Medtech companies look to post-pandemic home testing beyond COVID-19

 Encouraged by the development of rapid at-home coronavirus tests, medtech companies are now betting on the potential to sell over-the-counter and direct-to-consumer diagnostics for diseases beyond COVID-19.

The pandemic has enabled consumers to get tested for the virus in the privacy of their homes, a convenience that companies like Abbott Laboratories and Quest Diagnostics are hoping will appeal to people when it comes to other diagnostics.

Home testing was already rising worldwide, as consumers take a more proactive role in their healthcare. COVID-19 is likely speeding that shift, analysts and companies say.

"Home testing and home collection will fundamentally reshape the diagnostics industry and healthcare in general by providing more testing options," said William Blair analysts, who contend that OTC tests will be one of the key long-term impacts of the pandemic on the industry.

Abbott last week announced it began shipping its over-the-counter BinaxNOW COVID-19 Ag Self Test to retailers, including CVS Pharmacy, Walgreens and Walmart. However, the company has set its sights on a broader at-home testing market.

CEO Robert Ford told investors last week Abbott is looking to bring rapid self-testing to the masses that extends beyond coronavirus diagnostics. Ford envisions an "accelerated" move from "more hospital lab-based testing to more rapid testing outside of that environment where consumers and people can get their results at a much faster rate and, quite frankly, with a little bit of less hassle."

Ford is positioning BinaxNOW as a model for "seeding" the consumer at-home test market and building new testing channels for other ailments that don't have to be performed at a hospital, physician's office or pharmacy.

"Being able to have access to fast, affordable and digitally connected testing is something that I think is going to be here, and here to stay, whether it's a COVID test or other tests. I think that is a change in the delivery, at least in the diagnostic side," Ford said.

Quest estimates consumer testing to be a $2 billion opportunity by 2025, growing at a 10% compound annual growth rate. The lab giant is expanding its existing direct-to-consumer operation to try to capture $250 million of this post-pandemic emerging market.

CEO Steve Rusckowski contends the market is at "an inflection point" due to COVID-19 when it comes to delivering healthcare in new ways. "We have invested in the past and will continue to invest going forward...in the direct-to-consumer opportunity that we see in our space," Rusckowski said at Quest's investor day last month. 

Cathy Doherty, senior vice president for clinical franchises and marketing at Quest, noted that payers are seeing the value, which could spur growth.

"Health plans are now covering consumer-initiated testing for COVID-19," Doherty said. "If health plan support were to expand beyond COVID, this could also be a catalyst for the market to be even bigger."

Quest plans to expand its home kit collection offering by shipping InSure ONE fecal immunochemical tests directly to consumers to go after the colorectal cancer screening market dominated by Exact Sciences' Cologuard. 

"With the pandemic, we do see a catalyst that will accelerate the opportunity in front of us," said Quest's Rusckowski. 

Regulatory uncertainty

Despite the potential for a home testing bonanza, test developers will need to get diagnostics authorized using traditional premarket review processes to support post-pandemic use. 

FDA has granted emergency use authorizations to four over-the-counter home COVID-19 antigen tests and two prescription antigen at-home tests, as well as two OTC molecular tests and one molecular prescription at-home test. There are also 49 molecular EUAs and one antibody authorization that can be used with home-collected samples.  

Looking beyond COVID-19, there are many areas of testing that FDA considers important, including at-home tests, according to Toby Lowe, CDRH's associate director of the Office of In Vitro Diagnostics and Radiological Health.

"Right now, we have a lot of questions and not a lot of answers yet. But some of these areas include home collection and testing," Lowe said earlier this month during a Food and Drug Law Institute webinar on the impact of COVID-19 on the in vitro diagnostics industry.

Lowe added that FDA is "looking to consider how we can expand [home-collected samples and home testing] to other test areas, what might some of those impediments be, and how we can resolve them." 

Specifically, Lowe said the agency is assessing whether specimen types such as saliva, authorized for SARS-CoV-2, are also useful test samples for other respiratory diseases and different kinds of diseases.     

BioFire Diagnostics last month became the first company to win a full FDA marketing authorization for a COVID-19 test, with their granted De Novo request clearing the way for subsequent applicants who can demonstrate substantial equivalence to BioFire's PCR-based respiratory panel through the 510(k) pathway.

"We have authorized the first test for marketing beyond the public health emergency with the BioFire De Novo," Lowe said during a virtual FDA town hall meeting earlier this month. "That does open up the 510(k) pathway for other molecular diagnostic SARS-CoV-2 tests both individual or a single analyte SARS-CoV-2 test as well as multi-analyte panels, which the BioFire test is. But that De Novo does not impact any other EUA."

