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Sorry, it is shareholders. Hadn't heard about a board meeting.
Wrong month. July 22nd.
Such solid support at $4.20. Every time the share price bounces down there, the bid always has at least 20k shares. And then the price bounces back up, often to $4.22. Really strong.
It's (leronlimab) infrastructure week!
Now available: A patented, easy to use test panel that tests everything Leron, the IL6 drugs and the GM-CSF drugs are supposed to impact in one handy package.
We'll need these by the 100 thousands.
HIV BLA: FDA 60-day vs. 74-day letter.
We all understand that by July 11th, 74 days post the April 27th filing, the FDA will send a letter with the "PDUFA date" for the approval decision for use of leronlimab in HIV combo therapy.
Also note that if there is exceptionally good or bad news - a decision not to file, or a decision to move forward with a priority review - that is conveyed by day 60 - Saturday June 26th. It could be any day this week.
Chuckles - please confirm we read this the same.
Sub-q is typical, but they did switch to IV for the first shot in the trials. Save a few hours getting it into the bloodstream.
Thanks, worth reading. It seems a number of cytokine storm wannabes who spent their time courting BARDA were left in the lurch.
Some on this board have been worried CytoDyn couldn't garner BARDA support. Now we can say it was smart (in retrospect) not to waste our time on that.
More likely concerned about a buyout of the company.
I get a newsletter called "This week at NEJM.org." It has links to NEJM-family articles this week and, somewhat, looking backward.
Interesting to note that the link to the Montefiore correspondence "Covid-19 and Kidney Transplantation," featuring leronlimab, is still in the email, with slightly higher positioning than "Compassionate use of Remdesivir."
All I can guess is that people are still reading it.
Yes, Chuckles, you are correct. Sixty days from the April 27th filing (that is, June 26th) is also the date we should hear whether we get a priority review designation in HIV.
I had misread that to be 60 days from CytoDyn's requesting same.
The exchanges with the FDA (re: data table formatting, manufacturing) are part of the normal back and forth to my understanding - there is no particular name for those activities.
Chuckles - The "74 day letter" (due from the FDA July 10th - 74 days post BLA filing) is what we care about. Day 60? Only impact is that any refuse-to-file designation (won't happen) is due by then.
https://www.nuventra.com/resources/blog/submitting-your-fda-marketing-application/#:~:text=Refuse%20to%20file%20designations%20are,as%20the%2074%2DDay%20Letter.&text=Following%20review%20planning%2C%20FDA%20will,any%20major%20review%20milestone%20timelines.
Given that science by press release is now standard, does that mean we'll put out a press release the night the s/c trial hits 28 days?
I'd add an upside: that lenzi is validation that the immunomodulator path is the way to go.
Actemra (tocilizumab) is another in that path. Their Phase III - Actemra+RDV vs. RDV - hasn't started per clinicaltrials.gov.
We know Fauci likes a cocktail - one shot for virus replication and one for cytokine storm (even if the virus rep shot doesn't really reduce the virus).
Whatever the BS games the stock people are playing, this drug has credibility as another example that immunomodulators, like leronlimab, are the solution. Hey, the FDA granted them a Phase III, just like they granted us.
I note, from clinicaltrials.gov, that their trial excludes those who are intubated prior to randomization, and the primary endpoint is either intubation or death by day 28.
Patterson said a RANTES test costs $5 in some interview.
I keep thinking there should be some way to combine the evidence from the mild/mod and sev/crit trials.
If they had exactly the same measurement at the same date, a statistical technique called meta-analysis would be appropriate. Not sure if you could just treat them as one pool, but certainly the statistical power would be greater than either alone.
Alas, I could not find an identical metric at 14 days in both trials.
Dr. Doughty, any ideas on some sort of pooled analysis?
Thanks. So I'm taking it these numbers don't indicate to you this population is out of the ordinary, or showing treatment effectiveness. Any idea how to think about the half of patients in the study you cited that are on ECMO for an extended period?
Thanks, got your points: (1) just to qualify for RDV these people are probably a selectively healthier group (though we don't know that is true for the compassionate use group), and (2) what will happen to those not yet discharged?
As to (2), a little cross-tabulation shows that, even if only one severe case is still in the hospital (only 10% death in severe group even if they die!), then the critical/ecmo group has 20 still hospitalized, 11 of which are extubated/improved. Even if all the other 9 eventually died, that would be 15/34 (44%) dead in the critical/ecmo group.
Bobshmob, you looked into this. How does this data inform your thinking?
NEJM today. Remdesivir compassionate use. Not randomized, so no comparisons in the abstract, but better outcomes than I would have guessed from a population this sick.
"Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation.
During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated.
A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation."
More sites recruiting - got to be good.
Per clinicaltrials.gov, mild/moderate trial now has seven sites recruiting, severe/critical has six. May have been this way a few days.
I think the shortage of remdesivir might push people toward a leronlimab clinical trial. Opinions?
Thanks. I appreciate the work. This will be very dicey at the 50-patient look-in.
Right on. I would caution we may not get a one-sided test - Remdesivir deserved a two-sided test because it might kill more people. We don't, but.... That would typically require one less death in the leron group.
The deaths in the placebo group will depend on the severe vs. critical mix. We've seen estimates of critical death rates as high as 88%. I have no idea for severe.
What are are the group's upsides/downsides to a guess of 65% (=11/17) based on half severe at 50% and half critical at 80%?
You nailed it. Not only correct but focused on the features I think are key.
