Rare Disease Report

Emapalumab Approved for Rare Primary Hemophagocytic Lymphohistiocytosis

NOVEMBER 20, 2018
Cecilia Pessoa Gingerich
Emapalumab-lzsg (Gamifant) was approved by the US Food and Drug Administration (FDA) for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in pediatric and adult patients with refractory, recurrent, or progressive disease, or intolerance to conventional HLH therapy.

The interferon gamma (IFNγ) blocking antibody is the first approved treatment for this rare condition that causes hyper-inflammation.

The FDA’s decision was supported by data from a multicenter, open-label, single-arm phase 2/3 clinical trial of 34 patients with primary hemophagocytic lymphohistiocytosis who were treated with emapalumab and dexamethasone, which could be tapered off during the study.

Median age of the participants was 1 year (range: .1 to 13 years); 53% were female, and 65% were Caucasian. The participants received emapalumab for a median of 59 days (range: 14 to 245 days), and the median cumulative dose was 25 mg/kg (range: 4 to 254 mg/kg).

The study achieved its primary endpoint, with 63% of patients demonstrating overall response at the end of the treatment period (P = .013). Overall response included either a complete or partial response, or HLH improvement. Additionally, 70% of trial participants continued on to hematopoietic stem cell transplant (HSCT).

Most commonly reported adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and fever (24%). Serious adverse reactions occurred in 53% of patients and the most common reactions (occurring in ≥3%) included infections, gastrointestinal hemorrhage, and multiple organ dysfunction. Fatal adverse reactions occurred in 2 (6%) of patients (septic shock and gastrointestinal hemorrhage).
"HLH is a disorder of immune regulation in which many cytokines are deranged, but interferon gamma appears to play a critical role. While we have long understood the pivotal role of this cytokine in HLH, until emapalumab's approval we did not have a medicine that could specifically hit this target," Michael Jordan, MD, a physician-scientist in the division of Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children's Hospital Medical Center HLH Center of Excellence, and primary investigator in the emapalumab clinical trial said in a statement. "Emapalumab represents an entirely new approach to treating primary HLH and helping these very sick patients reach hematopoietic stem cell transplant."

Further results from the clinical trial will be presented at future international meetings.

“Gamifant is the first drug specifically targeted to neutralize IFNγ. Based on the clinical validation of this new target, additional clinical studies are ongoing or being planned with emapalumab in diseases for which IFNγ is considered pathogenic,” Cristina de Min, MD, chief medical officer at Novimmune said.

Novimmune developed emapalumab and submitted an NDA to the FDA for approval. Earlier this year, Sobi acquired the global rights from Novimmune through an exclusive licensing agreement announced in July 2018 and closed in August 2018.

Sobi expects to have emapalumab available in the United States in the first quarter of 2019.

An earlier version of this article was published as, “FDA Approves Emapalumab for Rare Primary Hemophagocytic Lymphohistiocytosis,” on MD Magazine.com.

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