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Friday, April 2, 2021

Home-Based Medical Care During Coronavirus Disease 2019 and Beyond

 

Abstract and Introduction

Abstract

Ms. H is a 78-year-old woman with a history of congestive heart failure, chronic obstructive pulmonary disease, and recent stroke who was discharged 1 month ago from a subacute rehabilitation facility. She moved in with her son because she now requires a walker and cannot return to her third-floor apartment. One evening, Ms. H develops a low-grade fever and mild shortness of breath intermittently relieved by her albuterol inhaler. Her son is worried, but knows that his mom does not want to return to the hospital.

Introduction

Introduction: Home-based Medical Care

The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented strains on our healthcare system. Emergency rooms, hospitals, and nursing facilities around the nation have been particularly affected. Given capacity limitations during the initial crisis and continuing into another season of increasing infection rates, there is tremendous pressure to keep high-risk patients out of acute care settings and discharge those who are admitted to appropriate post-acute care. At the same time, disease outbreaks and visitor restrictions at skilled nursing facilities (SNFs) create barriers to placement, both at an individual and public health level. In this context, care at home became and continues to be an increasingly critical option, particularly for older, comorbid patients who represent a large proportion of those affected. Patients discharged from an acute care setting to their homes, as well as those in the community diagnosed with both COVID and non-COVID illness, require robust systems for monitoring and support with an interdisciplinary team of providers.

Home-based medical care (HBMC) is a powerful modality to address these challenges. Importantly, HBMC already functions across the continuum of care, providing primary, hospital-level, post-acute, and palliative care to multimorbid and functionally impaired older adults throughout the United States.[1–4] Additionally, HBMC providers work closely with other home care services and often utilize technology for remote monitoring and virtual care. Many of these programs have been shown to reduce healthcare costs through lower rates of hospitalization, emergency room visits, and institutionalization while improving quality of life and patient satisfaction.[1,5–8]

The HBMC model, quietly evolving over the last two decades, has rapidly transformed in response to COVID-19 with many health systems expanding established home-based care programs to further meet the needs of vulnerable populations. The potential contributions of HBMC during this challenging time include (1) to continue tending to the chronic but substantial health needs of medically complex patients, thus reducing the need for emergent care in overburdened hospital systems; (2) to provide hospital-level care for both COVID and non-COVID illness ("hospital at home"); (3) to provide post-acute level care as an alternative to SNFs; and (4) to provide palliative care to help clarify patient goals and manage symptoms of acute and chronic illness. With additional resources, HBMC has the potential to not only decompress the healthcare system, but also provide high-quality, patient-centered care during this time of crisis and beyond.

Expanding HBMC to Face the COVID-19 Crisis

As an exemplar of value-based care both before and during this pandemic, we suggest several steps to incorporate HBMC more fully into our country's coordinated response to COVID-19:

Leverage Existing HBMC Practices

It is estimated that there are over 1,000 practices providing HBMC visits in the United States.[9] Home care practices within a health system should work with clinical and strategic leadership to determine how existing programs can expand with the support of the health system. In systems without HBMC programs, the American Academy of Home Care Medicine directory or the Centers for Medicare & Medicaid Services (CMS) claims data can help identify established HBMC providers across the nation. HBMC teams are already adept at the triage of frail, high-risk patients and prompt appropriate referral to community agencies for collaboration with skilled and unskilled home care. However, there is wide heterogeneity in the structure of existing HBMC practices.[10] For example, a national survey of HBMC programs (excluding those affiliated with the Department of Veterans Affairs (VA)) found that 20% were sponsored by a hospital or health system whereas the majority were owned by an independent provider or provider group. Practices more often served urban and suburban patient populations, with only 30% reaching rural patients.[10] In contrast, more than half of home-based primary care sites affiliated with the VA serve rural veterans.[11] Given this variation in practices, it is essential to develop a standardized quality framework to identify programs that are providing effective care as HBMC expands. To start, CMS must add codes for home-based medical visits to Merit-based Incentive Payment System quality measures relevant to medically complex home care patients so that practices can begin to quantify value-based care.[12] Notably, many of the widely used disease-specific quality measures often do not apply to the health goals of multimorbid, frail HBMC patients. Experts in the field are actively working to develop a quality framework for HBMC that overlaps with accepted quality metrics and may better align business incentives with patient and caregiver outcomes.[9]