Thanks for your interest. I'm using the confidence interval for the difference in two binomials as calculated using Wolfram Alpha. You can play with the parameters. Note the button for one-sided vs. two sided tests.
https://www.wolframalpha.com/input/?i=two+binomial+distribution+test&assumption=%7B%22F%22%2C+%22ProportionDifferenceTest%22%2C+%22p0%22%7D+-%3E%220%22&assumption=%7B%22F%22%2C+%22ProportionDifferenceTest%22%2C+%22n1%22%7D+-%3E%2217%22&assumption=%7B%22F%22%2C+%22ProportionDifferenceTest%22%2C+%22k1%22%7D+-%3E%229%22&assumption=%7B%22F%22%2C+%22ProportionDifferenceTest%22%2C+%22n2%22%7D+-%3E%2234%22&assumption=%7B%22F%22%2C+%22ProportionDifferenceTest%22%2C+%22k2%22%7D+-%3E%229%22
Hey, Rockleo,
1) my recollection is that a sneak peek at 50 people was built into the approved study design and does not have to be requested.
2) I don't think the front line doctors have the info to say who is getting placebo. They may ethically want to throw additional treatments at waning patients, but I don't think they have the perspective to say "damn, he needs leronlimab."
I really doubt they would (or could) break the protocol that way. And that's one reason it's hard to get people into a clinical trial. It's a cost of advancing science.
And the ex-statistician jumps in again to note that, in the 51-patient severe/critical trial "sneak peak," if (a) at least of 9 of 17 initial placebo patients die and (b) the death rate in the 34 person leronlimab group is half or lower than the placebo group, the significance level (p-value) will be strong enough to argue for early termination.
IMO, assuming the usual formula for difference in binomials. Actual randomization may not be 34/17.
Inreasing from 51 to 125 patients would narrow the confidence interval by about 36%, I'd roughly say a 20-35% mortality improvement would be significant, the narrower numbers if a large proportion of the placebo treated patients die, and Amarex can argue for a one-sided test. (no response from Dr. Dhoudy on that issue.)
Remember, we need to cut 28-day mortality roughly in half to obtain significance in the severe/critical trial if the actual randomization is 34 leron / 17 placebo. (A 40% cut will do it under some parameters/assumptions).
I've wondered as well. I know Patterson doesn't have direct info on who got what, but if he has access to almost any blood results (e.g. Rantes levels and CD4 ratios) he'd be pretty sure. Anyone know if he can see this?
Well, Clinicaltrials.gov has 8 studies featuring HCQ and Zinc, but only 2 are in the US and only one is recruiting. Keep the faith, ye zinc faithful!
NEJM latest re: HCQ as post-exposure prophylaxis: No significant benefit.
800 people identified as having high exposure to a confirmed case were randomized to receive either HCQ or placebo. Outcome = covid test or symptoms at 14 days. Favorable, but non-significant trend for HCQ, which also had 2.5 times as many side effects.
"The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was -2.4 percentage points (95% confidence interval, -7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported."
https://www.nejm.org/doi/full/10.1056/NEJMoa2016638?query=TOC
The published remdesivir intervals are 2-sided (hence wider for the same p-value) because we need to consider its potential for harm. I agree that argument shouldn't apply to leronlimab.
Thanks for asking. I must not have been clear.
The technical issue is whether we need a one-sided (leron better than placebo) or two sided (leron not equal to placebo) confidence interval. A 95% interval (p<.05) one-sided is a 90% interval (p<.1) two sided. The latter makes sense with a drug that might do damage.
So, given 17 placebo and 34 leronlimab patients, my table could read
___________Maximum Leronlimab deaths for significance (p<.05):
If Placebo____One-sided test_____Two sided
deaths are
10 (59%)__________12 (35%)____________11
12 (71%)__________15 (44%)____________14
Right. If results are outside a 95% confidence interval, then P<.05.
Just ran some confidence intervals using Wolfram Alpha assuming 34 leron patients / 17 placebo in the severe/critical trial.
(jargon: read P(die|leron) as "probability of death given received leronlimab")
I assume one-sided 95% intervals, that is, testing whether P(die|leron) < P(die|placebo). Some would argue two-sided - that's not appropriate given leron's safety profile. Results:
If observed P(die|placebo) = .71 (12/17)
result is significant if observed P(die|leron) =< .44 (15/34)
If observed P(die|placebo) = .59 (10/17)
result is significant if observed P(die|leron) =< .35 (12/34)
In each case, the two-sided interval would require leron to save one additional person.
So, to be clear, traders, and hence volume, follow the noise (not saying that can't be profitable) while investors follow the signal. The investors are staying and adding. Trying to be positive to your response.
Derf - you may not be aware CYDY constituted over 50% of total dollar volume on the OTC in April. Rather hard to maintain. What is true is that some catalysts thought to be days away may take a few weeks. So the high speed trader folks have left for now - they may be back. Investors are consistently adding shares.
Question for the pros on this: There have been tens of millions of CYDY warrants exercised, with new float created and the shares disposed of in the open market. In looking at market action, how would sale of new float be distinguishable from naked shorting? Thanks.
BP ganging up on CytoDyn:
https://www.bloomberg.com/news/articles/2020-05-28/roche-partners-with-gilead-in-covid-trial-of-drug-combination
Actemra is an IL-6 blocker, so shooting at the same cascade as CytoDyn.
Look closely at the table, especially if you are an old statistician.
The only statistically significant improvement was in the "score 5" supplemental oxygen group, but in the footnote:
"P-values and confidence intervals have not been adjusted for multiple comparisons."
lame, Lame, LAME