Asthma inhalers being trialed for treatment of COVID-19

Researchers from Queensland University of Technology and Oxford University are working in collaboration to begin human clinical trials of inhaled corticosteroids, commonly used for asthma patients, on patients with COVID-19. The researchers believe that this could be useful for patients with the novel coronavirus infection.

The COVID-19 pandemic

The novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 11.79 million people around the world and killed over 543,000 individuals to date.

The virus has led to severe respiratory complications and hospitalization in some individuals. These individuals have needed intensive care and ventilation, and the outcome of these patients is usually poor.

As of now, there are no definitive medications to treat and cure the infection, and there are no effective vaccines to prevent viral infection.

Researchers around the world are in search of drugs that could help reduce the severity of complications of COVID-19. There are currently 21 candidate vaccines in clinical evaluation and 139 candidate vaccines at the preclinical evaluation stage.

Role of corticosteroids in COVID-19

COVID-19 is known to cause severe respiratory illness in some individuals. Studies have shown that some corticosteroids, such as dexamethasone, could reduce the inflammation of the respiratory tract in these patients and benefit them by alleviating the symptoms of severe disease.

Researchers in this new trial are studying if the steroid inhalers used for reducing the exacerbations of asthma could be useful for patients with early COVID-19 and reduce their risk of severe disease.

The paradox

Lead researcher on this team Dan Nicolau, an associate professor at QUT, explained that the asthmatics and those with chronic lung disease and chronic obstructive pulmonary disease (COPD) were on regular inhaler therapy with corticosteroids, were found to have a lesser risk of severe illness in the early phase of the pandemic. He said that this was paradoxical because those with long term lung disease were initially considered to be at a higher risk of a respiratory viral infection such as SARS-CoV-2. He said in his statement, “This seemed paradoxical because COVID-19 affects the lungs – and these patients have lung problems – so they should be more at risk of severe disease from the virus.”

Nicolau said, “One explanation for the low numbers was that something these people were doing regularly was protecting them and that, logically, was that they routinely used inhalers for their chronic lung problems.” “Ideally, it may be that the corticosteroid therapy would be given to anyone with a new, dry cough, and while they are awaiting their COVID test results,” he added.

He explained that based on their speculation, the earlier a corticosteroid inhaler is started for those with symptoms of COVID-19, the lesser their risk of getting severely ill. This speculation, he said, was based on the mathematical modeling by the research team.

The STOIC trial plan

The clinical trial has been registered under the name of STOIC (STerOids In COVID-19). It has begun recruiting patients at the Churchill Hospital in Oxford, England.

The study is being led by Associate Professor Nicolau, who is also a mathematician, physician, and Australian Research Council Future Fellow.

As per the trial details, the researchers have plans to recruit a total of 478 participants in the study. Some of the patients would be administered the corticosteroid (Budesonide) containing inhaler while others would be prescribed a placebo inhaler. Budesonide is widely used for control of symptoms of asthma and prevent its exacerbations.

The trial participants would be those with new-onset symptoms of COVID-19. The researchers wrote that the trial aims to “Evaluate the effect of inhaled corticosteroid (ICS) therapy compared to standard care in participants with early CoVID-19 illness in reducing COVID related emergency department presentations or hospital admissions”. Both male and female patients over the age of 18 years would be included in the trial.

The trial endpoints that would be recorded for each of the participants would be the need for hospitalization within 28 days of inclusion into the trial. Participants would be evaluated and followed up at baseline and then on days 7, 14, and 28.

Implications

If successful, Budesonide inhaler therapy could be a low cost and readily available therapy for early COVID-19 patients. It would reduce their risk of getting severe respiratory complications, Nicolau said. Panic buying and hoarding the inhalers could be a problem in some countries, but in Australia, this should not be a problem.

Nicolau said, “There wouldn’t be the kind of panic buying you see with consumer goods, because there are checks in place… There is a lot of stock around, and, as above, checks and balances on the dispensation of the inhalers would come into play to stop any [panic buying].”

Nicolau added that it would be September before any conclusive results could be obtained from the trial and the efficacy of the inhalers proven. Before that, it is important to wait for concrete evidence, he warned.

Sources:

• QUT and Oxford researchers collaborate on new COVID-19 asthma drug trial- https://www.qut.edu.au/news?id=165889
• EU Clinical Trials Register – https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001889-10/GB#E

https://www.news-medical.net/news/20200707/Asthma-inhalers-being-trialed-for-treatment-of-COVID-19.aspx

Sorrento to acquire COVID-19 therapy developer

Sorrento Therapeutics (SRNE -0.6%) has signed a letter of intent to acquire Cambridge, MA-based SmartPharm Therapeutics, a developer of non-viral DNA and RNA gene delivery platforms for COVID-19 and rare diseases.

The company plans to accelerate development of multiple candidates for in vivo gene-encoded expression of Sorrento antibodies, starting with COVID-19 “cure” STI-1499.

It says SmartPharm’s Gene Mab platform enables intramuscular delivery of low-immunogenic DNA plasmid encoded with a therapeutic antibody for long-lasting expression.

