Search This Blog

Tuesday, March 31, 2020

Biotech Investors: Mark Your Calendar For These April PDUFA Dates

The FDA worked overtime through the coronavirus (COVID-19) crisis, framing new guidelines for approving SARS-CoV-2 diagnostic tests, reviewing tests and treatments.
Even amid its response to the emergency, the agency went about its business as usual. Bristol-Myers Squibb Co’s BMY 2.48% combo therapy was approved for advanced liver cancer.
Two new molecular entities – Novartis AG’s NVS 0.68% Isturisa oral tablets for adults with Cushing’s disease and Sanofi SA’s SNY 2.17% Sarclisa, in combination with omalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma – were approved during the month.
Here are the key PDUFA dates scheduled for April.
Acceleron, Bristol-Myers Squibb Seek Label Expansion For Anemia Drug
  • Company: Acceleron Pharma Inc XLRN 5.09% and Bristol-Myers Squibb Co BMY 2.48%
  • Type of Application: sBLA
  • Candidate: Luspatercept
  • Indication: myelodysplastic syndromes
  • Date: April 4
The sBLA for Luspatercept, sponsored by Acceleron and Celgene, which has since then been acquired by Bristol-Myers Squibb, was accepted for review by the FDA in June 2019, with the agency setting a PDUFA action date of April 4.
In early December, the companies said the FDA cancelled a review of the BLA by the Oncologic Drugs Advisory Committee, which was scheduled for Dec. 18.
Luspatercept, an erythroid maturation agent, has already been approved for treating anemia in patients with beta thalassemia, who require regular red blood cell transfusions.

Go Or No-Go For Urogen’s Kidney Cancer Drug?

  • Company: Urogen Pharma Ltd URGN 1.76%
  • Type of Application: NDA
  • Candidate: UGN-101 (mitomycin gel)
  • Indication: low-grade upper tract urothelial cancer, or LG UTUC
  • Date: April 18
The FDA accepted the NDA for review Dec. 19 and granted priority review status. UGN-101 already has Orphan Drug, Fast Track and Breakthrough Therapy designations.
“If approved, UGN-101 would be the first non-surgical treatment option for LG UTUC,” the company had said.

FDA To Rule On Sanofi’s Vaccine For Bacterial Form Of Meningitis

  • Company: Sanofi SA SNY 2.17%
  • Type of Application: BLA
  • Candidate: MenQuadfi
  • Indication: vaccine for meningococcal meningitis
  • Date: April 25

Neurocrine’s Parkinson’s Drug Under FDA Scanner

  • Company: Neurocrine Biosciences, Inc. NBIX 5.5%
  • Type of Application: NDA
  • Candidate: Opicapone
  • Indication: Parkinson’s disease
  • Date: April 26
Opicapone, a once-daily, oral, selective catechol-O-methyltransferase inhibitor is being evaluated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing OFF episodes. The FDA accepted the regulatory application in July.

Can United Therapeutics’ Drug-Device Combo For Hypertension Scale Regulatory Hurdle?

  • Company: United Therapeutics Corporation UTHR 2.31%
  • Type of Application: NDA
  • Candidate: Trevyent
  • Indication: pulmonary arterial hypertension
  • Date: April 27
Trevyent is a drug-device combination product that combines two-day, single use, disposable PatchPump technology with treprostinil, for the subcutaneous treatment of PAH.
The company, however, indicated in its Feb. earnings release it received a mid-cycle information request from the FDA, noting several deficiencies in the NDA. Although the company has given a written response, based on interactions with the FDA, it said the PDUFA date could be extended beyond April.

Pfizer’s Combo Therapy To Treat Colorectal Cancer Awaits Clearance

  • Company: Pfizer Inc. PFE
  • Type of Application: sNDA
  • Candidate: Braftovi in combination with Bristol-Myers’ Erbitux
  • Indication: metastatic colorectal cancer
  • Date: April (date not specified)
The Braftovi-Erbitux combo is being evaluated as a treatment option for patients with advanced BRAFV600E-mutant metastatic colorectal cancer, following one or two lines of therapy. The FDA accepted the sNDA for review on Dec. 18.
https://www.benzinga.com/general/biotech/20/03/15665215/attention-biotech-investors-mark-your-calendar-for-these-april-pdufa-dates

Group Testing Is Our Surefire Secret Weapon Against Coronavirus

Group testing all Americans every day is our surefire secret weapon to save potentially millions of lives and immediately restart the economy. Group testing is a super efficient way of finding out who’s infected and who’s not. Iceland’s doing it. Israel’s doing it. Even Nebraska’s doing it. The President needs to implement this policy immediately with the help of the military. It’s that simple.

