As anticipation mounts over the prospects for an experimental Gilead Sciences (GILD) drug to combat the novel coronavirus, two Wall Street analysts suggested it remains uncertain whether the antiviral therapy will be successful after assessing a new paper that examined a dozen U.S. patients.

The paper, published on a preprint server without peer review, described the epidemiology, clinical course, and viral characteristics of the first 12 U.S. patients with Covid-19, only three of whom were treated with remdesivir, which was developed to treat the Ebola virus but shelved after proving less effective than other drugs during testing. The analysis was conducted by the Centers for Disease Control and Prevention Covid-19 response team.

The team looked at patients with mild to moderately severe illness, which was detected early, and the findings indicated that “the window for diagnosis is long” and hospitalized patients showed signs of worsening in the second week after illness began. But RBC Capital Markets analysts examined individual patient data and decided the Gilead drug showed mixed results, at best.

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“Based on our review of the clinical and virological courses, we believe remdesivir’s contribution to efficacy remains unclear, and with a side-effect profile that may not be completely benign,” the RBC analysts wrote in a note to investors. “We continue to see a less than 50/50 possibility that the drug is ultimately proven effective.”

More specifically, they maintained there was not a “clear temporal association” between treating patients with remdesivir and improvements in oxygen requirements, fever, and viral results, compared with hospitalized patients who did not receive the investigational drug. The analysts also noted that remdesivir patients experienced nausea, vomiting, rectal bleeding, and elevated liver enzymes.

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As the pandemic spreads, a race is underway to develop therapies and vaccines, but also cull existing treatments for ways to combat the virus. The Gilead drug, which was revived recently, is high on the list and testing has begun in the U.S. and China. The drug maker, which distributed the drug on a compassionate use basis to several hundred patients, expects to start its own late-stage trials this month.

Consequently, every twist and turn involving each product and each test will be closely scrutinized for signs of effectiveness. Even preliminary findings will be picked through for clues, given that countless lives depend on such outcomes. The Covid-19 response team, which includes public health officials from around the U.S., noted the paper was not peer-reviewed and research has not yet been evaluated.

Nonetheless, the RBC analysts wrote there is “good news and bad news” about the course of the disease. Besides side effects, several patients were hospitalized despite being under 60 years old and with limited comorbidities. Several also worsened in the second week of treatment, suggesting prolonged monitoring and management will be required, they wrote.

On the other hand, the study authors concluded that “the overall clinical course appears more favorable than what was observed in China, for patients in the U.S.” Notably, 42% did not require hospitalization. But the analysts cautioned that it is “unclear whether this represents a different level of medical care or an evolving viral profile.”

Some qualifiers are worth noting. Again, the analysis was not peer reviewed. Under the circumstances, there is likely to be a much lower bar than usual for various side effects. And as the analysts acknowledged, interpretation of the findings is “confounded by multiple other medications, including steroids and antibiotics, given to many of these patients.”

Moreover, the Gilead drug was typically given to patients as they worsened, so it remains possible the drug prevented them from taking an even worse turn. Finally, the analysts noted that remdesivir was given to the patients at a later stage of illness than in the clinical trials, suggesting the therapy can yield a better outcome if administered sooner rather than later.

“The small sample size and mixed results highlight the difficulty in obtaining a clear picture of efficacy,” the analysts conceded.

[UPDATE: Later, a Gilead spokeswoman wrote us that remdesivir is being assessed in multiple clinical trials globally in order to evaluate its safety and efficacy in treating COVID-19… We also have safety information from trials… in Ebola.” In Phase 1 single and repeated dose safety and pharmacokinetic studies in more than 80 healthy humans, the drug exhibited “predictable dose-proportional pharmacokinetics with no observed serious adverse effects. Transient low-grade elevations in liver transaminases were observed during the Phase 1 studies in some participants – the clinical significance of these laboratory changes is not known.

“Clinical trials have also been conducted in Ebola survivors in West Africa, and in patients with acute Ebola virus disease in the Democratic Republic of Congo. As of January 18, 2020, more than 500 individuals have received at least a single IV dose of remdesivir, of which 400 were patients in the DRC with acute Ebola and were treated either in a Phase 2/3 trial or in emergency investigatioanl protocols, or MEORI. In these studies, no significant adverse events or laboratory abnormalities were attributed to remdesivir by study investigators.”]

  • Remdesivir is not actually such a new drug it is a reformulation/pro-drug of tenofovir already in use/approved for HIV and Hepatitis C so while I understand need to tweak the molecule and get patent extension or orphan status, this is not clear at all that tenofovir is the active/MOA.

    And I think this opaque patent/IP platform/science will be unpopular and reflect negativley on Gilead and WHO regardless if it works or not.

  • i think most of these drugs fall under the investigational new drug legal statues.
    Brincidofovir
    DZNep
    Favipiravir
    FGI-106
    JK-05
    Lamivudine
    MK-608
    Ribavirin
    TKM-Ebola
    Triazavirin
    ZMapp

    if your trying to steal from each other and weaponize these things i think all your facilities should be shut down or they should not be controlled by the government.

