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Txzen

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Posts posted by Txzen

  1. 16 minutes ago, BabaYaga said:

    We can "hope", but hope is not a plan.  Nor does the economy or people's livelihood have 18 months to gamble on this.  In 18 months if maintaining our current SOP of being locked up, would make the Great Depression look like a wet fart in a windstorm.  

    There are way more resources being thrown at COVID-19 than SARS across the entire pharma industry right now. There is a plan, and hope. 

    • Like 1
  2. 23 minutes ago, BabaYaga said:

    We are a decade removed from the earlier Coronavirus (SARS) and still without a vaccine.  I have little faith 18 months from now this will change.  I hope it will, but pinning the removal of SIP on a vaccine seems incredibly dangerous.  

    That gives me pause as well, though I'm still hopeful. In the end, SARS didn't have nearly the long-lasting or global impact, and so I think there was less motivation to continue with the research. The paucity of infectious disease research in large pharma I think also contributed to this - in the last 10 years so many have gotten out of the business all together. So perhaps there are some economical and business factors driving this (as well as some potential scientific hurdles posed by the coronovirus itself). 

    • Like 1
  3. 2 hours ago, Newdoc said:

    Also, the protocols are all borked from a surface glance. The drug is given to various people at various stages in their illness. End points appear to discharge or death. You’re going to need a LARGE sample size to get good data out of that.

     

    It's kind of important to understand when in the patient management cycle the drug will be effective. Obviously if you are in the middle of CRS and multi-organ failure, the clinical situation is more complicated. But that's why you run the study with wide inclusion criteria. 

  4. 2 hours ago, Anastasis said:

    Posted this on the #stonk thread, because I am inclined to short GILD each time they pull one of these bullshit announcements. 

    I believe that this is the right study. https://clinicaltrials.gov/ct2/show/NCT04280705  The primary endpoint they are touting is time to recovery.  They are quiet on the secondary mortality endpoints in the releases that I read. I be interested to hear @ChiTownDoc @Newdoc and others chime in, I would be more interested if it actually reduces mortality, time to discharge, hospitalization days, etc. A time to recovery outcome could represent a very modest benefit, similar to antivirals for treatment of flu. They also bloated the release up with some open label results that don't provide any real insight into effectiveness.  

    Aways easy to slam big pharma, but this is a good first trial with additional data coming. Details of the trial:

    • Two, randomized multi-center Phase 3 trials in countries with high COVID prevalence
    • 397 patients received 200mg on the first day, followed by 100mg until day 5 or day 10 in addition to standard of care
    • Patients had severe COVID manifestations: pneumonia but not under mechanical ventilation
    • An additional expansion phase of the study will enroll and additional 5,600 patients including those on mechanical ventilation, conducted at 180 trial sites (US, China, France, Germany, Hong Kong, Italy, Japan, Korea, Netherlands, Singapore, Spain, Sweden Switzerland, Taiwan, UK)
    • A second trial will read out in May, comparing safety and efficacy of 5 and 10-day durations compared to standard of care. The first data from 600 patients will be available at the end of May. 

    Data from the trial:

    • Study sought to see if 5-day was as effective as the shorter 5-day course (10-day is currently being used world-wide)
    • 10-day treatment course as effected in achieving clinical status as 5-day
    • No new safety signals seen
    • Benefit as measured by improvement in clinical score as determined by a seven point scale including hospital discharge, increasing levels of oxygen support, and death
    • Patients achieved clinical recovery if they no longer required oxygen support and medical care or were discharged from the hospital. 
    • Time for clinical improvement for 50% of patients was 10 days in the 5-day treatment, and 11 days in the 10-day treatment
    • Clinical outcomes varied by geography - Outside of Italy, the overall morality rate at day 14 was 7% across both groups
    • 61-64% of patients were discharged from the hospital on the 5 and 10 day regimens, respectively
    • Patients who received the drug within 10 days of symptom onset had improved outcomes compare to those treated after 10 days
    • Worst tox I see is Grade 3 ALT in 7% of patients, with 3% discontinuing due to liver tox. 
    • Like 1
  5. For those who don't want to sit through 4 minutes of Tucker talking before you get to the the actual guest (and if you don't think Tucker's preamble that 'fear is hurting people' isn't political, well...) : Jay Bhattacharya, Stanford. He also authored an article in the WSJ recently. 

