FDA Approves Emapalumab for Rare Primary Hemophagocytic Lymphohistiocytosis

The US Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant) for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) 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.

"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," said 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. "Emapalumab represents an entirely new approach to treating primary HLH and helping these very sick patients reach hematopoietic stem cell transplant."

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

The participants’ median age was 1 year (range: .1 to 13 years); 53% were female, and 65% were Caucasian. Patients 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).

The study’s 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 (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).

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,” says Cristina de Min, MD, Chief Medical Officer at Novimmune.

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 US in the first quarter of 2019.