We are doing the unimaginable to escape coronavirus, from shuttering stores and restaurants, to mandating quarantines, to stopping international travel. Now some states are demanding that out-of-state visitors quarantine for two weeks. And President Trump Saturday tweeted he was considering quarantining New Jersey, New York, and Connecticut, before backing off that idea. My wife and I took a drive today to Crane’s Beach, which is an hour north of Boston. We found the beach closed to all but locals. Soon the small towns will use their police to keep big city “foreigners” out. Then we might see different parts of cities seal themselves off. For example, Queens, Brooklyn, and the Bronx could close the bridges and tunnels from and to Manhattan.
If you woke up a year ago to today’s reality, you’d think you were somehow transported into a dystopian movie. Not yet Mad Max, but heading that way.
Fortunately, there is a foolproof way to defeat coronavirus. The president simply needs to make it happen. Here’s the secret weapon.
Group Test Every American Every Day.
As I’ve written and as Iceland is showing, testing every American every day and giving those who test negative a badge for the day to work, shop, frequent restaurants, etc. will let us separate those who are healthy from those that are sick and let those who are healthy go back to work, shop, reopen their businesses, and, most important, rehire the workers they have just fired. Equally important, it will give workers and employers the confidence they need that participating in the economy and reopening their business is fully safe.
I’ve received three sets of negative responses to this proposal.
The first: “Testing everyone every day is impossible. We can just test people who have symptoms and if they are positive, trace their contacts.”
This approach is fraught with problems. We’re not China, South Korea, Hong Kong, Taiwan, or Singapore. We don’t have an electronic record of where everyone was over the past two or so weeks, let alone with whom they interacted. And we can’t confiscate people’s cell phones and download their contact lists. Hence, contact tracing will be poor at best. Moreover, infected people may be asymptomatic. Hence, they’ll never get tested in the first place and have two weeks or more to spread the infection. To make matters even worse, the current PCR test produces a false negative between 14 percent and 30 percent of the time depending on which study you read. Hence, many infected people are being told they aren’t infected when they are. When this happens, they head off to spread the infection, which they will continue to do for days or weeks if they don’t land in a hospital with worse symptoms.
The second objection to daily universal testing is that it’s too costly. This can’t possibly be true compared to the cost of having so many people become terribly sick or die, not to mention destroying the economy.
The third concern with testing everyone every day is that there aren’t enough testing kits, labs, testing machines, reagents, etc. available. This is where the miracle of group testing comes in. It’s an old idea developed by a Harvard economist named Robert Dorfman during WWII. I’m old enough to have met Professor Dorfman when I was in grad school. But I never knew anything about group testing until yesterday, let alone that Dorfman was responsible for the idea.
Dorfman was tasked with figuring out how to efficiently test new recruits for syphilis. The test, a blood test, was expensive. Dorfman proposed drawing blood from a group of recruits, say 20, and mixing it together. Then you’d test the batch. If syphilis wasn’t found, it meant that one test had cleared 20 recruits. If the test came back positive, you could split the sample into 10 and 10 and run another test using extra blood retained from the original blood draw. If one of the two blood groupings tested negative, you’d know the problem was in the remaining 10 and split those 10 into two groups of 5. If both of the tests of 10 were positive, you’d move to four tests of 5 recruits. And so on.
The point is that if the share of recruits with syphilis was low, group testing could dramatically reduce the number of tests needed to separate the healthy from the sick. And it could still identify precisely who was sick.
What worked in WWII for syphilis can work today for coronavirus. This is the marvelous insight of three French economists — Christian Gollier, Jean-Luc Travernier, and Olivier Gossner — from the Toulouse School of Economics, the National Institute of Statistics and Economic Studies, and the Ecole Polytechnique, respectively. They sent me and other economists, including The Hoover Institute’s John Cochrane, their papers yesterday. John wrote about the group testing idea in his blog. But we academics are behind the curve. Governor Ricketts of Nebraska adopted group testing several days ago.
There is now a 15-minute coronavirus test. What we need to do is group-household test each day. The method is simple. A testing mobile, manned by military personnel, would come to your street early each morning. The members of your household and maybe another 9 (the best number is yet to be determined) would be invited to provide a swab sample. All the swabs of all the households would be collectively used to test if any of the swabs was positive. Fifteen minutes later your group of households would either be cleared to go to work and frequent stores, restaurants, and other establishments for the day or not. If you’re cleared, you’d get a green bracelet that would automatically change to red after 24 hours. Those with green bracelets would be returned to normal society. If your group of households tested positive, subgroup testing would be done, on the spot, until it was discovered which of your group’s 10 households was infected and which weren’t. Those households that were infected (had one or more infected members) would need to go into quarantine.
The military is the only group that can conduct this critical mission across the country efficiently and effectively in the time required. The military personnel doing the testing would be extensively trained, have protective gear, and follow a protocol would be established to limit, to the maximum extent possible, uninfected people becoming infected in the course of the testing. The public fully trusts our women and men in uniform and will comply with their instructions.
Yes, the testing won’t be perfect. But by limiting the number of tests, we can better ensure that the people doing the testing are the best qualified and that the testing is done at the highest level. And yes, some infected people will spend the day at work, in restaurants, in shops, etc. But workplaces, shops, and restaurants would take temperatures before letting people enter, continually disinfect surfaces, and implement the best social-distancing practices.
Initially, the best we may be able to do is test every household once a week. But over time, we can get to daily testing. And, as the tests improve, we’ll reach the point that less frequent testing is needed.
This can all be started very rapidly, maybe in time for Easter — the president’s proposed date to restart the economy!
PS, Here’s an email from an Atlanta doc that I received after writing the above.
I agree 100% with all you say about coronavirus and agree with Paul Romer. Please be as vocal as possible about mass screening of the population. And start today. Any positives we remove today will impact the level of disease we see in 3-4 weeks.
STOP testing sick people at the end. The treatment is not different.
START screening the population. Remove the fuel and the fire will go out. I am a doctor and waiting for this to crest in Atlanta. We could have a huge impact on the crest if we started screening the population now and isolated positives. Instead they test sick people after the fact. I don’t want to see all of these patients and healthcare workers die.
Israel is now using pooled testing of 60 samples to screen. If the pool is negative all are negative. We do this to screen our blood supply. Handsomely pay a biotech firm to work on this strategy. But with pools of 60, you can screen a lot faster than 1 by 1.
https://www.forbes.com/sites/kotlikoff/2020/03/29/group-testing-is-our-secret-weapon-against-coronavirus/#3c73462c36a6

