These findings were reported in the study, “Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis,” published in The New England Journal of Medicine.
HLH is characterized by excessive inflammation and organ damage due to an overactivation of the immune system. The disease is considered primary when it is caused by mutations in specific genes that control immune system activity, or secondary when it is associated with other autoimmune disorders or malignancies.
The primary form of HLH usually manifests during childhood, and is usually fatal if not managed properly. The main course of treatment for primary HLH consists of medications to reduce inflammation, so that children may undergo an allogeneic hematopoietic stem cell transplant (HSCT), which is currently the only way to cure the disease.
In allogeneic HSCT, a patient receives blood cell precursors (hematopoietic stem cells) from a genetically similar donor.
Gamifant, originally developed by Novimmune (now called Light Chain Bioscience) and later by Sobi, is the first therapy approved by the U.S. Food and Drug Administration (FDA) to treat primary HLH patients who failed to respond to standard treatments. It was approved in November 2018.
The therapy, which is meant to be administered in combination with the steroid dexamethasone, is an antibody that blocks the activity of interferon-gamma (IFNγ), a pro-inflammatory molecule mainly produced by natural killer (NK) immune cells as part of the body’s overall immune response against a threat.
In addition to being used as a second-line treatment, Gamifant was investigated as a potential first-line therapy for patients who never received any form of treatment for primary HLH.
Investigators at Cincinnati Children’s Hospital Medical Center and colleagues report in this study the findings of a Phase 2/3 open-label trial (NCT01818492), sponsored by Novimmune, that assessing the safety and efficacy of a combination Gamifant and dexamethasone in children with primary HLH.
This study included children who had never been treated for their condition, and those who failed to respond or became intolerant to standard therapies.
During the eight-week treatment period — which could be shortened or extended depending on the timing of the transplant — patients were given Gamifant in doses ranging from 1 mg/kg to 10 mg/kg along with dexamethasone through intravenous infusions.
Children also had the possibility of entering a one-year follow-up study (NCT02069899) after their transplant or, for those who did not receive a transplant, their last dose of Gamifant. This study, taking place at sites across the U.S. and Europe, is due to conclude in September.
A total of 34 children had been given the combination therapy as of July 20, 2017, the study reported. Of these, seven were new to treatment. Twenty-six children completed the study.
More than half of the patients (65%) and those previously treated with other therapies (63%) responded to the combo therapy during the trial.
From those who had previously failed or became intolerant to standard treatment, 70% were able to have a stem cell transplant from a healthy donor. In the overall population, 65% of children received the transplant.
At the last study visit, 74% of previously treated children and 71% of all those participating in the trial were alive.
Gamifant’s use was not associated with organ toxicity. A total of 10 children developed severe infections after receiving treatment, but only one had to discontinue due to disseminated histoplasmosis, an infection caused by inhalation of fungal spores.
“This is a very important advance. For the first time we have a truly targeted way to treat HLH and a drug with very low toxicity,” Michael Jordan, MD, the trial’s co-principal investigator and a physician-scientist in the divisions of Immunobiology and Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children’s, said in a news story.
Based on the results, the researchers concluded that Gamifant “was effective with a low level of toxic effects in patients with primary hemophagocytic lymphohistiocytosis.”
They also added these findings support future studies assessing Gamifant’s therapeutic potential to treat secondary forms of HLH, in which IFNγ is also thought to play a key role.