Sustain Expanded Reimbursement for Remote Care Delivery

Congress should extend the regulatory modifications of the CARES Act to cover telehealth modalities that minimize exposure to COVID-19 for providers and patients. Both properly protected in-person home visits and telehealth tools for remote management are vital to providing acute and chronic care in the safety of patients' homes. The adaptation of telehealth during the pandemic depends on many factors, including access to technology and connectivity for both providers and patients, clinical circumstances amenable to remote evaluation, local rates of COVID-19 transmission, staffing, and availability of personal protective equipment (PPE). It is essential that home care practices can pivot between virtual and in-person care modalities in the face of an unpredictable pandemic. For example, Northwell Health, which provides home-based primary care to approximately 2000 patients in downstate New York, was able to complete telehealth visits with 48.6% of eligible enrollees from March to May 2020, while 11.5% of patients who consented to telehealth ultimately required a face-to-face visit during this time frame.[13] The authors' home-based primary care colleagues at the University of Pennsylvania adopted similar practice patterns, with telehealth utilized for the majority of visits early in the pandemic and then carefully integrated with face-to-face evaluation as local transmission rates fell and PPE became more widely available. In addition to primary care, telehealth is also a powerful tool to engage subspecialists in the team-based care of complex older adults. Pre-COVID research supports the benefits of telehealth for select patient populations.[14] However, the rapid transformation of telehealth services during the current crisis is uncharted territory, and efforts to engage older adults with new technologies can be particularly challenging.[15] We must prioritize telehealth research, and we must be deliberate about including medically complex older adults in these studies to evaluate feasibility and effectiveness. Moreover, we must select appropriate outcomes measures that reflect the goals of value-based care.

Develop COVID-specific Care Delivery Protocols Backed by Robust Supply Chains

Home-based care delivery during the COVID pandemic requires adequate PPE, as well as kits to administer COVID-19 testing in the home. HBMC providers at some institutions are already coordinating at-home COVID-19 testing, which is crucial to reducing community spread of disease among this high-risk population. HBMC practices require a protected supply chain of PPE to reduce the risk of virus transmission as providers move between patients. In addition, as hospital treatment protocols for COVID-19 are rapidly developed and modified, the application of these protocols to COVID patients receiving treatment in the home will need to be researched and standardized. Examples include appropriate use of dexamethasone and venous thromboembolism prophylaxis.

Expand Inpatient-level Care at Home

"Hospital at home" is a model that provides acute care services typically requiring inpatient hospitalization to patients in their homes. It has already been adapted by several health systems across the United States and shown to reduce cost, healthcare utilization, and readmissions when compared to usual hospital care.[2,3] We agree with Drs. Nundy and Patel that expansion of hospital at home should be a priority in our country's COVID-19 response.[16] Home management of acute non-COVID illness can reduce bed utilization, avoid isolating patients from their families, and reduce the risk of hospital-based transmission of disease. When backed by adequate resources, it may also be safe and effective to enroll lower-risk COVID-19 patients in a hospital at home program. The hospital at home model has rapidly gained traction during the pandemic. For example, the relatively new Boston-based company Medically Home, which partners with hospitals across the United States to provide acute care to patients at home, has seen a 10-fold increase in patient volume compared to 1 year ago.[17] Well-established hospital at home programs, such as Mount Sinai at Home in New York and those operated by the Veterans Health Administration, have also seen an increase in patient volume.[17] Northwell Health in New York has developed COVID-specific hospital at home protocols that utilize telehealth and support from pulmonologists to offset pressure on hospitals.[18] Continued expansion of this model requires coordinated efforts between health systems, HBMC providers, homecare agencies, telemonitoring infrastructure, durable medical equipment suppliers, and mobile diagnostic services. Care for COVID-19 patients also requires enhanced respiratory monitoring and access to respiratory therapists. Beyond clinical operationalization, CMS must consider reimbursement for inpatient-level care at home commensurate with usual hospitalization.

