"Pre-medication", or how to sell $50 worth of generic drugs for $600,000!

The curious case of Onpattro, siRNA in lipid nanoparticle now being considered by some as a potential treatment for mRNA injuries

I had a friend in school, who needed a “pre-dinner” before dinner, and then a pizza slice after the dinner. He was skinny. I still hate him.

This is not a hit piece. This is a “pre-crime” novel.

A couple of weeks ago, many of us were rather shocked by the following publication:

BREAKING Publication--Strategic Deactivation of mRNA COVID-19 Vaccines: New Applications for siRNA and RIBOTAC Therapy

In their review paper, Huschler, McCullough and Marotta proposed that treatment of mRNA induced vaccine injury may be mitigated with small interfering RNA (siRNA) and ribonuclease targeting chimeras (RIBOTACs). Quoting from the Substack post by Dr. McCullough:

It may seem unfathomable for doctors to inject more RNA to deactivate Pfizer and Moderna synthetic mRNA that has accumulated in the body after multiple injections. However, siRNA used today in my practice (patisiran, inclisiran) appears to be safe and well-tolerated only notable for injection site reactions.

I am one of the people for whom this idea is unfathomable, and I would like to provide some reasons as to why. I am not accusing anyone of anything. I believe that there is important information missing from this review, which I am going to discuss here.

While proposing siRNA as a treatment for mRNA injury, the paper does not discuss the current on-market siRNA drugs (patisiran - Onpattro, and inclisiran- Leqvio) in detail.

To address Leqvio briefly: it is administered by subcutaneous injection that targets the liver, has many severe counterindications, is known to cause fetal damage, has warnings for cardiovascular adverse events (while being indicated to presumably improve cardiac condition!), and it has never been shown to improve any real health outcomes. As many “new-new-science” drugs on the market, it treats test results, flowcharts, “standards of care” and income statements, not real humans. It is designed to “modify lipids”, i.e. make your cholesterol test look better in the eyes of the establishment/government medicine. The label states that “the effect of inclisiran on cardiovascular morbidity and mortality has not yet been determined”.

This article will focus on Onpattro, as it is similar to the covid shots, being a synthetic RNA (albeit a much smaller strand vs mRNA), encapsulated in LNP containing polyethylene glycol (PEG) - a known extremely toxic substance, which may account for a large % of known covid jab toxicities.

Onpattro (patisiran) is an injectable small interfering RNA that may be used to treat polyneuropathy (multiple nerve damage) caused by hereditary transthyretin-mediated amyloidosis (ATTR) in adults. ATTR occurs when liver produces faulty transthyretin (TTR) proteins and TTR deposits accumulate in organs and tissues, most commonly the peripheral nerves. While I have not delved into ATTR, when exactly it was discovered and what evidence makes it hereditary, I strongly suspect that it is yet another BS new “rare genetic disease” made up as a cover for vaccine and/or environmental toxicity.

The mechanism of action for Onpattro is described as breaking down mutant and wild-type transthyretin (TTR) proteins through RNA interference. TTR is a protein primarily produced by the liver, that carries the thyroid hormone thyroxine and retinol (vitamin A) throughout the body.

Onpattro was FDA-approved on August 10, 2018.

Reviewing the FDA-approved label, I was immediately struck by the following (p.1, Dosage and Administration):

Premedicate with a corticosteroid, acetaminophen, and antihistamines

All patients should receive premedication prior to ONPATTRO administration to reduce the risk of infusion-related reactions (IRRs) [see Warnings and Precautions (5.1)]. Each of the following premedications should be given on the day of ONPATTRO infusion at least 60 minutes prior to the start of infusion:

• Intravenous corticosteroid (e.g., dexamethasone 10 mg, or equivalent)

• Oral acetaminophen (500 mg)

• Intravenous H1 blocker (e.g., diphenhydramine 50 mg, or equivalent)

• Intravenous H2 blocker (e.g., ranitidine 50 mg, or equivalent)

Pre-medication here is a requirement and involves 4 generic drugs, including a steroid, a known big “fire extinguisher” for any inflammatory symptoms. It is not something that should be used long term. Yet, here we have prescribed chronic use of it, for life. Long-term side effects of steroids include:

Long-term side effects:

• Osteoporosis (bone loss)

