I love puzzles.
Let's turn over some pieces.
When I was in my mid-20s, I didn’t do much of anything but 3D puzzles and goof around. I was making up for lack of teenaged year fun. Never mind.
Yes, I am that nerdy. Me and my friend bought every single 3D puzzle that came out from Toys-R-Us and we did not sleep for 4 years. We did these puzzles, day and night, and ate a lot chocolate cheesecake. From Il Duomo to the Taj Mahal, we did them all. So yeah, I love puzzles.
Here’s one for you guys. I was asked if I wanted to write up a story and I thought I’d have some fun with this and in turn, prevent myself from painting an even bigger red target on my forehead. I was provided with 4 URLs and I am going to copy and paste a single paragraph from each article (one of them is a Science article) here and let’s see if we can figure out what’s going on, ok?
Interjection…
You’ll never believe me. I have a large shoebox full of photos next to me on my floor where I do all of my work from (no, I do not own a chair), and I open the lid and the frikkin’ photo on top, is the following. I kid you not.
Back to the article. Although all I want to do now is build a 3D puzzle.
Let me make this even more fun by swapping out a name that repeats in the following quotes with ‘Sméagol’. My precious. And let’s swap out a drug regulatory body name too. Let’s call it: WTF. I was thinking to swap out the recurring drug’s name as well to ‘bigbuttsndat’, but I don’t want this to fall completely into the category of comedy. Parody will do. Seriously though. Where do these jerks get the drug names from? I can hear it now: ‘Hey Grandma! It’s time for your bigbuttsndat!’ Did I digress?
Oh and one more thing that you’ll need to know. Interleukin 6 (IL-6) is an interleukin (an immunological mediator) that is involved in both anti- and pro-inflammatory responses as part of immune system regulation and homeostasis. In some cases, a defect in IL-6 (which can arise as the by-product of autoimmunity) can cause all sorts of problems since it is responsible for many important things like stimulating synthesis of acute phase proteins1, production of neutrophils, B cell growth support and regulatory T cell antagonism. Like any immunological mediator, if you leave it in the ‘on’ position for too long…
An IL-6 antagonist would bind the cognate receptor of IL-6, that would probably be called the IL-6 receptor (IL-6R), and would prevent IL-6 from effecting its function - sort of like an exogenous ‘off’ switch. Such an antagonist might take the form of say, monoclonal antibodies, and be used to treat Rheumatoid Arthritis and other inflammatory autoimmune diseases. For example.2 3 4 How could anything possibly go wrong?
Sorry, one more thing. Really. The revolving door phenomenon is more than a bit of laughs with your drunk friends in the doorway of that fancy hotel you’re not allowed to stay in. This phenomenon involves people who think it’s ok to work at drug regulatory bodies - the places that approve drugs - and shortly thereafter work at a drug company that, say, makes a drug that you just helped get approved. And vice versa. Not incestuous at all!
Vinay Prasad has been talking about this quite a bit.
In a study published Tuesday in the journal BMJ, researchers who studied the careers of [WTF] medical reviewers found that more than half of the hematology-oncology assessors who reviewed drugs between 2001 and 2010 went on to work for the biopharmaceutical industry.
Prasad wonders if reviewers might make more favorable calculations if they are looking ahead to more lucrative industry work in the future.
Hmm. I wonder that as well Vinay. I really do.
Article #1 can be found here.
[Sméagol], director of the [WTF]’s Office of Drug Evaluation Sciences, was transported from his home to a hospital for “mental disorder” at 3 a.m. on May 9, according to Montgomery County, Maryland, police dispatch logs reviewed by The Daily Wire. Police declined to release a report on the incident despite a Freedom of Information Act request, but [Sméagol] wrote about being taken from his home in a rambling note left on a neighborhood listserv.
Article #2 can be found here.
