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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.”]

  • I am not a doctor but have been following Remdesivir very closely. It seems clear to me that the medication is effective but has to be given early on for maximum effectiveness. Of course, the drug must go through these formal studies first, but I don’t see how anyone can question its merit at this stage. I saw this first for two main reasons. First, the drug has already been tested extensively for safety and was found found to be safe, but ineffective with Ebola. So, we already know, the drug is safe.

    Second, and most important, at least two U.S. patients who were quickly deteriorating were saved by the medication. And by saved, I mean saved. The first patient was the very first patient the U.S. had. The second, more recently, was a woman in California who was expected to die, and then reversed course after being given the drug and is now doing well. Some might say, “Well, that’s only two patients.” But imagine if that had been you waiting to die or be placed on ECMO and you were given this medication and immediately improved. Would you still demand months more of study? Well, yes, that’s exactly what the FDA is still requiring. But so be it. I don’t need a study to tell me what I can see with my own eyes. And since both of these patients were in the process of worsening, there should be no question of, “Well how do we know they weren’t going to get better on their own?” The reason they were both in the hospital is because they weren’t getting better and one was getting ready to die.

    Everyone can pontificate about studies, but the writing is on the wall for this.

    This medication works and it is safe, but it must be given early on just like Tamiflu and everything else. If given late, the virus has already done its damage and the course may be irreversible.

    I’m thankful for Gilead and how fast they are moving to show Remdesivir’s effectiveness.

    Ask yourself, if you were being considered for intubation, would you want to take the medication yourself or would you demand further studies to test its effectiveness? It’s a rhetorical question because the answer is self-evident.

    • Sorry about that Kevin! If I had seen your post I would have changed my name to Kevin B. Two Kevin’s posting so close together is rather comical. My information is from clinical data being published. I might add the estimated cost per regiment will be $900 to $1,000 which is higher than normal flu intravenously but cheaper than same in antibiotics.

  • Am I the only one wondering why anyone would name their company (ESPECIALLY one dealing with pharmaceuticals, and by extension, public health) ‘Gilead’?!
    Seriously? “The Handmaid’s Tale,” anyone?
    Also, my focus being on that as opposed to the factual content (or lack thereof) of this article speaks volumes- at least to me, anyways.

    • Dear Elizabeth,

      Thanks for writing in. I’ll have to let the company address your question about the origins of the name, although perhaps it has some Biblical connection?

      Sorry if you thought the post lacked factual content, whatever that might mean, but I’m happy to answer any questions as best I can. Meanwhile, feel free to click on the link to read the COVID19 response team paper if you need more info.

      Regards
      ed at pharmalot

    • A well-known African-American spiritual applies the words of the text this way:
      There is a balm in Gilead …(Jesus)
      To make the wounded whole;
      There is a balm in Gilead
      To heal the sin sick soul.

  • Hi ped.. from a junior doctor 1st month residancy program in one of the Lung/respiratory centers .. we are facing many cases per day ,, asking my slef where is the drug of choice and when.. hoping my life will go back to its normal base soon and planing for summer trip

  • Really? Stock market analysts studied a report that covered 3 patients that received Remdesivir and then published their own report that said it was still unclear how effective Remdesivir is? What is their motivation for this?

    What islikely is that RBC has been downplaying Gilead/Remdesivir publicly while privately accumulating shares for themselves and their best clients.

    • So Michael,

      what is your stock investment background and/or expertise? Any? Ever heard of buy low sell high?

      I applaud what RBC is doing. They are there to make profits for themselves and their clients! Anything wrong with that? Speculative analysis based on limited clinical study results and subsequent stock recommendation are dime a dozen!

      About the RBC Interview:

      https://www.bloomberg.com/news/articles/2020-03-05/gilead-analyst-sees-only-50-chance-that-coronavirus-drug-works

      The analyst Brian Abrahams I do follow him and I can state categorically that he is not exactly ranked as one of the top analyst for Gilead, period. What he said in the interview are mostly common sense and nothing earth-shattering nor insightful. The onlt thing he said I agree and applaud him was the fact that at least in the US, the IP/patent status of Remdesivir is fine until well into the 2030’s. But would coronavirus/pandemic/epidemic outbreaks last that long? I don’t think so.

      The absolutely best scenario IMHO would be Remdesevir China clinal results outcome turns out to be very positive, rapid approval (via XI)) and marketing in China, subsequent expedited approval in the US, (via Trump), GIlead able to mass produce in huge quantities globally with tens of billions in revenue, and by 2030, file for the OTC status with the FDA and obtain approval, have Remdesevir available in every CVS and Walgreen’s (just like Tamiflu which was actually discovered by Gilead) and make another dozens of billions!

    • Hi Michael and Ped,

      Thanks for writing in. I know there were other recent stories, Ped, about the Gilead drug. I noted in an earlier reply to you that the WSJ story came out later on Friday, after the RBC report was issued. And as I indicated, I hope the NIH scientist’s observation is correct.

      And Michael and Ped, you asked a fair question about motivation.