Expand Post-acute Care at Home

Patients with intensive rehabilitation or medical needs after acute hospitalization often receive post-acute care in a SNF. Recent work by Augustine et al suggests that it is both feasible and effective to deliver SNF-level post-acute care in patients' homes.[19] Malone and Fain highlight the key infrastructure necessary to make this a sustainable model, namely: involvement of a mature interdisciplinary clinical practice with organizational support, participation of home-based primary and palliative care, and collaboration with community resources.[20] Many of these building blocks have already been mobilized in response to COVID-19. Encouragingly, outpatient physical, occupational, and speech therapy visits have successfully pivoted to telehealth ("telerehabilitation") during the pandemic with high patient satisfaction.[21] In addition to rethinking skilled care delivery, the home-based SNF model requires formal training and reimbursement of caregivers to support patients' daily needs and to oversee rehabilitation.[22] The staggering impact of COVID-19 on nursing facilities gives us a strong incentive to invest in further expanding the home-based model of post-acute care.[23] Notably, existing studies of home-based acute and post-acute care have largely been conducted in urban settings, such as Boston[3] and Manhattan.[19] There are unique logistical barriers to providing intensive skilled home services in rural America, where access to healthcare remains a major challenge. Ariadne Labs, the center for health systems innovation at Brigham and Women's Hospital and Harvard School of Public Health, is currently working with University of Utah Health to test a novel rural home hospital program.[24] Their proposed model of care utilizes local paramedics who travel to patients' homes and work under the guidance of hospital-based physicians via video conference. If successful, incorporation of telerehabilitation services for ongoing post-acute care at home certainly warrants further investigation.

Expand Palliative Care at Home

The current pandemic has driven increased demand for palliative care services, as well as innovative ways of delivering this care to patients.[25–27] Home-based palliative care is not new, and has been shown to improve patient satisfaction while reducing emergency room visits and hospitalizations in the last year of life.[4] More recently, advances in technology have allowed us to bring virtual palliative care support to patients in their homes.[28] Home-based palliative care, ideally in partnership with other HBMC providers, can help manage the symptom burden of acute and chronic illness and thus avoid unnecessary hospitalizations. In addition, frail, older adults who decompensate despite the support of home-based primary care or hospital at home may prefer to pursue palliative goals rather than present to an emergency room or hospital. Organizations such as VitalTalk and the Center to Advance Palliative Care have developed publicly-available, COVID-specific communication tools to help providers engage in these difficult conversations.[29,30] Close collaboration with palliative care would allow teams to elicit patient preferences and rapidly implement supportive measures to provide true patient-centered care.

Conclusion

As it has for decades, HBMC stands ready to meet the challenges of a strained healthcare system. With the services described above, a patient like Ms. H could receive timely COVID-19 testing in the safety of her home, utilize hospital at home for management of her chronic obstructive pulmonary disease exacerbation, and participate in intensive physical and occupational therapy at home to promote functional recovery. She would avoid COVID-19 exposure in the emergency room, hospital, and SNF, the risks associated with multiple transitions of care, and the isolation imposed by visitor restrictions. Unfortunately, Ms. H's course followed the more common trajectory in our current health system. She ultimately had delayed access to primary care evaluation and was readmitted to the inpatient ward via the emergency room, with stay complicated by hypoactive delirium. Her son opted for discharge home with twice-weekly physical therapy given concerns about virus transmission and visitor restrictions at SNF, and she struggled to regain her baseline function.

Like other medical services which improve patient safety and outcomes during an unprecedented public health emergency, HBMC is a critical resource in urgent need of expanded investment, reimbursement, and research. Thousands of HBMC providers across the nation are ready for the challenge and equipped to work together with their colleagues on the front lines to provide high-quality, comprehensive, and patient-centered care. HBMC's valuable services at this important time will undoubtedly change how we approach healthcare delivery and pandemic response in the decades to come.

https://www.medscape.com/viewarticle/945323

Pandemic guidance for immunosuppressed transplant patients

 Immunosuppressed patients face a potential triple threat from COVID-19: higher risk of serious illness from infection, lack of immune response to that illness, and reduced vaccine effectiveness.

In the second part of this exclusive MedPage Today video (watch part one here), Editor-in-Chief Marty Makary, MD, MPH, of Johns Hopkins University in Baltimore, speaks to Dorry Segev, MD, PhD, associate vice chair of surgery at Johns Hopkins University School of Medicine and professor of epidemiology at Bloomberg School of Public Health, who authored a study on immunosuppressed patients' response to the COVID-19 vaccine. They discussed ongoing research into transplant patients and COVID-19, how to treat the disease in this population and how to handle post-vaccination risk when they're already starting "three steps behind" their immunocompetent counterparts.

