Arcturus self-amplifying RNA: US approval expected this year.

saRNA platform Kostaive is already approved in Europe and Japan and is being tested in the US now.

Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (NASDAQ:ARCT) is a commercial mRNA medicines and vaccines company with enabling technologies:

• LUNAR® lipid-mediated delivery;

• STARR® mRNA technology (sa-mRNA);

• mRNA drug substance and drug product manufacturing.

Arcturus KOSTAIVE, a self-amplifying messenger RNA (sa-mRNA) COVID vaccine platform is now approved in the EU and Japan. The approval in the United Kingdom is anticipated in Q2 2025, followed by a U.S. BLA filing expected in Q3 2025.

Self-amplifying mRNA vaccine program:

In April 2025, Arcturus received U.S. FDA Fast Track Designation for ARCT-2304, an sa-mRNA vaccine candidate for Pandemic Influenza A Virus H5N1. Arcturus states that its self-amplifying mRNA injection program is 100% funded with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50122C0007. The total amount is $63M of which approx. $24M has been spent to date. In its shareholder disclosures, Arcturus states that:

[Using these funds], Arcturus has completed the recruitment of 212 adults in Phase 1 (132 participants 18-59 years old; 80 participants over 60 years old) for the randomized and claimed as placebo-controlled Phase 1 trial (NCT06602531), which is being conducted at multiple sites in the U.S. and the company expects interim Phase 1 data in H2 2025.

About that “placebo-controlled” statement above. In the new age of gold standard, evidence based, fully transparent, make-America-healthy, imagine-if-it-were-Kamala!!(TM) “good”-FDA, the “placebo-controlled” vaccine study means they are using a, drumroll….

“placebo vaccine”!

Thank you MAHA-FDA! Imagine if those bad Democrats were in power. Phew, did we doge a bullet in Butler, PA or what…

Here is my typical dialogue with MAH-Anons on this topic:

• Me: the study was designed, submitted to and accepted as sufficient design for a US approval by the “bad” FDA run by the bad Democrats in September of 2024.

• MAH-Anons: shut up already and stop splintering the movement!

• Me: this study design is fully compliant with the new FDA policy for “pandemic emergency” mRNA vaccines pre-written during Biden Administration and presented as the work of Dr. Makary (FDA Commissioner) and Dr. Prasad (head of CBER FDA), which does not require any placebo controlled or long term safety studies for shots deployed on the “vulnerable” groups, including children and pregnant women!

• MAH-Anons: it was the best RFK Jr could do to fight BigPharma, baby steps!!!

Maybe I am being unfair to the new, good-FDA. Turns out, Arcturus recently published data for KOSTAIVE self-amplifying mRNA covid vaccine, with a 12-month follow-up from the pivotal clinical study in Vietnam (NCT05012943), which had 17,582 participants and even allegedly had a “true saline placebo, I swear!” control.

Let’s review this published paper.

Study Design:

This study allegedly had a true saline placebo group for 92 days, after which point the witnesses control group were eliminated by shooting injected with Arcturus vaccine, because having an long-term control group walk around unscathed for longer than 3 months would ruin everything! I am saying an “alleged” placebo group, because there are a lot of interesting data anomalies in this study even during the first 92 days when that alleged true-placebo-pinky-swear! group was still around.

The study was conducted entirely in Vietnam, at several sites, one of them being the Central Military Hospital in Hanoi! Wow. Remember that Pfizer’s famous pivotal trial, full of data fraud, had the famous Central Military Hospital site in Buenos Aires, Argentina, which miraculously produced the largest number of participants for any site in the study (several thousand!), and even more miraculously, enrolled ~1700 of them in a split second before the deadline for the entire study enrollment. Those military types can do the jobs nobody else can, trust me…

Another interesting observation about the study design is the subject enrollment criteria. The protocol states that having received any SARS-cov or MERS vaccines is an exclusion criterion, i.e. any previously covid-vaxxed persons are disqualified from participation in this Arcturus trial. Vietnam happens to be one of the highest covid-vaxxed countries in the world, with 90%+ of the population having received at least 1 dose by 2022. How likely is that 17,500 fully unvaxxed persons, i.e. representatives of the 10% of the Vietnamese who resisted the tyrannical bullshit in 2020, 2021, 2022, 2023, but totally changed their mind about it in 2024 were found to VOLUNTEER for a self-amplifying mRNA shot? I would sooner believe Arcturus found 17,500 willing visitors from Alpha Centauri to enroll in this experiment…

If anyone from Vietnam is reading this, please comment.

Safety, Adverse Events and Deaths

Table 3 summarizes short-term safety/adverse events. I have highlighted several anomalies in my opinion.

