Daily MoS: The Disaster of Drug Trial TGN1412

No drug trial is ever without risk. We’re in a new world of biologics, stem cells, and mRNA vaccines. The safety rules change to keep up as we go. I mean I’m in a vaccine trial and I feel fi- KILL ALL HUMANS. KILL ALL HUMANS.

Ahem.

Back in ancient times- 2006, when we thought George Bush was the worst president ever- we still had a lot to learn in the new medical horizon. Phase one of the drug trial for TGN1412 nearly goddamn killed everyone who didn’t receive the placebo.

Today in a Moment of Science… In Mother Russia, drug trials YOU!

TGN1412 was an immunomodulator being researched by the German pharmaceutical company TeGenero. I know we all got our PhDs on monoclonal antibodies via youtube, but indulge me. This monoclonal antibody had potential mainly for autoimmune disease treatment. It activated T cells by binding to one receptor site on it- the CD28 receptor, this will come up again- when normally multiple receptors needed to be engaged. At a low dose, mainly regulatory T cells were engaged. As the name suggests, regulatory T cells go Warren G up in this bitch and help suppress the immune system. We often do this with steroids, which can be nasty business. So this potential monoclonal antibody treatment seemed…

Safer?

For the phase one trial, also known as the “fuck yeah we’ve tried this before… in a baboon’s ass” phase, eight men were recruited. They were told about minor side effects including things like allergic reaction. They were not told the study director had a warning that a major potential side effect was cytokine release syndrome. But I’m pretty sure ‘heart attack’ is a potential side effect of Viagra. And some of y’all want that shit “just in case.” So.

At the private testing facility in London leased by the drug company- not a hospital- the men were divided into two rooms. Six were given drug infusions, two the placebo, all dosed just ten minutes apart. Before the last man in the second room was being administered his dosage, the first man who received his infusion already felt like a particularly ornery rhino crapped in his skull. Knowing this, they continued to infuse the last volunteer anyway. From there the fan blades slung a continual shit stream violently against the walls. Fevers, cold sweats, vomiting, incontinence hit them all.

That was before it got really terrifying.

Their faces swelled, earning one of them a comparison to the Elephant Man (his fiancee said his face looked like a ball with slits for eyes). Their internal organs shut down. Most of them were released from the hospital in under a month, but the worst of them, a 21 year old plumber, was comatose for nearly three weeks and spent five months in hospital. He had parts of his fingers, toes, and feet amputated, and still cannot walk unaided. It’s unclear how their immune systems will recover long term and if they’ve been left susceptible to new illnesses over their lifetimes. The company threw undisclosed amounts of cash at them that’s been best described as “wads.”

So if you’re anything like me you have one question: what the fuck? Their dosages were 1/500th what was administered to macaque monkeys, how are we all such weak soyboy cucks compared to the macaques? For some quirk of nature, engaging the CD28 receptor in macaques does not have the potential to produce cytokine release syndrome. Furthermore, it was calculated- after the fact, clearly- that the volunteers were dosed with enough TG1412 to bind virtually all of their CD28 receptors. Remember, a low dose was needed to engage regulatory T cells. That “low dose” needs to be measured for the species you’re dosing.

Huge changes have been made to safeguard from this kind of disaster happening again. When administering a receptor specific drug like this, dosing guidelines take into account the minimum anticipated biological effect level (MABEL). For first-in-human trials, the drug is administered to one person the first day followed by observation. And high risk trials like these must be performed at facilities with ICUs.

TG1412 is now safely in phase two trials, reborn as TAB08, a Russian drug for treating lupus. Which I’m sure is totally safe. In Mother Russia… oh, fuck, I already told that one.

This has been your daily Moment of Science, and don’t worry, I’m sure the tracking chips will be fixed by the time you get your vaccines.

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