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Friday, August 28, 2020

Viking Therapeutics’ VK2809 shows durable effect in mid-stage fatty liver study

Viking Therapeutics (NASDAQ:VKTX) announces new data from a 12-week Phase 2 clinical trial evaluating VK2809 in patients with nonalcoholic fatty liver disease (NAFLD) and elevated low-density lipoprotein cholesterol (LDL-C) (“bad” cholesterol). The results were virtually presented at the European Association for the Study of the Liver (EASL) Annual Meeting.

Treated patients experienced durable statistically significant reductions in liver fat content that were maintained at week 16, four weeks after the last dose of VK2809, a thyroid beta agonist.

Specifically, the median reduction in liver fat content was 45.4% at week 16, compared to a median reduction of 18.7% for placebo. 70.4% of treated patients were considered responders (at least a 30% relative reduction in liver fat content), versus 22.2% of patients in the control arm. 100% of patients receiving 5 mg of VK2809 each day were still considered responders at week 16.

New analyses of week 12 data showed significant reductions in the liver enzyme ALT, body mass index (at least 30) and high blood pressure compared to placebo.

The company previously announced results from the study in April 2019.

A Phase 2 trial, VOYAGE, assessing VK2809 in NASH patients with fibrosis is ongoing.

VK2809 has the same mechanism of action as Madrigal Pharmaceuticals’ (NASDAQ:MDGL) Phase 3-stage resmetirom (MGL-3196).


Thursday, August 27, 2020

Age more than occupational risk is key in allocating vaccines

In this age of coronavirus, with vaccine experimentation moving at historic pace to the clinical trials phase, the ideal inoculation policy would emphasize age more than work-exposure risk, according to a study involving Washington University in St. Louis economists.

There are numerous facets and factors to their modeling, including stay-at-home orders—with or without designating certain occupations as essential—that try to limit the possible spread of workplace infection.

For the most part, though, they found the key that unlocks the mystery to potentially optimal vaccine distribution is age: While all employed people age 60-plus would receive the vaccine, in many occupations people would receive the vaccine starting from age 50. In fact, the largest volume of vaccines would be allocated to populations ages 50-59, due to its group size, followed by 60-69.

As the researchers focused across the occupation spectrum and not merely age or exposure risks, they found that a 50-year-old food-processing worker would be equally prioritized as a 60-year-old financial advisor.

“We expected that age would be a driving factor in allocating vaccines,” said Ana Babus, assistant professor of economics in Arts & Sciences and co-author of “The Optimal Allocation of COVID-19 Vaccines.” “But we have also learned that it may be better to vaccinate, say, a 50-year-old bus driver instead of even a 30-year-old health-care worker, when vaccine doses are limited.”

Babus and SangMok Lee, assistant professor of economics at Washington University, joined Sanmay Das of George Mason University in estimating age-based and work-based infection risks, using age-based fatality rates estimated elsewhere. That’s how they emerged at the conclusion that age meant more than occupation.

Furthermore, they discovered that designating some occupations as essential doesn’t affect optimal vaccine allocation unless a stay-at-home order also is in effect.

COVID-19 won’t die with the first emergence of a vaccine, they learned.

Even if a limited vaccine were allocated optimally, their model showed that 1.37% of the employed workforce still would be expected to get infected until a vaccine becomes widely available. That means if, say, the United States used 60 million vaccines on only current members of the workforce, some 2.5 million workers ultimately would get infected. And these numbers are based on a vaccine that’s 50% effective.

A vaccine that’s 70% effective could cut that number of 2.5 million infected-workers only by 8%, to 2.3 million, they found.

“We easily agree to prioritize high-risk populations,” Lee said. “However, risk level isn’t one-dimensional—it’s exposure and mortality—and putting one person ahead of another by risk isn’t so obvious. The goal of our study is to find which risk dimension to emphasize more.”

While a recent history of vaccinating U.S. schoolchildren greatly decreased the transmission of flu, COVID-19 is a different animal. It kills older adults in far greater numbers, as well as the underrepresented. In this case, the study attempts to provide a best-practice scenario to supplement a vaccine distribution strategy with a targeted stay-at-home order preventing certain age-occupation groups from returning to their workplaces and spreading infection.

They tracked eight age-groups—16-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 and 80-plus—over 454 occupations, using data from the 2017 American Community Service and a sample thus representative of 60% of the U.S. population (now roughly 330 million).

