FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19

In continuation of my update on baricitinib and remdesivir

Emergency use authorization was issued for baricitinib in combination with remdesivir for hospitalized patients with COVID-19, the U.S. Food and Drug Administration announced Thursday.

                               

The EUA for the combination treatment applies to hospitalized patients ages 2 years and older with suspected or laboratory-confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. The janus kinase inhibitor baricitinib is currently FDA-approved for treating moderately to severely active rheumatoid arthritis.

Based on the agency's review of the evidence, the FDA "determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population. And, when used under the conditions described in the EUA to treat COVID-19, the known and potential benefits of baricitinib outweigh the known and potential risks for the drug."

The FDA granted the EUA based on data from the ACTT-2 trial, a randomized, double-blind, placebo-controlled clinical trial conducted by the National Institute of Allergy and Infectious Diseases. The trial included 1,033 patients -- 515 randomly assigned to baricitinib plus remdesivir and 518 randomly assigned to placebo plus remdesivir. Patients were followed for 29 days. Median time to recovery from COVID-19 was seven and eight days for patients receiving baricitinib plus remdesivir and those receiving placebo plus remdesivir, respectively. Patients receiving baricitinib plus remdesivir had significantly lower odds of progressing to death or being ventilated at 29 days and significantly higher odds of clinical improvement at 15 days compared with patients receiving placebo plus remdesivir.

Baricitinib is not authorized or approved as a stand-alone treatment for COVID-19, the FDA notes. Its safety and effectiveness for use in the treatment of COVID-19 continue to be evaluated.

https://en.wikipedia.org/wiki/Baricitinib

https://en.wikipedia.org/wiki/Remdesivir

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19  

Experimental antiviral prevents MERS-CoV in rhesus macaques

In continuation of my update on remdesivir 

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

https://www.pnas.org/content/early/2020/02/12/1922083117
https://en.wikipedia.org/wiki/Remdesivir

Chinese scientists ask for patent on US drug to fight virus

In continuation of my update on Remdesivir

Scientists in the city at the center of China's virus outbreak have applied to patent a drug made by U.S. company Gilead Sciences Inc. to treat the disease, possibly fueling conflict over technology policy that helped trigger Washington's tariff war with Beijing.

The government-run Wuhan Institute of Virology said this week it applied for the patent in January along with a military laboratory. An institute statement acknowledged there are "intellectual property barriers" but said it acted to "protect national interests."

Granting its own scientists a patent might give the Chinese government leverage in negotiations over paying for the drug. But it also might fuel complaints Beijing abuses its regulatory system to pressure foreign companies to hand over valuable technology.

On Thursday, the official Xinhua News Agency said clinical trials of the drug, remdesivir, were due to start.

Gilead, headquartered in Foster City, California, said it applied in 2016 for a Chinese patent on use of remdesivir against coronaviruses and is waiting for a decision. The coronavirus family includes the novel coronavirus, or 2019-nCoV, blamed for the outbreak in Wuhan.

"Gilead has no influence over whether a patent office issues a patent to the Chinese researchers," said a company spokesman, Ryan McKeel. "Their application has been filed more than three years after Gilead's filing and will be considered in view of what is already known about the compound and pending patent applications."

The institute said its application was filed Jan. 21. Two days later, Chinese authorities suspended most access to Wuhan, a city of 11 million people. That lockdown has expanded to surrounding cities and some in other provinces, isolating a total of about 60 million people in the most sweeping anti-disease measures ever imposed.

China has the right under World Trade Organization rules to declare an emergency and compel a company to license a patent to protect the public. It would be required to pay a license fee that is deemed fair market value.

The government might be able to avoid that fee if the patent were granted to the Wuhan institute, part of the elite Chinese Academy of Sciences.

The institute said it applied for a "use patent" that specifies the Wuhan virus as the drug's target. Gilead's patent application, filed before the virus was identified, cites only the overall family of coronaviruses.

The Chinese researchers made their patent application "from the perspective of protecting national interests," said the institute statement.

"If relevant foreign companies plan to contribute to China's epidemic prevention and control, we both agree that if the state needs it, we will not require enforcement of rights given by the patent," it said.

Gillead said last week it was working with U.S. and Chinese health authorities on studying remdesivir. The company said it has provided the drug for emergency use in a small number of patients with the Wuhan virus "in the absence of any approved treatment options."

https://www.bloomberg.com/news/articles/2020-02-03/gilead-drug-to-undergo-human-trials-in-china-to-cure-coronavirus

https://www.med-chemist.com/search?q=remdesivir

Experimental Antiviral Drug to Be Tested Against New Coronavirus

In continuation of my update on Remdesivir

A clinical trial to test an experimental antiviral drug's effectiveness against the new coronavirus will be conducted in China as it battles a coronavirus outbreak there.

The drug Remdesivir -- created to fight infectious diseases such as Ebola and SARS -- will be tested by a medical team from Beijing-based China-Japan Friendship Hospital, a hospital spokeswoman told Bloomberg News. The trial will be conducted in the central Chinese city of Wuhan, the epicenter of the outbreak that has sickened more than 17,000 people and killed more than 360 in China. Researchers will recruit up to 270 patients with mild and moderate pneumonia caused by the virus, according to Chinese news outlet The Paper, Bloomberg News reported.

Remdesivir is not approved for use by any drug regulator in the world, but it is being given to patients infected with the new coronavirus because there are no approved treatments, drug maker Gilead said in a statement. The company said it is working with Chinese health officials to organize the clinical trial to determine its effectiveness and safety of the drug in patients infected with the new coronavirus. The HIV medication Kaletra has also been recommended by China's health regulator as an antiviral treatment for the new coronavirus, and clinical trials of that drug are also being arranged, according to The Paper.

