NIH tests therapies to help cut hospital stays for COVID-19 patients

(Reuters) – The U.S. National Institutes of Health (NIH) has started a late-stage trial to evaluate if immune-modulating therapies from three drugmakers can help reduce the need for ventilators for COVID-19 patients and shorten their hospital stay.

The NIH said on Friday it has selected three agents for the study – Johnson & Johnson unit Janssen Research’s Remicade, Bristol Myers Squibb’s Orencia and Abbvie Inc’s experimental drug cenicriviroc.

The study will enroll up to 2,100 hospitalized adults with moderate to severe COVID-19 symptoms in the United States and Latin America.

Immune-modulating therapies are medications that alter the way the immune system works. Severe infections are believed to be triggered by an over-reaction of the immune system, known as a “cytokine storm,” and drugs that suppress certain elements of the immune system can play a role in arresting a rapid escalation of symptoms.

This can lead to acute respiratory distress syndrome and multiple organ failure, among other life-threatening complications.

The NIH said its clinical trial – ACTIV-1 Immune Modulators (IM) – will last six months, and the agency will study if the therapeutics can restore balance by modulating that immune response.

All patients will be given Gilead Sciences Inc’s antiviral drug remdesivir – the current standard of care – and also be randomly assigned to receive a placebo or one of the immune modulators as an add-on treatment, the NIH said in a statement.

Remdesivir was one of the drugs used to treat U.S. President Donald Trump’s coronavirus infection, and has been shown in previous studies to have cut time to recovery, though the European Union is investigating it for possible kidney injury.

(Reporting by Vishwadha Chander in Bengaluru, Editing by Sherry Jacob-Phillips)

Split screen: Trump and Biden to headline dueling town halls

By Joseph Ax

(Reuters) – U.S. President Donald Trump and Democratic challenger Joe Biden will hold dueling prime-time town halls on Thursday instead of their second presidential debate, which was canceled after Trump declined to take part in a virtual matchup.

With less than three weeks to go until the Nov. 3 vote, the Republican president is searching for ways to change the dynamics of a race in which Biden has a double-digit advantage in some national polls.

Nearly 15 million Americans, a record for this date, have cast ballots, according to the U.S. Elections Project at the University of Florida, as voters seek to avoid in-person lines on Election Day because of concerns about the novel coronavirus.

North Carolina, a highly competitive state, began more than two weeks of in-person early voting on Thursday. Local news reports showed long lines of voters eager to cast ballots, and Trump was due to hold an afternoon rally in Greenville in the eastern part of the state.

Trump’s campaign is counting on a surge of last-minute votes. But Reuters/Ipsos polling conducted between Oct. 9 and Oct. 13 shows there are far fewer undecided likely voters this year – around 8% – and they are just as likely to pick Biden as they are Trump.

Four years ago at this stage of the campaign, more than twice as many people were similarly wavering between Trump and his Democratic opponent, Hillary Clinton.

The Reuters/Ipsos polling shows Biden holding a 10 percentage-point lead nationally, with a tighter margin in the battleground states that will help decide the election.

Both candidates have been visiting those states this week, with Trump holding rallies in Florida, Pennsylvania and Iowa and Biden traveling to Ohio and Florida.

Trump has pulled into a statistical tie with Biden in Florida, a key battleground, with 47% support versus Biden’s 49%, and a credibility interval of 4 points, a Reuters/Ipsos opinion poll showed.

Thursday’s town halls, in which each candidate will field questions from voters, will take place at 8 p.m. EDT (0000 GMT), with Trump on NBC from Miami and Biden on ABC from Philadelphia.

Trump pulled out of the scheduled debate when the commission in charge of organizing the event said it would be held virtually after the president contracted the coronavirus. A final debate is still scheduled for Oct. 22 in Nashville, Tennessee.

On Thursday, the Biden campaign said two people involved in the campaign had tested positive for COVID-19, including one on the staff of U.S. Senator Kamala Harris, Biden’s running mate.

Although neither Biden nor Harris was in close contact with the people, the campaign said it was cancelling Harris’ travel until after Sunday, “in line with our campaign’s commitment to the highest levels of precaution.”

Trump has returned to the campaign trail after spending several days being treated for the virus in a military hospital.