They factored a worker’s contribution to output as measured by GDP, infection fatality rate and age. Using the United Kingdom’s Office for National Statistics data between March and May, they were able to infer the infection deaths for each occupation group. They related that to U.S. occupations, particularly considering physical proximity—lack of social distance at work—means higher infection risk.

They conducted three exercises plugging the data into their model. In essence:

  1. Everybody works, vaccine or no;
  2. Targeted stay-at-home with no work from home;
  3. Targeted stay-at-home with a mixture of work from home.

The stay-at-home orders in their experimentation lasted two months.

The results: In exercises Nos. 1 and 2, the 50-59 and then 60-69 age groups presented the largest volumes of vaccine allocation. In exercise No. 3, the largest age group was 30-39. In the latter sample, teachers taught online from home and more, younger health-care workers were able to get vaccinated.

Remove any stay-at-home order, the researchers determined, and all employed people age 60-plus could receive the vaccine.

If more occupations work from home, and workers 70-plus were mandated to stay at home, that would allow vaccines to be distributed to, say, nurses and food-preparation workers as young as 20-plus, the researchers found.

They realize that their model takes into account solely the possibility of infection exposure at work. If people face the same infection risk in their social and home life, their analysis tilts “even more toward the elderly,” they wrote.






More information: The Optimal Allocation of Covid-19 Vaccines. www.anababus.net/research/vac_dist.pdf


Employers Face Increase In COVID-19 Wrongful Death Lawsuits

As COVID-19 cases and deaths continue to rise, so too does the number of lawsuits filed against employers. Recently, an increasing number of families of employees who died from COVID-19 have asserted wrongful death actions against employers for failing to keep their family members safe while at work. What can employers learn from these lawsuits to not only keep their workers safe but avoid being on the receiving end of such a claim?

Throughout the country, employers are starting to be served with wrongful death lawsuits alleging an employee’s exposure to COVID-19 at work should lead to employer liability, despite the general rule that the workers’ compensation system is the exclusive remedy for such claims. The below matters are some examples of the types of claims that have been asserted against employers by families of deceased workers:

Lanzo v. Generations Behavioral Health

The plaintiff, the wife of a deceased employee working as a nurse at a mental health facility, alleges wrongful death under Ohio law. In support of her claim, the plaintiff alleges that the mental health facility failed or refused to follow COVID-19 directives issued by the state in order to reduce the spread of the virus. This, the complaint states, exposed her husband, Raymond Lanzo, to COVID-19.

The complaint does not claim the facility was wrong to operate during the pandemic, but that it failed to implement the policies and procedures that it should have in place to follow the state’s pandemic directives. The plaintiff further alleges that the company was “negligent” in its failure to provide “appropriate safety equipment.” Allegations in the complaint also include that the mental health facility’s conduct was “wanton and willful,” likely both to enhance damages and avoid any argument by Generations Behavioral Health that workers’ compensation bars the claims, as simple negligence claims against an employer are typically barred by the workers’ compensation laws. Nevertheless, the plaintiff is seeking more than $25,000 in damages, including medical bills and funeral expenses.

Norwood v. Rodi Marine LLC

This wrongful death lawsuit was filed by the wife of a deceased crew member against a vessel owner/Jones Act employer in the Eastern District of Louisiana. The plaintiff alleges that her husband, Michael Norwood, was a crew member aboard a supply vessel owned and operated by Rodi Marine. In March and April 2020, the vessel reportedly was located at the Austal Marine facility in Mobile, Alabama. During that time, the vessel’s captain reportedly was dispatched to New Orleans to perform services on behalf of Rodi Marine.

Following his return, he reportedly fell ill. Although somewhat unclear, it appears that the vessel captain sequestered himself in his quarters for two to three days until Rodi Marine was told of his illness. The company then removed the captain from the vessel for testing, which revealed that he had COVID-19. Norwood reportedly returned home when the captain was removed from the vessel and was isolated from contact with others except for his wife when he too fell ill. He reportedly succumbed to the virus despite medical treatment.

The lawsuit alleges that Rodi Marine negligently caused Norwood’s death for: (1) failing to provide Norwood with a safe workplace; (2) failing to implement policies and procedures to protect the crew from COVID-19; (3) failing to train vessel crew members regarding the actions necessary to prevent contracting and spreading COVID-19; (4) allowing the vessel captain to remain aboard the vessel while infected with COVID-19; and (5) permitting the vessel captain to travel to New Orleans when it was on “lock down” and known to be a COVID-19 hotspot. The plaintiff did not identify a specific sum of alleged damages.