[Sméagol], who was [a WTF] staff member specializing in reviews for arthritis drugs, oversaw the 2010 approval of Genentech's arthritis drug tocilizumab (Actemra). Months later, he left the agency to join the company and its parent, Roche, as director of the division that includes Actemra and related offerings. [Sméagol] represented Roche before his former [WTF] colleagues when the company sought approval to promote Actemra for new conditions. Last year, he told STAT that the timing of his decision to join Roche and Genentech was coincidental.
Article #3 can be found here.
[Sméagol] is Office Director of the Office of Drug Evaluation Sciences at [WTF]. Previously, [Sméagol] was Executive Director, Head – Translational Medicine in the Clinical Research, Inflammation group at Gilead Sciences from March 2019 through December 2020. Before that, [Sméagol] was Senior Group Medical Director, Global Head of Rheumatology & Rare Diseases in Product Development Immunology at Genentech / Roche from 2010-2019. While at Genentech/Roche, his group initiated and completed a Phase 2 and Phase 3 program for tocilizumab (Actemra) for systemic sclerosis, achieved 2 Breakthrough Therapy Designations and filed 2 sBLA’s – both approved – and achieved 2 orphan drug designations.
Article #4 can be found here.
In one striking example, obtained through the Freedom of Information Act, a doctor said no factor other than the drug could have explained a 73-year-old man’s fatal brain bleed two days after receiving an intravenous Actemra treatment. Another said of a 62-year-old German woman’s heart attack in 2014: “The company assessed fatal myocardial infarction as related to (Actemra).” That company was Roche, Actemra’s manufacturer.
But neither Roche nor the [WTF] has moved to change Actemra’s label to alert patients and doctors that potential risks turned up in the reports, as well as in clinical studies completed after the drug went on the market.
And here’s a bonus article from me.
In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists Actemra (tocilizumab) and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707. opens in new tab.)5
Reaaallllllllheeeeeheeeeeelllyyyy. Well that sounds almost as good as remdesevere.
If the NEJM says it is so, then it must be so. Remember, ‘The only way we’re gonna know if these products are safe is if we start giving them to people. THAT’S JUST THE WAY IT GOES’.
You guys really need to read everything you can about acute phase proteins. They are liver-derived and include C-reactive protein and fibrinogen. Hmm.
Mima T, Nishimoto N. Clinical value of blocking IL-6 receptor. Curr Opin Rheumatol. 2009 May;21(3):224-30. doi: 10.1097/BOR.0b013e3283295fec. PMID: 19365268.
Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm. 2008 Aug 1;65(15):1413-8. doi: 10.2146/ajhp070449. PMID: 18653811.
Maini RN, Taylor PC, Szechinski J, Pavelka K, Bröll J, Balint G, Emery P, Raemen F, Petersen J, Smolen J, Thomson D, Kishimoto T; CHARISMA Study Group. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006 Sep;54(9):2817-29. doi: 10.1002/art.22033. Erratum in: Arthritis Rheum. 2008 Mar;58(3):887. PMID: 16947782.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. April 22, 2021. N Engl J Med 2021; 384:1491-1502. DOI: 10.1056/NEJMoa2100433.
From Article #4: Dr. Vinay Prasad, an oncologist and medical ethicist at the Oregon Health and Science University. “The system is broken, and all the financial incentives are lined up to keep it broken.”
It's a shame that it took COVID-19 for me to realize just how hopelessly broken the system is, and unfortunately, the corruption of the FDA/Big Pharma is just one example of the regulatory capture that infects our entire government.
Love that you out all this crap. I stopped using any pharma years ago. I'm 68, pretty darn healthy, still work, and it's heavy laborious work, and my go to modalities are homeopathy, osteopathy and herbal medicines. TCM fascinates me but there are no practitioners near me. I do read and have books on TCM and the food as medicine I dabble with. I had a doc who is now retiring and according to him me & hubby are the only 2 over 50 y.o. patients not taking a single pharmaceutical in his county wide practice! He even said to me that pharma is corrupt and he thought I was doing the right thing, yet it bugged me that he would treat patients allopathically with pharma. If a physician knows he's using unethical methods, he needs to go back to school, and learn alt modalities and hang a different shingle. I imagine money is the driving force. It is beyond sad.