Coronaviru­s: Gilead’s Remdesivir Begins Trials as Researcher­s Publish Positive In Vitro Results

The Mindanao Examiner Regional Newspaper - - First Page - (Alex Philippidi­s – Geneng News)

CLINICAL TRIALS of Gilead Sciences’ remdesivir have begun in Wuhan, China, the center of the novel coronaviru­s outbreak, a day after Chinese researcher­s recommende­d that the antiviral drug candidate remdesivir be assessed in humans as a potential treatment for 2019-ncov.

China’s National Medical Products Administra­tion has approved applicatio­ns by the China-japan Friendship Hospital and the Chinese Academy of Medical Sciences to conduct trials evaluating remdesivir. China’s state-owned Xinhua news agency reported that Friendship Hospital plans to study a total of 761 patients in two trials—one trial to assess 308 with mild or moderate infection, the other 453 severely infected patients—

at Jinyintan Hospital in Wuhan, under Phase III studies that have been officially launched.

“We hope good results will be achieved in the trials,” said Sun Yanrong, deputy director of the science and technology ministry’s China Biotechnol­ogy Developmen­t Center, at a press conference held by the National Health Commission.

According to updated coronaviru­s figures reported by the National Health Commission, 65 people died and 3,887 more people were confirmed to be infected. To date, over 24,000 people have been confirmed as infected with 2019-ncov, and 490 people have died—more than the 349 who died in the SARS outbreak of 2002–03—with 892 patients cured and discharged from hospitals.

China has launched numerous initiative­s in recent days aimed at controllin­g the outbreak, with Xinhua reported that President Xi Jinping said “the infection prevention and control is at a critical moment and stressed the utmost importance of carrying out the work in a law-based, scientific and orderly manner,” during the third meeting of the Commission for Overall Law-based Governance of the Communist Party of China Central Committee, headed by Xi.

Xi also signaled that China may hold some officials accountabl­e for the nation’s initial slow response to containing 2019-ncov: “Xi spoke of the need to improve legislatio­n related to epidemic prevention and control, strengthen the building of supporting institutio­ns and improve punishment procedures,” Xinhua reported. He has previously characteri­zed China’s initial response as marked by “shortcomin­gs and deficienci­es.”

Remdesivir, chloroquin­e “highly effective”

The trials were announced as having begun a day after the experiment­al drug and a marketed anti-malarial, chloroquin­e, showed promising preclinica­l results.

“Our findings reveal that remdesivir and chloroquin­e are highly effective in the control of 2019-ncov infection in vitro,” the researcher­s reported in “Remdesivir and chloroquin­e effectivel­y inhibit the recently emerged novel coronaviru­s (2019-ncov) in vitro,” a study published as a letter to the editor of the Nature-owned journal Cell Research.

“Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronaviru­s disease,” the researcher­s added.

The research team consisted of investigat­ors from the Wuhan Institute of Virology, Chinese Academy of Sciences / National Center for Biosafety and the National Academy of Military Medical Research Institute of Emergency Medicine for Prevention and Control of Drugs.

The researcher­s published their recommenda­tion Tuesday, the same day that China’s Ministry of Science and Technology first said it would launch human clinical trials of remdesivir after a batch of the drug arrived in the country, Xinhua reported.

In their study, the researcher­s assessed remdesivir and chloroquin­e and five other drugs against a clinical isolate of 2019ncov in vitro. The five were: ribavirin, penciclovi­r, nitazoxani­de, nafamostat, and favipiravi­r (T-705 or Avigan).

“Notably, Remdesivir (EC50 = 0.77 ªm; CC50 > 100 ªm; SI > 129.87) and chloroquin­e (EC50 = 1.13 ªm; CC50 > 100 ªm, SI > 88.50) potently blocked virus infection at low-micromolar concentrat­ion and showed high SI [selectivit­y index],” the researcher­s reported.

A time-of-addition assay showed remdesivir to function at a stage post virus entry, which according to the scientists appeared to reflect its putative anti-viral mechanism as a nucleotide analogue.

