3. Efgartigimod

Santa Monica Pier ferris wheel lights teal for MG Awareness/Argenx
A myasthenia gravis campaign in 2020 lit the Santa Monica Pier in teal, as Argenx built awareness in the market it hopes to enter in 2021 with efgartigimod.

Drug: efgartigimod
Company: Argenx
Used for: IgG-mediated autoimmune diseases
Est. 2026 sales: $2.5 billion

Argenx’s efgartigimod looks on track to be the first to land an approval within the anti-FcRn drug class, which according to analysts at SVB Leerink could target a market worth $20 billion to $25 billion in the U.S. alone by 2030.

The Belgian company recently filed it in generalized myasthenia gravis (gMG) with the FDA and expects to do the same with regulatory agencies in Japan and the EU this year. With that timeline, Argenx believes it has an estimated three-year head start against a short list of other clinical FcRn competitors, which includes Johnson & Johnson’s newly acquired Momenta Pharmaceuticals, UCB and Alexion Pharmaceuticals (soon to be AstraZeneca), among others.

FcRn is known as a protection receptor of immunoglobulin G (IgG). The idea behind drugs like efgartigimod is that blocking FcRn could lower pathogenic IgG antibodies, which are implicated in several autoimmune diseases.

RELATED: Argenx's autoimmune phase 3 hits goals, teeing up FDA filing

Efgartigimod showed it could work in MG by improving the symptoms of a significantly bigger proportion of patients than placebo did in the phase 3 Adapt trial. Among trial patients who tested positive for acetylcholine receptor (AChR) antibody—an indicator of MG—67.7% of efgartigimod takers were counted as responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, while only 29.7% placebo patients could say that. As for duration of treatment response, 56.8% of patients responded to efgartigimod for at least eight weeks, and 34.1% at least 12 weeks.

The trial also enrolled AChR-negative patients, and a secondary endpoint analysis of all-comers also reached significance. However, as Argenx pointed to an unusually high placebo response, SVB Leerink’s Thomas Smith, in a note in May, suspected the non-AChR subgroup didn’t meet statistical significance, suggesting the final FDA label could still be up for discussion. About 85% of MG patients have anti-AChR autoantibodies.

It marked the first phase 3 win for the FcRn class. UCB’s rival anti-FcRn drug rozanolixizumab is slated to report phase 3 MG results this year; J&J’s Momenta read out positive phase 2 interim results for its lead product nipocalimab last June; Immunovent’s IMVT-1401 was looking at a possible phase 3 MG trial in the first half this year after a phase 2a win last August, but it recently hit pause on a broad phase 2b trial after noticing elevated cholesterol levels in patients; and Alexion’s ALXN1830 (formerly SYNT001) is earlier in development.

At an SVB Leerink event in July, two industry experts noted some differences among the five clinical-stage FcRns but admitted that more data are needed to determine whether they would affect prescription behavior. Specifically, UCB’s rozanolixizumab was linked to a relatively high rate of headaches in its phase 2 MG trial, while it wasn’t a major problem in efgartigimod’s phase 3 Adapt trial.

RELATED: J&J inks $6.5B Momenta buyout to bag autoimmune drug

Administration route and frequency could be a key differentiating feature, the experts noted, according to an SVB Leerink note. Both experts expected most patients would prefer subcutaneous formulation over intravenous injection. Efgartigimod currently comes in IV but Argenx is exploring an under-the-skin version with a 50-person gMG bridging study comparing the two formulations. UCB’s and Immunovent’s drugs are subcutaneous, and Momenta’s IV, while Alexion’s have both formulations.

Payer coverage will also likely drive prescriber decisions, the experts told SVB Leerink, noting that Alexion’s C5 inhibitor Soliris has limited use only in refractory MG due to payer pushback. But Alexion’s follow-up drug Ultomiris could be a better drug, and development is underway for gMG and with a subcutaneous version.

Argenx, like its FcRn competitors, is exploring a wide range of autoimmune indications. Across the entire class, these include primary immune thrombocytopenia, pemphigus vulgaris and pemphigus foliaceous, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, thyroid eye disease and others.

“We see much broader potential across the broader spectrum of IgG-mediated diseases, which we estimate could represent a total addressable market of ~$20bn to ~$25bn in the U.S. by 2030,” the SVB Leerink team has said of the FcRn drug class.

3. Efgartigimod