Open 2022 Pilot study in Norway - Daratumumab in ME/CFS

Jaybee00 said:
Subcutaneous dara is dara plus hyaluronidase-FIHJ. Does anyone what FIHJ stands for? Thanks.
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I cannot find a specific explanation but I suspect it means that the hyaluronidase is specifically a human recombinant preparation. FIHJ might mean something like 'for infection, human recombinant- type J'.

Why you would want to use hyaluronidase for treatment of autoimmunity is hard to follow. The use of hyaluronidase is said to relate to tumour penetration, which would not be relevant. In this case it might be intended to improve absorption from subcutaneous tissue but that seems a bit dubious.
 
It's not "FIHJ", it's "fihj". When you see a hyphen followed by four lowercase characters after the name of a biologic, that's what is called a "distinguishing suffix":
A distinguishing suffix that is devoid of meaning and composed of four lowercase letters will be attached with a hyphen to the core name of each originator biological product, related biological product, or biosimilar product
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https://www.fda.gov/files/drugs/pub...Biological-Products-Guidance-for-Industry.pdf

ETA: found the specific one!
Janssen was notified of the Agency’s intention to designate a nonproprietary name that includes a four-letter distinguishing suffix that is devoid of meaning for their product in an Advice Letter.
daratumumab and hyaluronidase-fihj
FDA generated a four-letter suffix, -fihj. This suffix was evaluated using the principles described in the applicable guidance.
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https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761145Orig1s000NameR.pdf
 
Jonathan Edwards said:
Why you would want to use hyaluronidase for treatment of autoimmunity is hard to follow. The use of hyaluronidase is said to relate to tumour penetration, which would not be relevant. In this case it might be intended to improve absorption from subcutaneous tissue but that seems a bit dubious.
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From the page for the study at Haukeland University Hospital (Google translate) :

«In order for daratumumab to be absorbed by the body, it is combined with another substance called hyaluronidase. Hyaluronidase is an enzyme (protein) that regulates how quickly daratumumab is absorbed by the body.»
 
sneyz said:
From the page for the study at Haukeland University Hospital (Google translate) :

«In order for daratumumab to be absorbed by the body, it is combined with another substance called hyaluronidase. Hyaluronidase is an enzyme (protein) that regulates how quickly daratumumab is absorbed by the body.»
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Yes, it's odd because other monoclonals have been given subcutaneously without hyaluronidase.
Moreover, there doesn't seem to be any hurry about getting a monoclonal absorbed if it is intended to act over a period of days or weeks.

The technology may have changed since I was involved. It may be that without hyaluronidase a significant amount antibody is lost to local tissue degradation.

Most of the sites mentioning hyalronidase- fihj in the context of daratumumab say the hyaluronidase is to penetrate tumour, which maybe is wrong.
 
@Jonathan Edwards

Do these data potentially change your mind about Daratumumab being a viable treatment for MECFS?

Also why is it that people with lower initial IGG respond better to both dara and cyclo?

I thought that high IGG potentially indicated autoimmune diseases involvement. So therefore wouldn’t you expect high IGG patients to respond better to these treatments?
 
I wouldn't expect total IgG levels to be terribly relevant to any response.
And we are expecting a fall over that time frame so not sure it needs to link to symptoms.
The improvement in symptoms is substantial but then we don't have any controls and we saw things like that with rituximab.

Initial levels of IgG are unlikely to mean anything. I don't see enough data to generalise ?
 
Jaybee00 said:
I thought high IGG meant a more severe disease state, therefore harder to treat?
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Total IgG is not usually raised in autoimmunity. It can be, in some very specific conditions like Felty's Syndrome and Sjögren's syndrome but these are anomalous. Low IgG is a more typical feature of lupus - it can be seriously low. Autoimmunity is also more common in people with various Ig deficiencies. High IgG levels are much more a mark of benign or malignant B cell neoplasia.
 
Just want to add my comments to these slides as I am impressed (and hopeful)

1. slide RCT 2025?
- results Pilot study in Norway n= 10 after 1 year : promising and well tolerated
- A larger placebo controlled RCT trial is going to be planned (in 2025?)

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2. With regards to the second slide (attached) : 2 responders + 1 non-responder

- The 3 patients seem to be Moderate ME CFS - according to steps (2000/day)
- 2 responders increase daily steps from around 2000 to around 10,000 in 1 year ( + big increase SPF PF + DSQ score)

I am impressed by these results - basically going from Moderate to Mild
- Maybe even severe/moderate to very mild - as average 10,000 might allow to work
- making the assumption that the no-nonsense Norwegians Fluge & Mella know by now how to select the ‘hard-core’ ME CFS patients (long-term pre-Covid, severely disabled, Mostly housebound etc.)
I guess all Moderates would sign for that - if chances of worsening are minimal

So the only possible concerning is the 1 non-responder (with little IgG Change) dipped in steps / functionality for 4 months - and recovered to the same baseline (roughly).

Purely based on my exposure to 100s of long-term ME CFS patients anecdotes and reading research trials:
- the chances of having a crash from anything (e.g. visiting a hospital for a trial when severe-moderate) are much bigger than having a huge remission in 1 year

Still, we need to wait for the actual results and hopefully they can start the placebo RCT trial very soon.

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3. Hope they will give more data and clarity on their theory on the relation between (a) lowering IgG and (b) A positive treatment response.
- from their presentation it seems a defining marker for them
 

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Jonathan Edwards said:
I wouldn't expect total IgG levels to be terribly relevant to any response.
And we are expecting a fall over that time frame so not sure it needs to link to symptoms.
The improvement in symptoms is substantial but then we don't have any controls and we saw things like that with rituximab.

Initial levels of IgG are unlikely to mean anything. I don't see enough data to generalise ?
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I thought measuring IgG in this study was to have a proxy measure of plasma cell depletion and therefore aberrant IgG autoantibodies potentially driving ME?
 
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leokitten said:
I thought measuring IgG in this study was to have a proxy measure of plasma cell depletion and therefore aberrant IgG autoantibodies potentially diving ME?
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But if you know that there will be some plasma cell loss and that will lead to lower IgG the occurrence of a fall across the board tells you nothing much. Plasma cell populations are very heterogeneous and autoantibody producing plasma cells fall into different compartments in different diseases and different individuals with those diseases so individual IgG falls do not tell us anything useful about relative autoantibody falls in those individuals.

My main point was that high or low IgG levels at the start do not tell us anything about presence of autoimmunity. In autoimmunity people have a different spectrum of antibody affinities, not more antibodies.
 
Am I the only one who’se quite excited by this. 2 near remissions out of 3 sounds quite promising. Do the researchers who did this have a good reputation?

Edit, the 3 patients is an example group while the pilot has 10 ppl total. my bad.
 
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Something else he mentioned in the video that might be interesting: "We just got a paper accepted in Molecular Psychiatry, where a few patients with OCD were treated with Rituximab, and actually, it worked."

Thread: Three cases with chronic obsessive compulsive disorder report gains in wellbeing and function following rituximab treatment, 2024, Gallwitz et al
All cases showed clear and sustained gains regarding symptom burden and function for over 2.5 years. Brief Psychiatric Rating Scale and Yale-Brown Obsessive-Compulsive Inventory Scale scores decreased 67-100% and 44-92%, respectively. These complex cases, prior to rituximab, had very low functioning and disease duration has been eight, nine and 16 years respectively.
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