    I'm not saying that we shouldn't look at the death rate with some skepticism until we know more. But there's something at the center of his argument that 'what if it's only 1/1000 who die, we've overreacted' that misses the point. 

    I think it is likely true that the extent of people exposed, infected and asymptomatic is higher than we'll ever know, given the paucity of testing. The fact that the first evidence of Covid infections and deaths in California were in the Vacaville-Sacramento corridor, and not SF, LA or SD, and from people with no association of foreign travel suggests community spreading. It was, and likely has been, very widespread. That certainly means that the death rate is lower than initially thought, certainly lower than some of the dire estimates in the early days.

    Right now, the deaths per capita in the Netherlands, Belgium, Spain, Italy, UK and France already eclipse the ~0.01% per capita deaths from the common flu. If you assume everyone got infected in those countries, the death rate of 0.02 - 0.04% is higher than the flu, happened in a short time, and has proved to be disastrous for some areas in that resources were totally overwhelmed. 

    But not everyone has been exposed to it, and we ensured that (and the low death rate) by cratering the world economy and telling everyone to stay home. Also, unlike the flu, this is more contagious, widespread, and deadly (even Bhattacharya agreed with that) and there's no vaccine. 

    Spoiler

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  6. It's pretty dubious - basically, someone did some molecular modeling and said that Covid could bind heme in red blood cells, and that would be a major mechanism for the clinical outcome. It hasn't been proven that this is occurring, it's not very likely based on current understanding of the mechanism of coronoviruses, and the research is a bit shite. 

  7. Compassionate use of Remdesivir for Patients with Severe Covid-19 New England Journal of Medicine, April 10

    Details : 

    • 53 patients with severe complications, international cohort
    • 34/53 (64%) were on mechanical ventilation
    • Treatment resulted in an improvement in oxygen support class for 68% or patients over a median of 18 days following the first dose
    • More than half were extubated
    • 47% were discharged following treatment
    • Clinical improvement less frequent among patients on severe ventilation versus noninvasive ventilation, and among patients at least 70 years of age

     

    Spoiler

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    Spoiler

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    • Like 1
  8. 9 hours ago, SydneyCarton said:

    Well this seems like good news, and I don’t remember it being posted yet.

    https://www.jpost.com/HEALTH-SCIENCE/Israeli-COVID-19-treatment-shows-100-percent-survival-rate-preliminary-data-624058
     

     

    Perhaps for a few who are very ill, but it's a placental-derived stem cell therapy, and not likely to be mainstream therapy any time soon. 

    • Like 1
  9. 5 minutes ago, Skipper said:

    I don't think you necessarily need a 'cure'.  You just need something that significantly limits the severity.   If you could reduce hospital admissions/ICU admissions to a point that it would be extremely unlikely to overrun the increased infrastructure and reduce death rates to something that looks like a really bad flu season, that would drastically change policy and may be a risk most could live with then you continue to isolate those (elderly) that would continue to be most as risk.   I don't know how likely we are to find that, determine it's safe, and mass produce it before a vaccine, but that's probably our best bet.

    Perhaps, but it's also the scale of production for whatever that treatment is. We know already that there are shortages of hydroxycholoroquine (and that's due to some minor hoarding and its expanded used in trials), and while Gilead is spooling up production of rendemisvir, right now the supply is only 1.5 million doses. It's possible that the production and rollout of a vaccine may be the only way to really 'control' this. I'm not sure there's enough supply of drugs worldwide for everyone to be prescribed these meds, and certainly not for prophylactic use. 

  10. Study to test if COVID was in California earlier than previously thought

    Will be interesting to see the data from this.

    Quote

    Researchers at Stanford Medicine are working to find out what proportion of Californians have already had COVID-19. The new study could help policymakers make more informed decisions during the coronavirus pandemic.

    The team tested 3,200 people at three Bay Area locations on Saturday using an antibody test for COVID-19 and expect to release results in the coming weeks. The data could help to prove COVID-19 arrived undetected in California much earlier than previously thought.

    The hypothesis that COVID-19 first started spreading in California in the fall of 2019 is one explanation for the state's lower than expected case numbers.

