Remdesivir and coronavirus challenge

Remdesivir and coronavirus  challenge

Even as the global scientific community is scrambling to find a cure for the emergent COVID-19 infection, several experimental therapies are being investigated for their potential to contain the deadly virus.

Remdesivir, a nucleotide analogue developed by Gilead as a treatment for Ebola virus disease and Marburg virus infections, is considered the most promising of the potential drug candidates.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have found that remdesivir was able to reduce severity, virus replication and lung damage in monkeys with Middle East Respiratory Syndrome Coronavirus (MERS-CoV). They suggest that it may also have utility for other, related coronaviruses, such as SARS-CoV-2.

Previously, remdesivir had been shown to be protective in monkeys infected with the Ebola virus, but it did not succeed in fighting the virus in humans.

Reports said that one person in the US had survived a COVID-19 infection in January after being treated with remdesivir.

Gilead has initiated two phase 3 trials using the drug in China in association with regulatory authorities.

One study is evaluating remdesivir in patients with confirmed disease who have developed more severe clinical manifestations such as a requirement for supplemental oxygen. The other study is testing remdesivir in patients with confirmed COVID-19 infection and who have been hospitalised, but are not displaying significant clinical manifestations of the disease such as oxygen requirement.

Both studies began enrolling patients in February. Clinical trial results are anticipated in April. Remdesivir could be approved by Chinese authorities as early as May. 

Several patients with COVID-19 have also received the drug under a compassionate use protocol.

Gilead is also planning to launch two new phase 3 studies in March on around 1000 COVID-19 patients across Asian countries following the granting of investigational new drug status after a rapid review by the USFDA.  

Meanwhile, BrightGene, a Chinese pharma firm, disclosed that the company successfully made a generic copy of remdesivir. The Suzhou-based firm has already mass-produced remdesivir’s active ingredient and is in the process of making finished doses. 

Favilavir: First approved drug

In February, China’s National Medical Products Administration approved anti-viral drug favilavir to treat COVID-19, making it the first approved drug against the new coronavirus.

Fapilavir has demonstrated efficacy with minor side effects in an ongoing 70-patient clinical trial in Shenzhen, Guangdong province. 

Favipiravir is already approved for the treatment of influenza in China. 

China has launched a few trials on chloroquine, an antimalarial, which showed activity against SARS-CoV-2 in cell culture.

Innovation Pharmaceuticals is planning to explore its defensin mimetic drug candidate brilacidin as a potential treatment for COVID-19

Brilacidin is a small molecule in late-phase development. In preclinical studies, the drug demonstrated antiviral properties, added the company. 

Other medications, including arbidol and darunavir, have also recently been found capable of arresting viral growth in lab cells, but require clinical trials to confirm their safety and potency on humans.

Experimental antibodies

A slew of experimental biologic therapies are also under examination for fighting COVID-19.

Regeneron, a leading biotechnology company, recently expanded its collaboration with the US Department of Health and Human Services (HHS) to develop new treatments for combating the novel coronavirus.

The New York-headquartered firm, which developed experimental three-antibody cocktail REGN-EB3 against Ebola, is currently working on potential monoclonal antibodies to tackle COVID-19.

“We feel well equipped to tackle the challenge of this novel coronavirus, given our turn-key technology for rapid antibody therapeutic development, as well as our track record in infectious diseases,” says Christos Kyratsous, Vice President of Infectious Disease R&D at Regeneron.

CytoDyn Inc has recently joined hands with Longen China Group for developing leronlimab for the treatment of COVID-19 and cancer.

Leronlimab, a humanized IgG4 mAb that blocks CCR5, has been granted Fast Track designation by the US FDA as a combination therapy along with HAART for HIV-infected patients and for metastatic triple-negative breast cancer. 

Leronlimab has successfully completed nine clinical trials in over 800 people, and met its primary endpoints in a pivotal phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients), Cytodyne said.

Another study tests serum from COVID-19 survivors in 300 people to check whether the antibodies one person builds up to fight a virus can help someone freshly infected to fight it off.

Two stem cell trials are also listed in China’s registry. 

Trials involving traditional medicine

Currently, China is running more than 80 clinical trials on potential treatments for COVID-19. The trials include new pharmaceutical drugs as well as thousand-year-old traditional therapies, reports said.

More than 15 clinical trials involving a variety of traditional Chinese medicines are listed. One of them assesses shuanghuanglian, a Chinese herbal medicine that contains extracts from the dried lianqiao (Forsythiae fructus), which is used for treating infections for more than 2,000 years. The trial has 400 participants, including a control group given standard treatment. 

WHO recognised traditional Chinese medicine in its compendium of diseases in a controversial move last year. 

WHO is working with Chinese scientists to set a standard clinical trial protocol that could simultaneously be run by clinicians around the world. It will compare an HIV-drug combination (lopinavir and ritonavir) with remdesivir. 

Lopinavir+ ritonavir combo

Currently, COVID-19 is being managed using protease inhibitors lopinavir and ritonavir used in the treatment of HIV, in combination with flu drug oseltamivir in large doses.

Following the outbreak in China, the Indian drug regulator has also given emergency approval to Indian Council of Medical Research (ICMR) to use lopinavir and ritonavir tablets for the treatment of the infection.

It is an “experimental repurposed drug” and should be used only in cases where there is documented evidence of the person suffering from the infection, ICMR informed. 

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