WALTHAM, Mass.—Sobi and Novimmune announced today that the US Food and Drug Administration (FDA) has approved Gamifant (emapalumab-lzsg), an interferon gamma (IFNγ) blocking antibody for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) who have refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. This FDA approval is the first for a drug specifically for HLH.
“Primary HLH is a rare and life-threatening condition typically affecting children and this approval fills an unmet medical need for these patients,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “We are committed to continuing to expedite the development and review of therapies that offer meaningful treatment options for patients with rare conditions.”
Primary HLH is an ultra-rare syndrome of hyper-inflammation with high morbidity and mortality for which there was previously no approved drug. The body’s immune cells become overactive, leading to inflammation which damages the body’s own organs, including the liver, brain and bone marrow. It can be inherited, known as primary or familial HLH, and it can also have non-inherited causes. People with primary HLH usually develop symptoms within the first months or years of life. Symptoms may include fever, enlarged liver or spleen and decreased number of blood cells.
Gamifant represents a major advance in the treatment of these patients through a targeted mode of action. Gamifant is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNy), which nonclinical data suggest plays a pivotal role in HLH. Gamifant is indicated to be administered in combination with the steroid therapy dexamethasone, through intravenous infusion over one hour twice per week until hematopoietic stem cell transplant (HSCT).
“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,” noted 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 approval of Gamifant was based on results from a global, multicenter, open-label, single-arm pivotal Phase 2/3 clinical study, which enrolled 34 primary HLH patients. The efficacy of Gamifant was evaluated in the cohort of 27 patients with refractory, recurrent or progressive disease during conventional HLH therapy or who were intolerant to conventional HLH therapy, meaning that they had not responded, achieved a satisfactory response, maintained a satisfactory response or been able to tolerate conventional therapy. Gamifant was administered concomitantly with dexamethasone, which could be tapered during the study.
The primary endpoint was achieved, with 63% of patients demonstrating an overall response at the end of treatment, defined as achievement of either a complete or partial response, or HLH improvement. In addition, 70% of patients proceeded to HSCT. Of the 27 refractory patients treated in the study, 82% had a genetically confirmed primary HLH diagnosis. The most common adverse reactions reported during the study were infections (56%), hypertension (41%), infusion-related reactions (27%), and fever (24%). Results from the pivotal study will be presented at forthcoming 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. We would like to extend our heartfelt thanks to the patients, families and the healthcare providers who participated in the emapalumab clinical study in primary HLH and whose efforts helped make today’s approval possible. We would also like to thank the FDA for their continuous support during emapalumab development,” added Cristina de Min, Chief Medical Officer at Novimmune.
In the US, Gamifant was reviewed under Priority Review and received Orphan Drug Designation, Breakthrough Therapy Designation and Rare Pediatric Disease Designation from the FDA. Gamifant is expected to be available for administration in treatment centers across the US in the first quarter of 2019. While Gamifant was developed and submitted for approval to the FDA by Novimmune, Sobi acquired the global rights to Gamifant through an exclusive licensing agreement announced in July 2018, which closed in August 2018.
“Today’s landmark approval of Gamifant will allow Sobi to bring the first and only FDA-approved treatment for primary HLH to a rare disease community that has faced high mortality without much improvement in care for the past 24 years,” said Rami Levin, President of Sobi in North America.