    [snip]

    Hanson said he thinks it is possible COVID-19 has been spreading among Californians since the fall when doctors reported an early flu season in the state. During that same time, California was welcoming as many as 8,000 Chinese nationals daily into our airports. Some of those visitors even arriving on direct flights from Wuhan, the epicenter of the coronavirus outbreak in China.

    "When you add it all up it would be naïve to think that California did not have some exposure," said Hanson.

    For years California has been the No. 1 travel destination for Chinese tourists in the United States. Even after the U.S. halted flights from China this winter Chinese travelers were still able to come to California on flights from Europe and Canada.

    Hanson said through all of this the Chinese have been disingenuous about the timing of the initial outbreak of COVID-19.

    "They originally said it was in early January, then it got backdated to December and then early December and now they are saying as early as November 17," said Hanson.

    If Californians were exposed earlier than the rest of the country to COVID-19 we may have had a chance to build up some herd immunity to the disease. We won't know if that is the case until results from the Stanford Medicine study come back.

     

    • Like 2
  11. 1 hour ago, Captainant said:

     

    Haven't seen much discussion here yet on some early challenges with HCQ treatments. Medical professionals, have y'all seen or heard much on this yet?

    Yes, cardiac issues are a potential side effect of both hydroxychloroquine and azithromycin for a population of patientis even when given individually, which is why co-administration is potentially tricky. 

    American College of Cardiology

    Quote

    - Hydroxychloroquine or chloroquine therapy should occur in the context of a clinical trial or registry, until sufficient evidence is available for use in clinical practice.

    - Hydroxychloroquine or chloroquine use outside of a clinical trial should occur at the direction of an infectious disease or COVID-19 expert, with cardiology input regarding QT monitoring.

    - The intensity of QT and arrhythmia monitoring should be considered in the context of potential drug benefit, drug safety, resource availability and quarantine considerations.

     

    • Like 1
  12. On 4/3/2020 at 9:03 PM, strangulation! said:

    Would tests on people be the next stage? Or would they need to test on certain animals and then progress to humans?

    Full disclosure, I'm a cancer research guy, not infectious disease. But certainly many of the animal models for human infectious diseases are fraught with limitations just like those in oncology. 

    The Gilead drug remdesivir, for instance, looked good in vitro for Ebola, and pretty good in primate disease models models - but perhaps has not shown as much promise in the field. The primate models are so-called semi-permissive for Ebola (and also some respiratory viruses), meaning that the disease often doesn't quite take hold as well in monkeys or is not as sustained as it is in humans. So, testing of the drugs in these models often is early on after exposure to the infectious agent to show if it has an impact. 

    Compare that to treating people in the field where Ebola has sprung up - people in all the various stages of disease, long after being infected with various levels of disease burden and the resulting complications of other systems involved. It's not so simple to make the leap from preclinical to clinical. 

    It all highlights the need for the continued clinical trials of all of these agents alone or in combination, as is ongoing now. Sporadic reports of a few patients treated here or there is not conclusive evidence of efficacy. 

    • Like 1
  13. 2 hours ago, PittsburghTiger said:

    https://abc7.com/coronavirus-drug-covid-19-malaria-hydroxychloroquine/6079864/

     

    LOS ANGELES (KABC) -- A Los Angeles doctor said he is seeing significant success in prescribing the malaria drug hydroxychloroquine in combination with zinc to treat patients with severe symptoms of COVID-19.
    [snip]
    Hydroxychloroquine has been touted as a possible treatment for COVID-19 by President Trump among others, but it remains controversial as some experts believe it is unproven and may not be effective.

    He said he has found it only works if combined with zinc. The drug, he said, opens a channel for the zinc to enter the cell and block virus replication.
     

    One never knows if this is just lazy science ignorant journalism, or if he actually said this. Among all the mechanisms of action described for hydroxycholorquine from it's use in rheumatology, autoimmunity and infectious disease, 'opening a channel' ain't one of them. The fact that he thinks this illuminates the need for the (current ongoing) world-wide clinical trials. 

  14. 6 hours ago, cam4mav said:

    Cheers from Seattle,

    I don't know how or where to look at graphs like that on a state level. At this point, I feel like it would be useful to be able to show the curves of the major international places and compare them to each state in the US as each state is on it's own curve, with unique exposure, length of time, testing access, stay at home measures in place, etc etc.... Have all states with X min cases on the graph along with S. Korea, Italy, China, Spain, UK, etc.