Reusing N95 Masks Against COVID-19 Coronavirus? The Risks And Options

This is not like the time that you miscalculated your underwear count when traveling and tried to make a single pair of underwear go for as long as possible. With the COVID-19 coronavirus pandemic, many healthcare professionals are faced with the horrible reality that they don’t have access to enough N95 face masks to properly protect themselves and have to reuse N95 masks way beyond guidelines. The associated risks of reusing N95 masks don’t just apply to health care professionals but to practically everyone out there wearing such masks.
There are reasons why some items are designed as “single-use” or “limited use.” For example, would you consider re-using the same sheets of standard toilet paper through multiple trips to the toilet? Of course, disposable N95 masks are not exactly the same as toilet paper. Using a N95 mask more than once may still fall within the manufacturer’s guidelines for that given mask. And while not using toilet paper according to guidelines poses risks to your butt, not following guidelines for N95 respirators could put more than your butt on the line. With the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreading, straying from guidelines could put the butts of everyone whom you contact on the line, which is a lot of people if you are a health care professional. Note that in this case, butt is the proverbial butt and not the actual butt. If you are wearing an N95 respirator on that end of the body, you are doing it wrong and should absolutely throw the mask away immediately.
The question of mask reuse during a pandemic was already extensively addressed over a baker’s dozen years ago. Consider what a National Academies of Science Engineering and Medicine Report from 2006 entitled Reusability of Facemasks During an Influenza Pandemic: Facing the Flu offered as one conclusion: “The committee could not identify or find any simple modifications to the manufacturing process that would permit disposable N95 respirators to be reused without increasing the likelihood of infection.”
When it comes to N95 masks, what you don’t see can help or hurt you. As I described on Saturday for Forbes, the mask doesn’t just consist of layers of relatively simple materials like paper towels or commonly used fabric. Like many introverts, the mask is more complex than it may seem. It typically consists of polypropylene fibers woven in ways to create tortuous paths challenging for small particles to travel through without getting stuck. The fibers also have electrostatic charges that further help the particles stick to the fibers. You can’t see all of these things when the mask is filtering air before it reaches your nose and mouth. You also can’t see how these features degrade over use and time. Bending the mask, getting the mask wet from your hot, hot breath, and having different things land on the mask like air pollutants, moisture, or a musk rat can hasten the degradation of the mask.
Moreover, you can’t see all of the viruses that may accumulate in the mask during use, because they are teeny-weeny. The N95 mask is a filter and not Captain America’s shield or Iron Man’s face plate. Viruses don’t just bounce off of the mask but instead get trapped inside it. That’s why you’ve got to be super careful when handling a mask that has been used. If the outside of the mask ends up touching your face while you are removing the mask, you will actually be rubbing on your face something that collects and concentrates viruses from the air.
Wondering why you can’t just find some way of cleaning the disposable N95 mask? Well, as you probably know or at least should know, washing used disposable toilet paper doesn’t quite work. If you use soap and water, the toilet tissue can readily disintegrate. If you use milder cleaning methods like just spraying some hand sanitzer on it or yelling at it, well, do you really want to use it again? Again, N95 masks and TP are not exactly the same. However, some of the issues with the tissues can translate somewhat to disposable N95 masks. Here was another finding from the NASEM report: “Any method of decontaminating a disposable N95 filtering facepiece respirator must remove the viral threat, be harmless to the user, and not compromise the integrity of the various elements of the respirator. The committee found no method of decontamination that met all three criteria.”
So, got it? In “normal” pandemic situations, science says that you should not be reusing N95 masks. But. But. The current pandemic isn’t even a “normal” pandemic situation. Yes, despite the NASEM report from over 13 years ago, despite warnings that N95 mask shortages may be a problem, did hospitals and health care systems really prepare to appropriate levels? Did they maintain adequate stockpiles to account for the additional demand that would occur with an epidemic? Did they have systems in place to make sure that their health care professionals would be protected according to what science has been saying? The current situation makes you wonder.
Well, the NASEM report did also provide recommendations on what to do if N95 mask shortages were to lead to situations where such mask reuse would be necessary. Of course, the committee may have been thinking that this could occur somewhere later during a pandemic rather than near the beginning.
For example, take a look at the letter accompanying the following tweet from when COVID-19 cases were just starting to really rise in New York City:
Saman Nematollahi @TxID_Edu
🚨🚨
This is a very scary message from @Columbia
They will run out of ICU beds and PPE soon @Atul_Gawande @EricTopol @CMichaelGibson @drsanjaygupta @CNN @mlipsitch @MackayIM @CarlosdelRio7 @kevinmd @NIHDirector
View image on Twitter
Just one N95 mask for each employee is not exactly in line with the NASEM report guidance.