EUAs for all other products are set to expire when HHS determines the circumstances that justified the U.S. public health emergency declaration no longer exist. While Lowe said that FDA can't anticipate when the PHE in response to COVID-19 will end, she said the agency is working on a transition plan for devices that are offered under EUA.

Nonetheless, Craig-Hallum analyst Alex Nowak is optimistic about the future of post-pandemic home testing, not just for SARS-CoV-2 but for other diseases.

"Previously tests were confined to the hospital and physicians' office. With the pandemic, diagnostics are in more locations than ever. We expect all diagnostic companies will use the OTC COVID approval as a beachhead and successful implementation may lead to OTC tests for flu, strep, potentially STDs, GI and Lyme, among others," Nowak wrote in a note earlier this month.

At-home tests in particular are a "game changer" for the diagnostics industry, according to Nowak.

"Tests can be stored next to the Band-Aids and tested when exposed to positive cases, or symptoms emerge from any number of pathogens (COVID, other coronaviruses, flu, enterovirus, rhinovirus, etc.)," the analyst wrote. 

https://www.healthcaredive.com/news/medtech-companies-look-to-post-pandemic-home-testing-beyond-covid-19/599116/

Lilly, citing FDA feedback, won't seek speedy approval of Alzheimer's drug

 

• An Eli Lilly executive said on a conference call Tuesday that the company won't seek an accelerated U.S. review of its experimental Alzheimer's disease drug donanemab based on Phase 2 data the company disclosed last month.
• Lilly is still in discussions with the Food and Drug Administration and is "fully exploring any opportunities for early submissions," said chief scientific officer Dan Skovronsky. But in the meantime, the company announced plans to start a new donanemab study in presymptomatic Alzheimer's patients. That trial will begin later this year and should take a year to fully enroll. Disease progression will be measured after three years, Skovronsky said.
• Winning an early approval of an Alzheimer's drug based on mid-stage data is unlikely "based on feedback from the FDA," he said. Nonetheless, interest has grown because of the FDA's unusually friendly stance toward Biogen's experimental drug aducanumab. That could change, however, should the regulator reject it by a review deadline of June 7.

Drugs that target the accumulation of a protein called amyloid in the brains of Alzheimer's patients have a long history of showing promise in early trials before falling short in larger Phase 3 tests. Until Biogen's aducanumab, no drug been shown to significantly delay disease progression — and many have argued Biogen failed on that measure as well given controversial and conflicting data. 

Eli Lilly, which had its own disappointing and expensive setback with an drug called solanezumab, is optimistic donanemab might be different based on the findings from the TRAILBLAZER-ALZ study. In the Phase 2 trial, patients who took donanemab experienced disease progression, as measured by a scale that tests function and cognition, that was one-third slower than those who received a placebo.

The results were from a small group of just 257 patients. But they were persuasive enough for Lilly to alter its clinical plan for the drug, which involved enlarging a study called TRAILBLAZER-ALZ 2 and designating it as a Phase 3 trial intended to support FDA approval. At the time, the company wanted to explore the possibility of gaining accelerated approval — a tool the FDA uses for drugs that treat serious diseases where no or few other options exist — based on TRAILBLAZER-ALZ 1. That option now appears off the table.

"We currently do not see a path forward for near-term submission and approval based on the first TRAILBLAZER-ALZ study alone," Skovronsky said on the conference call Tuesday.

Testing in presymptomatic patients is likewise a high-risk strategy, but also one with a big payoff if Lilly succeeds. The setting is also one Lilly is well familiar with. Its once highly touted Alzheimer's antibody solanezumab fell short in a study, DIAN-TU, testing the drug in presymptomatic patients.

Lilly hasn't been deterred, however. Skovronsky said because amyloid accumulates in the brain for years before patients show symptoms, treating people earlier could have a greater effect on slowing disease progression. And it's possible to do so now because of improvements in diagnostic technology. Potential enrollees can be identified with blood tests rather than expensive brain scans.

"That's a huge advance that just unlocks this trial," he said.

https://www.biopharmadive.com/news/lilly-donanemab-fda-accelerated-review-alzheimers/599118/

Designing 'nanotraps' to catch, clear coronavirus

 Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have designed a completely novel potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses within the body and then use the body's own immune system to destroy it.

These "Nanotraps" attract the virus by mimicking the target cells the virus infects. When the virus binds to the Nanotraps, the traps then sequester the virus from other cells and target it for destruction by the immune system.

In theory, these Nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus going forward. Though the therapy remains in early stages of testing, the researchers envision it could be administered via a nasal spray as a treatment for COVID-19.