Elijah v. Port Authority Trans-Hudson Corporation

The plaintiff, the wife of a deceased power rail mechanic for a rail carrier, filed this wrongful death lawsuit under New Jersey law. The plaintiff alleges that her husband was exposed to COVID-19 when he embraced a co-worker who later tested positive for COVID-19. The decedent was not wearing a mask because his employer allegedly “instructed its workers at safety meetings not to wear masks at work unless they were performing their specific job functions.”

Approximately 10 days after being exposed, the decedent began to experience symptoms of COVID-19, which progressively worsened. The complaint alleges that decedent was hospitalized, and over the next 20 days, experienced a “horrible and protracted death.”

The plaintiff alleges that the employer was negligent by: (1) failing to provide employees with a safe place to work; (2) failing to properly train employees about contracting COVID-19 at work; (3) failing to timely provide PPE to employees; (4) failing to conduct contact tracing; (5) failing to test employees for COVID-19; (6) failing to timely quarantine decedent and other employees who had been exposed to COVID-19; (7) failing to apply social distancing measures for employees; (8) failing to properly clean areas; (9) failing to warn employees of the dangers of contracting COVID-19 at work; (10) failing to medically treat the decedent; and (11) failing to follow its own safety rules, practices, and procedures. The plaintiff did not identify a specific sum of alleged damages.

Deciding which actions to take and when is no simple task in this constantly changing environment. However, the more effort an employer makes toward providing for the safety of its workers, the stronger the defenses will be.

How To Defend Against Such Lawsuits?

The question at the heart of many of these wrongful death lawsuits revolves around whether the employer took reasonable measures, based on then-existing guidance, to do its best to prevent the spread of COVID-19 in the workplace. Accordingly, the timing of any COVID-19-related precautionary safety measures, including policies and procedures, implemented in any given case will be critical evidence. Deciding which actions to take and when is no simple task in this constantly changing environment. However, the more effort an employer makes toward providing for the safety of its workers, the stronger the defenses will be.

Here are some “best practices” to keep in mind, both to help protect employees from illness and to help avoid potential litigation.

Follow the CDC’s Interim Guidance for Businesses, including best practices for social distancing, Guidelines for Cleaning and Disinfecting the workplace, and quarantining employees who have an exposure to a confirmed COVID-19 case, found at the CDC’s Public Health Recommendations for Community Exposure. Also, send employees who are symptomatic home until released by a medical professional or until they meet the guidelines for discontinuing self-isolation.

If you are an essential business employing critical infrastructure workers, the CDC has adopted different guidelines to follow, including allowing asymptomatic employees who have had a direct COVID-19 exposure to continue to work as long as certain guidelines are met.

Utilize OSHA’s most recent guidelines as a resource when creating return to work plans and policies. OSHA’s directives on implementing the identified guiding principles and FAQs may assist employers in safely reopening their businesses and workplaces. While the guidance is in the form of non-mandatory recommendations, OSHA has stated that an organization’s good faith efforts to comply with its recommended guidance will be taken into “strong consideration” when determining whether to cite violations and has indicated the General Duty Clause may be the basis for violations if employers do not engage in such good faith efforts. Such citations could also be evidence of an employer’s failure in a civil lawsuit.

Educate your employees and engage with them. Make sure employees know what measures you are taking to protect them. Be sure you stay aware of their health — while respecting their legal rights to privacy and confidentiality. Constantly remind employees of the symptoms of COVID-19 and urge them to seek medical attention if symptoms appear. Check in with isolated sick employees at least once a day to ask about their health. An employee with whom you engage will be less likely to seek litigation against their employer. If a COVID-19 death does occur, consider how you can assist the family, including assistance with funeral costs. Some workers’ compensation laws may also provide for funeral expenses if the illness was determined to be work-related.

The CDC recommends that employers notify potentially exposed co-workers of confirmed cases. Err on the side of transparency.

Inform employees of confirmed cases of COVID-19 in the workplace. The CDC recommends that employers notify potentially exposed co-workers of confirmed cases. Err on the side of transparency. Although no case law currently exists, we believe the Occupational Safety and Health Administration may ultimately determine that a failure to notify employees of a confirmed COVID-19 case is a violation of OSHA’s General Duty Clause. Employers should still maintain the privacy of the confirmed employee.

