We Have Good Reason To Be Hopeful For Gilead's Remdesivir for Covid-19

Seeking Alpha ^ | 03/31/2020 | Richelle Cutler-Strom

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* Gilead is testing efficacy of remdesivir against the COVID-19 in multiple international trials.

* Remdesivir prevented severe lung damage from MERS coronovirus infection in a mouse and monkey model.

* Preclinical data and an explanation for the Ebola trial failure indicate that remdesivir will be a successful treatment for COVID-19.

* Inevitable remdesivir licensing deals, with exclusivity until 2034, and its forthcoming marketing of a blockbuster arthritis drug, filgotinib, will increase Gilead's revenue significantly.

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Gilead Sciences Inc. (NASDAQ:GILD) is currently testing remdesivir in multiple human trials for efficacy against the novel coronavirus (COVID-19). Remdesivir is an adenosine nucleotide prodrug that inhibits replication in a broad range of viruses (Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxovirida) in vitro. Remdesivir reduced lung damage inflicted from the MERS coronavirus in mice and monkeys. The animal studies showed that optimal therapeutic efficacy requires early dosing. However, MERS patients were found to have prolonged viral replication, so remdesivir may still benefit the most severe coronavirus cases.

Remdesivir failed in Ebola virus trials even though remdesivir inhibited Ebola virus replication in vitro and in a monkey study. These preclinical studies indicated that remdesivir would be effective against the Ebola virus in humans. So, what went wrong? Could disappointment be around the corner for remdesivir in the COVID-19 trials?

The Ebola monkey study showed that a high remdesivir concentration (10 mg/kg) was critical for maximum suppression. The trial also indicated that too high a concentration, over consecutive days, could cause liver injury. Gilead played it safe by using a low dosage in the Ebola trial (~3 mg/kg loading dose, 1.5 mg/kg maintenance dose, assuming a 66 kg patient). Thus, the dosage may not have reached an effective concentration in all cell types. Furthermore, Ebola causes systemic intravascular coagulation, which could have restricted remdesivir circulation through organs.

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WHY REMDESIVIR WILL WORK DIFFERENTLY FOR COVID-19

Ebola causes systemic intravascular coagulation, which could have restricted remdesivir circulation through organs. The stronger efficacy of the Ebola targeting antibodies could be attributed to their ability to enter the lymphatic system, circumventing the coagulated capillaries - the antibodies could reach infected cells, whereas remdesivir could not.

Gilead is using the same remdesivir dosage in the COVID-19 trials as used in the Ebola trial. Fortunately, COVID-19 infected patients do not have circulatory problems.

Also, COVID-19 targets the lungs, and remdesivir robustly inhibits COVID-19 replication in human airway epithelial cells in vitro. The selected trial dosage is based on the effective in vitro inhibitory concentration along with in vivo pharmacokinetics and toxicity data. Accordingly, lung epithelial cells of COVID-19 infected patients receive an effective concentration of remdesivir.

Remdesivir may also be more readily incorporated into coronavirus RNA than Ebola RNA since remdesivir appears to have a higher affinity for the coronavirus polymerase than the Ebola polymerase.

[Kriggerel]

There is a balm in Gilead?

[Spirochete]

I was waiting for a Gilead thread. I'm pretty sure this is the reason for the extreme resistance to cloroquine or hydroxychloroquine therapy.

I suspect some of the posters here were/are Gilead trolls or board members.

[WildHighlander57]

Kriggerel wrote:

“There is a balm in Gilead?”

That is what pops into my mind every time I see that company name.

[RideForever]

REMDESIVIR is a trade mark drug, cost of treatment hundreds of dollars (to recover development costs). It can’t recover costs on the original intent of the drug, so they’re throwing it at COVID-19 to see relative effectiveness.

The HCQ-ZPak w/ zinc is closer to $20.

Follow the money ....

[Steve Van Doorn]

Gilead Sciences (Financed by Bill Gates.) This company makes Remdesivir which either stops or mutates the production of RNA in the body. Which over time this will create huge genetic flaws which the body will forget.
With the fast tracking going on Remdesivir will almost assuredly be allowed.

[RinaseaofDs]

I will NEVER take this drug.

[SeekAndFind]

I am interested in knowing your reasons. It might help other people if the reason is sound.

[windsorknot]

I’ve also seen Kaletra mentioned as possibly useful to fight Wuhan-19. It is a combination of two antivirals.

[RinaseaofDs]

I don’t trust vaccines bankrolled by Bill Gates

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RE:I don’t trust vaccines bankrolled by Bill Gates

Remdesivir is NOT a vaccine.