Following is a transcript of their remarks; note that errors are possible.

Makary: Hi, I'm Marty Makary with MedPage Today. I'm here with Dr. Dorry Segev, a professor and transplant surgeon at Johns Hopkins, a good friend and colleague. Dorry, I want to switch gears for a second. You've also done broader research on COVID risk among those who are immunosuppressed and those who have had organ transplant. Trying to get at the question, are those groups at higher risk of getting COVID infection and are they at higher risk of dying from COVID?

So can you talk a little bit about that body of research that you've been working on and how those come out over the last couple months?

Segev: Yeah, so, early on in the pandemic, transplant patients did not fare well whatsoever to COVID infection. There were more reported mortality rates in the 40-50% range from the U.S., from Europe -- this was really, really scary for transplant patients.

As we've learned how to take care of this disease of COVID-19 in general in everybody, we've learned also how to take care of it in transplant patients. It's interesting because, the immunoinflammatory stage 3 of COVID infection is quite similar biologically to the immunoinflammatory process of allograft rejection, right?

You have an immune system reaction that activates the inflammatory system that causes end organ damage. And we see that in transplant recipients. And we also see that in sort of that last stage of really bad COVID-19 infection. So it wasn't a huge surprise to us when administration of steroids, which is what we do for rejection, also worked for COVID-19 infection, right?

So we're learning a lot about sort of how best to treat this in both our transplant patients and non-transplant patients, to the point where even recently -- our report for example, at Hopkins showed that we were able to get the mortality of transplant patients to equal the mortality of non-transplant patients who get COVID-19.

Now some of this may have to do with the fact that transplant patients, if you think about who is most carefully following public health guidelines, it is the people who know that they are at higher risk. And one of the things we have hypothesized is that the level of inoculum of disease that you get kind of dictates how aggressive that disease is going to be.

And so if a transplant patient is sitting in the vicinity of somebody who is spreading the virus, but they're wearing a mask, their risk of getting a higher inoculum is lower.

And it's possible that they're actually coming in with less of an immune activation because they have less of sort of an immunoinflammatory activation, because they have seen a smaller inoculum of the virus.

So that's one of the things that might actually be helping transplant patients in all of this is because they know they're immunosuppressed. They know they need to be more careful.

Our transplant patients are always more careful in the community anyway around flu season and things like that. They're incredibly careful to keep themselves as healthy as possible. So it may be that we're seeing some of that from there.

Now, one question that comes to mind, of course, is, if somebody is a transplant patient, they've gotten a full vaccine series and they still have no detectable antibodies, what do we do for them?

And the emergence and success of monoclonal antibodies could potentially help patients. So my understanding right now is that at least, on the day that we're speaking today, post-exposure prophylaxis is available readily on a clinical level to people.

So I would say if you're a transplant patient, you have no antibodies, and there was any question of exposure to COVID-19, we should be treating those patients with post-exposure or monoclonal antibody prophylaxis.

What I'm hoping is that the pre-exposure trials prove efficacious, and we may even be able to give pre-exposure prophylaxis to transplant patients. But that's something for hopefully the near future.

Makary: So in terms of a summarizing or an estimate of the quantified risk to transplant recipients and the quantified risk to those on immunosuppression who are not transplant recipients, of getting the infection and dying of the infection, where would you put those numbers, roughly?

Segev: So pre-vaccine era, I would have said that immunosuppressed patients were in exactly the same scenario -- probably five to 10 times more likely of acquiring the disease compared to immunocompetent people. And that then their mortality could be the same or higher depending on the care that they give. So I think that would be quite variable.

Makary: Could it be better?

Segev: I don't think it could be better, but I think if with really good care and with the luck of detecting it early, et cetera, et cetera, it could be equivalent.

I think post-vaccine now this risk difference is even higher, right? Because immunocompetent people are going to get vaccinated. They're gonna be fine.

As we've discussed before, people who are immune, who are around other people who are immune, it's almost life as it was ever before. And even the CDC guidelines are kind of catching up with that.

