Daratumumab, isatuximab (CD38 drugs)

[Jonathan Edwards]

Except we don’t know of any MECFS patients who took Isatuximab. It may be a better drug than Dara, and will have a sub Q formulation in 2026. Needs a trial.

But then if we think anti-CD38 does anything it is because of Dara, which takes 6 weeks. If Isatuximab makes you better overnight then it must be a different mechanism, so nothing to do with the Dara result. Unicorns sometimes come in pairs but not that often.

 

[jnmaciuch]

If Dara is found to be effective it would be pretty easy to figure out whether it’s the enzymatic activity or plasma cell targetting that are responsible. There are natural compounds that inhibit CD38 enzymatic activity. If that’s the source of the benefit, those compounds should be similarly effective without any NK cell dependence or demonstrable drop in IgG

 

[ryanc97]

Anecdotally, there is a patient out there who has taken a high dose of Teclistamab (much higher than the Habets dose). If he improves, it will let us know something about CD38.

 

[melihtas]

Hi @melihtas

Long time no post—hope you are doing OK.

“You have hit on a crucial physiological reality that separates simplistic biochemical theory from the complexity of human illness. You are absolutely correct: if the mechanism were only about plugging the "NAD+ leak," patients receiving Isatuximab (which inhibits the enzyme immediately) should theoretically feel a surge of energy within 24 to 48 hours.”

Except we don’t know of any MECFS patients who took Isatuximab. It may be a better drug than Dara, and will have a sub Q formulation in 2026. Needs a trial.

Hi, I am not a social person. I only post when I'm really interested in a topic.

I've tried many treatments in the past including some experimental ones like Suramin. None of them worked, and some made me worse.

For the last few years, I wasn't interested in trying a new treatment until the daratumumab study was published. Now, I am excited again.

It may be a better drug than Dara, and will have a sub Q formulation in 2026. Needs a trial.

Yes, working on it

 

[Jonathan Edwards]

It may be a better drug than Dara, and will have a sub Q formulation in 2026. Needs a trial.

I am uncertain about the value of subcutaneous formulations. If you are going to have a needle stuck in it makes more sense to put it straight into the circulation rather than into some poor piece of leg or tummy skin that may have a nasty reaction and leads to 25% loss of drug activity.

The big advantage of IV that I see is that you can monitor for adverse events minute by minute and once the whole lot has gone in you are unlikely to get any immediate hypersensitivity (lung effects may occur later). For sub-cut immediate hypersensitivity may not kick in until you have got home and there aren't any ambulances available.

 

[Jaybee00]

Ok but anecdotally and maybe in the literature also they say there are less adverse reactions to sub Q.

 

[Jonathan Edwards]

Ok but anecdotally and maybe in the literature also they say there are less adverse reactions to sub Q.

I cannot see why there should be. I strongly suspect that the drug companies push sub-cut as a way of getting their drug to sound more attractive than existing options.