The first NASEM report recommendation for reuse was to “protect the respirator from external surface contamination when there is a high risk of exposure to influenza (i.e., by placing a medical mask or cleanable faceshield over the respirator so as to prevent surface contamination but not compromise the device’s fit).” Even though the SARS-CoV2 is not the same as the flu virus, repeat is not the same as the flu virus, in this case, you may be able to replace “influenza” with “SARS-CoV2.” This is where do-it-yourselfers (DIY) who don’t have the materials and technical capabilities to replicate N95 masks may be best able to help. If they can create something that can shield or protect the N95 respirator without suffocating the user, which incidentally would be a bad thing, then this could potentially extend the effective lifetime of the respirator. Note the emphasis on the word potentially.
The second NASEM report recommendation was to “use and store the respirator in such a way that the physical integrity and efficacy of the respirator will not be compromised.” This certainly means no head butting, planned or unintentional, while wearing the respirators. But even more subtle pressure to the mask could end up deforming it somewhat. Also, the mask is not a condom or a diaphragm. You shouldn’t keep it in your pocket, wallet, purse, handbag, or fanny pack. Instead, the Centers for Disease Control and Prevention (CDC) website suggests that you “hang used respirators in a designated storage area or keep them in a clean, breathable container such as a paper bag between uses.” Also, store respirators as you would make bed arrangements for an overnight school class trip. Don’t have respirators pushed against each other: “To minimize potential cross-contamination, store respirators so that they do not touch each other and the person using the respirator is clearly identified. Storage containers should be disposed of or cleaned regularly.
“Can’t touch this” applies to everything. Minimize touching the respirator with anything that may in any way deform, contaminate, or be contaminated by the mask. The third NASEM report recommendation was to “practice appropriate hand hygiene before and after removal of the respirator and, if necessary and possible, appropriately disinfect the object used to shield it.” The CDC website recommends that you “use a pair of clean (non-sterile) gloves when donning a used N95 respirator and performing a user seal check. Discard gloves after the N95 respirator is donned and any adjustments are made to ensure the respirator is sitting comfortably on your face with a good seal.”
While there is no established method of cleaning these disposable N95 masks, some have looked at different approaches. A study published in a 2009 issue of the Annals of Occupational Hygiene evaluated five possible decontamination methods: ultraviolet germicidal irradiation (UVGI), ethylene oxide, vaporized hydrogen peroxide (VHP), microwave oven irradiation, and bleach. Two of the approaches didn’t work very well. For example, microwave oven irradiation caused the samples to melt. By the way, a N95 mask is not like cheese. Melting it doesn’t make it better. The most promising options were UVGI, ethylene oxide (EtO), and VHP, but the evidence at the time was far from conclusive.
These three approaches have since gotten more attention. For example, the ABSA International website has a link to the preprint of a manuscript has been accepted to Applied Biosafety, the association’s journal. In this case, ABSA stands for the Association for Biosafety and Biosecurity‎ and not for the Association of Bulgarian Schools in America. The manuscript described how a team from Duke University put a cohort of N95 respirators through VHP treatment and subsequently conducted testing. The testing suggested that the masks were adequately decontaminated and retained their structural integrity and function. The manuscript also cited a 2016 study for the U.S. Food and Drug Administration (FDA) that had similar conclusions.
The findings from these studies are encouraging in what’s currently a desperate situation. However, it does not mean that getting new N95 masks shouldn’t still be a priority. N95 masks aren’t cars, where used ones may replace new ones. So many things could happen during the wearing of mask that could limit what such a decontamination procedure can do. For example, what if the mask gets splashed by liquids such as blood or other body fluids? What if the mask gets bent in any way? What if the load of microbes in the mask is so high that decontamination is tougher?
If you’ve been wearing your N95 mask for more than the manufacturer’s guidelines (or more than five times if there is no specific guidance for that mask), your mask may not really be that effective anymore. In fact, it may have become more like a sponge for microbes. The more you reuse your mask, the greater the risk. Not just for you but also for all those who come into contact with you.
Might telling people that they can reuse their N95 masks well beyond normal guidelines be a bit like telling people that they can go to a lengthy battle wearing nothing but one pair of underwear? It could them a false sense of re-assurance while leaving them very much exposed.
The only real solution to the shortage is to fix the shortage as soon as possible. Manufacturers must make many, many, many more legitimate and National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as quickly as possible. Hospitals and health care systems need to purchase them and provide them to health care professionals without any delay. Time spent negotiating or pretending that other approaches are adequate means more and more potential deaths that could have been averted. It is a sad statement that the wealthiest country in the world can’t even provide basic pandemic protection to health care professionals, the most important people in the fight against the pandemic.
https://www.forbes.com/sites/brucelee/2020/03/30/reusing-n95-masks-against-covid-19-coronavirus-the-risks-and-options/#4a77b87cdf7e