One of the data anomalies is the higher rates of adverse events in the placebo group, especially after Dose 2, and strange correlation between the dose and BOTH placebo and active drug groups having higher or lower number of adverse events (e.g. see the “Vascular disorders” line, where this trend is the most prominent. This correlation is even acknowledged in the text of the paper:

A true placebo (saline) should not systematically produce higher rates of adverse events vs. an active drug injection, especially in larger groups of subjects! And this rate should not be correlated with the active drug group, because why would it be? Just to refresh my memory on this topic, I searched for a few unrelated clinical trials of injectable drugs using saline placebo control, and I found that in those studies the unsolicited AEs in the placebo group were always lower than in the active drug group, as they should be. I don’t know what is going on here, but the data are indicative of either placebo being not true saline placebo or some data manipulation during study conduct or analysis of the data.

Deaths

The data anomalies continue in the table summarizing deaths during the trial. As a reminder, from Day 1 to 92 there was a “true” placebo group (allegedly), and on Days 92 and 120 that group was eliminated by injecting all with the sa-mRNA (Dose 3 and 4), while the group that received the vaccine for the first 2 doses received placebo as dose 3 and 4. This is what the text of the paper states:

Between Days 1 and 92 there were 21 deaths in the pooled Phase 1/2/3a/3b cohort, 5 (0.1%) of 8,807 ARCT-154 vaccinees and 16 (0.2%) of 8,249 placebo recipients, respectively (Table 5). These included 10 deaths related to COVID-19, one ARCT-154 vaccinee and 9 placebo recipients, an indication of the efficacy of vaccination [Citation5]. From the onset of the switchover vaccination series at Day 92 to the end of the study there were a further 20 deaths reported: 12 (0.2%) deaths were reported in 7,678 ARCT-154 recipients who received placebo as doses 3 and 4, and in 8 (0.1%) in 7,582 placebo recipients who received ARCT-154 as doses 3 and 4. Two deaths of participants who received ARCT-154 as Dose 3 after initially receiving placebo as doses 1 and 2 were assessed as COVID-19-related; one a 65-year-old male with no reported medical history and one a 68-year-old female with a history of type 2 diabetes mellitus and hypertension. Four deaths were reported in the Phase 3c cohort during the study period, all four being observed in the ChAdOx1-S group.

I highlighted some things that jump out at me as strange in this table. First anomaly is the total number of deaths during Days 1-92 vs. 93-394, regardless of the study group. To understand this, we need to estimate an approximate total number of all-cause mortality in a population of 17,000 Vietnamese adults. The world population data indicates that all cause mortality in Vietnam is about 5-6 per 1000 population/year. Taking the lower value 5, we arrive at the estimated number of deaths expected in this many people in 3 months, which happens to be exactly what was found in total during Days 1-92, i.e. 22 deaths (including one in the AZ “control” vaccine group). However, for the remainder of the study Days 93-394, we should see another 64 or so deaths. Yet, the total number dramatically drops to only 23! Again, I don’t know how to explain this, but my guess would be that either there was no proactive follow up to track all outcomes in all subjects until the end of the study, or there was some data manipulation involved.

The apparently deadly effects of getting placebo instead of vaccine are even more interesting. There is a MUCH higher death rate in the allegedly “true” placebo group (Days 1-92), with only some of them claimed “with covid”. How would one explain that placebo injected people had more non-covid deaths vs vaccine-injected ones? Were they older, sicker or at a higher risk of death due to lifestyle or profession? Of course, the study authors are portraying this as evidence of life-saving qualities of their vaccine. However, what is the mechanism of this life-saving effect on the all-cause (non-covid) mortality? This became even more stark when the group that already received the “life saving vaccine” at Doses 1 and 2 received Doses 3 and 4 as placebo. Suddenly placebo undid the vaccine magic and killed 12 people, or 4 higher than in the vax group that got more vax, and all of these are not from/with covid!

Do I trust these numbers? Not at all. Since we know that nobody dies “from covid” other than via an mRNA injection or hospital murder with Remdesivir/sedatives/ventilator, and given that the setting of at least the main site for this study is a military hospital, we can imagine a few scenarios of how these data anomalies might have been generated.

Pregnancy data

Of course the reproductive toxicity study in animals was conducted for “another similar” vaccine! Duh. That’s by now a standard operating procedure for all mRNA vaccines. They are claiming that no harms were detected in that study, but there is no way to verify this:

No animal developmental and reproductive toxicology studies have been conducted specifically with ARCT-154, but animal developmental and reproductive toxicology studies were conducted with ARCT-021, a similar vaccine containing mRNA encoding spike glycoprotein of SARS-CoV-2 virus encapsulated in the same LNP. None of the studies conducted with ARCT-021 indicate any direct or indirect harmful effects with respect to fertility, embryo-fetal development, parturition, or postnatal development.

Next, they discuss the pregnancy outcomes in the Vietnamese study, where pregnancy was an exclusion criterion (just like in Pfizer and Moderna studies), but surprise! they got 50 pregnant ladies anyhow:

In this study, there were 50 pregnancies reported between Day 1 and Day 92: 23 cases after the ARCT-154 vaccine, 22 cases after the placebo, and 5 cases after the ChAdOx1-S vaccine. Three spontaneous abortions were reported: 1 in the ARCT-154 group and 2 in the placebo group.

