[HN Gopher] In a Phase III trial, Proxalutamide reduced mortalit...
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In a Phase III trial, Proxalutamide reduced mortality of Covid
patients
Author : hu3
Score : 46 points
Date : 2021-03-19 15:30 UTC (7 hours ago)
(HTM) web link (www.europeanpharmaceuticalreview.com)
(TXT) w3m dump (www.europeanpharmaceuticalreview.com)
| tpmx wrote:
| The company behind the drug tripled their market cap between
| November 2020 and March 2021. It's now at 11B HKD: Kintor
| Pharmaceutical (9939 HK).
| tyingq wrote:
| I wonder what the cost is...the drug appears to be almost brand
| new.
| temp0826 wrote:
| Medications for people with rare conditions tend to be
| astronomically priced (attempting to recover r&d costs from few
| buyers?). Covid doesn't seem to be particularly rare
| tyingq wrote:
| The original purpose of the drug was for prostate and breast
| cancer.
| allturtles wrote:
| > there were 141 deaths in the control arm, a 47.6 percent
| mortality rate
|
| That seems very high to me. I checked quickly for data, and I
| found a study[0] showing mortality rates for hospitalized covid
| patients in the U.S. between from 9% to 15%.
|
| So where did they find a control group with 47.6% mortality? Is
| care that much worse in Brazil vs. the U.S? Are they only giving
| this to mortally ill patients? The claim of 92% efficacy depends
| on this very high control group mortality.
|
| [0]:
| https://jamanetwork.com/journals/jamainternalmedicine/fullar...
| klmadfejno wrote:
| I've been trying to find this stat for the whole pandemic. To
| what degree are our medical systems reducing mortality rates?
| NovemberWhiskey wrote:
| I think it's going to depend very much on the distribution of
| patients with the different WHO Covid Ordinal Scale categories
| within the cohorts.
|
| If there were a lot more 5s (severely ill hospitalised patient
| on non-invasive ventilation or high-flow oxygen) vs. 3s
| (hospitalised patients not needing oxygen therapy), it would
| presumably make a large difference.
| lbrito wrote:
| >So where did they find a control group with 47.6% mortality?
| Is care that much worse in Brazil vs. the U.S?
|
| Yeah, unfortunately it is -- 38% according to this news piece,
| 80% for ICU patients[1]. It makes sense that it is even higher
| in Amazonas, the Brazilian state reported in the study. Over
| there they had a very serious health system collapse the last
| few months; even oxygen supplies were completely depleted
| statewide for a couple of weeks.
|
| [1] "Mortality in hospital patients admitted with Covid in
| Brazil is one of the world's largest"
| https://saude.estadao.com.br/noticias/geral,mortalidade-por-...
| hu3 wrote:
| It doesn't help that a very aggressive strain of covid was
| discovered in that region of Brazil:
|
| > P.1 infections can produce nearly 10 times more viral load
| than in other COVID-19-infected persons
|
| https://en.wikipedia.org/wiki/Lineage_P.1
| IfOnlyYouKnew wrote:
| I believe the trial data is from summer 2020? Survival rates of
| hospitalized patients improved dramatically over time.
| EMM_386 wrote:
| This is an antiandrogen. Androgens are thought to play a role in
| COVID, and apparently there is a "high prevalence of androgenic
| alopecia in hospitalized patients with COVID-19".
|
| Also callled "male-pattern baldness" but affects both sexes.
|
| More information here:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557269/
| fspeech wrote:
| Good they actually have some understanding of the underlying
| mechanism. Also this is an oral drug! It reduced mortality risk
| by 92%:
| https://www.europeanpharmaceuticalreview.com/news/147167/pro...
| sterlind wrote:
| Summarizing, it looks like the TMPRSS2 protein is necessary for
| the virus to replicate, and the Androgen Receptor modulates its
| transcription.
|
| But where I'm confused is why this drug in particular was
| studied, instead of an approved AR antagonist like bicalutamide
| or enzalutamide. Way easier to dispense those than some
| clinical trial drug, right? And is it important that the drug
| is a silent antagonist of AR rather than an inverse agonist?
|
| Also, how does this affect women? Are we at less risk of
| mortality through this mechanism? My T levels are very low, but
| all of us have androgens and their receptors. Maybe TMPRSS2
| gets transcribed even when T or DHT levels are low?
| dang wrote:
| I've changed the URL above to that one from
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899267/, which
| has the paper.
|
| Generally with specialized papers we've found that it's best to
| link to the best third-party article and then have a link to
| the paper in the thread. Unfortunately the third party article
| often isn't great, but it's at least an easier place to get
| some context, and we can replace the URL when people point out
| a better one.
| hu3 wrote:
| I appreciate it. Hopefully the trials can confirm this drug
| as another tool against covid.
| DoofusOfDeath wrote:
| > Also this is an oral drug!
|
| Asking as a layman:
|
| Would that be a problem for patients who are unconscious or
| with breathing tubes?
| fspeech wrote:
| You can always crush the pill and put it into the feeding
| tube.
| spdionis wrote:
| > 171 were randomized to the Proxalutamide arm and 65 were in the
| placebo group.
|
| Maybe I'm missing something but, how does that happen? I'd expect
| a 50/50 split
| lrem wrote:
| (Intuitively, I'm not an expert) Apart from the statistical
| reasons already mentioned, there is also an ethical one. If you
| expect the study to confirm the treatment to be highly
| beneficial, you prefer not to withhold it from your patients.
| Closi wrote:
| Somewhat unintuitively the statistics in trials don't require a
| 50/50 split.
| lisper wrote:
| Here is an extreme example: suppose you are an HIV skeptic
| who believes that AIDS is not caused by the HIV virus but
| rather by drugs [1]. How large a study would you need to
| falsify your hypothesis?
|
| Answer: one HIV-positive subject, left untreated, would be
| enough, if that person were otherwise healthy. If that person
| died of AIDS, that would leave one of two possibilities:
|
| 1. HIV causes AIDS, or
|
| 2. Something else causes AIDS and that person JUST HAPPENED
| to have that other causal factor AND a (harmless) HIV
| infection.
|
| The odds of #2 are low (because AIDS and HIV infections are
| both uncommon) so that just leaves the first possibility.
|
| As a side-note, that experiment was actually done by an HIV
| skeptic, on both herself and her unfortunate daughter [2].
| Needless to say, both are now dead.
|
| [1] http://duesberg.com/
|
| [2] https://en.wikipedia.org/wiki/Christine_Maggiore
| mlyle wrote:
| What split is optimal depends on what effect size you expect.
| If you expect a very large effect, you get more statistical
| confidence from allocating more subjects to the treatment
| group.
|
| On the other hand, if your treatment is very costly, adding
| subjects to the control group may be an effective way to
| increase study power without as much increase in study cost.
| victor106 wrote:
| > Previously, we have reported that men affected by androgenetic
| alopecia (AGA) are overrepresented in severe coronavirus disease
| 2019 (COVID-19).
|
| That's very interesting. Never read that anywhere else.
| batter wrote:
| Might be red herring:
| https://twitter.com/schneiderleonid/status/13721485262396006...
| ve55 wrote:
| This is great news and an amazingly strong outcome! Proxalutamide
| is an antiandrogen, which reduces some of the effects of
| androgens including testosterone, so I wonder if this has a
| stronger effect in males than in females. Although the paper
| mentions the sex distribution of the patients, it doesn't seem to
| mention the details necessary to conclude this, but unless I'm
| mistaken over something trivial I'm unsure as to why. Anyone have
| any thoughts?
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(page generated 2021-03-19 23:02 UTC)