     

    Best source of graphs, per capita at state/regional level, as percent of population (super helpful way to look at the data, frankly) https://twitter.com/isfBob

    Case density as percent of population, worldwide:

    Spoiler

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    Mid-West

    Spoiler

    EUZlxjDUUAAX3k9?format=jpg&name=4096x409

    South: 

    Spoiler

    EUZlq4PU8AAihYJ?format=jpg&name=4096x409

    Northeast:

    Spoiler

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    West:

    Spoiler

    EUZld9NVAAA1_PF?format=jpg&name=4096x409

     

    • Like 8
  15. 3 hours ago, G650 said:

    A friend who is a chemist for a pharma co said that it [chloroquine] had been approved, fwiw.

    No. Not approved - authorized for emergency use, there's a difference. 

    Along those lines, Gilead pulled back remdesivir from compassionate use - which is a process that allows a new, unapproved drug to be used for people who have no other treatment available. The issue is that those are often done as one-off, small group studies as was done for Ebola. It's not the best way to understand the efficacy of a drug during a pandemic. 

    This was done to enable larger, world-wide clinical studies like the SOLIDARITY Study by the WHO, as a part of a process called 'Expanded Access' which allows the testing of larger groups of people simultaneously under a single blanked designation. The study will test thousands across the globe in a randomized adaptive trial looking at multiple single-agents and combinations : 

    Quote

    The drugs to be tested are the antiviral drug remdesivir; a combination of two HIV drugs, lopinavir and ritonavir; lopinavir and ritonavir plus interferon beta; and the antimalarial drug chloroquine. All show some evidence of effectiveness against the SARS-CoV 2 virus, which causes Covid-19, either in vitro and/or animal studies.

     

  16. Amid frenzy over potential COVID-19 drug, patients see shortages and states fight reckless scripts

    Quote

    Enthusiasm around the drug stems partly from early learnings from a French study conducted by professor Didier Raoult and his team. In that study, 70% of patients who were given hydroxychloroquine tested negative for the virus after six days. In the control arm, only two out of 16 patients were negative after six days. Some of the hydroxychloroquine patients also received the antibiotic azithromycin; all six of them tested negative.

    Despite the "small sample size," the evidence showed that "hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin," Raoult wrote.

    Weighing the findings, two experts told investigative journalist Mary Beth Pfeiffer the results are enough for them to recommend the treatment regimen of hydroxychloroquine and azithromycin for patients who are hospitalized with COVID-19 considering the graveness of the global pandemic and lack of available treatments.

    Separately, one early study from China had been characterized as a “positive” result, but Evercore ISI analyst Umer Raffat saw things differently after looking into the data for himself. Hydroxychloroquine failed to beat placebo at virological clearance rate and temperature normalization at day 7, the analyst wrote in a Monday note to clients. The drug did beat placebo at radiological progression, but the data are tough to interpret because of the size of the study, Raffat added.

     

  17. Sorry if already posted Party Zero : How a Soiree in Connecticut Became a 'Super Spreader'

    Quote

    About 50 guests gathered on March 5 at a home in the stately suburb of Westport, Connecticut, to toast the hostess on her 40th birthday and greet old friends, including one visiting from South Africa. They shared reminiscences, a lavish buffet and, unknown to anyone, the coronavirus.

    Then they scattered.

    The Westport soirée — Party Zero in southwestern Connecticut and beyond — is a story of how, in the Gilded Age of money, social connectedness and air travel, a pandemic has spread at lightning speed. The partygoers — more than half of whom are now infected — left that evening for Johannesburg, New York City, and other parts of Connecticut and the United States, all seeding infections on the way.

    Westport, a town of 28,000 on the Long Island Sound, did not have a single known case of the coronavirus on the day of the party. It had 85 on Monday, up more than 40-fold in 11 days. At a news conference Monday afternoon, Gov. Ned Lamont of Connecticut said that 415 people in the state were infected, up from 327 on Sunday night. Ten people have died. Westport, with less than 1% of the state’s population, now makes up more than one-fifth of its COVID-19 infections with its 85 cases. Fairfield County, where Westport is, has 270 cases, 65% of the total.

     

    • Like 4
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