeno-associated virus vectors, from basic vector design through clinical development. Dr. Crystal has 14 approved gene therapy investigational new drug applications and has published more than 300 papers on gene therapy, with experience in CNS, cardiac, pulmonary and liver-mediated diseases.

I am excited to work with LEXEO Therapeutics to move our extensive academic portfolio into clinical development and ultimately bring it to patients, said Dr. Crystal. LEXEOs AAV-mediated gene therapy programs have the potential for broad applicability across a range of therapeutic indications, and in a single company pipeline present an opportunity for the natural evolution of gene therapy from rare genetic conditions to more common diseases.

LEXEO Therapeutics Chairman, Dr. Steven Altschuler, is currently Managing Director at Ziff Capital Investments and was formerly Chairman of gene therapy biotech pioneer Spark Therapeutics, which was responsible for the first FDA-approved gene therapy, Luxturna, and was acquired by Roche in 2019 for $4.3 billion.

LEXEOs impressive management team, with Nolans years of rare disease leadership experience at Pfizer, as well as its pioneering scientific founder and high-quality investor syndicate, will propel the development of the companys pipeline of promising and innovative programs, said Dr. Altschuler. I am honored to have the opportunity to partner with Nolan and his team to build a leading gene therapy company.

LEXEO Therapeutics has also appointed Dr. Jay Barth as Executive Vice President and Chief Medical Officer to oversee Medical Affairs, Regulatory Affairs and Clinical Development. Dr. Barth was formerly the Chief Medical Officer at Amicus Therapeutics and Senior Vice President, Clinical Development, at PTC Therapeutics, where he oversaw all clinical development programs and the approval of Galafold for Fabry disease at Amicus, as well as Translarna, the first approved treatment for Duchenne muscular dystrophy at PTC Therapeutics.

Other members of LEXEO Therapeutics Board of Directors include CEO R. Nolan Townsend, Sandip Agarwala of Longitude Capital, Bernard Davitian of Omega Funds and Mette Kirstine Agger of Lundbeckfonden Ventures.

Initial Indications

Friedreichs ataxia (FA) is a rare, degenerative multi-system disorder affecting approximately 1 in 50,000 people in the United States. FA is caused by a gene mutation that disrupts the normal production of the protein frataxin, critical to the function of mitochondria (the energy producing factories) in a cell. FA is inherited in an autosomal recessive manner, usually begins in childhood, and leads to impaired muscle coordination (ataxia) that worsens over time, typically progressing to serious heart conditions, includinghypertrophic cardiomyopathy and arrythmias.FA is also associated with vision impairment, hearing loss, scoliosis, diabetes and slurred speech. Friedreichs ataxia can shorten life expectancy, with heart failure the most common cause of death. Supported by de novo, soon to be published pre-clinical research, LX2006 is an IV-administered AAV-mediated frataxin gene therapy treatment focused on the cardiac pathology of FA. The company is completing IND-enabling pre-clinical studies and expects to initiate a Phase 1 trial in 2021.

CLN2 disease (late infantile Batten disease) is an autosomal recessive lysosomal storage disease with fewer than 1,000 cases worldwide, with typical onset in children between 2 and 4 years of age. The disease is caused by mutations in the CLN2 gene, resulting in progressive cognitive impairment, visual failure, seizures and deteriorating motor development. LX1004 is an AAV-meditated gene therapy treatment delivering CLN2 to the central nervous system. In December 2020, clinical data published in Science Translational Medicine found a single administration of AAV-mediated CLN2 gene therapy (LX1004) slowed the progression of CLN2 disease in children. Treatment with LX1004 was well tolerated, with minimal serious adverse events in the acute/post-operative period (0-14 days) and over the 18-month study period (14 days 18 months). With this Phase 1/2 study complete, the company plans to advance the program into a pivotal study in 2022.

Alzheimer's disease is the leading cause of late-onset dementia, characterized by progressive memory loss and cognitive decline in humans. APOE is a major cholesterol transporter and is in part linked to the pathogenesis of Alzheimer's disease due to development of amyloid plaques and tau-tangles in the brain. People who inherit APOE4 alleles are at significantly higher risk for developing Alzheimers disease and at an earlier age of onset than people who inherit APOE3 or APOE2 alleles, which have normal and reduced risk of disease onset, respectively.iiLX1001 is an AAV-mediated gene therapy treatment delivering APOE2 to the central nervous system of people with two APOE4 alleles (homozygotes), via a CNS route of administration. A Phase 1 clinical study is ongoing.

About LEXEO Therapeutics, Inc. LEXEO Therapeutics is a New York City-based, fully integrated biotechnology company currently headquartered at the Alexandria Center for Life Science that aims to apply the transformational science of gene therapy to address some of the worlds most devastating genetic and acquired diseases. LEXEO Therapeutics pipeline consists of adeno-associated virus (AAV)-mediated therapies primarily developed at Weill Cornell Medicines Department of Genetic Medicine. Beyond LEXEO Therapeutics lead programs which are focused on both rare and non-rare monogenic (single gene mutation) diseases the companys preclinical pipeline spans monogenic diseases, as well as hereditary and acquired diseases across a spectrum of patient population sizes and a range of unmet medical needs. Importantly, LEXEO Therapeutics will focus on advancing clinical programs through to commercialization, with the goal of maintaining an ongoing research collaboration with Weill Cornell Medicines Department of Genetic Medicine to help advance the companys pre-clinical pipeline. For more information, please visit http://www.lexeotx.com or LinkedIn.