NBC said on Wednesday that Clifford Lane, clinical director at the National Institutes of Health, and the government’s top infectious disease specialist, Anthony Fauci, had concluded “with a high degree of confidence” that Trump was no longer “shedding infectious virus.”

The election could be the most closely contested in recent memory due to a deeply divided electorate and the possibility that Trump will challenge widely used mail-in ballots, claiming without evidence they are fraudulent.

(Reporting by Trevor Hunnicutt and Chris Kahn in New York and Doina Chiacu and James Oliphant in Washington; Writing by Joseph Ax and Sonya Hepinstall; Editing by Colleen Jenkins and Matthew Lewis)

Eli Lilly says other COVID-19 antibody drug trials ongoing after study halted for safety concern

By Carl O’Donnell and Michael Erman

(Reuters) – Eli Lilly & Co on Wednesday said other trials of its experimental coronavirus antibody therapy remain on track after a government-run study testing the treatment in hospitalized COVID-19 patients was paused due to safety concerns.

Lilly said on Tuesday that an independent safety monitoring board requested a pause in the trial, called ACTIV-3, due to a potential safety issue.

The National Institutes of Health (NIH), which is collaborating with Lilly on the trial, said the advisory board paused the trial after seeing a “difference in clinical status” between patients on Lilly’s drug on those who received a placebo, without providing further detail.

Lilly on Wednesday said the paused trial is distinct from others it is conducting because it focuses on hospitalized patients who are more severely ill and being treated with other drugs as well, including Gilead Sciences Inc’s antiviral remdesivir.

The company had already asked U.S. regulators for an emergency use authorization (EUA) for the antibody drug, called bamlanivimab or LY-CoV555, to treat mild to moderate COVID-19 patients, based on interim data from a different study in those less severe illness. It is also testing the drug in nursing homes to see if it can prevent staff and residents from getting infected.

The U.S. Food and Drug Administration did not immediately respond to a request for comment on the status of the EUA application.

LY-CoV555 is similar to the experimental dual-antibody therapy from Regeneron Pharmaceuticals Inc that was used to treat U.S. President Donald Trump. That treatment is also awaiting clearance by U.S. regulators.

Trump touted both drugs as being tantamount to cures in a video he posted last week after being released from the hospital.

Lilly said in a statement that these type of treatments may prove to be less beneficial for hospitalized patients than for those with more mild cases of the disease. A Lilly spokeswoman declined to comment further on why the trial was halted.

The paused trial is being conducted in partnership with the U.S. National Institute of Allergy and Infectious Diseases, a division of the NIH that is working with several drugmakers on COVID-19 treatments and vaccines.

It was halted at the request of an independent oversight panel, called a Data Safety and Monitoring Board (DSMB). It is not uncommon to pause drug trials to investigate safety concerns, and such actions do not necessarily indicate a serious problem.

“Lilly trusts the judgment of the independent DSMB and supports its decisions to exercise caution in ensuring the safety of the patients participating in this study,” the company said in a statement.

(Reporting by Carl O’Donnell; Editing by Chizu Nomiyama and Bill Berkrot)

NIH starts clinical trial testing antibody treatments in COVID-19 patients

(Reuters) – The U.S. National Institutes of Health (NIH) said on Tuesday it has started a study to evaluate two antibody treatments in COVID-19 patients as part of the agency’s program to identify promising drugs to help tackle the new coronavirus.

The trial will test AbbVie Inc’s psoriasis drug risankizumab along with Gilead Sciences’ antiviral remdesivir, compared to a placebo and remdesivir.

The study will also test Humanigen’s experimental drug lenzilumab with remdesivir, compared to placebo and remdesivir.

“The goal here is to identify as quickly as possible the experimental therapeutics that demonstrate the most clinical promise as COVID-19 treatments and move them into larger-scale testing,” said NIAID Director and U.S. infectious diseases expert Anthony Fauci.

Gilead’s remdesivir, which was among the first to be used to treat COVID-19 and received emergency use authorization from the U.S. Food and Drug Administration in May, has since been authorized for use in several other countries.