Financial terms are not disclosed.

https://seekingalpha.com/news/3594811-sorrento-to-acquire-covidminus-19-therapy-developer

LeMaitre Vascular’s Q2

LeMaitre Vascular’s (LMAT +12.8%) Q2 sales declined 16% Y/Y to $24.9M with sales in the Americas (-15%) and Europe/Middle East/Africa (-21%) due to COVID-19 pandemic. Asia/Pac sales was flat.

Gross margin decreased to 68.5% in 2Q20, compared to 68.9% a year ago primarily due to manufacturing inefficiencies offset by favorable product mix. Net income down 24% to $3.5M.

During the quarter, the company completed the acquisition of Artegraft, a processor and seller of vascular grafts derived from bovine carotid arteries, for $90M.

The company will pay a quarterly dividend of $0.095/share on September 10; record on August 27.

Further, LeMaitre Vascular expects to suspend or discontinue its $10M buyback program at any time prior to its conclusion on February 14.

https://seekingalpha.com/news/3594843-on-lemaitre-vasculars-q2-results

As long waits for results render COVID-19 tests ‘useless,’ states seek workarounds

States frustrated by private laboratories’ increasingly long turnarounds for COVID-19 test results are scrambling to find ways to salvage their testing programs.

Montana said Wednesday that it is dropping Quest Diagnostics, one of the nation’s largest diagnostic testing companies. The Secaucus, New Jersey-based company had done all the state’s surveillance COVID-19 testing—drive-thru testing that moves from community to community to help track COVID-19’s spread. But it told state officials last week that it was at capacity and would be unable to accommodate more tests for two or three weeks.

“We don’t want to be left high and dry again in the event that the national demand for testing puts a state like ours onto the back burner,” Democratic Gov. Steve Bullock said.

Instead, he said, the state is enlisting Montana State University’s lab to process up to 500 tests a day and has finalized a contract with a new private lab, North Carolina-based Mako Medical, for an additional 1,000 tests a day.

California, Florida and other states that work with Quest have started experimenting with separate, expedited lines for people who have symptoms of the disease. Some states are contracting with other private labs. And CVS, which uses Quest for COVID-19 tests at many of its sites nationwide, said it is looking for more lab partners to reduce wait times for results.

Quest, LabCorp and other private labs have struggled to expand quickly enough to meet demand as states expand their testing and cases soar across the nation. Officials for Quest, which handles about 130,000 tests daily in 20 laboratories, said its ability to expand has been limited by a global shortage of the machines and chemical reagents needed to perform COVID-19 testing.

Monday, Quest announced that turnaround times had slowed to a week or more, up from three or four days in June. It also said some patients may face wait times of up to two weeks. Quest officials warned this week that could get worse as flu season starts this fall.

A wait of a week or more for results can make the tests moot, since few people, especially those without symptoms, are likely to remain quarantined that long — and if the test comes back positive, they may already be over the disease.

“We are working with a number of different organizations to provide as much testing as possible, but some of these constraints are out of our control,” Quest spokesperson Wendy Bost said. “We’ve taken the step of asking our clients to modulate the testing demand by focusing on patients who are most in need at this time.”

The Trump administration is also trying to speed up turnaround times by allowing some labs to use an approach known as pooled testing, which combines samples from multiple people and then screens the individual samples only if the batch comes back positive for the virus. But public health experts worry it may be too late to try pool testing, as the percentage of positive results has doubled or tripled in many parts of the country.

States grappling with rising caseloads amid the testing slowdown have grown exasperated. Colorado Gov. Jared Polis, a Democrat, told NBC’s “Meet the Press” on Sunday that it can take up to nine days to get test results from Quest and LabCorp.

“Almost useless from an epidemiological or even diagnostic perspective,” Polis said.

LabCorp officials say turnaround times are improving.

Those who worry they have COVID-19 are also frustrated. In San Francisco, Mark Mackler, a 71-year-old retired law librarian, went with his husband to get a free test at the Bernal Heights Recreation Center on June 28 for peace of mind. He expected results after five days, but the test, processed by Quest, took 16 days—it came back negative for COVID-19.

“I was just annoyed and concerned the taxpayers were getting taken for a ride on something expensive and useless to a lot of people,” Mackler said.

In California, Democratic Gov. Gavin Newsom acknowledged Quest’s slow turnaround times at a press conference Wednesday.

“It’s rather preposterous that you get a test and 13, 14 days later you get the results,” Newsom said, adding that the results in those cases are “utterly meaningless.”

But, he added, “We’re not going to abandon Quest. We need them as one of our partners.”

California is partnering with other private and university labs to expedite test results, ramping up from 2,000 tests a day early in the pandemic to an average of more than 125,000 a day, Newsom said. Test results now average between five and seven days, and state health officials said they have told all labs to first process from high-risk groups, such as people with COVID-19 symptoms, those in hospitals and those in long-term care facilities.

In Florida, Quest has performed more than 600,000 COVID-19 tests, the most of any lab. After reports of labs taking seven to 10 days to turn around test results, health officials created special lanes at four testing sites for symptomatic people that will allow them to receive their results faster. If that program goes well, Florida officials said, it will be expanded to all 50 state-run sites.

