The Efgartigimod (Vygart) Phase 2 RCT, first discussed here on this forum, for Post-COVID-19 POTS, which also has an open label extension arm, has finished enrolment and will have results in the next few months (possibly by June).
Efgartigimod is a novel therapeutic and acts as an FcRn inhibitor (IgG1–derived antibody Fc fragment). It was recently approved for the treatment of Generalised Myasthenia Gravis as well as for the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).
It effectively reduces IgG levels 1,2,3. As such it’s one of the few drugs where both negative and positive trial results can tell you something about the pathogenesis of a disease based on the trial (and seemingly this was already the case in CIDP). As such I thought it would be interesting to discuss what this trial data could possibly tell us about Post-Covid POTS and possibly even ME.
Of course the majority of this discussion would heavily depend on the trial data itself, is further complicated by the size of the trial (53 participants) as well as the rather very vague criteria of “Post-Covid POTS” and the unknown relationship between this and ME and until then everything remains highly speculative.
However, it might still be valuable do discuss possible implications of this drug such as:
Alongside the above Efgartigimod trials, Phase 2 Proof-of-concept studies for the following conditions will have their readouts in 2024:
Efgartigimod is currently in review as a treatment for Primary Immune Thrombocytopenia (ITP) in Japan after a phase 3 study was conducted 2 years ago (4,5,6).
Efgartigimod is well placed in a competitive market (and could even be seen as a competitior to BC007) and extremely similar biologics exist that are currently undergoing different clinical trials. The direct competitors are Batoclimab (by IVMT-Roivant) and Nipocalimab (Johnson & Johnson). Batoclimab is currently undergoing Phase 2 studies for Graves Disease and CIDP, as well as Phase 3 studies for Graves Ophthalmology (see also 7) and Generalized Myasthenia Gravis, whilst Nipoclimab has undergone a Phase 3 trial for Generalized Myasthenia Gravis and a Phase 2 trial for Sjörgens, supposedly there have also been positive results in Rheumatic Arthritis and haemolytic disease of the foetus and newborn https://www.clinicaltrialsarena.com/news/jj-touts-success-of-nipocalimab-in-two-rare-disease-trials/.
When looking at all the trials that have been conducted and are planned with Efgartigimod (and other anti-FcRn drugs that degrade IgG) the Post-Covid POTS trial sticks out like a sore thumb. It is the only trial for a condition that hasn’t been shown to be an autoimmune disease or an autoimmune-like diseases and it is also the only trial for a condition where Rituximab and/or steroids haven’t shown to have efficacy.
Argenx has stated that the rational for the trial is the possible role of Anti-adrenergic receptor AutoAbs in POTS. In fact none other than Artur Fedorowski is involved in this trial after he was approach by Argenx to contribute his POTS knowledge to the trial (more details are mentioned here). Some of his work on POTS includes some work on Anti-adrenergic receptor AutoAbs but also includes the study showing that the very questionable with Celltrend is not be able to differentiate between POTS and healthy controls. The second rational for their trial is efficacy of IVIG/PLEX in POTS, that as well is questionable and a recent IVIG trial found no effects for POTS.
Compared to many of the other Post-Covid trials this trial appears to be somewhat half-decently run (POTS assessment via measuring supine and standing heart rate, evaluation of compass score during treatment, evaluation of Malmö POTS symptom score, PROMIS fatigue scale and also the PROMIS cognitive function scale and of course pharmacodynamics and pharmacokinetics and immunogenicity of efgartigimod), or at least has stricter recruitment criteria than some other trials (POTS assessment, PCR confirmed infection, Compass score of at least 35 points, i.e. moderate to severe dysautonomia, BMI below 35 and a few more detailed criteria).
Perhaps the trial should be more accurately viewed as a complete shot in the dark by Argenx, than anything concrete, with the hopes of being able to expand their product to a massive market of patients. A market that surpasses anything that their other current trials could deliver, as they estimate the US prevalence numbers of Post-Covid POTS to be far higher (at 500 000) than for all of their above trials combined (it’s still interesting though that they have prioritised Post-Covid POTS rather than something like Multiple Sclerosis which has a similar patient population in the US or even Rheumatic Arthritis which affects a larger population and for which trials are far easier to conduct).
It’s probably also important to mention some conditions in which Efgartigimod underwent large studies, but failed to show efficacy. As far as I could find out this currently only applies to: Pemphigus (Vulgaris or Foliaceus) (see also 8).
Efgartigimod is a novel therapeutic and acts as an FcRn inhibitor (IgG1–derived antibody Fc fragment). It was recently approved for the treatment of Generalised Myasthenia Gravis as well as for the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).