But I would say that immunosuppressed people will not have as robust of an immune response. And now we'll be even more at risk than their sort of general population counterparts. Again, emphasizing that their bubbles, the people that they live with, the people that they see on a regular basis, need to be vaccinated and need to be prioritized for that vaccination.

Makary: And how much of that surprise in the data, that those immunocompromised who get COVID don't have a significantly worse mortality risk. How much of that do you think is the steroids that they may be on chronically?

Segev: It could be. A year ago I would have told you transplant patients are not going to do well with COVID-19 because this is a really bad disease. They're immunosuppressed, they're already three steps behind, and then they're going to get really, really hurt from this. And early on that indeed was the case. And it was very, very scary.

I think as we're learning the fact that they're already on a regimen to stop immunoinflammatory responses from harming their allograft -- they were three steps behind, now they're like back to being sort of on par with their immunocompetent counterparts. I would use a golf analogy, but I know nothing about golf. So I would totally get the golf analogy wrong, but you can insert one if you would like, Marty.

Makary: It's good for your mental health that you don't play golf. And now this is what I love about your work, Dorry. I think we were all really worried about organ transplant recipients and immunosuppressed patients. I was certainly warning the public and a lot of media channels back in the spring and pre-pandemic that when we realized this could be bad, that this might be an exceptionally vulnerable group.

So, thanks for all your research, great study in JAMA, congratulations. Any final thoughts here?

Segev: I guess my final thought is, there's a lot we have left to learn about the immune system in immunosuppressed patients and its response to vaccines, but we are working hard to learn as much as we possibly can.

And in the meantime, the thing I'm telling transplant patients is, do not assume you're immune just because you were vaccinated. For immunocompetent people, that is a totally reasonable assumption. For immunosuppressed people, we need more data.

Makary: And so just to follow up on that point, Dorry. In your own clinical practice, how are you using the results to change your practice? Are you testing patients after vaccination for antibodies?

Segev: So I would say that any transplant patient who wants to do anything other than what they were doing prior to vaccination, which is to socially distance, to wear masks, to minimize contact with anybody else, anyone who wants to relax their restrictions in any way should be antibody tested before allowing themselves to do that.

Even antibody testing is not a 100% guarantee. Remember nothing is 100% here, but if you're going to say to yourself, I really need to hug my grandkids in order to feel alive, I got the vaccine, I'm going to say to you, if we don't check your antibodies, you can't have any reassurance that you actually had a response to the vaccine.

https://www.medpagetoday.com/blogs/marty-makary/91884

Vaccines, fiscal stimulus boost U.S. employment in March

 The U.S. economy created the most jobs in seven months in March as more Americans got vaccinated and the government doled out additional pandemic relief money, marking the start of what could be the strongest economic performance this year in decades.

The Labor Department’s closely watched employment report on Friday suggested the jobs market has finally turned the corner after hitting a ditch in December. All industries added jobs last month and more people rejoined the labor force. A measure of the economy’s ability to create employment also improved.

But the road to full recovery remains long. More than four million Americans have been unemployed for over six months.

“The economy is roaring back to life,” said Brian Bethune, professor of practice, Boston College.

Nonfarm payrolls surged by 916,000 jobs last month, the biggest gain since last August. Data for February was revised higher to show 468,000 jobs created instead of the previously reported 379,000. Still, employment remains 8.4 million jobs below its peak in February 2020.

Economists polled by Reuters had forecast payrolls increasing by 647,000 jobs in March.

The employment report marked a painful anniversary for the labor market. The March 2020 employment report was the first to reflect the mandatory closures of non-essential businesses such as restaurants, bars and gyms to slow the onset of the just-emerging COVID-19 pandemic.

Nearly 1.7 million jobs were lost that month, and another 20.7 million would vanish in April. Economists estimate it could take at least two years to recoup the more than 22 million jobs lost during the pandemic.

Job gains last month were led by the leisure and hospitality sector, where employers hired 280,000 workers. Restaurants and bars accounted for nearly two-thirds of the industry’s employment gains. Construction employment rebounded by 110,000 jobs after being depressed by harsh weather in February.

Manufacturers hired 53,000 employees. Public and private education payrolls also increased as more schools resumed in-person learning and other school-related activities.

The dollar was steady against a basket of currencies. U.S. Treasury prices were lower. The U.S. stock market is closed for Good Friday.