The results were published April 19 in the journal Matter.

"Since the pandemic began, our research team has been developing this new way to treat COVID-19," said Asst. Prof. Jun Huang, whose lab led the research. "We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential."

Designing the perfect trap

To design the Nanotrap, the research team -- led by postdoctoral scholar Min Chen and graduate student Jill Rosenberg -- looked into the mechanism SARS-CoV-2 uses to bind to cells: a spike-like protein on its surface that binds to a human cell's ACE2 receptor protein.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Similarly, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when someone is infected and are designed to latch onto the coronavirus in various ways).

Both ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, the researchers created an even more robust system for trapping and eliminating the virus.

Made of FDA-approved polymers and phospholipids, the nanoparticles are about 500 nanometers in diameter -- much smaller than a cell. That means the Nanotraps can reach more areas inside the body and more effectively trap the virus.

The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus -- a less potent model of a virus that doesn't replicate -- in human lung cells in tissue culture plates and found that they completely blocked entry into the cells.

Once the pseudovirus bound itself to the nanoparticle -- which in tests took about 10 minutes after injection -- the nanoparticles used a molecule that calls the body's macrophages to engulf and degrade the Nanotrap. Macrophages will generally eat nanoparticles within the body, but the Nanotrap molecule speeds up the process. The nanoparticles were cleared and degraded within 48 hours.

The researchers also tested the nanoparticles with a pseudovirus in an ex vivo lung perfusion system -- a pair of donated lungs that is kept alive with a ventilator -- and found that they completely blocked infection in the lungs.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.

A potential future treatment for COVID-19 and beyond

Next the researchers hope to further test the system, including more tests with a live virus and on the many virus variants.

"That's what is so powerful about this Nanotrap," Rosenberg said. "It's easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants."

The Nanotraps can be stored in a standard freezer and could ultimately be given via an intranasal spray, which would place them directly in the respiratory system and make them most effective.

The researchers say it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, creating an ultimate therapeutic system for the virus.

"This is the starting point," Huang said. "We want to do something to help the world."

The research involved collaborators across departments, including chemistry, biology, and medicine.

Other authors on the paper include Xiaolei Cai, Andy Chao Hsuan Lee, Jiuyun Shi, Mindy Nguyen, Thirushan Wignakumar, Vikranth Mirle, Arianna Joy Edobor, John Fung, Jessica Scott Donington, Kumaran Shanmugarajah, Yiliang Lin, Eugene Chang, Glenn Randall, Pablo Penaloza-MacMaster, Bozhi Tian, and Maria Lucia Madariaga.

Story Source:

Materials provided by University of Chicago. Note: Content may be edited for style and length.

---

Journal Reference:

1. Min Chen, Jillian Rosenberg, Xiaolei Cai, Andy Chao Hsuan Lee, Jiuyun Shi, Mindy Nguyen, Thirushan Wignakumar, Vikranth Mirle, Arianna Joy Edobor, John Fung, Jessica Scott Donington, Kumaran Shanmugarajah, Yiliang Lin, Eugene Chang, Glenn Randall, Pablo Penaloza-MacMaster, Bozhi Tian, Maria Lucia Madariaga, Jun Huang. Nanotraps for the containment and clearance of SARS-CoV-2. Matter, 2021; DOI: 10.1016/j.matt.2021.04.005

https://www.sciencedaily.com/releases/2021/04/210427122411.htm

SARS-CoV-2 variant sacrifices tight binding for antibody evasion

 The highly infectious SARS-CoV-2 variant that recently emerged in South Africa, known as B.1.351, has scientists wondering how existing COVID-19 vaccines and therapies can be improved to ensure strong protection. Now, researchers reporting in ACS' Journal of Medicinal Chemistry have used computer modeling to reveal that one of the three mutations that make variant B.1.351 different from the original SARS-CoV-2 reduces the virus' binding to human cells -- but potentially allows it to escape some antibodies.

Since the original SARS-CoV-2 was first detected in late 2019, several new variants have emerged, including ones from the U.K., South Africa and Brazil. Because the new variants appear to be more highly transmissible, and thus spread rapidly, many people are worried that they could undermine current vaccines, antibody therapies or natural immunity. Variant B.1.351 bears two mutations (N501Y and E484K) that can enhance binding between the receptor binding domain (RBD) of the coronavirus spike protein and the human ACE2 receptor. However, the third mutation (K417N; a lysine to asparagine mutation at position 417) is puzzling because it eradicates a favorable interaction between the RBD and ACE2. Therefore, Binquan Luan and Tien Huynh from IBM Research wanted to investigate potential benefits of the K417N mutation that could have caused the coronavirus to evolve along this path.