It effectively reduces IgG levels 1,2,3. As such it’s one of the few drugs where both negative and positive trial results can tell you something about the pathogenesis of a disease based on the trial (and seemingly this was already the case in CIDP). As such I thought it would be interesting to discuss what this trial data could possibly tell us about Post-Covid POTS and possibly even ME.
Of course the majority of this discussion would heavily depend on the trial data itself, is further complicated by the size of the trial (53 participants) as well as the rather very vague criteria of “Post-Covid POTS” and the unknown relationship between this and ME and until then everything remains highly speculative.
However, it might still be valuable do discuss possible implications of this drug such as:
- What could negative trial results tell us about an autoimmune hypothesis of POTS?
- Are there plausible mechanisms by which Efgartigimod could work in ME, even if RTX doesn’t work? How should short term data vs long-term data be interpreted?
- Are there antibodies that an RTX treatment addresses that Efgartigimod doesn’t address and vice versa?
Alongside the above Efgartigimod trials, Phase 2 Proof-of-concept studies for the following conditions will have their readouts in 2024:
- Lupus Nephritis
- Sjogren’s
- Myositis (IMNM, ASyS, DM) (this is actually a Phase 2/3 trial with 240 participants)
Efgartigimod is currently in review as a treatment for Primary Immune Thrombocytopenia (ITP) in Japan after a phase 3 study was conducted 2 years ago (4,5,6).
Efgartigimod is well placed in a competitive market (and could even be seen as a competitior to BC007) and extremely similar biologics exist that are currently undergoing different clinical trials. The direct competitors are Batoclimab (by IVMT-Roivant) and Nipocalimab (Johnson & Johnson). Batoclimab is currently undergoing Phase 2 studies for Graves Disease and CIDP, as well as Phase 3 studies for Graves Ophthalmology (see also 7) and Generalized Myasthenia Gravis, whilst Nipoclimab has undergone a Phase 3 trial for Generalized Myasthenia Gravis and a Phase 2 trial for Sjörgens, supposedly there have also been positive results in Rheumatic Arthritis and haemolytic disease of the foetus and newborn https://www.clinicaltrialsarena.com/news/jj-touts-success-of-nipocalimab-in-two-rare-disease-trials/.
When looking at all the trials that have been conducted and are planned with Efgartigimod (and other anti-FcRn drugs that degrade IgG) the Post-Covid POTS trial sticks out like a sore thumb. It is the only trial for a condition that hasn’t been shown to be an autoimmune disease or an autoimmune-like diseases and it is also the only trial for a condition where Rituximab and/or steroids haven’t shown to have efficacy.
Argenx has stated that the rational for the trial is the possible role of Anti-adrenergic receptor AutoAbs in POTS. In fact none other than Artur Fedorowski is involved in this trial after he was approach by Argenx to contribute his POTS knowledge to the trial (more details are mentioned here). Some of his work on POTS includes some work on Anti-adrenergic receptor AutoAbs but also includes the study showing that the very questionable with Celltrend is not be able to differentiate between POTS and healthy controls. The second rational for their trial is efficacy of IVIG/PLEX in POTS, that as well is questionable and a recent IVIG trial found no effects for POTS.
Compared to many of the other Post-Covid trials this trial appears to be somewhat half-decently run (POTS assessment via measuring supine and standing heart rate, evaluation of compass score during treatment, evaluation of Malmö POTS symptom score, PROMIS fatigue scale and also the PROMIS cognitive function scale and of course pharmacodynamics and pharmacokinetics and immunogenicity of efgartigimod), or at least has stricter recruitment criteria than some other trials (POTS assessment, PCR confirmed infection, Compass score of at least 35 points, i.e. moderate to severe dysautonomia, BMI below 35 and a few more detailed criteria).
Perhaps the trial should be more accurately viewed as a complete shot in the dark by Argenx, than anything concrete, with the hopes of being able to expand their product to a massive market of patients. A market that surpasses anything that their other current trials could deliver, as they estimate the US prevalence numbers of Post-Covid POTS to be far higher (at 500 000) than for all of their above trials combined (it’s still interesting though that they have prioritised Post-Covid POTS rather than something like Multiple Sclerosis which has a similar patient population in the US or even Rheumatic Arthritis which affects a larger population and for which trials are far easier to conduct).
It’s probably also important to mention some conditions in which Efgartigimod underwent large studies, but failed to show efficacy. As far as I could find out this currently only applies to: Pemphigus (Vulgaris or Foliaceus) (see also 8).
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