As of Tuesday morning, the United States had administered 147.6 million doses of COVID-19 vaccines in the country and distributed 189.5 million doses, according to the U.S. Centers for Disease Control and Prevention.

The White House’s massive $1.9 trillion pandemic relief package approved in March is sending additional $1,400 checks to qualified households and fresh funding for businesses.

Economists expect job growth will average at least 700,000 per month in the second and third quarters. That, combined with the fiscal stimulus and about $19 trillion in excess savings accumulated by households during the pandemic, is expected to unleash a powerful wave of pent-up demand.

First-quarter gross domestic product estimates are as high as an annualized rate of 10.0%. The economy grew at a 4.3% pace in the fourth quarter. Growth this year could top 7%, which would be the fastest since 1984. The economy contracted 3.5% in 2020, the worst performance in 74 years.

The unemployment rate fell to 6.0% last month from 6.2% in February. The unemployment rate has been understated by people misclassifying themselves as being “employed but absent from work.” Without the misclassification, the unemployment rate would have been 6.4% in March.

But the labor market is making progress. About 347,000 people entered the labor force in March. That lifted the labor force participation rate, or the proportion of working-age Americans who have a job or are looking for one, to 61.5% from 61.4% in February.

The employment-to-population ratio, viewed as a measure of an economy’s ability to create employment, increased to 57.8% from 57.6% in the prior month.

Long-term unemployment, however, is becoming entrenched. About 4.218 million people have been out of work for more than 27 weeks, accounting for 43.4% of the 9.7 million people classified as unemployed last month. That was up from 41.5% in February.

“The labor market has begun to turn around, but we still have a long way to go before substantial progress is made and the labor market fully recovers,” said Charlie Ripley, senior investment strategist at Allianz Investment Management.

https://www.reuters.com/article/us-usa-economy/vaccines-fiscal-stimulus-boost-u-s-employment-in-march-idUSKBN2BP09L

Emergent: Experimental Covid treatment failed in Phase 3 trial

 Emergent BioSolutions Inc. EBS, -13.40% said Friday that its experimental COVID-19 treatment did not demonstrate a clinical benefit in a late-stage clinical trial. The study was testing Emergent's immunoglobulin candidate with the standard of care, which uses Gilead Sciences Inc.'s GILD, +2.80% Veklury, in hospitalized patients with COVID-19 symptoms. "Emergent will continue to explore COVID-HIG as a treatment in ongoing clinical trials," Dr. Laura Saward, the head of the company's therapeutics business unit, said in a news release. The trial had received funding from the federal government. Emergent was in the news this week after Johnson & Johnson JNJ, -0.92% confirmed that some of its COVID-19 vaccines manufactured at an Emergent plant did not meet "quality standards." Emergent is the U.S. manufacturing partner to J&J for its coronavirus vaccines. Shares of Emergent have gained 71.0% over the past year, while S&P 500 SPX, +1.18% is up 53.7%.

https://www.marketwatch.com/story/emergent-says-experimental-covid-19-treatment-failed-in-phase-3-trial-2021-04-02

Proteomics firm SomaLogic eyes $1.2B public valuation via SPAC

 SomaLogic is a unicorn among unicorns: Not only did the company, which builds AI-powered technology for protein analysis, wait to close its series A funding round until it had more than two decades of experience under its belt, but it has quickly followed up its $214 million fundraising late last year with new plans to go public.

“The weird thing about SomaLogic, of course, is that we had our series A at age 21, so that puts us at a slightly different category than most companies that are doing their series A as real startups,” CEO Roy Smythe told Fierce Medtech in an interview. “We had already been thinking about public transition plans, and it was really a combination of market dynamics and competitive dynamics that made us decide to speed up.”

In a deal valuing the not-quite-starting startup at $1.23 billion, SomaLogic will link up with CM Life Sciences II—a blank check company backed by Corvex Management and Casdin Capital that recently filed its own $240 million IPO in February for the sole purpose of pursuing an acquisition like this.

The decision to go public with the help of a special purpose acquisition company, or SPAC, rather than following the traditional IPO pathway, was an easy one, Smythe said.

“If you have the right SPAC partner, then you get more than just money—you get some expertise and help to grow the business beyond just the cash that you bring in,” he said.