• Aseptic necrosis (death of bone tissue)

• Adrenal insufficiency (reduced adrenal gland function)

• Cataracts

• Glaucoma

• Increased risk of infections

• Mood disorders (depression, anxiety, psychosis)

• Reduced libido

• Weight gain and obesity

• Skin thinning and easy bruising

• Hair loss

• Increased risk of diabetes

• High blood pressure

• Cardiovascular disease

Other risks:

• Withdrawal symptoms when stopping steroid use, such as fatigue, muscle weakness, and joint pain

• Increased risk of developing osteoporosis and fractures

• Reduced immune system function

• Increased risk of infections, including pneumonia and tuberculosis

• Increased risk of gastrointestinal problems, such as stomach ulcers and bleeding

Was Onpattro, the first-ever synthetic RNA product approved for market, ever studied alone, without the use of 4 “pre-medications”?

Turns out, no!

I found the published Phase 3 study for Onpattro, based on which it received the FDA approval. In my opinion, the study has a lot of highly questionable design features. I am not a clinical trial statistician, so I can’t provide a re-analysis and I am not sure it is possible from the information given in the paper. I am just going to list what I find very concerning:

• The study was small (~225 patients enrolled, 193 completed the study), and the number of clinical sites is very large 44 in 19 countries. This means, on average, 1 clinical trial site handled ~4-5 patients in the period of ~3+ years it took to complete the study. A small study divided among a large number of international sites is a recipe for large variability in a small dataset, and also an easy scenario for data manipulation. This is also a market-capture strategy. Pay lavish fees to every “key” doctor in a particular disease area to participate in the clinical trial where they might have to see a couple of patients a year and they become your devoted sales team. They get to be co-authors of the prestigious NEJM paper discussing “first”, “breakthrough”, “innovative” tech that Elon Musk says will cure cancer one day! Who cares about little things like data variability, we are saving the world here!

• While using 5 (!!!) drugs in the study regimen (4 “pre-medications” + Onpattro), none of them are studied alone. Onpattro is never studied alone. The 4 pre-meds are not studied alone in this patient population either! We have no idea what each drug does by itself in this patient population. There are only 2 arms in the study - “pre-meds”+ saline IV and “pre-meds”+Onpattro. This is not a valid clinical trial design for a new medicine, and remember that this was the first and only “real” approval of RNA+LNP therapeutic. So, we are not just talking new medicine, but an entire new medicine class.

• siRNA (just as mRNA products) is a pro-drug! It makes your liver act in certain way and produce the medicinal effect (allegedly). Again, combining a pro-drug with 4 drugs - who knows what interactions are happening? Nobody does…

• The patients in the treatment arm were allowed to leave the study if the treatment didn’t work for them. Reasonable for severely ill people. However, this of course creates a bias for the study results, similar to what happens to your GPA if you are allowed to drop a course that you know you are going to fail. It is not explained in the paper whether this bias was properly handled in the statistics.

• The study was not entirely blinded. Due to infusion-reactions, which were far more numerous, and characteristic in the active group of the study, it is likely that the investigators became unblinded after the first visit where a patient experienced a particular reaction. There was no mention of how this potential bias was handled.

• The rate of adverse events was a staggering 97% in both placebo and active groups, but there was a much higher rate of severe and serious adverse events in the placebo group (4 generics + IV saline) vs the treatment group. The frequency of severe adverse events (28% in the patisiran group and 36% in the placebo group) and serious adverse events (36% and 40%, respectively). Adverse events leading to discontinuation of the trial regimen occurred more frequently with placebo (14%) than with patisiran (5%). Death occurred in seven patients (5%) in the patisiran group and in six patients (8%) in the placebo group. All seven deaths in Onpattro group were cardiac arrests or failure. All deemed “unrelated”! This is absolutely staggering - 7 deaths in 18 months in 140 people who all received “new, innovative, breakthrough, we-are-going-to-Mars” medicine. Same cause of death.

At best, I would consider this study inconclusive. The study proclaims Onpattro is efficacious and similarly “safe” as the placebo regimen. However, from presented data, a conclusion can be made that the 4 generic drugs in the “placebo” regimen are dangerous for this patient population. In addition, a conclusion can also be made that apparent “efficacy” of Onpattro is simply due to the study design that favored those in whom the 4 generics produced an improvement (steroids will make some people feel much better) to complete the Onpattro group of the study. In other words, the $50 regimen can be now marketed for $600K!

