FDA Regulated signifies that a drug’s category is regulated under the FDA; it does not mean that a product is approved or indicated for use for a specific condition. Example, the FDA regulates the safety and effectiveness of medicines, but does not regulate medical practice and how physician prescribe medications FDA Approval signifies that a product has been reviewed and deemed safe and effective Example, IVIg is an FDA approved medicine used to treat many conditions, including some for which IVIg is indicated. FDA Indication signifies that a product has been determined to be safe and effective by the FDA for a specific condition Example, Certain brands of IVIg are indicated to treat CIDP. Open label administration means that a drug in a clinical trial is given to every participant, and they know that they are taking the clinical trial drug Treatment naive patients are patients who have not received any treatment for their specific condition *University of Texas MD Anderson Cancer Center

FcRn receptor is a receptor that lives in a cell called endothelial cells This receptor is the gateway receptor to determine what proteins are friendly and should be recirculated and what needs to be destroyed. Protein or immunoglobulins try to flow down the vasculature and try to bind with the FcRn receptor Those that bind get kicked back into the body’s circulation Those that don’t bind get destroyed by the body or metabolized by that cell antibodies or proteins that cause damage will be destroyed This does diminish the levels of normal Ig!

An Immunosupressant that uses monoclonal antibodies to target and deplete B-cells that carry a CD20 marker. Two completed studies 1.Study conducted in Japan Purpose: Is rituximab effective in patients with and without IgG4 auto-antibodies? Weekly retreatment 4 times versus placebo Outcome: Patients improved at 26 and 52 weeks Awaiting full results 2. Study conducted in Italy Purpose: Does rituximab induce remission? Retreatment at 6 months; full year study Outcome: Patients worsened after IVIg treatment stopped Relapse rates at 12 months were similar for both rituximab and placebo patients Those on rituximab has a longer interval between infusion and relapse than placebo patients but in the end the results were the same Take away: Based on the Italian study, rituximab is not for everyone with CIDP. The more we learn about rituximab, we will understand if there is a group of patients who are specifically good candidates for CIDP. We need to study rituximab more to learn the best way to use rituximab.

Part of the Immune System that enhances the ability of antibodies to: Attack cells Promote inflammation Clear debris or dead tissue In auto-immune diseases, complements destroy healthy and “friendly” cells and in our community’s case: the peripheral nervous system

Speaker Series Webinar: "Current Treatments and Emerging Trials for GBS, CIDP, and MMN"

Q: Standard Treatments known to improve symptoms

CIDP IVIg Coricosteroids SCig (subcutaneous) for maintenance MMN IVIg is the only officially approved medicine for MMN GBS Plasma-exchange or plasmapheresis IVIg

Q: The knowledge gained from clincal trials over the past 10 years

1.IVIg overtreatment in CIDP (IOC) trial Adrichem et. A. Brain 2022 30-40% of CIDP patients on IVIg do not need treatment as much or at all 2. Efficacy and safety of 3 different doses of IVIg in CIDP (ProCID trial) Cornblath DR et al. JPNS. 2018 The standard dose of IVIg is fine for some but others may need a higher dose to get the same results 3. Dose Response of IVIg in CIDP (DRIP) Kuitwaard K et al. Eur J Neurol 2021 High Doses should be taken less frequently whereas smaller doses should be taken more frequently Infusions should occur every 2-4 weeks The efficacy of IVIg treatment is dependent on the timing and amount of dosage a patient receives; each patient is different with different needs 4. IVIg Treatment-Related Fluctuations (GRIPPER) Allen JA and Lewis R. Neurology 2016 This study quantified the changes patients experience with treatment to understand the importance of infusion rates and how to avoid IVIg wear off

Q: In the past 7 years, 4 clinical trials have researched FcRn Receptors

Completed trials Rozanolixizumab (sponsored by UCB Pharma) A clinical trial that attempted to find a treatment using FcRn receptors but was stopped because its results were unsubstantiated Efgartigimod (sponsored by Argenx) This clinical trial was completed and the drug studied was granted FDA approval and indicated to treat CIDP in June 2024 Ongoing Trials Nipocalimab (sponsored by Janssen) Batoclimab (sponsored by Immunovant) Visit https:clinicaltrials.gov for a complete list of enrolling sites

Q: Efgartigimod (sponsored by Argenx)