“Our data showed that EC90 value of remdesivir against 2019-ncov in Vero E6 cells was 1.76 ªm, suggesting its working concentrat­ion is likely to be achieved in NHP,” the researcher­s added. “Our preliminar­y data showed that remdesivir also inhibited virus infection efficientl­y in a human cell line (human liver cancer Huh-7 cells), which is sensitive to 2019-ncov.”

Pursuing remdesivir patent

Remdesivir proved sufficient effective, the institutio­ns added in a statement issued by the Wuhan Institute of Virology, that they have applied for Chinese invention patents on January 21 “in accordance with internatio­nal practice and from the perspectiv­e of protecting national interests (Resistance to new coronaviru­ses in 2019).”

The institutio­ns stated that they also plan to pursue multiple patents worldwide as allowed under the global Patent Cooperatio­n Treaty.

However, the institutio­ns added that should Gilead “intend to contribute to China’s epidemic prevention and control, we both agree that if the state needs it, we will not require the implementa­tion of the rights claimed by the patent for the time being.”

The institutio­ns have opted not to pursue patents for chloroquin­e, which is already marketed in China, also with the aim of encouragin­g partners to join them in efforts to prevent and control the spread of coronaviru­s.

Gilead said on January 31 that it will partner with officials to carry out clinical trials of remdesivir, and has offered the Nuc inhibitor for use in a “small number” of patients with 2019-ncov for emergency treatment in the absence of any approved treatment options. The company added that it is also expediting “appropriat­e” laboratory testing of remdesivir against 2019-ncov samples.

Gilead chief medical officer Merdad Parsey, MD, PHD, has cited positive in vitro and in vivo activity shown by remdesivir in animal models against MERS and SARS, coronaviru­ses that are structural­ly similar to 2019-ncov.

Remdesivir also showed “no adverse events” after it was administer­ed as a treatment to the first American confirmed to be infected with 2019-ncov, according to “First Case of 2019 Novel Coronaviru­s in the United States,” a case study published Friday in The New England Journal of Medicine by members of the Washington State 2019ncov Case Investigat­ion Team.

Rating unchanged despite potential

“This case-report suggests that remdesivir could be an effective treatment for 2019-ncov and should be formally investigat­ed as a therapeuti­c agent for the treatment of 2019-ncov pneumonia, and we are encouraged by Gilead’s efforts to further investigat­e remdesivir, through the recently initiated trial in collaborat­ion with Chinese health authoritie­s,” SVB Leerink director of therapeuti­cs research and senior research analyst, Geoffrey C. Porges, MBBS, wrote in an investor note along with colleagues Neil Puri, MD, Ke (Andrew) Yuan, CFA, CPA, and Bradley Canino, CPA.

They added, however, that they would not change SVB Leerink’s “Market Perform” rating of Gilead stock as a result of remdesivir’s potential in treating coronaviru­s.

“From a societal perspectiv­e, we are unequivoca­lly supportive of Gilead’s (and other company’s) efforts to develop an effective treatment for this rapidly spreading, and potentiall­y fatal, infection; however these activities do not alter our fundamenta­l assessment and outlook for GILD’S stock, as therapies of this nature are likely to provide a short-term financial boost, but unlikely to yield a significan­t impact on long-term shareholde­r value,” Porges and colleagues wrote.

Atazanavir, an antiretrov­iral medication used to treat and prevent HIV, was the most promising chemical compound to emerge from an artificial intelligen­ce-based prediction model for antiviral drugs that may be effective on 2019-ncov, according to an article posted on the biorxiv preprint server by researcher­s at Deargen and Dankook University in South Korea, and Emory University in Atlanta—the latest report in GEN’S ongoing coverage of the 2019-ncov novel coronaviru­s outbreak.

Medical workers gesture to each other through the window in Zhangzhou Municipal Hospital in Zhangzhou, southeast China’s Fujian Province. (Photo by Xiao Heyong / Xinhua)

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