ASH: With immune thrombocytopenia win, argenx proves efgartigimod's no one-trick pony in autoimmune disease

As efgartigimod gains traction in myasthenia gravis, argenx is out to prove its antibody fragment is no one hit wonder. Now, armed with a phase 3 win in primary immune thrombocytopenia (ITP), the company is bolstering its thesis that the neonatal-receptor-binding drug can drive down antibodies implicated across a host of autoimmune diseases.

In the late-stage Advance study, argenx’s efgartigimod helped more adults with heavily pre-treated primary ITP hit sustained platelet count responses versus placebo. Further, the drug helped patients maintain those platelet counts longer than the control group and helped curb bleeding events, too.

Specifically, around 22% of patients in the efgartigimod group reached a sustained platelet count response—meaning they had a platelet count of greater than 50,000 in more than four of their last six visits during weeks 19 through 24 of the trial, Catherine Broome, M.D., one of Advance’s principal investigators, said in an interview ahead of the 64th annual meeting of the American Society of Hematology (ASH) in New Orleans.

Conversely, just 5% of patients who got placebo charted a sustained response, allowing the study to meet its primary endpoint.

Those efgartigimod benefits were seen across patient types “regardless of age, disease severity, time since diagnosis, prior ITP treatment or background medication,” argenx said in a press release earlier this year.

Further, “the vast majority of patients who achieved that response had a significantly increased number of weeks of disease control,” Broome pointed out. Efgartigimod patients enjoyed around 6 weeks with platelet counts greater than 50,000 versus just 1.5 weeks in the control cohort, she explained.

The study investigators also tracked patients’ bleeding events, which again favored efgartigimod over placebo numerically, though the results were not statistically significant.

Immune thrombocytopenia is an autoimmune disorder where immunoglobulin G (IgG) autoantibodies destroy platelets and reduce platelet production, which can increase a person’s risk of excessive bleeding and bruising. In severe cases, frequent bleeds can lead to anemia or even rare cases of brain hemorrhage.

Efgartigimod—approved last winter in generalized myasthenia gravis (gMG) as Vyvgart—works by lowering the total level of IgG in the blood by binding to the neonatal Fc receptor (FcRn), which protects those antibodies from lysosomal clearance in the bloodstream, Broome explained. By attaching itself to the neonatal receptor, efgartigimod prevents IgG antibodies from binding, robbing them of protections so they get degraded and cease to recirculate through the body.

The main takeaways from the trial, in Broome’s estimation, are validation of efgartigimod’s “very unique” mechanism of action (MOA) tackling pathogenic IgG antibodies in ITP, as well as the fact that the drug offers another option for patients who’ve struggled on other thrombocytopenia therapies.

“The vast majority of these patients really had what we consider to be fairly difficult to treat disease,” Broome noted.

As for the therapies ITP patients currently have on offer, Broome pointed to steroids and intravenous immunoglobulin—both of which have “very short activity in ITP.” Among other drugs, patients also have the option of Roche’s Rituxan (rituximab), “and although patients do get a pretty good response rate” on that therapy, “those responses can be relatively short-lived,” too, Broome pointed out.

While argenx has notched another efgartigimod win with its Advance readout, it will be some time before the drug has a chance to take a bite at the commercial ITP apple. Before the company can file for approval, it must run a second pivotal trial on a subcutaneous formulation of efgartigimod, from which topline data are now expected in the second half of 2023, an argenx spokesperson said over email. Efgartigimod was given intravenously in the Advance study. Vyvgart also comes in IV format, though the company is homing in on a subQ nod in myasthenia gravis.

As for why the company must run that subQ study for ITP, “[c[onducting two registrational trials is a standard that the FDA has set for new potential ITP treatments,” the company explained, noting the requirement is “consistent” with those other thrombocytopenia players have had to meet.

Should the drug eventually snare approval in ITP, it’s unclear whether efgartigimod would carry the Vyvgart brand, or adopt a new, distinct name. On that topic, argenx noted that it’s “too early in the process to say,” adding that it would have more information to share closer to a potential launch.

In a prior interview with Fierce Pharma, argenx CEO Tim Van Hauwermeiren said the company will roll out efgartigimod’s subcutaneous formulation in generalized myasthenia gravis as its own “standalone product,” complete with its own brand name and pricing. The strategy will effectively allow argenx to “take a second bite at the apple” in the disease where it’s med first scored approval, the CEO said in January.

Meanwhile, argenx is already laying the commercial groundwork for a potential pivot into immune thrombocytopenia, the company’s spokesperson said, noting that it has “already begun the work toward market understanding,” as well as “engaging with patient advocacy groups.” Argenx noted that strategy is “similar to the proactive approach we took with gMG.”

The company’s established myasthenia gravis infrastructure should come in handy for a potential ITP launch, too.

“While the patient populations and physician communities for neuromuscular and hematology are different, the commercial infrastructure and experience we’ve gained through the preparation and execution of a successful Vyvgart launch will position us well to successfully commercialize efgartigimod for additional indications,” the company added in its email.