Daratumumab, isatuximab (CD38 drugs)

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]”
 
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Jaybee00 said:
Anyone have any guesses why Fluge’s group went with Dara over isatuximab?
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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.
 
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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.
 
Jaybee00 said:
Who said that Daratumumab is a high risk drug?
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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".
 
Collecting all the threads we have about daratumumab:

ME/CFS
Other conditions
 

Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase III IRAKLIA Study​


The Isatuximab SubQ formulation will be via an “on body injector”.

These pharma companies always need to find a way to charge more for something that could be done much more cheaply.
 
From the Fatigatio live stream today: Carmen Scheibenbogen says they have secured funds to trial Isatuximab (she mentioned a CD38 depleting drug from Sanofi and there's only one).

She says Sanofi are interested in cooperating based on recent results.



At 2:47:00, but it's in German.
 
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OrganicChilli said:
From the Fatigatio live stream today: Carmen Scheibenbogen says they have secured funds to trial Isatuximab (she mentioned a CD38 depleting drug from Sanofi and there's only one).

She says Sanofi are interested in cooperating based on recent results.
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Any sense of whether that's for a pilot trial or a full trial, and when it might be ready to go?

Would isatux be expected to be better/safer than dara? I'm trying to work out where this trial lies on the 'good news' scale and whether an isatux trial already being funded means that funding the dara trial would be less of a priority.
 
Sasha said:
Any sense of whether that's for a pilot trial or a full trial, and when it might be ready to go?

Would isatux be expected to be better/safer than dara? I'm trying to work out where this trial lies on the 'good news' scale and whether an isatux trial already being funded means that funding the dara trial would be less of a priority.
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No idea unfortunately. She only mentioned it briefly at the end of her presentation before she ran out of time. The study was funded privately so I wouldn't expect anything massive. But perhaps I'm underestimating the German charities. She also said they're waiting for government funding for CD19 and CD20 depleting drugs and that they want to trial everything at the same time.

Isa and dara work similarly in that they inhibit CD38. Chatgpt says Isa may be less dependend on NK cell levels, but take it with a grain of salt.

I don't think this means we should deprioritise dara. If anything, dara's biosimilar will be cheaper.
 
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OrganicChilli said:
No idea unfortunately. She only mention it briefly at the end of her presentation before she ran out of time. The study was funded privately so I wouldn't expect anything massive. But perhaps I'm underestimating the German charities. She also said they're waiting for government funding for CD19 and CD20 depleting drugs and that they want to trial everything at the same time.
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That's odd - I'd thought that the failure of rituximab (a CD20-depleter) would have meant not bothering with other CD20-depleters.
 
OrganicChilli said:
But perhaps I'm underestimating the German charities.
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German and Austrian pwME have done some unbelievable work. If my memory does not deceive me both countries had little going on 10+ years ago. I used to live in Germany for a couple of years and at least online, I feel like there was never really anything from Germany. The amount of progress has been incredible.
 
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