A Day In The Coronavirus-Driven Feeding Frenzy Of N95 Mask Sellers And Buyers

You never know what a new day will bring. What started as an early morning call with a friend to help get N95 masks to hospitals in desperate need turned into a roller coaster of contacts in a frenzied, pandemic-driven market. For the next 10 hours, I sat in on calls between brokers selling masks and potential buyers, watching the psychology of market pressures play out in real time as millions of masks changed hands in a matter of hours.
The buyers—from state government purchasing departments and hospital systems representing facilities throughout the Northeast, Midwest and California—expressed desperation for masks to protect their healthcare workers, but in the end not a single deal was completed with any of these groups, and millions of masks were earmarked to leave the country, purchased by foreign buyers.
In the interest of brevity, I’m going to summarize what I learned below and then jump into a bit more detail. 
  • Millions of N95 masks have been available throughout the U.S., Canada and the UK during the pandemic, according to brokers trying to sell them.
  • The high price point per mask, driven by extreme demand, has contributed to an overwhelmed reaction among potential buyers, especially in the U.S.
  • Scrutiny surrounding these deals is high because of ongoing scams and claims of price-gouging, both of which are triggering emotionally charged reactions and fear of making deals.
  • Millions of masks are being purchased by foreign buyers and are leaving the country, according to the brokers, while the domestic need remains alarmingly high.
My main contact in this frenzy was a medical supplies broker named Remington Schmidt who spends nearly every working hour of the day on phone calls trying to make deals between potential buyers and sellers with personal protective equipment (PPE) available to sell in the U.S. and abroad.
“This is the craziest market I’ve ever seen,” he told me between calls while scanning through a stream of text messages from sellers and other brokers.
Like most brokers in this market, Remington represented other products before the COVID-19 outbreak and jumped into action to sell masks when the need arose. Just a couple of weeks ago he was selling hazmat suits.
When contacting potential buyers, Remington needs two things to secure a deal with a seller: a letter of intent to purchase and proof of funds.
“If you are working with a seller who has masks but you can’t quickly show proof of funds, someone else is going to buy them,” he told me.
And I watched that happen repeatedly throughout the day. Buyers from state procurement departments and hospital systems expressed desperate need for masks, but the deals bogged down when it came to providing proof that they could commit and follow through. In the meantime, another buyer provided proof of funds and the masks were gone, sometimes within the hour.
The masks in play are those we’ve been hearing about in every press conference since the pandemic began: N95 3M brand masks, mainly in model types 1860 and 8210, which, according to 3M, are “NIOSH (National Institute of Occupational Safety and Health) approved for at least 95% filtration efficiency against certain non-oil based particles.” Some buyers are also looking for alcohol-based sanitizer sprays, hospital gowns and a few other items, but mostly the demand is for N95 masks. And the demand is only getting more intense as hospitals rapidly run low on the supplies they have due to increased need for masks to protect staff as numbers of COVID-19 infections, and suspected infections, increase each day.
Remington explained that his business is all about networks. “It’s a contact to contact to contact market.” Through his network of contacts, he finds a seller with masks in a warehouse—several million masks in each lot—and attempts to link the product with buyers in need.
I felt like I was getting whiplash throughout the day by the insane pace of negotiations and how often the price point changed as the market frenzy continued. Prices ranged from anywhere between $6 – $7 per mask depending on volume and location. The same masks were selling for closer to $4 just a week before.
Remington received text updates from his network about ever-changing quantities of masks in Houston, New Jersey, Miami, Los Angeles and other U.S. cities, along with cities in Canada and the UK. I was astounded by the numbers of masks at these locations. At one point he received an update that 43 million masks were available in New Jersey, in the same time-frame that federal and state leaders were saying in press conferences that they were “scouring the globe” for masks. But the masks in New Jersey, along with many million more, didn’t go to any domestic buyer. Instead, according to the broker, they were all purchased by foreign buyers.
“Most of the masks are leaving the country,” he told me.
That is not the case in countries that have cracked down on exports, he added, but as of now the U.S. is allowing many types of medical supplies to leave the country even as states and hospital systems are expressing desperate need for masks and other PPE.
While he is aware of brokers selling masks that will leave the country, Remington doesn’t participate in those deals. “This is a national crisis and we need these masks in the country,” he said.
Scrutiny in the market is sky high. People are understandably concerned about being taken in scams. The insanity of this market has created opportunities for fraudsters claiming to sell everything from masks to hospital gowns to ventilators, and every potential buyer is on guard to avoid being the next victim. More than once, a representative from a potential buyer also noted concerns about price gouging.
“Some people don’t understand that the market sets the price,” Remington said.
I read through a list of mask lots sent to him from U.S. sellers along with their expected price points and, at that time, none were under $6 per mask. This is clearly a seller’s market and price is driven by demand.
Added to this, potential buyers trying to secure PPE for their medical personnel are often not empowered to make fast, high-dollar deals, no matter how desperately they’d like to close a deal and get masks to those in need. I listened to the range of emotions playing out in negotiations and it seemed to me that the domestic procurement process is simply unprepared to operate in this frenzied market. Individuals want to do the right thing, but the systems in which they operate are hamstrung by rules that weren’t created to approve enormous transactions in hours or less.
By the end of the day, roughly 280 million masks from warehouses around the U.S. had been purchased by foreign buyers and were earmarked to leave the country, according to the broker — and that was in one day.
To his knowledge none of the masks had been purchased by buyers in the U.S.
Remington told me that his focus now is to try to sell masks to federal agencies like FEMA responsible for securing PPE so the items can go directly to the states that will distribute to hospitals, but it’s been extremely challenging to close a deal and the number of “middle men” in the negotiations keeps rising.
“Many people are marking up the prices in the middle,” he said. “People are just trying to make as much money as possible.”
https://www.forbes.com/sites/daviddisalvo/2020/03/30/i-spent-a-day-in-the-coronavirus-driven-feeding-frenzy-of-n95-mask-sellers-and-buyers-and-this-is-what-i-learned/#7699276b56d4