“This just allows us to more quickly double down on a more comprehensive approach to proteomics, in both measurement and applications, in ways that might be hard for some of our competitors to recapitulate over the next period of time,” he continued. “It also allows us to bring more minds and assets to the table to help us build the business.”


The deal is projected to close in the third quarter of 2021, when CMLS II will take on the SomaLogic name and be listed on the Nasdaq as SLGC. SomaLogic’s existing management team will continue to oversee operations, but several more life sciences industry leaders will be added to the board of directors after the deal is complete, and Smythe said the company may add some of CMLS II’s directors to the board as well.

In the process, SomaLogic will receive up to $651 million in cash from CMLS II’s IPO earnings and common stock purchases from a handful of investors, bringing its total amount of cash available after various transaction-related expenses to $686 million.

But the influx of capital won’t change SomaLogic’s strategy in any way—“It’s just that we can actually do it now,” Smythe said. After the deal closes and public trading begins, the company will be able to direct more funding to R&D and the partnerships needed to further develop its technology and to significantly speed up that development.


SomaLogic creates proteomics assays that can measure thousands of human proteins at once, churning out data that can be used for drug development and other life sciences research. Those measurements are further analyzed by AI and machine learning algorithms alongside a database of more than 450,000 samples for diagnostic purposes.

Currently, available tests can determine cardiovascular risks, glucose tolerance, body fat percentage, resting energy rate and more, and a recent paper demonstrated the technology’s ability to monitor the long-term effects of COVID-19 on the heart.

https://www.fiercebiotech.com/medtech/proteomics-company-somalogic-to-go-public-through-reverse-merger-deal-1-2b-valuation

Breast cancer studies pinpoint potential new drug targets to fight resistance

 Several types of treatments are used against breast cancer, including chemotherapy, immunotherapy and drugs that target specific genes and proteins. But not all patients respond to them, so new options for reducing treatment resistance are in high demand.

Now, two research groups from Italy and the University of California, San Francisco (UCSF) have identified different mechanisms in breast cancer that they say could inspire the development of new drugs to improve response to existing treatments.

The Italian team, led by Francesco Nicassio from the Center for Genomic Science at the Italian Institute of Technology in Milan, focused on cancer stem cells, which can self-renew and give rise to new cancer cells. These stem cells are considered an attractive target in cancer research, not just because they promote tumor formation and progression, but also because they’re often resistant to traditional radiation therapy and chemotherapy.

Nicassio and colleagues hypothesized that short non-coding RNA molecules called microRNAs might assist cancer stem cells by regulating mRNA to control the types and amounts of proteins the cells make.

“We wanted to identify microRNAs required for the maintenance of normal mammary stem cells that are inherited by cancer stem cells and could represent potential therapeutic targets in breast cancer,” Nicassio explained in a statement.

The team pinpointed two related microRNAs, miR-146a and miR-146b, that are present in both breast cancer stem cells and normal adult stem cells. The two microRNAs were found to be elevated in aggressive breast cancers bearing a high number of cancer stem cells.

According to the study, published in the Journal of Cell Biology, the researchers showed that the two molecules are essential for maintaining cancer cell populations. Patient-derived cancer cells without these two miroRNAs showed a reduced ability to form new tumors when transplanted into mice.

Removing miR-146a/b made breast cancer stem cells over 20 times more sensitive to methotrexate, a chemotherapy that works by inhibiting cancer cells from replicating its DNA. The researchers suggested that mir-146a/b regulates processes that are key for cell metabolism and DNA replication.

“While the molecular details remain to be determined, our results clearly show that reducing miR-146a/b levels represents an attractive approach to overcome some forms of drug resistance in the clinical setting, unmasking a 'hidden vulnerability' exploitable for the development of anti-cancer stem cell therapies,” Nicassio said.


The UCSF team focused on the extracellular matrix surrounding triple-negative breast cancer cells (TNBC) for clues to fighting treatment resistance. They pointed to NF-kB, a transcription factor that regulates genes related to inflammation, as a possible target, according to a study published in the Journal of Experimental Medicine. Its activation has been linked to enhanced cancer cell proliferation and survival.

The UCSF team started by analyzing the extracellular matrix that surrounds TNBC cells that were taken from patients’ tumor samples. This matrix offers structural and nutritional support to the cells, with protein collagen its main component.