Stay on top of current and evolving guidelines. Recommendations from the Center for Disease Control (CDC), the Department of Labor (DOL), Occupational Safety and Health Administration (OSHA) and others, as well as state and local executive orders, continue to evolve, sometimes on a daily basis. Employers should assign individuals to keep up with changes and share them with management.

More Wrongful Death Lawsuits Are Likely On The Horizon

As noted above, it is anticipated employers will continue to be the target of these lawsuits, with family members potentially claiming that their loved ones were negligently or willfully exposed to COVID-19 due to inadequate safety policies and practices. You should take appropriate preventive steps not only to curtail litigation, but also provide viable defenses should such cases arise.


Thoughts On a New Coronavirus Test (And on Testing)

Word came yesterday that Abbott received an Emergency Use Authorization for a new coronavirus test, one that is faster and cheaper than anything currently out there. The two types of tests that we see in use now are RT-PCR, the nasal-swab test that detects viral RNA, and various antibody tests, that tell you if you have raised an immune response due to past exposure to the virus. This one has features of both, but its main use is more like the RT-PCR test: it will tell you if you are actively infected. It does that by detecting a particular antigen, the nucleocapsid protein (Np) of the coronavirus. It’s a key part of its structure, and in an actively replicating infection you can be sure that there will be plenty of that one floating around.

The test itself is one of Abbott’s “BinaxNOW” assays, and they have a whole line of these already as tests for malaria, RSV, various bacterial infections, and so on. It’s a lateral flow assay, which will be familiar to anyone who’s seen a pregnancy test, and I explained the general principles of those (as antibody tests) in this post. This new test is a sort of flipped version of what I described there, though. In this case, a nasal swab is taken, and several drops of solvent are used to put that sample onto the beginning of the absorbing strip inside the card. As it soaks up along the length of the strip, the sample will encounter a zone of antibodies that recognize the Np antigen, and these antibodies are also attached to nanoparticles of gold. This gold-antibody-Np complex is carried along in solution further along the strip until it runs into another antibody zone, one that’s immobilized on the solid support and which will bind the gold-antibody-Np complex molecules tightly. That stops them in their tracks and allows the gold nanoparticles to pile up enough to be visible as a pink or purple line. Along the way, the sample has also crossed a zone containing another soluble gold conjugate species as a control, which gets carried along until it runs into another separate zone of immobilized antibodies specific to it. The presence of a pink control line means that the test has been performed correctly; absence of such a control line means that the whole test has been messed up somehow and needs to be run again.

I had described earlier a test that looks for antibodies to the coronavirus by running them past gold-conjugated antigens on the test strip, but this one looks for antigens by running past gold-conjugated antibodies. Developing a test like this involves a lot of work to find the right antibodies, to make sure that they’re attached to the gold nanoparticles in ways that don’t impair their function, to find the right second immobilized set of antibodies that will develop that test line, and to make sure that the control line system is compatible with the test itself. You’ll also need to work on the composition of the test strip and the solvent that’ll be used to take the patient’s sample into it: these need to allow as much of the antibody complex to flow down the strip in a controlled fashion as you can get, and to do so in the same way every time. And finally, you need to validate the assay with a lot of coronavirus patients and controls, to see what your false positive and false negative rates are.

For this assay, those come out to a sensitivity of 97.1% (positive results detected when there should have been a positive) and a specificity of 98.5% (negative results when there should indeed have been a negative). Flipping those around, you’ll see that about 1.5 to 3% of the time, you will tell someone who’s infected that they’re not, or tell someone who’s not infected that they are. That’s about what you can expect for a test that sells for $5 and takes 15 minutes to read out with no special equipment, but such tests (if used properly) can be very valuable. Flipping that around, you can also infer that if used improperly, they can be sources of great confusion.

What’s proper? The FDA’s EUA is for testing people that show up with symptoms to see if they really do have SARS-CoV2. I think that’s appropriate, because you’re more likely to have a higher percentage of those folks who are really infected. If you tried to deploy this test across a large asymptomatic population with a very low true infection rate – everybody in New Zealand, for example – you would create turmoil. New Zealand’s real infection rate is vanishingly small, but Abbott’s quick $5 test would read out a false positive You Are Coronavirused for 1.5% of the whole country, never lower, which would be a completely misleading picture that would cause all sorts of needless trouble.