States Begin To Move COVID-19 Patients From Hospitals To Nursing Facilities

Last week, I suggested that in the wake of the coronavirus pandemic, nursing homes may need to take patients from over-burdened hospitals. At the same time, care settings such as assisted living facilities (ALFs) might have to accept nursing home residents who must be relocated to make room for those post-acute patients. Now, it looks like that is beginning to happen.
Massachusetts has designated 12 nursing facilities to take COVID-19 patients, and the state is beginning to move nursing home residents, starting with 147 in a Worchester facility. And the American Health Care Association, a trade group representing much of the nursing home industry, agrees with these changes, as long as they are managed carefully.
New York is doing this in a very different way. In an effort to free-up desperately-needed hospital beds, it has ordered all nursing facilities to accept hospital discharges, even those who have tested positive for COVID-19.
The crucial difference
The crucial difference: Massachusetts is organizing a system where only designated facilities take coronavirus patients discharged from hospitals. New York wants all nursing facilities to take these patients. The issue:  How to make this work while still protecting extremely vulnerable residents and patients at nursing facilities who do not have coronavirus. These transfers should not happen if they put current residents at risk.
The idea of using certain nursing facilities to offload some of the hospital burden was not mine alone. David Grabowksi, a professor of health policy at the Harvard University Medical School, made an even more detailed proposal in a March 25 column in JAMA (paywall). And Anne Tumlinson of the consulting firm ATI Advisory has made similar suggestions.
Equipment and skilled staff
The first priority should be to identify those facilities that already have ventilators, the staff skilled at managing them, and strong infection controls. It is essential to protect current residents, who are at extremely high risk form COVID-19. Remember, a typical nursing home may include both a skilled nursing facility (SNFs) that provides post-acute services such as rehabilitation and a unit for long-stay residents with severe functional of cognitive limitations.
In some cases, these units may be separate enough. But using SNFs to care for COVID-19 patients may require the facilities to move long-stay residents, many of whom have dementia or functional limitations, to other facilities. Some may go to other nursing homes, others to assisted living, and some back home.
Freeing up beds
What about post-acute patients, who may be in skilled nursing facilities (SNFs) for a few days to a few weeks. They must also be moved out before COVID-19 patients are allowed in. For them, those SNFs not designed for COVID-19 may be a good alternative.
Because so many hospitals have stopped doing elective surgeries, especially knee and hip replacements, the demand for that common SNF rehab has fallen off sharply. That may free-up more beds for non-COVID hospital discharges.
As I noted when I first raised the idea, even in the best of circumstances these moves will be incredibly disruptive to residents, their families, staffs, and the facilities themselves. But in a pandemic where hospital beds may be insufficient to handle the need, designated skilled nursing facilities are a smart alternative.
Issues to be resolved
But a number of complicated issues still have to be resolved.
How should the system handle someone who is suspected of having coronavirus but has not tested positive? Where should they stay? There is no room in hospitals. And nursing homes without intensive infection control are inappropriate. Until we have enough test kits and technology to read those tests within hours rather than days, this will remain a critical problem.
Then, there is staff. If aides, nurses, and techs are going to be required to treat sicker patients with more complex conditions, they need to be trained. And if they are going to be asked to care for COVID-19 patients, they absolutely must have essential personal protective equipment, such as masks, gowns, and gloves. Without the training and the equipment, this idea is a non-starter.
Finally, there is the matter of payment. Many long-stay nursing home residents are in those facilities only because it is where Medicaid will pay for their care. The current crisis is an ideal opportunity to change that. States should expand their home and community based programs for frail older adults and younger people with disabilities. They should pay enough for settings other than nursing homes so these vulnerable people can get the care they need in the safest and most appropriate place possible.
The system can make this shift work, but only if hospitals, nursing homes, assisted living facilities, home care agencies, states, and the federal government work together. And they don’t have much time.
https://www.forbes.com/sites/howardgleckman/2020/03/31/states-are-beginning-to-move-covid-19-patients-from-hospitals-to-nursing-facilities/#6afbfe834401