The researchers used molecular dynamics simulations to analyze the consequences of the K417N mutation in variant B.1.351. First, they modeled binding between the original SARS-CoV-2 RBD and ACE2, and between the RBD and CB6, which is a SARS-CoV-2-neutralizing antibody isolated from a recovered COVID-19 patient. They found that the original amino acid, a lysine, at position 417 in the RBD interacted more strongly with CB6 than with ACE2, consistent with the antibody's therapeutic efficacy in animal models. Then, the team modeled binding with the K417N variant, which changes that lysine to an asparagine. Although this mutation reduced the strength of binding between the RBD and ACE2, it decreased the RBD's binding to CB6 and several other human antibodies to a much greater extent. Thus, variant B.1.351 appears to have sacrificed tight binding to ACE2 at this site for the ability to evade the immune system. This information could prove useful to scientists as they work to enhance the protection of current vaccines and therapies, the researchers say.

---

Story Source:

Materials provided by American Chemical Society. Note: Content may be edited for style and length.

---

Journal Reference:

1. Binquan Luan, Tien Huynh. Insights into SARS-CoV-2’s Mutations for Evading Human Antibodies: Sacrifice and Survival. Journal of Medicinal Chemistry, 2021; DOI: 10.1021/acs.jmedchem.1c00311

https://www.sciencedaily.com/releases/2021/04/210428132949.htm

Pacific Northwest faces shutdowns amid rising virus cases

 When the coronavirus pandemic hit the Pacific Northwest states of Oregon and Washington, their governors quickly reacted with shutdowns. Now they are about to impose new restrictions again as infections and hospitalizations rise to alarming levels.

Oregon Gov. Kate Brown is putting 15 counties that encompass the state’s biggest cities into the state’s extreme risk category starting Friday, imposing restrictions that include banning indoor restaurant dining. As Brown issued her order on Tuesday, she said rising COVID-19 hospitalizations threaten to overwhelm doctors.

“If we don’t act now, doctors, nurses, hospitals, and other health care providers in Oregon will be stretched to their limits treating severe cases of COVID-19,” Brown said.

Washington Gov. Jay Inslee is expected to order new restrictions next week for several counties, likely including the state’s largest, that would force businesses and churches to reduce their indoor gathering capacity from 50% to 25%.

Inslee will decide which counties need to be rolled back to Phase 2 of his reopening plan after an evaluation of public health safety benchmark numbers. The public health director for King County, which includes Seattle, expects it will be included in Inslee’s order.

“We might as well just get prepared for that and not just wait,” Patty Hayes, director of Public Health – Seattle & King County, told the King County Council on Tuesday.

The moves come, ironically, as the supply of vaccines in many places is exceeding demand.

“There are appointments available right now all across the state,” Brown said.

For example, the public health director for northern Oregon’s Umatilla County, which was downgraded Tuesday from the moderate to the high-risk category, told state officials it can send last week’s vaccine allocation somewhere else and will likely do so again this week.

“Our demand level is dropping dramatically,” Public Health Director Joe Fiumara told the East Oregonian newspaper. The county has about 6,000 doses and last week administered fewer than 500 as health department staff sat idly, waiting for people to arrive for vaccinations.

The level of vaccinations in the mostly rural county is far short of what health experts say is needed: According to Oregon Health Authority data, only about 19,000 people have been fully or partially vaccinated in the county where 78,000 people live.

The restaurant sector objected to Brown’s action, with the Oregon Restaurant & Lodging Association declaring that the state lost more than 1,000 food service businesses in 2020 and that 200 more closed permanently so far this year.

“The move by the governor’s office is tone deaf and offensive to tens of thousands of Oregonians working in restaurants and bars across our state attempting to pay their bills,” said Jason Brandt, the group’s president and CEO.

Brown’s office said she is partnering with state lawmakers to approve a $20 million small business emergency relief package to immediately support affected businesses in extreme risk counties through the commercial rent relief program.

“It’s great that we have more money in the hopper for our clobbered hospitality industry,” Brandt said.

But he added: “The amounts that have been earmarked ... has never been close to enough to make these small businesses whole.”

In the Oregon Senate on Wednesday, Republicans accused Brown of “reimposing draconian, undemocratic lockdowns that threaten the livelihoods of tens of thousands of Oregonians.”

To protest Brown’s order, the Republican senators insisted that bills be read in full, slowing the legislative process.

“Republicans are standing shoulder to shoulder with working Oregonians,” declared Senate GOP leader Fred Girod.