Pennsylvania health officials plan to cut the number of drive-thru testing sites it runs with Quest and Walmart from 19 to 13. They also are relocating some site locations that have seen low testing numbers to more populated areas with higher positivity rates.

Weeklong waits for COVID-19 tests are not the norm everywhere. In Texas, state-run mobile test sites are providing results within two to three days because the state has “spread the load” of testing among many lab companies, said Seth Christensen, spokesperson for the Texas Division of Emergency Management. The state does not use Quest but instead uses more than 10 other lab companies, including LabCorp, another of the nation’s largest lab chains.

Return times vary widely by company. LabCorp said turnaround time for outpatient test results improved to three to five days this week from four to six last week. BioReference Laboratories, another big lab chain, said it has improved turnaround time from about six days in June to three or fewer this month. Walmart, which has used Quest and eTrueNorth for more than 150,000 COVID-19 tests, said on its website that Quest results take a week, compared with three to five days with eTrueNorth.

In Montana, the Quest delays forced the state to pause its community testing program, which aims to serve as an alert system for how the virus is spreading. Officials plan to resume next week once it has Montana State and the North Carolina lab in place, Bullock said.

Montana, with 2,813 confirmed cases as of Tuesday, has one of the lowest per-capita rates in the nation. But the average daily caseload in the state has risen 112% in the past two weeks—the country’s third-highest rate increase, according to an analysis by NPR.

Quest started running the state’s mass-testing events in the spring, with promised turnaround times of two or three days. But that started to stretch into a week or longer, Bullock said.

Bost, the Quest spokesperson, described the delay in community testing as a temporary agreement with state officials.

“We mutually agreed to postpone some community events for the general population in order to ensure testing is available for the patients who are most in need, such as those who are symptomatic and ill in the hospital,” she said.

Montana hasn’t canceled its contract with Quest, but state officials said they are unsure whether the state will resume using the company.

“We can meet the need that we have in Montana with these two solutions,” Bullock said, referring to the Montana State University and North Carolina laboratories. “But that doesn’t mean that we won’t be returning to Quest at some point.”

https://www.fiercebiotech.com/medtech/as-long-waits-for-results-render-covid-tests-useless-states-seek-workarounds

Columbia team pinpoints potent antibody cocktail for COVID-19

Scientists at Columbia University have identified a cocktail of antibodies they say could be a potent option for treating and preventing COVID-19. The team, led by renowned HIV researcher David Ho, collected neutralizing antibodies from five severely ill COVID-19 patients and picked 19 candidates that aggressively killed off the novel coronavirus in lab dishes.

What makes the findings notable is that some of the antibodies the researchers identified target areas of the virus that were not previously described, according to results published in Nature.

Most antibodies bind to the spike protein on the surface of SARS-CoV-2, the virus that causes COVID-19. The Columbia researchers showed that their antibodies target one of two locations on the S protein: either the receptor binding domain (RBD), which helps the virus latch onto and infect human cells, or the N-terminal domain (NTD).

Among nine of the most potent antibodies, four are specifically directed at the RBD and three at the NTD. But in what they believe is an unprecedented discovery, the Columbia team found two powerful neutralizing antibodies that recognize a site on the top of the S protein that crosses from one RBD to another.

Physicians are already using antibody-containing plasma from recovered COVID-19 patients to treat patients. But because convalescent serum contains a variety of antibodies, each patient may need a different plasma product with varying concentrations or strengths of neutralizing antibodies. So purified antibodies that can be mass produced by drugmakers could be a better option, the team argues.

Ho is best known for his research that laid the groundwork for controlling HIV replication in patients with combination antiretroviral therapy. Now, he’s suggesting a similar strategy for combating COVID-19.

“Using a cocktail of different antibodies that are directed to different sites in spike will help prevent the virus becoming resistant to the treatment,” Ho said in a statement.

Regeneron is currently leading the race to develop COVID-19 neutralizing antibody cocktails for potential treatment and prevention of the disease. In collaboration with the National Institute of Allergy and Infectious Diseases, the company recently started a phase 3 study testing whether a mixture of two neutralizing antibodies, dubbed REGN-COV2, can prevention infections in people who have had close contact with an infected person. The company has also advanced the candidate into two clinical trials for treating hospitalized and non-hospitalized COVID-19 patients.

Eli Lilly is testing two antibody treatments, LY-CoV555 and JS016, through separate partnerships with Canadian biotech AbCellera and Chinese company Junshi Biosciences. The Indianapolis pharma is also considering a potential combination of the two.

Ho and colleagues have validated their antibody strategy in a virus challenge study in hamsters. The researchers are now designing further studies in other animals in the hopes of eventually progressing to human trials. “[W]e believe several of our monoclonal antibodies with exquisite virus-neutralizing activity are promising candidates for development as modalities to treat or prevent SARS-CoV-2 infection,” the researchers wrote in the study.

https://www.fiercebiotech.com/research/columbia-team-identifies-potent-antibody-cocktail-for-covid-19