Vyvgart Hytrulo A phase II trial with CIDP patients where patients were asked to stop their normal treatments so that their condition would relapse for a little and then take Vyygart to see if there were any improvements in patients. Those whose condition did improve were randomly assigned to continue taking Vyvgart or completely stop treatment in the placebo group. Patients were studied to determine a relapse rate at 48 weeks with weekly 1–2-minute subcutaneous injections. Results Compared to the placebo group, patients on Vyvgart had a 61% reduction in risk of relapse Now Vyvgart is FDA approved

Posted on October 24, 2024

Speaker Series – Episode 12 Summary

Video Recording

PDF

In this Speaker Series episode, Dr. Jeffery Allen educates us about the current treatments for GBS, CIDP, and MMN as well as explain current trials and their findings. Dr. Allen is an associate professor of neurology at the University of Minnesota, adjunct faculty at Northwestern University, and the chairman of out global advisory board.

Key Terms

FDA Regulated signifies that a drug’s category is regulated under the FDA; it does not mean that a product is approved or indicated for use for a specific condition.

Example, the FDA regulates the safety and effectiveness of medicines, but does not regulate medical practice and how physician prescribe medications

FDA Approval signifies that a product has been reviewed and deemed safe and effective

Example, IVIg is an FDA approved medicine used to treat many conditions, including some for which IVIg is indicated.

FDA Indication signifies that a product has been determined to be safe and effective by the FDA for a specific condition

Example, Certain brands of IVIg are indicated to treat CIDP.

Open label administration means that a drug in a clinical trial is given to every participant, and they know that they are taking the clinical trial drug

Treatment naive patients are patients who have not received any treatment for their specific condition

*University of Texas MD Anderson Cancer Center

Standard Treatments known to improve symptoms

CIDP

IVIg
Coricosteroids
SCig (subcutaneous) for maintenance

MMN

IVIg is the only officially approved medicine for MMN

GBS

Plasma-exchange or plasmapheresis

IVIg

What trials strive to understand

Best Dosage of treatment
Best Frequency of treatment
What combination of therapies work
Duration of treatment
How to personalize maintenance
Other treatment options

The knowledge gained from clincal trials over the past 10 years

1.IVIg overtreatment in CIDP (IOC) trial Adrichem et. A. Brain 2022

30-40% of CIDP patients on IVIg do not need treatment as much or at all

2. Efficacy and safety of 3 different doses of IVIg in CIDP (ProCID trial) Cornblath DR et al. JPNS. 2018

The standard dose of IVIg is fine for some but others may need a higher dose to get the same results

3. Dose Response of IVIg in CIDP (DRIP) Kuitwaard K et al. Eur J Neurol 2021

High Doses should be taken less frequently whereas smaller doses should be taken more frequently
Infusions should occur every 2-4 weeks
The efficacy of IVIg treatment is dependent on the timing and amount of dosage a patient receives; each patient is different with different needs

4. IVIg Treatment-Related Fluctuations (GRIPPER) Allen JA and Lewis R. Neurology 2016

This study quantified the changes patients experience with treatment to understand the importance of infusion rates and how to avoid IVIg wear off

Completed trial for SCIg

Hyqvia (sponsered by Takeda)

Combines Hyaluronidase + SCIg for CIDP treatment
- Hyaluronidase is a compound that lives in the subcutaneous tissue that prevents diffusion of anything that penetrated the subcutaneous tissue
This combination of hyaluronidase a + SCIg allows patients to take a high dose with less frequency by expanding the tissue to allow more product to be injected and then diffused
- For example: standard SCIg may be taken once a week or more but this combination drug might increase the treatment interval to every 3-4 weeks.

Results:

Those who took this combination drug had significantly less of a relapse rate of 10% than the placebo group who had a relapse rate of 30%
The relapse rate was at 6 months
Patients on this combination drug only needed infusions once a month for 2 hours; it only requires with 2 needles

What we learned: SCIg + Hyaluronidase is a safe and effective drug that allows patients to take a high dosage of SCIg at a lesser frequency.

FcRn Antagonist

FcRn receptor is a receptor that lives in a cell called endothelial cells

This receptor is the gateway receptor to determine what proteins are friendly and should be recirculated and what needs to be destroyed.