Brown, aiming to soften the blow to businesses, is also increasing the outdoor capacity limits for bars, restaurants and other sectors from 50 to 100 people in extreme-risk counties as long as they have physical distancing and other safety measures in place.

Some of Oregon’s biggest cities — including Portland, Salem, Bend and Eugene — are in the counties that will be in the most dire category, effective Friday.

Portland Mayor Ted Wheeler, whose city partially lies in Multnomah County, which was moved to extreme risk, urged people to use safety protocols to prevent further spread of the coronavirus.

“The key to reopening our city is ending the pandemic,” Wheeler said.

The Oregon Health Authority said counties won’t be moved into the extreme risk category unless the peak daily number of hospital beds occupied by COVID-19 patients statewide is at least 300, including a 15% increase over the previous seven days. The state is now beyond that threshold, with the current daily peak at 328 beds. Oregon’s population is more than 4.2 million.

Washington is also taking a step back. In March, Inslee allowed restaurants and other indoor establishments throughout the state to operate at half capacity, up from 25%

But like in Oregon and other states, coronavirus case numbers and hospitalizations have been steadily rising in recent weeks.

As of Tuesday, King County was recording 229 newly confirmed coronavirus cases per 100,000 residents over the last 14 days and 5.5 new COVID-19 hospitalizations per 100,000 residents over the last seven days, the Seattle Times reported.

To avoid stricter restrictions, counties in Washington need to report fewer than 200 cases per 100,000 residents and less than five hospitalizations.

As of Monday, the Washington Department of Health reported about 675 people hospitalized due to COVID-19 across the state, an increase of more than 100 in two weeks. Washington’s population is more than 7.7 million.

https://apnews.com/article/business-coronavirus-lifestyle-government-and-politics-health-0701bfd2edd76b00a6770f3358783f41

Biological age acceleration and telomere 2 shortening in COVID-19 survivors

 Alessia Mongelli,  

View ORCID Profilecarlo gaetano, michela gottardi zamperla,  View ORCID Profileveronica barbi,  View ORCID Profilesandra atlante,  View ORCID Profilemaria teresa la rovere,  View ORCID Profiletiziana bachetti,  View ORCID Profileoronzo catalano,  View ORCID Profilemaurizio bussotti, laura della vecchia,  View ORCID Profilesimona nanni,  View ORCID Profileantonella farsetti,  View ORCID Profilefabio martelli

doi: https://doi.org/10.1101/2021.04.23.21255973

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1.full.pdf

Abstract

Introduction & Background: the SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis,inflammatory cytokines release, and immunodepression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called post-COVID19 syndrome (PPCS) is a common finding. In patients who survived the SARS-CoV-2 infection, overt PPCS presents one or more symptoms such as fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. The pathophysiology of PPCS is currently poorly understood, and whether epigenetic mechanisms are involved in this process is unexplored. Methods & Results: In this study, a cohort of 117 COVID19 survivors (post-COVID19) and 144 non-infected volunteers (COVID19-free) were analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. Besides, telomere length (TL) and ACE2 and DPP4 receptor expression were determined. The results show a consistent biological age increase in the post-covid population (mean 58,44 DS 14,66 ChronoAge Vs. mean 67,18 DS 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 DS 7,29 years (+5.25 years above range of normality) compared to 3,68 DS 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 DS 2,39 Kb vs. COVID19-free: 10,67 DS 11,69 Kb; P<0,0001). Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change. Conclusion: In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID19 condition, particularly in the younger (<60 years). Although the consequences of such modifications on the long-term clinical outcome remain unclear, they might 46 indicate a direction to investigate the pathophysiological basis of the post-COVID19 syndrome

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Ethical commettee ICS Maugeri document ID: 2543 CE

https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1

Mexico will bottle, package Sputnik V vaccine

 Mexico will begin bottling and packaging the Russian Sputnik V vaccine, Mexico Foreign Affairs Secretary Marcelo Ebrard said Wednesday during a visit to Russia.

Mexico has already received more than 1 million doses of Sputnik V in recent months. Ebrard says the state-owned company Birmex is working with the Russian Direct Investment Fund to prepare the bottling operations.

Mexico has already been bottling the Chinese-developed CanSino vaccine.

The domestic finishing of vaccines is part of Mexico’s efforts to obtain more shots. In addition to Sputnik V and CanSino, Mexico has been using the Pfizer, AstraZeneca and Sinovac vaccines.

The country has received 16.6 million doses and given some 12 million shots, coverng about 9.4% of the population. Mexico has vaccinated many of its senior citizens and plans to begin vaccinating people between ages 50-59 in May.

https://www.nbcnews.com/news/latino/mexico-will-bottle-package-sputnik-v-vaccine-rcna790