The independent Safety Monitoring Committee (SMC) has completed review for RedHill Biopharma’s (NASDAQ:RDHL) of opaganib (Yeliva) in Phase 2 study, in patients hospitalized with severe COVID-19 pneumonia and recommended that the study continue unmodified.
The SMC reviewed unblinded safety data from the first 12 patients treated for at least seven days.
Phase 2 study is more than 50% enrolled and enrollment is expected to complete in the coming weeks.
Next scheduled SMC review will take place once 24 patients complete at least seven days of treatment.
It also received approval from the Italian Medicines Agency for its Clinical Trial Authorization application for the global Phase 2/3 study, evaluating opaganib in patients hospitalized with severe COVID-19 pneumonia. Subject to positive data, the company aims to apply for emergency use authorizations as early as next quarter.
Anticoagulation for patients hospitalized with COVID-19 was associated with lower risk of death or intubation in an observational study from New York City’s pandemic peak.
In-hospital mortality risk was a relative 50% lower with standard prophylactic dosing and 47% lower with higher therapeutic-level dosing after adjustment for other factors, both statistically significant when compared with COVID-19 patients in Mount Sinai hospitals not given an anticoagulant (mortality rates of 21.6%, 28.6%, and 25.6%, respectively).
Intubation was less likely for anticoagulant-treated COVID-19 patients as well (adjusted HR 0.69 with prophylactic dosing, 95% CI 0.51-0.94, and aHR 0.72 with therapeutic dosing, 95% CI 0.58-0.89), reported Anuradha Lala, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues in the Journal of the American College of Cardiology.
Major bleeding events adjudicated by clinician chart review turned up a “low” rate of 1.7% (33 of 1,959) on prophylactic anticoagulation and 3% (27 of 900) on therapeutic anticoagulation compared with 1.9% (29 of 1,530) on no anticoagulant during hospitalization.
“The study has severe limitations due to its retrospective nature,” cautioned Stephan Moll, MD, of the University of North Carolina at Chapel Hill Hemophilia and Thrombosis Center.
“However, NIH prospective studies on inpatient and outpatient [prophylaxis] comparing different anticoagulation management strategies are planned and hopefully starting soon so that we can get beyond all these retrospective studies and data of the last few months, which all have ascertainment bias,” he told MedPage Today.
Anticoagulation for patients hospitalized with COVID-19 was associated with lower risk of death or intubation in an observational study from New York City’s pandemic peak.
In-hospital mortality risk was a relative 50% lower with standard prophylactic dosing and 47% lower with higher therapeutic-level dosing after adjustment for other factors, both statistically significant when compared with COVID-19 patients in Mount Sinai hospitals not given an anticoagulant (mortality rates of 21.6%, 28.6%, and 25.6%, respectively).
Intubation was less likely for anticoagulant-treated COVID-19 patients as well (adjusted HR 0.69 with prophylactic dosing, 95% CI 0.51-0.94, and aHR 0.72 with therapeutic dosing, 95% CI 0.58-0.89), reported Anuradha Lala, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues in the Journal of the American College of Cardiology.
Major bleeding events adjudicated by clinician chart review turned up a “low” rate of 1.7% (33 of 1,959) on prophylactic anticoagulation and 3% (27 of 900) on therapeutic anticoagulation compared with 1.9% (29 of 1,530) on no anticoagulant during hospitalization.
“The study has severe limitations due to its retrospective nature,” cautioned Stephan Moll, MD, of the University of North Carolina at Chapel Hill Hemophilia and Thrombosis Center.
“However, NIH prospective studies on inpatient and outpatient [prophylaxis] comparing different anticoagulation management strategies are planned and hopefully starting soon so that we can get beyond all these retrospective studies and data of the last few months, which all have ascertainment bias,” he told MedPage Today.
Lala’s group had previously reported on their experience with anticoagulation among 2,773 patients treated early in the pandemic, finding an in-hospital survival advantage with therapeutic-dose anticoagulation among mechanically ventilated patients and with longer duration anticoagulation.
A subsequent study had suggested elevated mortality risk with preemptive therapeutic-dose anticoagulation in COVID-19 patients.
The new data included 4,389 adults with laboratory-confirmed SARS-CoV-2 infection admitted from March 1 to April 30, 2020, at the five New York City hospitals in the Mount Sinai system.
The researchers conservatively classified anyone treated for less than 48 hours with an anticoagulant as fitting the control group, unless the drug was stopped due to major bleeding. Patients discharged within 24 hours, as well as those treated with both therapeutic and prophylactic regimens, were excluded.