Vaccine From The 1920s Is Now Being Tested For Use Against Coronavirus

Researchers in a handful of countries are testing a century-old tuberculosis vaccine to see if it can give a boost to the immune system to help it fight off the novel coronavirus now causing the COVID-19 pandemic.
Clinical trials of the Bacille Calmette-Guerin (BCG) vaccine, which was first developed in the early 1920s, are planned in Europe and Australia to see if it can help reduce the prevalence and severity of COVID-19 symptoms.
Researchers from the Murdoch Children’s Research Institute (MCRI) in Melbourne are currently working to enroll 4,000 healthcare workers from hospitals around Australia in one study.
“This trial will allow the vaccine’s effectiveness against COVID-19 symptoms to be properly tested, and may help save the lives of our heroic frontline healthcare workers,” MCRI Director Professor Kathryn North said in a release.
A separate large-scale study is planned to include older patients and health care workers at several hospitals in Germany and similar trials are in the works in the Netherlands, the UK and Greece.
This work is very different from the efforts underway to develop a vaccine to confer specific immunity to the novel coronavirus, SARS-CoV2. BCG has a spotty track record giving immunity against even the disease it was developed for, tuberculosis. But as one of few tools available to fight that disease, it has stuck around for decades and a number of studies have shown that it seems to offer other benefits.
“There has been a long history of reports of BCG producing a series of beneficial immune responses,” Gonzalo H. Otazu from New York Institute of Technology’s Department of Biomedical Sciences told me. “For instance, a study in Guinea-Bissau found that children vaccinated with BCG were observed to have a 50 percent reduction in overall mortality, which was attributed to the vaccine’s effect on reducing respiratory infections and sepsis.”
A WHO review in 2014 gave the findings that BCG may reduce overall mortality a very low confidence rating, however. Other reviews have been more favorable.
Still, researchers hope that BCG could be a bridge that suppresses the overall impact of the coronavirus pandemic until a new, targeted vaccine is ready.
Scientists at the Max Planck Institute for Infection Biology developed the vaccine candidate VPM1002 based off of BCG earlier this century, which will be used for the trial starting soon in Germany. VPM1002 has been shown to protect the respiratory tracts of mice from viral infections.
“In addition, VPM1002 can be manufactured using state-of-the-art manufacturing methods which would make millions of doses available in a very short time”, says Adar C. Poonawalla, CEO and Executive Director, Serum Institute of India in a statement.
Otazu has been working with researchers to look at possible correlations between national BCG vaccination policies and the impact of COVID-19 on a country’s population.
“We found that there was a reduction in the number of deaths attributed to COVID-19 per million inhabitants in countries that have universal BCG vaccination (usually at birth) compared to the countries that never established such policy,” he said. “The earlier the establishment of such policy, the stronger the reduction in mortality, consistent with a protection to the elderly population which is more severely affected by COVID-19.”
Italy and the United States, two of the countries hit hardest by the pandemic, do not have universal BCG vaccination policies.
Otazu and his colleagues have produced a paper outlining their findings that is awaiting peer review. He stresses that “although correlations are strong, our study is correlational and does not demonstrate the effectiveness of BCG against COVID-19.”
BCG, if it works at all, may not be able to help everyone touched by COVID-19. It is not recommended for people with compromised immune systems or pregnant women.
We should know more about how helpful it may be for the rest of us in just a few months.
https://www.forbes.com/sites/ericmack/2020/03/31/a-vaccine-from-the-1920s-could-help-fight-the-coronavirus-pandemic/#654509dd1220

