Biotech Investors: Mark Your Calendar For April PDUFA Dates

 A slew of drugs, including four new molecular entities, were approved in the month of March. NMEs are drugs that contain active moieties that have never been approved by the Food and Drug Administration previously and are indicators of innovation in drug research.

Among the notable approvals that came through in the month were Abecma, the first-ever cell therapy for a type of blood cancer; Fotivda, AVEO Pharmaceuticals, Inc.'s AVEO 1.5% oral, next-generation therapy for treating advanced renal cell carcinoma; and KemPharm, Inc.'s KMPH 3.26% Azstarys, a once-daily product for the treatment of attention deficit hyperactivity disorder in patients age six years and older.

PDUFA dates are binary events that invariably serve as make-or-break catalysts for stocks. These dates are deadlines by which the FDA reviews a new drug application before announcing its decision concerning the approvability/non-approvability of the drug.

Here are the key FDA approvals scheduled for April.

Acadia Hopes Against Hope to Get Label Expansion Psychosis Drug

• Company: ACADIA Pharmaceuticals Inc. ACAD 0.81%
• Type of Application: supplemental new drug application
• Candidate: pimavanserin
• Indication: dementia
• Date: April 3

Pimavanserin, which is marketed under the trade name Nuplazid, has already been approved by the FDA for the treatment of hallucinations associated with Parkinson's disease psychosis. This time around, the company is seeking to get label expansion to include dementia-related psychosis.

An FDA communication the company disclosed March 8, nearly a month ahead of the scheduled PDUFA action date, poured cold waters on the company's hopes of a positive regulatory action.

FDA said it identified deficiencies that prevent discussion of labeling and post-marketing requirements. The agency, however, said the notification does not reflect a final decision on the information under review.

"Given the lack of feedback from the FDA to Acadia's multiple inquiries since the March 3 notification, a complete response letter is now the most likely outcome for pimavanserin by its April 3 PDUFA date," Raymond James analyst Danielle Brill said following the development.

Can Second Time Be Charm For Supernus?

• Company: Supernus Pharmaceuticals, Inc. SUPN 2.06%
• Type of Application: NDA
• Candidate: SPN-812
• Indication: attention deficit hyperactivity disorder
• Date: early April

SPN-812, chemically viloxazine hydrochloride, is being evaluated for the treatment of ADHD in pediatric patients 6 to 17 years of age.

In early November, FDA issued a complete response letter for the original NDA, primarily citing issues related to the company's in-house laboratory that conducts analytical testing. The company said the lab had since then moved to a new location.

Subsequently, the company said in late February it received notice from the FDA that its resubmission for SPN-812 is considered a Class I resubmission.

Can Avenue's Pain Drug Soothe In Its Second Attempt At FDA's Clearance?

• Company: Avenue Therapeutics, Inc. ATXI 0.49%, a Fortress Biotech, Inc. FBIO 9.07% company
• Type of Application: NDA
• Candidate: intravenous tramadol
• Indication: moderate-to-severe pain
• Date: April 12

Intravenous tramadol is a potential alternative that could reduce the use of conventional opioids for treating acute pain. The FDA issued a CRL for the original application on Oct. 10, with the agency stating that IV tramadol, intended to treat patients in acute pain who require an opioid, is not safe for the intended patient population.

If a patient requires an analgesic between the first dose of IV tramadol and the onset of analgesia, a rescue analgesic would be needed, and the likely choice would be another opioid, the FDA had said. This, according to the agency, would result in opioid stacking and increase the likelihood of opioid-related adverse effects.

Following a Type A meeting with the FDA, the company resubmitted the NDA Feb. 12 and the agency subsequently deemed it as a complete response.

Sol-Gel Seeks Approval For Inflammatory Skin Disorder Treatment

• Company: Sol-Gel Technologies Ltd. SLGL 0.65%
• Type of Application: NDA
• Candidate: Epsolay
• Indication: April 26
• Date: inflammatory lesions of rosacea

Epsolay, chemically benzoyl peroxide, is a topical cream that is being evaluated as a treatment option for inflammatory lesions of rosacea. Papulopustular rosacea is a chronic and recurrent inflammatory skin disorder that affects nearly 5 million Americans.

Can Protalix Finally Get The Nod After 3-Month Delay?

• Company: Protalix BioTherapeutics, Inc. PLX 0.22%
• Type of Application: Biologic License Application
• Candidate: pegunigalsidase alfa
• Indication: Fabry Disease
• Date: April 27

The BLA submitted by Protalix, along with its development and commercialization partner Chiesi, was accepted for priority review in August 2020 and the PDUFA date was set for Jan. 27. With COVID-19 constraining FDA's ability to carry out facility inspections, the review period was extended by three months.

Fabry disease is a rare genetic disorder that prevents the body from making an enzyme called alpha-galactosidase A, which helps our body to break down a type of fat for use by our body. Currently, it's being treated with enzyme replacement therapy, which would mean replacement of the enzyme through intravenous infusion once every week.

Pegunigalsidase alfa is designed to be a plant cell culture-expressed, and a chemically modified version of, the recombinant alpha-Galactosidase-A protein.

Go or No-go For Ardelyx's Drug to Treat Elevated Blood Phosphate Levels?