Protein or immunoglobulins try to flow down the vasculature and try to bind with the FcRn receptor
- Those that bind get kicked back into the body’s circulation
- Those that don’t bind get destroyed by the body or metabolized by that cell
  - antibodies or proteins that cause damage will be destroyed
This does diminish the levels of normal Ig!

In the past 7 years, 4 clinical trials have researched FcRn Receptors

Completed trials

Rozanolixizumab (sponsored by UCB Pharma)
- A clinical trial that attempted to find a treatment using FcRn receptors but was stopped because its results were unsubstantiated
Efgartigimod (sponsored by Argenx)
- This clinical trial was completed and the drug studied was granted FDA approval and indicated to treat CIDP in June 2024

Ongoing Trials

Nipocalimab (sponsored by Janssen)
Batoclimab (sponsored by Immunovant)

Visit https:clinicaltrials.gov for a complete list of enrolling sites

Efgartigimod (sponsored by Argenx)

Vyvgart Hytrulo

A phase II trial with CIDP patients where patients were asked to stop their normal treatments so that their condition would relapse for a little and then take Vyygart to see if there were any improvements in patients. Those whose condition did improve were randomly assigned to continue taking Vyvgart or completely stop treatment in the placebo group.
Patients were studied to determine a relapse rate at 48 weeks with weekly 1–2-minute subcutaneous injections.

Results

Compared to the placebo group, patients on Vyvgart had a 61% reduction in risk of relapse

Now Vyvgart is FDA approved

Rituximab

An Immunosupressant that uses monoclonal antibodies to target and deplete B-cells that carry a CD20 marker.

Two completed studies

1.Study conducted in Japan

Purpose: Is rituximab effective in patients with and without IgG4 auto-antibodies?

Weekly retreatment 4 times versus placebo
Outcome: Patients improved at 26 and 52 weeks
Awaiting full results

2. Study conducted in Italy

Purpose: Does rituximab induce remission?

Retreatment at 6 months; full year study
Outcome:
- Patients worsened after IVIg treatment stopped
- Relapse rates at 12 months were similar for both rituximab and placebo patients
- Those on rituximab has a longer interval between infusion and relapse than placebo patients but in the end the results were the same

Take away: Based on the Italian study, rituximab is not for everyone with CIDP. The more we learn about rituximab, we will understand if there is a group of patients who are specifically good candidates for CIDP. We need to study rituximab more to learn the best way to use rituximab.

Complement System

Part of the Immune System that enhances the ability of antibodies to:

Attack cells
Promote inflammation
Clear debris or dead tissue
In auto-immune diseases, complements destroy healthy and “friendly” cells and in our community’s case: the peripheral nervous system

Complement Clinical Trials

Riliprubart (sponsored by Sanofi)

Outcome was measured during the trial: Relapse rate or response rate at 52 Week
Phase II trial of patients with CIDP in an open label administration for 52 weeks

Results:

87% of standard of care patients improved or remained stable at 24 weeks
50% of Refractory patients showed improvement
71% of treatment naive patients improved and sustained response at 1 year

Sanofi is developing two phase III trials

Mobilize: For patients with failure or inadequate response to standard treatments
Vitalize: For patients receiving maintenance treatments with IVIg

Empasiprubart (sponsored by Argenx)

Trial name: “ARDA”

Phase II trial of patients with MMN that were randomized to transition from IVIg to Argenx’s treatment or be a part of the placebo group
Outcome: Time to IVIg retreatment in 52 weeks

Results:

The study drug reduced the risk of IVIg retreatment by 91%
Demonstrated improvement of grip and muscle strength
Improved patients’ ability to perform daily activities
Now it will go into global phase III studies to determine its safety and efficacy in adults with MMN

ANX 005 (sponsored by Annexon)

Phase III trial of patients with GBS that randomized patients to the study drug or placebo group
Outcome: GBS disability score at day 56 and how long recover took

Results:

2.4 improved disability assessment at week 8 (idk what he means by 2.4 he doesn’t say tbh)
Improved muscle strength at day 8 and week 8
Fewer days on artificial ventilation
Faster time to regain walking ability
Earlier treatment results in getting better faster

CIDP Diagnostic Criteria

A new CIDP guideline was published in 2021 by members on our GMAB board!

You can access it here: https://pubmed.ncbi.nlm.nih.gov/3408574

IncBase (2021)

A CIDP patient registry in efforts to*