The study also evaluated the first 26 autopsies on COVID-19 patients in the health system, which turned up thromboembolism in 11 (42%), while it had been suspected pre-mortem in only one. “Our findings are in line with what other studies have shown,” Lala said. “We’re seeing more clots than we would have ever suspected previously.” https://tpc.googlesyndication.com/safeframe/1-0-37/html/container.html
All told, 34.9% of the COVID-19 patients didn’t receive anticoagulation. These patients might have been treated earlier in the pandemic when practices were changing, said Lala, who pointed to the increasing observational data supporting prophylactic anticoagulation over time. But the predominant factor appeared to be less severe illness, she said.
Even so, there’s plenty of data from prior randomized trials supporting pharmacologic thrombotic prophylaxis that makes it the standard of care in-hospital, regardless of COVID-19, argued Behnood Bikdeli, MD, of Brigham and Women’s Hospital and Harvard in Boston, who has been involved with COVID-related anticoagulation consensus recommendations and clinical trials.
“Since this study has been completed, thank God New York is not under grips of COVID and we hope that it stays that way. But if I were to consider how to treat a patient if they came to my doorstep now, I would be inclined to use anticoagulation. Nonetheless, I think the dose and the agent need to be confirmed with clinical trials,” Lala agreed.
The current study has better explanation of methodology and more confirmatory analyses that make the results more believable than the previous study from the organization, but trials like INSPIRATION and the NIH’s ACTIV will be the ones to really provide answers, Bikdeli said.
“The question they are trying to answer is perhaps one of the top three or four important questions we face as clinicians dealing with COVID-19,” he told MedPage Today.
An interim final rule from the Centers for Medicare & Medicaid Services (CMS) that requires all Medicare-certified nursing homes test their staff for COVID-19 is drawing mixed reviews from the homes.
“The pandemic has already cost nursing homes tens of thousands of lives and billions of dollars, as dedicated workers have been shouting for help from the front line,” Katie Smith Sloan, president and CEO of LeadingAge, an association of nonprofit nursing homes, said in a statement. “Nursing homes will put the resources CMS announced today to good use. But the fight against this virus is far from over, and our members need continued support.”
She added that “the antigen testing machines HHS [the Department of Health and Human Services] is delivering to nursing homes will help, but members who already have the machines report that they are still waiting for instructions and test kits to make them usable.”
The interim final rule issued Tuesday calls for nursing homes to test all staff, although the frequency may vary even among staff members at a single facility. “We estimate that, based on the guidelines given regarding testing frequency, the criteria for conducting a test, and the response time for test result, not all staff will be tested on the same frequency,” the regulation says. “For example, a third of the staff population could be tested weekly and two-thirds of the staff population could receive a test every ten days or monthly.”
In general, “CMS recommendations for the frequency of staff testing will be based on the degree of community spread, to be announced shortly through guidance, that indicate the facility may be at increased risk for COVID-19 transmission,” the agency said in a press release.
The regulation also requires that nursing homes offer tests to residents, although they are not required to take them. “We’re offering it because this is a medical service and there are some residents that may refuse it or may not wish to have a test, and so we can’t force our nursing residents — nor would we want to force them — to have something they’re not comfortable with,” CMS administrator Seema Verma said Tuesday on a phone call with reporters.
In addition, “the administration is holding nursing homes accountable for the testing requirement by directing surveyors to inspect nursing homes for adherence to the new testing requirements,” according to the press release. “Facilities that do not comply with the new requirements will be cited for non-compliance and may face enforcement sanctions based on the severity of the noncompliance, such as civil money penalties in excess of $400 per day, or over $8,000 for an instance of noncompliance.”
To help nursing homes pay for the additional testing required, CMS is distributing $2.5 billion from the Provider Relief Fund “on top of almost $5 billion that HHS distributed” previously to nursing homes struggling to pay the additional costs required due to the pandemic; the new money “should be available later this week,” Verma said. The agency is also offering new training courses for staff “that incorporates recent lessons learned from nursing homes” on dealing with the pandemic; the free classes include modules on hand hygiene and personal protective equipment (PPE); screening and surveillance; and cleaning the nursing home.
AMDA – The Society for Post-Acute and Long-Term Care Medicine, which represents nursing home medical directors, expressed some concern about the rule. The additional funding for testing is welcome, “but how sustainable is this level of testing for the time being?” said Alex Bardakh, the organization’s director of public policy and advocacy, in a phone interview. “How prepared are nursing facilities to do this sort of mass testing?” And since the homes will mostly be doing point-of-care rapid testing, “what are we going to do about false positives?” he added, noting that some point-of-care tests have received notoriety recently over that issue.
