efgartigimod display
A display at the ASH 2022 conference in New Orleans, Louisiana, by Dutch pharma giant Argenx on efgartigimod (Vyvgart™), a potential therapy for patients with immune thrombocytopenia (ITP). (Photo by Larry Luxner)

NEW ORLEANS, Louisiana—The name of the newest potential therapy for people with chronic immune thrombocytopenia (ITP) is even harder to spell or pronounce than the disease itself: efgartigimod.

Dutch pharma giant Argenx won US Food and Drug Administration (FDA) approval in December 2021 to market efgartigimod as a treatment for generalized myasthenia gravis (MG)—a rare neuromuscular disease—under the brand name Vyvgart™. A neonatal Fc receptor blocker, the medication works in the 85% of patients with MG who test positive for the anti-acetylcholine receptor antibody.

In patients with ITP, that same therapy boosts platelet counts, which in such patients are dangerously low and lead to frequent and sometimes life-threatening bleeding episodes.

Findings from the phase 3 randomized, double-blind, multicenter ADVANCE IV trial are “very significant” for the roughly 1 in 100,000 Americans who have ITP, said Catherine M. Broome, MD, who presented them at the 64th ASH Annual Meeting and Exposition here.

“Multiple therapies are available for ITP. Most of them have been directed at trying to decrease the production of the IgG autoantibody,” said Dr. Broome, an associate professor of medicine at Georgetown Medstar University Hospital in Washington, DC. “They include things like steroids, intravenous immunoglobulin, and rituximab—all of which have their own set of potential side effects.”

Rituximab, in particular, is a problem because it affects B cells, which help the body make antibodies to fight infections, she told Rare Disease Advisor, adding that “in this era of COVID, we’ve become very concerned about patients not being able to adequately respond to vaccines and potentially being at risk for severe ramifications of a COVID infection.”

Efgartigimod Outperforms Placebo in Subgroups

In addition, some patients respond poorly to current approaches for lowering IgG antibody levels, she said, “which is why we embarked on this trial.”

In ADVANCE IV, researchers randomized 131 patients with chronic ITP to receive either intravenous efgartigimod or placebo for 24 weeks. Patients received infusions weekly for the first 4 weeks and then either weekly or every 2 weeks depending on response.

“This study looked at patients who in general had had more than 3 prior therapies and had had their ITP for more than 10 years—notoriously, a hard‑to‑treat population,” Dr. Broome said. Participants had a mean age of 46.9 years and lived in the United States, Europe, or Japan.

Catherine Broome, MD, a hematologist at Georgetown Medstar University Hospital in Washington, DC. (Photo courtesy of Georgetown Medstar)

The result: 38.4% of treated participants achieved a platelet count of 30,000 per microliter within the first week, compared to only 11.1% of those on placebo. After 24 weeks, 21.8% of those on efgartigimod but only 5% of the placebo group achieved a sustained platelet response.

“No matter what subgroup we looked at, efgartigimod showed a benefit over placebo,” Dr. Broome said. “Whether you were older or younger, whether you had had a splenectomy or not, whether you had been on a prior therapy for ITP or not, efgartigimod outperformed placebo in all of those groups. And from a safety perspective, it was well tolerated.”

Since then, she said, more than 90% of the patients who completed the ADVANCE IV trial have enrolled in the open-label extension.

“I think the fact that such a high number of patients were willing to go on to participate in the open‑label extension speaks to not only the efficacy of the drug, but also the fact that there were not any significant adverse events,” she said. Efgartigimod is not yet approved by the FDA as a treatment for ITP.

Research on New Formulation Underway

More specifically, there were no increased risks of infection attributed to efgartigimod. The most common adverse events were bruising, headache, hematuria, and petechiae (tiny purple, red, or brown spots on the skin that look like a rash).

“The trial looked at patients who had failed at least one prior therapy. I think it’s a great drug to look at for patients who have not responded to a steroid or another immunosuppressant,” Dr. Broome said. “Whether or not it can be utilized in patients up front, we just don’t have that data yet.”

“The drug has the potential for treating a host of autoimmune disorders,” David J. Hermel, MD, wrote in ASH News Daily.

An additional phase 3 trial is now underway looking at subcutaneous injection of the drug for ITP rather than intravenous administration. This new formulation would allow patients to inject themselves rather than having to go to a hospital for the infusions, Dr. Broome said.

“Getting that data may take as much as another 18-24 months,” she noted. “Then, of course, we’d have to apply to the FDA.”