Risankizumab and lenzilumab belong to a class of drugs known as monoclonal antibodies that are laboratory-made versions of proteins naturally produced by the immune system in response to invading viruses or other pathogens.

The treatment has come under the spotlight after U.S. President Donald Trump was treated with Regeneron Pharmaceuticals’ antibody drug earlier this month.

Regeneron and Eli Lilly have both applied to the U.S. FDA for emergency use of their antibody treatments.

(Reporting by Amruta Khandekar; editing by Ankur Banerjee and Ramakrishnan M.)

NIH launches trial of Rigel drug for severe COVID-19

By Deena Beasley

(Reuters) – The U.S. National Institutes of Health on Thursday launched a clinical trial of fostamatinib, currently used to treat a blood platelet-destroying autoimmune disorder, in patients hospitalized with severe COVID-19, the disease caused by the novel coronavirus.

The tablets, sold under the brand name Tavalisse by Rigel Pharmaceuticals Inc, have shown in lab and animal studies the ability to block production of sticky, web-like substances that the immune system produces to trap foreign invaders.

For reasons that are still not clearly understood, the immune systems of some COVID-19 patients can overreact, creating an inflammatory cascade that can be toxic to organs, cause blood clots and worsen pneumonia.

Fostamatinib is designed to block activity of an enzyme that regulates parts of the body’s immune response, including “neutrophil extracellular traps,” or NETs, that white blood cells release to ensnare and kill pathogens.

“I am most excited about this drug because I know that as a targeted therapy it inhibits NETs, which we think is a big contributor to mortality,” said Dr. Richard Childs, clinical director of the National Heart, Lung, and Blood Institute.

The randomized, placebo-controlled Phase 2 trial will enroll 60 patients at the NIH Clinical Center in Bethesda, Maryland, Inova Health System’s Northern Virginia hospital and possibly other Inova locations.

The primary objective is evaluation of safety.

The trial is likely to take two or three months, and Rigel is considering how a larger study might be conducted, said Raul Rodriguez, the company’s chief executive officer.

Other immune system-modulating drugs are being used in COVID-19 patients, including the decades-old steroid dexamethasone, which is so far the only medication shown to improve their chance of survival.

“The problem is the steroid is a non-targeted therapy. It will also hit parts of the immune system that are very important for fighting off the virus or other infections,” Childs said. “Some patients that get COVID will get a bacterial infection … we see that all the time with influenza.”

Researchers at Imperial College London are also running an open-label study of fostamatinib in patients with COVID-19 pneumonia.

The drug is approved in the United States and Europe for treating adult chronic immune thrombocytopenia, a rare autoimmune disorder in which the body’s immune system destroys healthy platelets, leading to easy or excessive bruising and bleeding.

(Reporting by Deena Beasley; Editing by Timothy Gardner)

AstraZeneca pauses coronavirus vaccine trial

LONDON (Reuters) – AstraZeneca has suspended global trials of its experimental coronavirus vaccine after an unexplained illness in a participant, knocking the British drugmaker’s shares on Wednesday as prospects for an early rollout dimmed.

The vaccine to combat COVID-19, which AstraZeneca is developing with the University of Oxford, has been described by the World Health Organization as probably the world’s leading candidate and the furthest developed.

However, AstraZeneca said on Tuesday it had paused trials, including late-stage ones, to allow an independent committee to review safety data, and it was working to minimize any potential impact on the timeline.

“It is obviously a challenge to this particular vaccine trial,” Britain’s Health Secretary Matt Hancock told Sky News.

The stakes are high because AstraZeneca, Britain’s largest drugmaker by market value, has already agreed to supply close to three billion doses to governments across the globe.

This is more than any other vaccine project, but asked whether the pause would set back the development process, Britain’s Hancock said: “Not necessarily, it depends on what they find when they do the investigation”.

Most states will contribute financially to developing the vaccine, even if the trial fails.

‘ROUTINE ACTION’

Britain’s medical regulator said it is urgently reviewing information available to determine whether trials can restart as quickly as possible.

A New York Times report citing a person familiar with the situation said a participant based in Britain was found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections.

Whether this was directly linked to AstraZeneca’s vaccine remains unclear, it said. AstraZeneca declined to comment.