After Day 92, a further 26 pregnancies were reported—12 in ARCT-154 vaccinees and 14 in placebo recipients – including one spontaneous abortion in a participant who received ARCT-154 after the switchover. In addition, two ectopic pregnancies were reported, one in the placebo group and the other in the ChAdOx1 group. Four serious adverse events associated with two pregnancies – preeclampsia and infant death in a participant in ARCT-154 group and a threatened miscarriage and premature birth in a participant who initially received placebo and then ARCT-154 after the switchover – were reported in the study. None was considered to be related to the study vaccine by the attending investigators and physicians.

Without access to the underlying data, all I can say here - while the numbers here are very small and thus subject to large variability, still placebo is somehow (by unknown mechanism) appears to be more dangerous. I find this highly implausible. Other concerning signs involve 1 miscarriage immediately after getting the vax in switch over, death of an infant and a premature birth in participants who received vaccine at doses 1 and 2 (in a small group that’s a safety signal!).

Here is what Arcturus says in their shareholder communications (emphasis mine):

• No serious consequences occurred in several pregnancies reported after vaccination, with normal outcomes when followed to term.

That qualifier at the end is telling. They know that they have a miscarriage/stillbirth safety signal, thus the “when followed to term” statement.

I won’t bore you with additional discussion about this study, there are more safety signals in it for other conditions and you can read that for yourself if you are interested.

Results of a biodistribution study in animals

I wanted to briefly highlight the animal biodistribution study which I found for the Arcturus product. In April, Arcturus' Japanese partner, Meiji Seika Pharma, published an analysis characterizing the distribution and clearance of ARCT-154 encoded spike protein and non-structural proteins nsP1, nsP2, nsP3 and nsP4 in the lymph nodes and injection-site muscle in mice following a single IM vaccination.

It became immediately evident to me that BARDA (the true owner and 100% financier of this product) has learned from prior mistakes of running extensive biodistribution studies for covid mRNA shots. Their mistake last time was to study the product distribution to all organs, which generated huge negative publicity, especially because of the distribution and accumulation of these substances in ovaries, testes and major vital organs such as liver, bone marrow, brain, eyes, heart, etc. This is covered in my articles about Pfizer preclinical studies and Moderna preclinical studies.

This time, BARDA and Arcturus clearly decided not to repeat that fiasco, and studied only 4 things in this “biodistribution” study - injection site, lymph nodes, spleen and presence of LNPs in the blood. This is like studying the flow of water through municipal system by studying the main water tank and the immediate pipes leading from it, but never looking anywhere downstream from there! Therefore no data exists for all the other organ classes. However, since we are talking about essentially the same LNP technology, rest assured, the distribution is expected to be the same, i. e., all over the body.

Here is what the paper says about their findings:

• The study showed the encoded spike protein reached its highest level approximately three days after vaccination and quickly disappeared from the injection site muscle.

• The spike protein levels also peaked at an early time point in the lymph nodes, remained detectable 28 days after the vaccination and disappeared by 44 days after the vaccination.

• Expression of nsP1, nsP2 and nsP4 was observed in the injected muscle and/or the lymph nodes for up to 15 days post-vaccination.

Comparing the time course of the Arcturus biodistribution vs Pfizer covid vax biodistribution is challenging, because Pfizer studied many organs but stopped the study after 48 hours while the LNPs were still accumulating in the organs:

Pfizer:

Arcturus, on the other hand, selectively studied only few endpoints, but observed them for a long time. Notice, however, that in the graph above, for Pfizer, just as I noted, as the product clears from the blood pretty rapidly the accumulation starts to increase in the downstream organ classes!

Here is Arcturus data for comparison:

I don’t know how to explain lack of product detected in spleen here (it maybe the effect of the scale used (the point estimates are all above zero). However, look at the accumulation in the lymph nodes! That’s massive. And who in their right mind wants this much spike in lymph nodes for 44 days?! In addition, the spike is not completely cleared from lymph nodes in 44 days, the point estimate of the last measurement is above zero and the upper confidence bound is quite substantially above zero.

Finally, there has been a lot of anxiety expressed about self-amplifying RNA being more dangerous in terms of shedding vs “regular” mRNA. It is hard to determine this by looking at this set of data, because a direct comparison to Pfizer and Moderna data is impossible, since we only have those charted for 48 hrs. However, I do not believe that shedding from this product will be materially different from the “regular” mRNA products, as in those the expression of spike was detected in some people years after vax! I have discussed my assessment of sa-RNA claims previously:

Addressing hysteria around "self-amplifying" sa-RNA injections.

Therefore, safe to assume, all of this junk hits all organs and the spike may be expressed, at least in some people, indefinitely.

Art for today: Waterlilies, watercolor, 11x14 in.