The scramble to reinvent the ventilator

As Smiths Group delays its split partly so it can focus on ventilator production, the US FDA grants emergency authorisation to other breathing devices to treat Covid-19.
The lack of mechanical ventilators to treat Covid-19 patients is a pressing problem across the world. A wide variety of efforts are being made by medtechs and non-medtech companies, regulators and academic researchers to accelerate production of approved devices, repurpose other breathing systems for emergency use, and to build new ventilators from scratch.
The engineering conglomerate Smiths Group today said it would delay the separation of its medtech unit, which had been scheduled for mid-year, partly so it can focus on the delivery of ventilators and other critical care devices. The company is part of the VentilatorChallengeUK alliance, from which the UK government has ordered 10,000 units.
The VentilatorChallengeUK consortium also includes Airbus, BAE Systems, Ford, Rolls-Royce, McLaren and Siemens, and is working to source and assemble parts for two ventilator designs, one of which is from Smiths Group. This device, made in the UK, is a portable ventilator usually used in ambulances and not typically used for long-term intensive care.
This consortium is only one of many deals in which engineering groups outside the medtech sector are retooling facilities to build breathing equipment. The US diversified company General Electric is working with Ford, which is to manufacture a simplified GE ventilator with the aim of producing 50,000 units by early July. Separately GE said it was adding manufacturing lines to its own ventilator production sites and increasing the number of shifts so the devices can be produced around the clock.
Even so, workers at GE’s aviation factory in Lynn, Massachusetts staged a protest yesterday, demanding that the company reconfigure its aircraft manufacturing facilities to make ventilators there, too.
Other groups including Mercedes and Dyson are also developing their own breathing devices more or less from scratch, in collaboration with various academic groups. And Medtronic has made the design schematics of one of its ventilators available for free, to allow other manufacturers to build and release the device.
Emergency
Even so, other initiatives will be necessary. Aware that US demand for ventilators will explode within days, the FDA is allowing breathing devices and their accessories not normally used in hospital contexts to be deployed in the fight against Covid-19.
Last week the agency issued an emergency use authorisation – a temporary permission that exists as long as America is in a state of emergency – for devices including anaesthesia gas machines and positive pressure breathing devices that have been modified for use as ventilators.
The devices that are eligible for inclusion under this EUA are those that are not currently marketed in the US, or that are currently marketed but have been subject to an alteration that would usually need a new 510(k) clearance application.
So far EUAs have been granted to ventilators made by two Chinese companies, Beijing Aeonmed and Mindray, and by the US group Vyaire Medical.
But many other companies could benefit. The table below summarises the companies with the most US approvals, from 2014 to date, of the kinds of respiratory devices now eligible for emergency authorisation, once they have been modified to work as ventilators.
Makers of modifiable devices eligible for EUAs
Company No of approvals
Resmed 24
Philips 12
Fisher & Paykel Healthcare 8
Getinge 6
General Electric 6
Hill-Rom 5
Hamilton Company 5
Mindray Medical International 4
3B Medical 4
Vyaire Medical 3
Drägerwerk 3
Medtronic 3
Thornhill Medical 3
Apex Medical 3
Drive Devilbiss Healthcare 3
Note: includes only manufacturers with at least 3 approved devices.
Source: EvaluateMedTech, FDA. 
It is no surprise to see Resmed way out in front. A large part of the company’s business is the manufacture of continuous positive airway pressure (CPAP) machines, which force air into sleep apnoea patients’ lungs as they sleep. CPAP machines would not be used as standard therapy for hospitalised patients who cannot breathe on their own, but ought to be reasonably easy to tweak so as to work in that way.
Resmed also makes ventilators for use when patients are awake, but this business is almost entirely focused on home care rather than the large machines found in hospitals; but again, these devices could be repurposed for the ICU. Resmed has said it is doing all it can to increase production of its ventilators and other respiratory devices and intends to double or triple its ventilator output, and scale up ventilation mask production more than tenfold.
The Philips devices that fall into the FDA’s categories came entirely though its 2008 acquisition of Respironics. One example is the Trilogy Evo portable ventilator, designed to be used initially in the hospital setting but then to be taken home by patients once they recover. The Dutch group also plans to double production of its hospital ventilators by mid-May and quadruple it by the third quarter of 2020.
These efforts are praiseworthy, but it still takes time to build these machines, and whether the overwhelming short-term demand can be met is in doubt. Some in industry insiders have been particularly sceptical about non-specialists attempting to develop their own ventilators without expert assistance.
And even the established respiratory tech developers could run into difficulty since the global supply chains for the components used in ventilator manufacture have been disrupted by the pandemic – as has staffing. Time will tell how much the obvious determination on the part of these various players can accomplish.
https://www.evaluate.com/vantage/articles/analysis/spotlight/scramble-reinvent-ventilator