  • REMDESIVIR, CHLOROQUINE & HYDROXYCHLOROQUINE
    These 3 drugs need IMMEDIATE consideration. Considering UK has already BANNED EXPORT OF CHLOROQUINE in order to have sufficient qualities for their own citizens. That says enough to convince me we need to get on the ball!!

    • Wow Stacie,

      Care to explain or share where and how did UK come with a supply of Gilead’s remdesivir?

    • Stacie didn’t say the UK has access to Remdesivir, John. She said they banned export of Chloroquine.

  • I think we should start using it widely. No significant adverse events with it for Ebola victims and also good antidotal and other data coming in. We should just use it. It’s an emergency.

  • During a pandemic, I would hope that Stat would place a high priority on managing potentially dangerous misinformation, especially anything that seems like an obvious ploy to drive up a penny stock. Stat has been a credible life sciences news source, and I hope will remain as such. Ed – please clean up the mess or shut down the comments.

    • Hi John,

      Thanks for writing in.
      And I stepped away for a bit but tending to comments now.
      Appreciate you taking the time to express concern.

      Best
      ed at pharmalot

  • It’s pretty irresponsible to post a non-clinician’a analysis about drug efficacy. WTH does RBS know about anything related to drug efficacy. And you show no journalistic integrity by posting this.

    • Who cares about journalistic integrity? There is no time to waste on POLITICS! POSITIVE RESULTS are where the investigation should begin. Rather than if it is fake news or not! INVESTIGATE RESULTS INSTEAD.

  • Remdesivir was given to the man in Snohomish County , Washington and he improved so much in one day that he was eventually released from the hospital …

  • Just watched ESR video featuring Josef Penninger. ACE2 normally heals lung damage, but SARS #2 (Covid 19) spike proteins uses ACE2 receptor to enter cells and is expressed in lungs, intestines, kidneys, and heart. Covid 19 reverses ACE2 benefits and harms lungs, etc.
    Penninger suggests using altered ACE2 receptors to attract Covid 19 away from ACE2 in lungs, etc.
    I suspect ACE2 inhibitors may suppress Covid 19 interaction, but no one has mentioned such therapy. There are side effects of lower blood pressure, but since one Chinese doctor said 40% of those requiring ICU intervention had high blood pressure, increased ACE2 inhibitors might increase survival rates in life threatening circumstances.
    I don’t know enough about Remdesivir and the method used to counteract the Covid 19 infection.

    • Here’s the preprint regarding the Gilead vaccine. I think its insane that they’re testing humans soo early. Do they know that they’re potential sacrificial lambs?
      I say that due to the fact that the early China vaccine research resulted in 3 vaccines being tested and when the mice were exposed to the pathogen, the response caused an acute overwhelming pneumoimmunopathology, via cytokine storm..then death.

    • @J the DC

      First of all this not a vaccine it’s an anti viral. Second, this is in phase 3 trial. This is a drug they have been testing for ebola for the past years on the humans. It’s showing signs that it can also help slow down the corona virus hence it’s being tested on Corona virus patients too. This isn’t something they just build a month ago and it’s suddenly being tested in humans. It’s been years in making and phase 1 and phase 2 of the drug also went through human testing.

    • ACE2 inhibitors are being assessed in China studies, hopefully we will learn more on their safety and efficacy soon.

    • Remdesivir is a nucleotide analog that confuses viral RNA polymerase and decreases the production of viral genetic material. But who knows, I could be lying. I’m just a physicist.

  • @Ed Silverman @Pharmalot Can you follow up with Dr Matt McCarthy, looks like he might have access to more data based on his tweet few hours ago.

    https://twitter.com/DrMattMcCarthy/status/1238939842588925954?s=20

    “The calculus has just changed; we now believe remdesivir is good enough to use in certain critically-ill patients with liver dysfunction. Formal guidance will soon change & will greatly expand the number of patients who can receive this potentially life-saving drug. Great news!”

    • Harsh,

      I am going to be harsh on you again. Please don’t ask Ed Silverman to waste his time. Did you see Dr. McCarthy’s credentials?

      Medical Education

      Autonomous University of Guadalajara (Degree earned: MD)

      Residency

      State University of New York Health Science Center – Psychiatry

      Fellowships

      Psychiatry – New York State Psychiatric Institute

      A psychitrist practicing is a small suburb in Wisconsin, with MD earned at
      Autonomous University of Guadalajara.

      And you feel he is credible and knows anything about infectious diseases? Really?

  • Problem I see is the information given was done sparingly. Per information from Clinical Trials dot Gov they were using different levels of the vaccine to two groups. Phase III was supposed to be done in China and South Korea but have now expanded to 50 sites world wide. Was it the change from 100mg daily to 200mg causing nausea and other effects? I found this information yesterday.

    https://clinicaltrials.gov/ct2/show/study/NCT04280705

    • There are five active studies for this drug to treat coronavirus – It is not a vaccine. Each study has a different design, and dosing regimens also vary.

    • It’s not a vaccine. It’s an anti-viral. It’s already been tested a lot. It works. People are dying. We need it ASAP.

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