• Company: Ardelyx, Inc. ARDX 3.63%
• Type of Application: NDA
• Candidate: tenapanor
• Indication: Hyperphosphatemia
• Date: April 29

Tenapanor is being evaluated for the control of phosphorus in the blood in adult patients with chronic kidney disease on dialysis. It's estimated to affect more than 745,000 dialysis patients in major developed countries.

Hyperphosphatemia is currently treated with phosphate binders, but without much success. Tenapanor is a non-binder therapy that targets the primary pathway of phosphorus absorption.

Pfizer Awaits Nod For Skin Inflammation Treatment

• Company: Pfizer Inc. PFE 0.06%
• Type of Application: NDA
• Candidate: abrocitinib
• Indication: moderate to severe atopic dermatitis
• Date: April

Abrocitinib, being evaluated in both 100mg and 200mg dose formulations, is an investigational oral once-daily Janus kinase 1 inhibitor, for the treatment of moderate to severe atopic dermatitis in patients 12 and older. Atopic dermatitis is a chronic skin disease characterized by inflammation of the skin. It's one of the most common, chronic, relapsing childhood dermatoses, affecting up to 10% of adults and up to 20% of children worldwide

"Abrocitinib has demonstrated strong efficacy at relieving the signs and symptoms of atopic dermatitis, including rapid reduction of itch, across multiple clinical trials. If abrocitinib is approved, it could make a meaningful difference in real-world clinical practice," said Jonathan Silverberg, a clinical dermatologist at the George Washington University School of Medicine and Health Sciences.

Adcom Calendar

FDA's Circulatory System Devices Panel of the Medical Devices Advisory Committee will meet April 6 to discuss TransMedics Group, Inc.'s TMDX 3.42% premarket approval application for the TransMedics Organ Care System Heart.

The heart system is a portable extracorporeal heart perfusion and monitoring system indicated for the resuscitation, preservation, and assessment of donor hearts in a near-physiologic, normothermic, and beating state intended for a potential transplant recipient.

https://www.benzinga.com/general/biotech/21/04/20405937/attention-biotech-investors-mark-your-calendar-for-april-pdufa-dates

CDC: Vaccinated people can resume travel at 'low risk'

 The U.S. Centers for Disease Control and Prevention on Friday said fully vaccinated people can safely travel at “low risk”, after the agency had held off for weeks on revising guidance that discouraged all non-essential trips.

The announcement lifting the agency’s guidance that all Americans should avoid non-essential travel should be a shot in the arm for a U.S. travel industry still struggling since the COVID-19 crisis began in early 2020. The new CDC guidance specifically greenlights vaccinated grandparents getting on airplanes to see grandchildren.

A group representing major U.S. airlines including American Airlines, Delta Air lines, United Airlines Southwest Airlines and other trade groups had urged the CDC on March 22 to immediately update its guidance to say “vaccinated individuals can travel safely.” Air travel still remains down 43% from pre-COVID levels and business and international travel remain even harder hit.

Roger Dow, CEO of the U.S. Travel Association, said the “new travel guidance is a major step in the right direction that is supported by the science and will take the brakes off the industry that has been hardest hit by the fallout of COVID by far.”

The new guidance also says fully vaccinated people do not need to get a COVID-19 test before or after travel and do not need to self-quarantine after travel.

“Vaccines can help us return to the things we love about life, so we encourage every American to get vaccinated as soon as they have the opportunity,” CDC director Rochelle Walensky said in a statement.

The CDC said grandparents who have been fully vaccinated can fly to visit grandkids without getting a COVID-19 test or self-quarantining as long as they follow CDC advice for traveling safely.

But the administration is not lifting restrictions that bar most-non U.S. citizens from the United States who have recently been in China, Brazil, South Africa and most of Europe. It is also keeping requirements that nearly all international U.S. air visitors getting a negative COVID-19 test before traveling to the United States.

A U.S. official briefed on the matter said the Biden administration is beginning to have conversations about how and when it might eventually lift those travel restrictions but no change is imminent. The U.S. also still maintains restrictions at the Canadian and Mexican borders that bar non-essential visitors.

The agency still “recommends delaying travel until you are fully vaccinated, because travel increases your chance of getting and spreading COVID-19.”

In a sign of some remaining concerns about travel, Walensky said that despite the change in guidance the CDC was still not recommending fully vaccinated people travel “at this time due to the rising number of cases”.

The CDC’s new guidance says fully vaccinated people do not need COVID-19 tests before international travel unless it is required by the international destination and vaccinated people returning from foreign travel do not need to self-quarantine after returning to the United States, unless required by state or local authorities.

The CDC had repeatedly declined in recent weeks to change the guidance and repeated it was still discouraging all non-essential travel because of a concern about new variants.

Many Americans have not been heeding the CDC’s advice. The Transportation Security Administration screened 1.56 million people at U.S. airports, just below Sunday’s 1.57 million, which was the highest daily total since March 2020. The last time the number of airport passengers screened was below 1 million was March 10.

The Biden administration has taken steps to reduce international travel and mandated masks in nearly all forms of public transit. The administration is not eliminating any mask rules.

https://www.reuters.com/article/us-health-coronavirus-usa-travel/u-s-cdc-vaccinated-people-can-resume-travel-at-low-risk-idUSKBN2BP142

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