A person familiar with the situation told Reuters the illness occurred in the British trial which began in May with more than 12,000 participants, from 5 years old to beyond 70.

The U.S. trial, with a targeted 30,000 participants, was launched last week for the vaccine AZD1222, which is also in late-stage clinical trials in Brazil and South Africa.

Additional trials are planned in Japan and Russia, with a targeted 50,000 participants globally.

South Korea said it would look into the suspension and review its plan to participate in manufacturing the vaccine and health ministry official Yoon Tae-ho added such suspensions of clinical trials were not rare “as various factors interact”.

This was echoed by Germany’s Leukocare, which is working on a vaccine similar to AstraZeneca’s but is at an earlier stage.

“When you are inoculating 20,000 people, it is a foregone conclusion that at some point you will have severe adverse events. As soon as a link to the vaccine can clearly be ruled out, the trial continues,” CEO Michael Scholl said.

Immune related conditions such as inflammations, however, would be subject to particular scrutiny, he added.

The Oxford vaccine is designed to instruct human cells to make distinguishing parts of the coronavirus. That allows the immune system to build an arsenal against future infections.

A harmless virus known as adenovirus is used to bring the genetic instruction into the body, an approach which is also being pursued by China’s CanSino, Russia’s Gamaleya institute or Johnson & Johnson.

Backers of the Gamaleya candidate, the first Russian COVID-19 vaccine, underscored the difference between their jab, based on a adenovirus in humans, and the British contender with an adenovirus found in monkeys.

“We have consistently drawn attention to human adenoviral platform being much safer and much more studied than any other new platform,” the head of Russia’s sovereign wealth fund Kirill Dmitriev told Reuters.

In choosing a monkey virus, AstraZeneca, as well as Leukocare, are trying to avoid the risk of the immune system attacking the vector, due to a previous bout with an adenovirus.

The decision to put the trial on hold has impacted clinical trials being conducted by other vaccine makers, which are looking for signs of similar reactions, Stat said.

Serum Institute of India said its trials of AstraZeneca’s vaccine were ongoing and had not faced any issues.

The U.S. National Institutes of Health, which is providing funding for AstraZeneca’s trial, declined to comment.

Moderna said in an emailed statement it was “not aware of any impact” to its ongoing COVID-19 vaccine study.

Leading U.S. and European vaccine developers pledged on Tuesday to uphold scientific safety and efficacy standards for their experimental vaccines.

Nine companies, including AstraZeneca, Moderna and Pfizer, issued an “historic pledge” after concerns that safety standards might slip under political pressure to rush out a vaccine.

The other signatories were Johnson & Johnson, Merck & Co, GlaxoSmithKline, Novavax Inc, Sanofi and BioNTech.

(Reporting by Guy Fauconbridge, Estelle Shirbon, Kate Kelland in London, Deena Beasley; Additional reporting by Peter Henderson in San Francisco, Rocky Swift in Tokyo, Sangmi Cha in Seoul and Miyoung Kim in Singapore; Editing by Alexander Smith)

U.S. NIH awards nine companies $129 million to scale up COVID-19 testing

(Reuters) – The National Institutes of Health is awarding $129.3 million to nine companies to support scaling-up coronavirus testing and manufacturing new testing technologies, the U.S. health agency said on Wednesday.

The funding is part of NIH’s Rapid Acceleration of Diagnostics (RADx) initiative that was launched in April to speed up innovation in the development, commercialization, and implementation of technologies for COVID-19 testing.

NIH said three of the selected companies, MatMaCorp, Maxim Biomedical Inc and MicroGEM International, offer point-of-care tests that produce immediate results.

The remaining six – Aegis Sciences, Broad Institute, Ceres Nanoscience Inc, Illumina Inc, PathGroup and Sonic Healthcare – offer lab-based tests.

The funding will help significantly expand national testing in September, with the laboratories managing collection, analysis and reporting of tens of thousands of tests a day, the agency said in a statement.

In July, NIH made a similar contribution of $248.7 million to seven companies.

“Diagnostic testing is a critical component of the nation’s strategy to meet the challenge of the COVID-19 pandemic,” said NIH Director Francis Collins.

(Reporting by Vishwadha Chander in Bengaluru; Editing by Shinjini Ganguli)