Investor ContactLEXEO Therapeutics, Inc.investors@lexeotx.com

Media Contact Sheryl Seapy, W2O Group(949) 903-4750sseapy@w2ogroup.com

ihttps://www.alzdiscovery.org/ iihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1350934/

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LEXEO Therapeutics Launches with $85 Million Series A Financing to Develop Gene Therapies for Rare and Non-Rare Monogenic Diseases - GlobeNewswire

Dive Brief:

Biogen is at a crossroads, awaiting a regulatory decision on the Alzheimer's drug aducanumab by early March that will have wide-ranging implications for the biotech's future.

But while aducanumab's fate hangs in the balance, Biogen has been stocking up on other early-stage assets, aiming to diversify its portfolio beyond risky neuroscience bets. Company executives in 2019 said they were putting more emphasis on ophthalmology and immunology, for instance, and that same year, the company spent $800 million on an acquisition of the eye gene therapy company Nightstar Therapeutics.

ViGeneron offers a novel technology for harnessing adeno-associated virus vectors to treat eye disease. Its vgAAV vectors are designed to get around some of the limits of the standard gene therapy delivery tools and target a variety of different cell types. The two companies noted the technology's potential to more efficiently transduce retinal cells via eye injections, which in theory could lead to more potent treatments.

The company is still fairly new, however, having being spun off in 2017 by Ludwig-Maximilians University in Munich. Its investors include WuXi AppTec and Sequoia Capital China. None of its experimental treatments, led by a gene therapy for retinitis pigmentosa, are in human testing.

The deal is another bet by Biogen on genetic medicine. Earlier this year, the biotech formed a gene editing alliance with Sangamo Therapeutics that could be worth billions of dollars.

Still, investors at the moment are most focused on aducanumab. The roller coaster ride for the drug began in March 2019, when the drug appeared to have failed two clinical trials. Seven months later, however, the company said a further analysis showed significant benefits for a high dose in one clinical trial, and the Food and Drug Administration agreed to review the medicine.

In November 2020, the FDA convened a panel of outside experts, whose review was overwhelmingly negative. Panelists criticized the agency for being too optimistic about Biogen's data and voted near-unanimously against approving the drug.

The committee's vote isn't binding for the FDA, though the agency typically follows its advice. Regulators are due to make their final decision on aducanumab by March 7.

Link:
Biogen pushes further into eye gene therapy with new deal - BioPharma Dive

For Immediate Release: January 04, 2021 Statement From:

Statement Author

Leadership Role

Acting Director - Center for Drug Evaluation and Research

Deputy Center Director for Operations - Center for Drug Evaluation and Research | CDER

Advances in scientific knowledge and drug development technology have provided an opportunity for new approaches to drug development, including the development of drugs for the treatment of rare diseases. These advances have contributed to an increase in development and approval of drugs for the treatment of rare diseases in recent years. In fact, in the past eight years, the U.S. Food and Drug Administration has approved more than twice as many drugs for rare diseases, often referred to as orphan drugs, as in the previous eight years.

For genetic diseases, recent approaches to testing and molecular diagnosis have allowed us to pinpoint, in some cases, the exact cause of a patients disease. For a patient with a very rare genetic disease, development of a drug product that is tailored to that patients specific genetic variant may be possible. This is an important advance in treatment for those with very rare genetic diseases, especially those for which there are no adequate therapies available to treat the disease. Often, these very rare diseases are rapidly progressing, debilitating, and in many cases, can lead to premature death if left untreated.

Developing these products also referred to as n of 1 therapies by some because they are designed for a patient population of one person brings a set of challenges and considerations not seen with the typical drug development process. First, as noted above, the disease is often rapidly progressing, requiring prompt medical intervention. Therefore, development needs to proceed very quickly to have a chance at helping the individual. Second, drug discovery and development for these drug products may be carried out by academic investigators, rather than by biopharmaceutical or pharmaceutical companies. These investigators may be less familiar with FDAs regulations, policies and practices, and less experienced in interacting with the FDA.

At this time, development of individualized genetic drug products is most advanced for antisense oligonucleotide (ASO) products. Therefore, we are taking the first steps in bringing clarity to this emerging area of individualized drug development by releasing a new draft guidance on investigational new drug (IND) submissions for individualized ASO drug products.

The guidance was developed to advise those developing ASO products on an approach to interacting with, and making regulatory submissions to, the FDA. The guidance addresses the following points:

As also discussed in a New England Journal of Medicine editorial in October 2019, we are fully aware that this new drug-discovery paradigm raises many ethical and societal issues that will need to be addressed throughout the process. For example, in these situations, the individuals and their families often function more like drug development collaborators than traditional trial participants. Therefore, it is important to discuss with the individual and family members how effectiveness will be measured. It is also important to ensure that the individual and family members understand the parameters for continuing administration of the investigational drug product before emotions influence decisions, and to recognize that some investigational drug products may fail, or worse, lead to unforeseen side effects.

The FDA understands that well need to work together with the developers of these drug products to bring them safely to patients, and we are willing to engage as needed to address the challenges. For example, for those developing these drug products, it will be important to further understand the required data and information that must be submitted to the FDA so that clinical testing can begin. The FDA is continuing to consider and further develop policy to address some of these issues.

We also are optimistic that development of these individualized drug products may spur gene sequencing that leads to the development of additional individualized drug products for the same disease (though perhaps caused by a different mutation). For this approach to drug development, we need to determine collectively how to effectively bring these drug products to all who need them. If we have the scientific ability to develop drug products for these rare diseases, we need to find a way to bring them to patients while ensuring there is the right balance of risk to benefit. This guidance, which provides clarity on the early development and IND submission process, is the FDAs first step in working with those who are developing these individualized drug products.

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

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FDA Takes Steps to Provide Clarity on Developing New Drug Products in the Age of Individualized Medicine - FDA.gov