The false positive issue is a serious one, he continued. “In nursing homes, you’re talking about a staffer coming into a facility or not, and disrupting the workforce, or ‘cohorting’ a resident or not cohorting a resident,” Bardakh said, referring to the idea of separately housing residents who have COVID-19 from those who don’t. And nursing homes in some parts of the country are having trouble getting the needed supplies, he added. “I consistently hear concerns about pipeline and supply chain issues…. Do we truly have a strategy for how to handle it all, including the flow of PPE, the tools that are necessary, the swabs?”
Bardakh also criticized the monetary penalties attached to non-compliance. “There are always concerns about deploying civil monetary penalties at a time when it’s an ‘all hands on deck’ situation,” he said. “We talk quite a bit about partnering with facilities in terms of what they’re facing rather than taking punitive approach.”
Another part of the rule requires hospitals to report daily “several important data elements to HHS,” including the number of confirmed or suspected COVID-19-positive patients, ICU beds occupied, and availability of equipment such as ventilators and PPE, Verma said. “While many hospitals are currently reporting this information, not all hospitals have done so consistently.” The rule says CMS will have the option of terminating or suspending Medicare and Medicaid funding from non-compliant hospitals — a provision that did not sit well with hospital groups.
“America’s hospitals remain fully committed to ensuring that the federal government gets the data it needs,” American Hospital Association President and CEO Rick Pollack said in a statement. “It’s beyond perplexing why CMS would use a regulatory sledgehammer — threatening Medicare participation — to the very organizations that are on the frontlines in the fight against COVID-19. This rule should be reversed immediately.”
Moderna’s first data drop for its Covid-19 vaccine, mRNA-1273, was criticised for not including older subjects – the ones who need protection from coronavirus the most. But results released today from the same phase I NIAID-sponsored trial show promise in older age groups. A 100µg dose of mRNA-1273, which Moderna is taking into phase III, elicited encouraging levels of neutralising antibodies in older people. These antibodies are a proxy for vaccine efficacy; as older people have weaker immune systems, there had been concerns that they would not respond to Covid-19 vaccines as well as younger people. There had also been worries about side-effects in the older population, but the adverse-event profile of the 100µg dose in those aged over 55 does not look too burdensome, the CDC’s Advisory Committee on Immunization Practices heard today. Moderna, whose stock rose 6% this morning, still has much to prove – not least that a neutralising antibody response translates into protection against Covid-19. Interestingly, 25-40% of the group’s phase III trial subjects will be either over 65 or at increased risk of complications of Covid-19. The study had enrolled over 13,000 patients as of Friday.
Abbott Laboratories (NYSE:ABT) +6.5% after-hours following news that the FDA granted emergency use authorization for the company’s 15-minute COVID-19 test that will be priced at just $5.
Abbott says BinaxNOW works without relying on lab equipment – at a time when labs can take as long as two weeks to produce results – and uses a nasal swab and a small reactive card that can be administered by a range of healthcare workers, including pharmacists.
The company plans to ship “tens of millions’ of test in September, ramping to 50M tests per month by the end of October.
The new test “can be used at a massive scale to help overcome the current waiting game for test results,” John Hackett, divisional VP of applied research and technology at Abbott Diagnostics, tells Bloomberg.
British military scientists have discovered that a product found in insect repellent can kill the strain of coronavirus that causes COVID-19, Sky News reported on Wednesday.
The product, Citriodiol, could offer a new layer of protection against COVID-19 according to scientists at the UK’s Defence Science and Technology Laboratory, Sky said.
Scotland is buying 300 COVID-19 testing machines that can give results in 12 minutes, the Scottish Government said on Wednesday, helping to locate potential outbreaks in remote locations.
The devolved Scottish Government, which has power over health policy, said UK life sciences firm LumiraDx would supply at least 500,000 tests under the 6.76 million pound ($8.9 million) deal.
The test was given emergency approval last week by the U.S. Food and Drug Administration (FDA). The Scottish government said the test was going through the final stages of validation for use in Scotland.
“The contract with LumiraDx to supply 12-minute test instruments to NHS Scotland is great news for communities across the country and for the global fight against this virus,” said Ivan McKee, Scottish trade minister.
The machines can be used anywhere, making them suitable for Scotland’s remote island communities, and are connected by a “cloud” system to help track outbreaks.
Scotland’s move to buy the machines comes ahead of an expected future procurement deal between the four nations of the United Kingdom.
UK health minister Matt Hancock said at the start of August that the government would roll out millions of 90-minute tests.
Last week, Hancock said he planned to bring in regular, population-wide testing for COVID-19 by the end of the year, and tests with faster turn-around times were being trialled.