On Sunday, officials reported three more cases of the new coronavirus in California, bringing the total in the United States to 11. Worldwide, there are now 146 coronavirus cases in at least 23 countries outside China, according to the World Health Organization. One death outside China has been reported in the Philippines.

https://www.bloomberg.com/news/articles/2020-02-03/gilead-drug-to-undergo-human-trials-in-china-to-cure-coronavirus

https://en.wikipedia.org/wiki/Remdesivir

AbbVie's HIV Drug Aluvia (Lopinavir/ritonavir) Seen as Potential Treatment for Coronavirus

In continuation of my update on Lopinavir/Fritonavior

 

More than 80 people have died from the coronavirus in China. The Chinese government is turning to a drug developed by AbbVie for HIV patients as a potential treatment for the outbreak that has reached the shores of the United States.

AbbVie said it was donating more than one million dollars’ worth of Aluvia, a combination of lopinavir and ritonavir as an ad-hoc treatment for pneumonia that is associated with the outbreak. The Chinese government suggested last week that taking two lopinavir/ritonavir pills and inhaling a dose of nebulized alpha-interferon twice a day could benefit these patients, Reuters reported. There are more than 2,000 known cases of the coronavirus in China. The illness has caused parts of China to grind to a halt as health officials seek to contain the spread of the virus.

The decision to use AbbVie’s medicine came after a noted respiratory expert at Peking University First Hospital in Beijing said he was given the HIV drugs to fight the virus after he contracted it following a visit to Wuhan, the capital of Hubei province in central China where the virus is thought to have originated. Wan Guangfa came down with the virus after interacting with coronavirus patients. He told China News Week that the HIV treatments worked for him.

The coronavirus family includes the common cold as well as viruses that cause more serious illnesses, such as SARS that spread from China to more than a dozen countries in 2002-03 and killed about 800 people. Also, the virus is similar to Middle Eastern Respiratory Syndrome (MERS), which developed from camels. The virus infects the lungs, and symptoms start with a fever and cough. It can progress to shortness of breath and breathing difficulties leading to pneumonia.

Aluvia is thought to be a potential treatment for the coronavirus due to its ability to block a protease that the virus needs to replicate within the human body. AbbVie’s drug has previously been tested in patients with SARS and MERS, which are similar viruses, Endpoints reported.

Other drugmakers are also responding. Gilead Sciences is looking at its Ebola virus drug remdesivir, an antiviral, as a potential coronavirus treatment, The Motley Fool reported. Moderna also has a treatment for the virus under investigation. The company received a grant from the Coalition for Epidemic Preparedness Innovations to investigate a treatment for the virus. Inovio also received a grant from CEPI to develop a potential vaccine.

https://en.wikipedia.org/wiki/Lopinavir/ritonavir

AbbVie's HIV Drug Aluvia Seen as Potential Treatment for Coronavirus  

Researchers identify three drugs as possible therapeutics for COVID-19

In continuation of my update on Amodiaquine and nebivolol

amodiaquine

Zuclopenthixol

Nebivolol

Based on virtual and in vitro antiviral screening that began in the earlier months of the COVID-19 pandemic, the researchers led at UTHSC by Colleen Jonsson, PhD, identified zuclopenthixol, nebivolol, and amodiaquine as promising therapeutics for the virus in its early stages.

Dr. Jonsson is a professor and the Endowed Van Vleet Chair of Excellence in Virology in the College of Medicine at UTHSC. She also directs the UTHSC Regional Biocontainment Laboratory (RBL), where this research was conducted. The university's RBL is one of roughly a dozen federally funded labs authorized to safely study contagious pathogens.

In a paper published in ACS Pharmacology & Translational Science, the researchers propose the drugs as possible candidates for testing in future clinical trials to improve immune response to the virus. Amodiaquine is an older antimalarial, zuclopenthixol is an antipsychotic, and nebivolol is a blood pressure medication.

"Particularly in the context of this pandemic, there is a stringent need for high-quality studies that can provide critical knowledge concerning the COVID-19 disease and reliable treatment proposals," the paper states. "With these caveats in mind, we conceived a computational workflow that included independent in vitro validation, followed by assessing emerging candidates in the context of available clinical pharmacology data with the aim of proposing suitable candidates for clinical studies for early stage (incubation and symptomatic phases) patients infected by SARS-CoV-2."

"Given the need for improved efficacy and safety, we propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection," the researchers wrote.

Comparing the drugs to hydroxychloroquine, the anti-malarial drug most-frequently studied in clinical trials for use as a COVID-19 therapeutic, the researchers examined 4,000 approved drugs and found these three to act similarly to the hydroxychloroquine, and in some cases, more safely. The research indicates they may also improve efficacy when combined in lower doses with remdesivir, an anti-viral given an emergency use authorization by the United States Food and Drug Administration as a therapeutic for COVID-19.

"Think of it as a whack-a-mole game," said Tudor Oprea, MD, PhD, professor of Medicine and Pharmaceutical Sciences, chief of the UNM Division of Translational Informatics, and corresponding author on the paper. "Instead of having one hammer, you have two hammers, which is more effective. We're trying to give the scientific community two hammers, instead of one."

Dr. Jonsson added, "This is a very exciting discovery and we are following up on the potential use of zuclopenthixol, nebivolol, and amodiaquine in additional research studies."

https://en.wikipedia.org/wiki/Amodiaquine

https://en.wikipedia.org/wiki/Zuclopenthixol

https://en.wikipedia.org/wiki/Nebivolol

Researchers identify three drugs as possible therapeutics for COVID-19