Isatuximab versus Daratumumab

Seems like isatuximab is a “stronger” CD 38 drug than Daratumumab.
Anyone have any guesses why Fluge’s group went with Dara over isatuximab?

https://en.wikipedia.org/wiki/Isatuximab


“Chemically, isatuximab is similar to the structure and reactivity of daratumumab, hence both drugs show the same CD38 targeting. However, isatuximab shows a more potent inhibition of its ectozyme function. The latter gives potential for some non-cross reactivity. Isatuximab shows action of an allosteric antagonist with the inhibition of the CD38 enzymatic activity. Additionally, isatuximab shows potential where it can induce apoptosis without cross linking.[22]Lastly, Isatuximab reveals direct killing activity when a larger increase in apoptosis is detected in CD38 expressing cancer cells. Furthermore, isatuximab demonstrated a dose dependent inhibition of CD38 enzymatic activity. However, daratumumab with the same experimental conditions shows a more limited inhibition without a dose response.[23]”

 

Also a subcutaneous formulation is underway.

https://www.ajmc.com/view/subcutaneous-isatuximab-meets-primary-end-points-in-phase-3-study-for-mm

 

Daratumumab is a high risk drug, so maybe isatuximab is even riskier?

I don't know, of course, but I find the idea of using immune-suppressing cancer drugs really scary. Even if effectiveness for ME/CFS was established, I wouldn't automatically accept treatment if the only option was a drug like this. I might be persuaded, but it wouldn't be an easy call.

 

Who said that Daratumumab is a high risk drug? It is pretty well tolerated, as is isatuximab.

https://www.nature.com/articles/s41598-024-83014-1

I’d rather take CD 38 mabs than cyclo. Also rather take these “simple” mabs over bortezomib or
the newer bispecific mabs like https://en.wikipedia.org/wiki/Teclistamab which has some rare but pretty serious SE’s.

(I know folks with ME/CFS adjacent diseases who are yearning for teclistamab)

 

I am not sure that the information given above tells us much about efficacy. I would not expect inhibitory effects on CD38 to be relevant. What is relevant is cell killing, which is unrelated. It says something about differences in killing but what matters is simply the effect on Ig levels in humans. Differences in pharmacology exist for rituximab and ocrelizumab etc but may not make a lot of difference to usage. There may well be patent reasons for making claims like this.

 

The fact that the common or very common side effects include sepsis, pulmonary oedema, pancreatitis, increased risk of infection, and others.

These aren't trivial.

Statements about drugs being well tolerated need questioning too. They could mean "well tolerated in a small and atypical group", or "well tolerated, considering the patients have relapsed blood cancer".