In untreated TNBC, the collagen proteins in the matrix were aligned in a way that made the matrix stiffer than it is in healthy breast tissue, the team found. But after chemotherapy, the collagen fibers in the surviving tumor became much softer.

“This raised the intriguing possibility that the softened, remodeled extracellular matrix might be causally linked to the pathogenesis of the treatment-resistant, residual tumor tissue,” team leader Valerie Weaver said in a statement.

Indeed, in both lab dishes and mice, tumors surrounded by a softer extracellular matrix were found to be more resistant to radiation and the widely used chemotherapy paclitaxel.

In that matrix, the activation of NF-kB counteracted another signaling protein called JNK, the team found. Cancer cells grown in a stiff matrix activated JNK, which made the cells prone to dying in response to stress.

The researchers treated mice with an NF-kB inhibitor and showed it could improve response when combined with radiotherapy. The team suggested that therapies that modulate NF-kB or JNK might be useful in improving treatment outcomes for TNBC patients.

https://www.fiercebiotech.com/research/breast-cancer-studies-pinpoint-potential-new-drug-targets-to-fight-resistance

Regeneron eyes longer Eylea dosing interval in diabetic retinopathy with NIH data

 When Regeneron snagged an FDA nod for eye drug Eylea in diabetic retinopathy in 2019, the agency opted against approving a 16-week dosing schedule despite positive data from a pivotal trial. Now, the drugmaker hopes a new study from the National Institutes of Health will change that.

In patients with non-proliferative diabetic retinopathy (DR), Eylea cut the risk of disease progression to vision-threatening complications—namely center-involved diabetic macular edema or proliferative diabetic retinopathy—by 68% compared with placebo after two years. The team published the results in the journal JAMA Ophthalmology.

The investigators tested Eylea at a dosing interval of every 16 weeks after an initial four doses given more frequently in the first four months.

At two years, 43.5% of placebo patients in the trial developed center-involved diabetic macular edema with vision loss or proliferative DR, compared with 16.3% for 16-week Eylea.

Currently, the anti-VEGF drug only carries an approval for a eight-week dosing regimen—even though the phase 3 Panorama trial used to win that FDA clearance included a 16-week arm. Now, the company said it will take findings from both trials to the FDA to discuss the 16-week dosing interval.

If eventually approved, the longer dosing interval could offer a convenience that further sets Eylea apart from Roche and Novartis’ rival VEGF inhibitor Lucentis, which is administered once a month for DR.


In the Panorama trial, Eylea given every 16 weeks following an initial dosing period cut the risk of proliferative DR or anterior segment neovascularization by 85% over control after one year of treatment, while the eight-week arm slashed that risk by 88%.

On the trial’s primary endpoint, 65% of patients on 16-week Eylea experienced at least a two-step improvement in a DR severity scale after one year, while 80% of patients on the eight-week dosing could say that. Only 15% of the control patients experienced such an improvement.

While all these data are displayed on Eylea’s label, the FDA only recommends the eight-week interval in the “dosage and administration” section.

Last year, Regeneron unveiled two-year data from Panorama showing Eylea reduced the likelihood of vision-threatening events by at least 75% over the period. About 50.4% of patients in the sham group developed a complication, versus 16.3% of those treated every 16 weeks with Eylea and 18.7% of patients who got Eylea every eight weeks.


Both Eylea and Lucentis have extended their dosing intervals before, but only in the bigger wet age-related macular degeneration (AMD) indication. Both are now allowed to go as long as 12 weeks between doses in that disease, although the FDA specifically said on their labels that the less frequent dosing is “not as effective” as their respective recommended dosing schedules. The FDA recommends Eylea every eight weeks and Lucentis once a month for AMD.

Regeneron and its ex-U.S. partner Bayer are trying to prolong Eylea’s intervals even further with a high-dose formulation of 8 mg versus the current 2 mg. Clinical trials are ongoing for high-dose Eylea in wet AMD and diabetic macular edema.

That could help the pair fend off looming competition from Roche, which is developing a VEGFxAng2 bispecific antibody called faricimab that just matched Eylea in wet AMD in two pivotal trials. That drug is administered up to every 16 weeks.

https://www.fiercepharma.com/marketing/regeneron-shoots-for-eylea-longer-dosing-interval-diabetic-retinopathy-nih-data