On the other hand, if you’re testing symptomatic people in a community where the virus is already known to be spreading, you can do a huge amount of good. Let’s imagine you test 1000 such coughing, worried patients under conditions where you expect that 10% of them really do have the coronavirus. In the course of testing all thousand, you’ll run those 100 positive folks through, and you’ll correctly tell 97 of them they they need to go isolate themselves immediately, which is a huge win for public health. Three of them, unfortunately, will be told that they’re negative and will go out and do what they do, but that’s surely far fewer than would be out and around without the test. You’ll also run the 900 other people through who actually have a cold or flu or something and not corona, and you’ll tell maybe 13 of them (900 x 0.015) that they’re positive for coronavirus and that they should isolate as well. That’s not great, either, but it’s worth it to get the 97 out of 100 real infectious coronavirus patients off the streets. And meanwhile you’ve correctly told the other 890 people in your original cohort that they do not have coronavirus, which is also a good outcome. But remember, with that 98.5% specificity you’re going to send 15 people out of every thousand you test home to quarantine even if no one really has it at all. If 1% of your sample of 1000 people is truly infected, you’ll probably catch all ten people who are really positive. . .but you’ll also tell 14 or 15 people who don’t have it that they do, crossing over to finding more false positives than there are real ones.

And let’s not forget the other really good aspects of this test: it’s cheaper than anything else out there but best of all, it’s fast. The delays in the RT-PCR testing have been killing its usefulness in too many cases – what good is knowing that you tested negative sometime last week, really? Far worse, what good is knowing that you tested positive last week if you didn’t isolate yourself because you weren’t sure if it was the coronavirus or not? But an answer in fifteen minutes, that’s actionable. As long as this test is deployed correctly, it can be very useful.

Addendum: I’m well aware that the CDC seems (controversially) to be changing its testing recommendations in general. This “only test if there are symptoms” guidance seems to apply to RT-PCR testing as well – and turnaround problems aside, that test still has far higher selectivity and specificity than this new 15-minute one and is far more appropriate for use in a broader, largely asymptomatic population. We need to be addressing the delay problems in RT-PCR, because we need to be doing a lot of those tests – not closing our eyes and whistling a happy tune instead. This appears to me, and to many others, to be political interference from above. What else is one to think when administration officials have suddenly started referring to the pandemic in the past tense? So here’s something I never pictured myself saying: it is my hope that this CDC guidance will be ignored. It’s a hell of a situation to get to, isn’t it? Update: I am very happy to report that the CDC appears this morning to be walking this one back. Good.


Veeva Systems gains after raising full-year outlook

Veeva Systems (NYSE:VEEV) shares are up 4% after hours following Q2 beats that included 33% Y/Y revenue growth. Subscription services sales totaled $283.5M (consensus: $276.8M). Professional services sales were $70.2M, above the $63.3M estimate.

Operating income was $144.4M, up 39%.

For Q3, Veeva forecasts $360-362M in revenue (consensus: $347.4M) and $0.66-0.68 EPS (consensus: $0.64) with operating income of $138-140M.

Veeva raises its full-year outlook to $1.415-1.42B in revenue (consensus: $1.39B; was: $1.38-1.395B), $2.642.67 EPS (consensus: $2.56; was: $2.50-2.55), and $540-545M in operating income.


Walmart files plans for standalone clinic in Florida

Walmart plans to open a 6,500-square-foot standalone clinic in Middleburg, Fla., according to the Jacksonville Record & Observer, which cited plans filed with the local water management district. 

The new clinic is part of the expansion Walmart Health announced July 22. The new health center will offer primary care, urgent care, labs, imagining, counseling, optical and hearing services, according to the report. A timeline for when the clinic will open has not been released. 

In addition to expanding into Florida, Walmart Health is also planning to open a few clinics in the Chicago market. The company already has freestanding health centers in Georgia and Arkansas. 


Judge warns Bayer’s $11B Roundup settlement at risk of collapse

Bayer (OTCPK:BAYRY -2.3%) slides after the judge overseeing consumer lawsuits involving its Roundup weedkiller says he has received several confidential letters from plaintiffs’ lawyers complaining that the company’s Monsanto unit is reneging on an $11B settlement plan for resolving 125K cases.

If Monsanto is “going back on its deal and the deal it announced in June, that seems to me something that should not be kept confidential,” U.S. District Judge Chabbria says, threatening to make the letters public.

Bayer reached a ~$10.5B settlement in June in tens of thousands of lawsuits with U.S. plaintiffs who have alleged the company’s Roundup herbicide causes cancer.