      Unfortunately, I cannot provide direct links to analyst reports, but I am free to quote and summarize, which I did. And in doing so, I tried to make clear the RBC report acknowledged various caveats about their view of the CDC paper.

      Beyond that, I am not going to defend RBC and its interpretation of the CDC paper. Perhaps they are wrong. We all need more data and hopefully, the trials in China will provide solid answers.

      You did ask whether RBC had been downplaying the stock. On March 9, the same RBC analyst team wrote they have a “bullish thesis around the underappreciated sustainability of the HIV franchise, GILD’s willingness to execute on meaningful BD (business development), and their undervalued pipeline / antiviral prowess is beginning to play out.” They rated it outperform, for what it’s worth.

      Feel free to take this with a grain of salt. Again, I am not defending their views. Just passing this along, since you asked.

      Regards
      ed at pharmalot

  • from other message boards

    Breaking news story from Dow Jones about GILD’s anti-coronavirus treatment

    Experimental Drug Helps Some Americans Ride Out Coronavirus, NIH Doctor Says
    6:42 am ET March 13, 2020 (Dow Jones)
    By Suryatapa Bhattacharya

    TOKYO–The antiviral drug remdesivir appeared to have an effect in American cruise passengers treated for the novel coronavirus in Japan, although data are limited, according to a doctor sent to Tokyo by the U.S. government.

    Rear Adm. Richard Childs, an assistant surgeon general and lung specialist at the National Institutes of Health, said 14 Americans who contracted the virus on the Diamond Princess cruise ship and were treated at Japanese hospitals received the experimental drug from Gilead Sciences Inc.

    Those 14 were “critically ill people and their average age is 75,” he said. “Many of them were probably going to die in a short amount of time, and two weeks later nobody has died and more than half of them have recovered. It’s just absolutely amazing.” But he cautioned, “It’s going to take us a while to figure out what the impact of the drug has been.”

    The drug is being tested in the U.S. and Asia by independent groups as well as Gilead, but no large-scale results are available.

  • Sir, do you have a scientific background?
    you seem to try to put a negative light on something as if you knew the science behind it
    this drug is the best hope we have at this point and many countries are begging for it ..
    please get a scientist or doctor at least do your science research

  • OK Harsh,

    You are clearly an astute reader and quick learner. So here is Clinical trials Basic 102:

    Would the US FDA accepts or acknowledges Chinese clinical trials results data? What do you think? Probably not. But ONCE AGAIN, all it would take is a personal phone call from President Xi to President Trump, right? After all, they are supposed to be good buddies?! And our USPTO is great with deals. SO what if Xi tells Trump that he would accelerate US products purchase in turn for FDA expedited approval in the US plus manufacturing technology and knowledge transfer from Gilead (US) to Brightgene (China)?

    Done deal. Both Presidents would come out smelling like a rose IMO. Xi would be forgiven by all Chinese citizens and global leaders for his possible missteps (i.e., under-reporting) in the early days of Coronavirus outbreak, and our USPPTO would solidify his chance for the re-election.

    LET’S MAKE A DEAL!!!

  • https://www.clinicaltrials.gov/ct2/show/NCT04292899?term=remdesivir&cond=coronavirus&draw=2&rank=3

    Harsh,

    You said:

    When can we expect the results from the china trials? Looks like it was started in the 6th and if they got 400 patients day 1 and started the study. We might get the results from the study on the 21st. 14 day period. Does that make sense? Or does it normally take more than that?

    Let’s start with clinical trial basics 101:

    If you have carefully read the entire clinical trial record for this Wuhan, China trial, you would see:

    Estimated Primary Completion Date  : May 2020

    Definition:

    The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The “estimated” primary completion date is the date that the researchers think will be the primary completion date for the study.

    Even after primary data completion, they have to be statistically analyzed for both efficacy and safety. That would take another week or two at least. Then comes the regulatory document assembly then official filing for the NDA or New Drug Application in the US with the FDA). Then comes FDA reviewers thorough scrutiny, analysis , and if necessary additional questions.

    SO unfortunately Harsh, I can’t see any approval until September at the earliest. Of course you never know, our USPTO, through Pence, with Anthonyy Fauci’s endorsement may exert enormous pressure on the FDA, for earlier approval. I can actually see a possibility, however remote, for Trump to use his enormous power of executive order for special approval exemption. Now for that move, it could be legally challenged with uncertain, unpredictable, and unknowable accountability if the drug either fails or causes unexpected major adverse events.

    But we are having an national emergency in uncharted waters with a totally novel and new virus so you never know.

    This whole thing is absolutely fascinating to me, as a retired former drug company staff.

    • John,

      Thank you John for the explanation. On the Estimated Primary Completion Date, I have noticed they do change that date if the study was going to be completed earlier. Considering they might have all 400 patients for the study now, and they only need 14 days, 10 days of dosage and 4 days of monitoring after they complete the 10 day dose. Wouldn’t that mean they the primary completion date would be sooner rather than in May?

      – Harsh

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