Forget about PED educators. There are even person to person differences that affect response to meds. 8 people can take same meds and 5 respond differently from 3. A lot of this is simple extrapolation.
This immunogenicity thing is being beaten to death.
There are actual peptides that provoke strong immune responses. Cjc, Tesa and Tb500 to mention a few. Tesa has been studied in particular, and most people develop immuogenicity to it. That response is the small lump or mosquito bite some folks feel after a tesa injection, and that's about where it ends. It doesn't affect efficacy.
A lot of other things can explain differences in response, especially to lyophilized peptides. Anything from fillers, to counterions to hidden modifications that the UGL lab doesn't disclose (like some folks modifying BPC to escape export restrictions), to lay everything on the alta of immumogenicity is too scape-goaty.
Unfortunately I cannot battle extrapolation with further extrapolation. There will be no definitive tests because main pharma will likely never invest in ugl research so the best we can run on is anecdotes.
Lastly, even purity as we know it can be quite misleading. There is a fundamental misunderstanding of purity. A slightly degrading peptide can actually increase in purity under HPLC, so there's that. It doesn't mean that the 96% is 'less pure' than the 98%.
Theoretically therefore HGH can degrade and give you 98-99% with very little dimer because the degraded fragments are more hydrophilic and elute outside the dimer's range, or the aggregates are too large and are missed by standard HPLC.. Not to mention that dimers themselves can actually degrade.
Let's stop looking for simple answers to complex physiological puzzles.
Immunogenicity as we know it is yet to affect efficacy of pharma. Why should we extrapolate that it is rife in UGL?
@bighunanballs
Here we go again:
No study of Tesamorelin concludes "Immunogenicity only results in lumps".
What the phase III trial, the most comprehensive study of Tesamorelin's immunogenicity says, in effect is:
"In clinical trials. when using our pharma formulation, manufacturing process and protocol of Tesamorelin, reconstituted to the specified concentration, in the specified dose, at the specified interval, in the demographic of subjects in this study, it does not produce immunogenicity that rises to a clinically significant level beyond local site reactions."
It DOES NOT say "Therefore any poorly produced UGL copy, supplied with random or absent excipients, in contaminant filled cheap containers, stored and transported in a wide range of uncontrolled temps, reconstituted to a random PH, using BAC of unknown quality, to a random concentration cannot create a much greater degree of immunogenic response that results in more substantial effects than 'creating lumps' ".
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Theratechnologies 2023:
"Hey, Middus says this immunogenicity shit is behind us, it only produces mosquito bite like reactions, let's release a more concentrated version of our 15 year old peptide, Tesamorelin, so the injection volume can be reduced and more patients will stick with it!"
FDA 2024:
The FDA has denied approval of Theratechnologies’ F8 formulation of tesamorelin
The FDA is also seeking additional information on the potential effects of the more concentrated formulation of tesamorelin on immunogenicity risk.
...the regulator pointed to issues regarding tesamorelin’s chemistry, manufacturing and controls, particularly regarding impurities, microbiological assays the stability of the lyophilized drug as well as the final reconstituted product.
The regulator’s Complete Response Letter flagged issues with the new formulation of tesamorelin’s chemistry, manufacturing and controls and sought more information about its immunogenicity risk.
www.biospace.com
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We'll look at that. The retards at the FDA think something we all know is meaningless, the reconstituted concentration of a peptide, is a reason to raise the alarm. Just reconstitute to whatever works, everyone knows that,
I suggest you let the FDA know this "immunogenicity thing" has been "beaten to death." and stop being concerned with nonsense. Why are they worried about a mosquito bite, and standing in the way of progress, costing that biotech company tens of millions of dollars with delays?
I'm debating whether it's worth the effort to bring you some of the countless examples of protein therapeutics. from GLPs to Hgh pharma products that even in their final, FDA approved form, STILL result in an immunogenicity that reduces or entirely neutralizes effectiveness, resulting in treatment failure for the patient. And again, these are drugs that pharma spent years developing, with everything from manufacturing, to containers, to handling focused on minimizing immunogenicity.
You make the mistake of assuming that you're seeing how inconsequential immunogenicity is based on the human trials, when what you're really seeing is the end product of years of effort to engineer immunogenicity out of the final peptide product. The "scary" data of the "sloppy" beta versions (more similar to UGL) is never made public.
I could show you countless examples of peptide therapeutics that got through all the initial stages of development and approval, but a microscopic drop of silicon lubricant in a syringe created aggregates that induced immunogenicity in the first human trials causing such a bad response, the e trials were cancelled and development stopped.
But I suspect you'll never be convinced it's worthy of paying attention. to.
This will always be some abstract, low probability threat, no matter how it's nearly impossible to put together a worse set of circumstances to generate maximum immunogenicity than what's going on with UGL peptides and HGH.
The "didn't lose an ass cheek so it's sterile enough" school of medicine.
For everyone else, filter your peptides. It'll not only reduce or eliminate site reactions, it may prevent the steady loss of effectiveness that many pharma peptides induce in a subset of patients, sometimes over very long periods of time.
