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NEW ORLEANS -- An antibody fragment targeting neonatal Fc receptor (FcRn) achieved sustained platelet response in significantly more patients with primary immune thrombocytopenia (ITP) in a placebo-controlled trial.

Sustained platelet response (≥50 x 10⁹/L between weeks 19 and 24) occurred in 21.8% of patients treated with efgartigimod (Vyvgart) as compared with 5% of those allocated to placebo. The drug outperformed placebo for all secondary endpoints, including weeks of disease control, sustained platelet response, bleeding score, and durability of platelet response.

Platelet-count response improved early with efgartigimod, as 38.4% of patients had a platelet count of 30 x 10⁹ after 1 week of treatment as compared with 11.1% of the placebo group, reported Catherine M. Broome, MD, of Georgetown University in Washington, D.C., at the American Society of Hematology annual meeting.

"The benefits of targeting the neonatal Fc receptor and lowering total IgG levels were demonstrated by statistically and clinically [significant] improvements in platelet counts compared with placebo," said Broome. "Efgartigimod was well tolerated, and most adverse events were mild to moderate, and there were no new safety signals."

"The results of this study supported both weekly and every-other-week administration, allowing for adjustments based on platelet counts. Over 90% of participants who completed [the placebo-controlled trial] enrolled in the open-label extension, which will allow us to continue to evaluate the durability of response as well as safety."

In response to questions from the audience, Broome said efgartigimod-treated patients did have rebound hypogammaglobulinemia, and evidence of trials of the drug in pemphigus demonstrated evidence of vaccine response in treated patients. Another question pertained to the relative safety and efficacy of efgartigimod and rituximab (Rituxan).

"I'm not sure I can compare it because we didn't compare it in the trial," said Broome. "It's a little hard to make assumptions from historical data. [Efgartigimod] has certainly demonstrated efficacy when compared to placebo, and that's really all that we have from this trial."

ITP causes substantial reductions in platelet count that can lead to an increased risk of bleeding, fatigue, and decreased quality of life (QoL). IgG autoantibodies from most patients target glycoproteins expressed on platelets and megakaryocytes, said Broome. Current treatment options for ITP are associated with comorbidities, lack of efficacy, and limited impact on QoL measures.

Efgartigimod is approved to treat generalized myasthenia gravis in adults who test positive for the anti-acetylcholine receptor antibody. The drug is a competitive inhibitor of FcRn, inhibiting binding of autoantibodies and other IgG antibodies and reducing levels of IgG and related autoantibodies, Broome said by way of introduction to the study.

The trial, known as , included 131 patients with previously treated ITP. Eligible patients had chronic or persistent ITP as indicated by response to prior ITP therapy, two platelet counts <30 x 10⁹/L, and at least two prior treatments or one prior and one concurrent treatment. Patients were allowed to continue concurrent medication if on a stable dose and frequency.

Investigators randomized 131 patients 2:1 to weekly efgartigimod or placebo for 4 weeks, then switched to weekly or q2w depending on platelet count for weeks 4 through 15, and then to fixed weekly or q2w on the basis of the dosing regimen at visit 16. Broome said 67 of 86 patients allocated to efgartigimod completed the trial, as did 38 of 45 in the placebo group.

Baseline characteristics included a mean disease duration of 10-11 years, mean platelet count of 17.3 (efgartigimod) and 14.2 (placebo) x 10⁹/L, and history of splenectomy in 37%-38%. From 65%-70% of patients in both groups had received three or more prior therapies for ITP.

The primary endpoint was sustained platelet response on at least four of six visits from weeks 19 to 24 with no intercurrent events. Efgartigimod proved superior for all key endpoints:

• Sustained platelet count response: 17/78 or 21.8% vs 2/40 or 5.0% (P=0.0316)
• Cumulative weeks of disease control: 6.1 vs 1.5 (P=0.0009)
• Sustained platelet response: 25.6 vs 6.7% (P=0.0108)
• Durable response: 22.1% vs 6.7% (P=0.0265)

The efgartigimod group had numerically fewer visits with a WHO Bleeding Score ≥1 (6.2 vs 8.3 for placebo, P=0.8287).

Broome said 33 patients in the efgartigimod group had a platelet count of 30 x 10⁹ after 1 week of treatment as compared with five patients in the placebo group. Nine of 10 patients who switched from dosing weekly to every 2 weeks maintained platelet count response, suggesting the drug offers flexibility in dosing.

Half the efgartigimod group met International Working Group (IWG) response criteria for response versus 20% in the placebo arm. IWG criteria incorporate absence of bleeding events.

Efgartigimod had an adverse event profile similar to that of placebo.

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