Looks like it is still only in clinical trials for cancer treatment
and the class of molecule is highly cytotoxic (meaning that taking it is an act of desperation hoping to kill the bad cells slightly sooner than it would kill all cells)
Also, to avoid confusion, please refer to it as ( S )- N -(( R )-1-(((3 S ,6 R ,7 S ,10 R ,11 S ,15 S ,17 S ,20 S ,25a S )-10-(( S )- sec -butyl)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-1,4,8,13,16,18,21-heptaoxodocosahydro-1 H -pyrrolo[2,1- f ][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl)amino)-4-methyl-1-oxopentan-2-yl)- N -methyl-1-(2-oxopropanoyl)pyrrolidine-2-carboxamide.
-a study completed in Dec 2020. The summary describes it as Phase I, but the drug is already licensed and there were also efficacy endpoints in the study (plus it’s called a proof of concept study) so I would say Phase I/II (though a study of 46 patients is not going to tell you a whole helluva lot).
This study aims to assess safety and toxicity profile and also preliminary efficacy of plitidepsin at each dose level administered according to the proposed administration scheme in patients with COVID-19 who require hospital admission. Main objective is to select the recommended dose levels of plitidepsin for a future phase II / III efficacy study.
The summary has no results reported and I haven’t found eg a pre-publication yet. If something has been posted, that would explain the uptick in interest. I’ll keep looking.
But hydroxychloroquine WAS promising, with good results in vitro. It was well worth testing, including testing it in desperate patients, as it’s not terribly toxic.
That drug didn’t pan out in vivo. But that doesn’t mean it’s not worth checking other drugs that might be helpful.
Correct. I was pretty clear that I would love for one of these to pan out and we should test all of them, but that doctors shouldn’t be prescribing them to all of their patients at this time. It became difficult to get hydroxychloroquine for those who needed it for its intended purpose and also for those who needed it for trials thanks to hoarding by others. In the meantime, that was a pretty long list I provided and every single one of them (and more) was at one point or another “effective against COVID-19” in various places. This one appears to look decent after Phase 2 trials, so let’s hope Phase 3 pans out.
Have you found any results from that Phase I/II study? I didn’t see anything yet.
However, I did see this:
PharmaMar said it was in talks with various regulatory agencies - the most advanced ones being with the Spanish and British regulators - to start Phase III trials. They are deciding how many patients should be included in the trial.
“At first we are not targeting ICU patients, there will be hospitalized patients, but doctors are collaborating with us to identify the different phases a sick person goes through, and determine which would be ideal to focus on to produce the best results we can get from plitidepsin,” he said.
(I imagine most readers of this thread understand the phases of clinical trials by now - but just to be sure, Phase III is the biggie used to licence the drug.)
The Science article that Senegoid posted has a link to the paper itself. This article references a second paper as well and states that the results warrant continued and expanded research.
So far, so good. Now let’s move forward with the next phase.
OK, those are both pre-clin (mouse; and human gastrointestinal and lung epithelial cell lines respectively).
So far as I can tell, the Phase I/II study I linked to is the only plitidepsin study performed in COVID patients. I would love to see the results of that. On the face of it, it looks like that was the dose-ranging for the Phase III study - unless it’s Phase II/III with a further dose ranging element at the beginning. Hectic times.
Not long after I posted the above, the police withdrew permission for this demo (or rather, a cluster of related demos). But today 5000 people showed up anyway to protest the lockdown and/or the very notion that the coronavirus exists. There’s been ample coverage of the event in both English and German media (see for example articles in The Guardian and Der Standard) but to briefly summarize:
The protests kicked off at 11:00 with a demonstration by certain Christians who claim that prayer to Jesus is the only effective cure for coronavirus.
As the day went on, thousands more people amassed downtown, including the usual lot of right-wing extremists and identitarians. Organizers tried to bus people into the city in rented coaches; police were able to intercept many of these. (Tour buses are pretty conspicuous these days due to the lockdown; hotels are closed to tourists.)
Herbert Kickl and the FPÖ stayed away, obeying the law, but their supporters were highly visible in the crowd, with many waving banners with FPÖ slogans.
The demonstrators attempted to march down the Ringstraße, Vienna’s grand boulevard, but since their permits had been withdrawn, they had to contend with the city’s usual Sunday traffic.
Riot police were deployed in the city, though were vastly outnumbered by the protestors, and so couldn’t do much to stop the ones who made it downtown.
The demonstration seems to have been largely peaceful, though not without a few skirmishes. Ten police were reported as being injured, and an undisclosed number of protestors were arrested. Also, some protestors attempted to direct the crowd to the chancellor’s private residence by circulating his address on social media, but this proposal doesn’t appear to have gained any traction. (Maybe the protestors are all upstanding, non-violent citizens, or maybe they just couldn’t be bothered to trudge the seven kilometres to Meidling in near-freezing weather.)
Hey-ho. This is what you get if you skim publications. Have I just found what you were referring to? In the Science preclin publication there are these throwaway lines:
Plitidepsin has also successfully completed a phase I/II clinical study for the treatment of COVID-19 (20, 21) by the pharmaceutical company PharmaMar and is moving forward into a Phase II/III COVID-19 study.
My Bold. What a tease! No further information - the refs just take you to study protocol synopses in English (discussed post 383) and Spanish.
I’m not going to re-read the plitidepsin article again just to find the minor points, but I do think I recall seeing these details:
It’s already authorized for use in Australia for treating multiple myeloma.
The dosage they are testing for Covid, IIRC, is some small fraction of the dosage they are using for the cancer treatment, and seems to have a fairly safe toxicity profile.
Still no new record highs in daily reported cases in any state in well over a week. And the number of new reported cases is still going down in the country as a whole.
Washington Post, but might not be paywalled as it’s coronovirus news. Some of it quoted below, in case.
More research needed, from the look of the article.
Although covid-19 often attacks the lungs, it is increasingly associated with a range of problems [url deleted] including blood clots ([url deleted], neurological disorders, and kidney and heart damage. Researchers say new-onset diabetes may soon be added to those complications — both Type 1[url deleted], in which people cannot make the insulin needed to regulate their blood sugar, and Type 2, [url deleted] in which they make too little insulin or become resistant to their insulin, causing their blood sugar levels to rise. But scientists do not know whether covid-19 might hasten already developing problems or actually cause them — or both.
[ . . . ]
As many as 14.4 percent of people hospitalized with severe covid-19 developed diabetes, according to a global analysis published Nov. 27 in the journal Diabetes, Obesity and Metabolism. The international group of researchers sifted through reports of uncontrolled hyperglycemia, or high blood sugar, in more than 3,700 covid-19 patients across eight studies. While those diagnoses might be the result of a long-observed response to severe illness, or to treatment with steroids, the authors wrote, a direct effect from covid-19 “should also be considered.”
Concerns that covid-19 might be directly implicated also were supported, they said, by the exceptionally high doses of insulin that diabetes patients with severe covid-19 often require and the dangerous complications they develop.
[ . . . ]
diabetes experts launched a global registry of patients with covid-19-related diabetes. After they spread the word with an editorial in the New England Journal of Medicine, more than 350 institutions from across the world responded, he said.
The database is accumulating patients — over 150 so far — although it will take months for researchers to sift through the data to draw any conclusions. “We really need to dig deeper,” Rubino said. “But it sounds like we do have a real problem with covid and diabetes.”