Another reason that I think siRNA is not a great idea to treat the mRNA injury: the covid jabs already contain (in addition to the toxic PEG) synthetic siRNA and miRNA in unpredictable quantities! Therefore, it is possible that covid vaccine injuries at least in some people are DUE TO these substances, and thus proposing the same as treatment is like pouring gasoline on a fire.

I have reported on this eons ago. At the time of issuing the EUA for these shots, the manufacturers could not demonstrate that they were able to make mRNA-LNP product even close to the specification. The RNA is supposed to be certain length of molecule to “instruct” your cells to make the specific antigen, remember? It’s supposed to be the mRNA for the “Wuhan variant”, or for “Omicron”, or for “RSV”, and those are quite different mRNAs! However, an ability to make such precise molecule reliably has never been demonstrated, by anyone. The regulators simply changed the prior standard of acceptance of RNA conformity to 50% of the batch being approximately the weight that the specified molecule should have, and the rest could be shards and pieces of RNA, including siRNAs and miRNAs. All of this was of course based solely on manufacturer self-certification, no independent analysis of batches was done by regulators.

However, we have a lot of data from independent vial tests since then. One such analysis was done by Vanessa Schmidt-Kruger in Germany in 2022, and here are her results for RNA composition by weight (length) in a Pfizer vial.

The first line is what was supposed to be found for RNA sequence in a Pfizer vial which is claimed to induce the cells to make a very specific protein against the “Wuhan” variant of SarsCov2 (should be 4300 nucleotides in length). The rest of the lines is what was actually found.

detail:

None of the findings correspond to what is supposed to be there for mRNA molecule composition. There are some strands that would pass the weight (length) test set by the FDA’s fake-acceptance criteria, but none have the composition that is claimed to produce some specific protein! There are many shorter clusters of RNA which would further degrade into shorter components such as siRNA or miRNA. It is important to emphasize, all these designations are models. There isn’t even a consensus on what the model of miRNA should be.

Side note: if you need another confirmation that it is not possible to make weaponized pandemic-causing viruses via gain-of-function molecular engineering in a lab, this is it. You are looking at the current, technological cutting-edge, state-of-the-art precision capabilities of making RNA viruses in labs! The GOF uses the same non-functioning biomanufacturing tools to allegedly build even larger very precise RNA constructs (full genome SarsCov is ~30K base pairs), reproducibly, in quantity, without a single error! They can’t make an RNA strand of ~4000 nucleotides to specification, even when it’s stabilized and encased in LNP, yet the fear porn producers tell you they can certainly make a “live virus” with scary-sounding features like “HIV insert” and “furin cleavage site”. This is when even 1 nucleotide error/change renders a potentially lethal virus into a dud. Yet, we must believe this is a world-ending scenario and demand banning this dangerous activity everywhere, but conveniently forgetting Fort Dietrick, because they are just poor confused soldiers following orders from bad Fauci, and also forgetting that this activity is already internationally banned. I agree, let’s ban this some more…

Finally, let’s examine the financial model:

In the United States, the cost of Onpattro is around $10,313 for a supply of 5 milliliters, depending on the pharmacy. The annual cost is estimated to be around $451,430 to $677,145 per patient, depending on the patient’s weight.

Inclisiran (Leqvio), an add-on therapy to other LDL-lowering drugs (statins and monoclonal antibodies), is priced at $3250/dose. I could not find annual cost estimates.

In case you didn’t know this, Medicare is not allowed to negotiate drug prices, and all private insurers follow Medicare’s pricing lead paying whatever price is demanded by pharma companies. Additionally, insurers are NOT interested in lowering costs of healthcare in general or drugs in particular. That is because their business model is based on charging a “premium”, which is dependent on the prior years’ cost increases. The more costs increase, the higher the “premium”, and thus profit. Finally, your doctor is also not interested in treating you with cheap generic medicines or things that make no profit at all, like lifestyle and diet changes. That is because the “physician charge” component for generics is zilch, while a $600,000/year treatment will have a pretty hefty allowance in the physician’s bill for the in-office infusion. Yes, they are all in on it.

Art for today: My Garden, watercolor, 8x10 in.