Replies to post #254803 on Biotech Values

[Fred Kadiddlehopper]

Raises the disturbing question of whether these phenomena will be seen in competing products.

[Mufaso]

Dew- Did you see the abstract conclusion on that paper?

Conclusion
Immunogenicity did not affect TZP pharmacokinetics or efficacy. The majority of hypersensitivity or injection site reactions experienced by TE ADA+ patients were mild to moderate in severity.

https://academic.oup.com/jcem/article/109/2/361/7272290

What is your take on the significance of >50% of pts develop ADA against Tirzepatide? Also - What is your take on the significance "2% has neutralizing Ab against TZP activity at GIPr & GLP1r" or any other conclusions you draw from this paper? TIA

[DewDiligence]

GLP-1 side effects are sex-linked—at least in mice:

https://www.prnewswire.com/news-releases/landmark-study-explains-why-obesity-drugs-work-differently-for-women-and-men-302406164.html

The study reveals that female mice have nearly double the GLP-1 receptor expression in brain regions linked to nausea, explaining their heightened side effects. If this receptor expression pattern is consistent across species it could explain why women experience higher rates of nausea and vomiting.

… Higher estrogen levels correlate with more severe side effects, highlighting the role of hormone levels in drug response.

[DewDiligence]

NEJM abstract_on Zepbound-vs-Wegovy study funded by LLY:

https://www.nejm.org/doi/full/10.1056/NEJMoa2416394

A total of 751 participants underwent randomization. The least-squares mean percent change in weight at week 72 was -20.2% (95% confidence interval [CI], -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001). The least-squares mean change in waist circumference was -18.4 cm (95% CI, -19.6 to -17.2) with tirzepatide and -13.0 cm (95% CI, -14.3 to -11.7) with semaglutide (P<0.001).

These results are broadly consistent with prior data that did not come from a head-to-head trial.