FDA Approves Gamifant (emapalumab-lzsg), the First and Only Treatment Indicated for Primary HLH

Sobi and Novimmune SA announced that the U.S. Food and Drug Administration (FDA) has approved Gamifant(emapalumab-lzsg), an interferon gamma (IFNγ) blocking antibody for the treatment of pediatric (newborn and older) and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. Primary HLH is an ultra-rare syndrome of hyper-inflammation with high morbidity and mortality and for which there was previously no approved drug. Gamifant represents a major advance in the treatment of these patients through a targeted mode of action.

The FDA approval of Gamifant was based on results from a global, multicenter, open-label, single-arm pivotal Phase 2/3 clinical study (NCT01818492), 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, not achieved a satisfactory response, not maintained a satisfactory response, or not 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 (p=0.013) 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 hematopoietic stem cell transplant (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.

“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.

“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, M.D., 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.”

Jeff Toughill, President of the Histiocytosis Association, said, “I applaud the FDA approval of Gamifant for the treatment of primary hemophagocytic lymphohistiocytosis. We are excited that this drug will be available to patients diagnosed with this rare, life-threatening disease, and we are optimistic that this approval will help to increase awareness and improve diagnosis, ultimately giving more patients a chance.”

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

Gamifant is expected to be available for administration in treatment centers across the U.S. in the first quarter of 2019. Sobi is committed to helping people access the medicines they are prescribed and will be offering support services for people prescribed Gamifant. More information on Sobi’s patient support programs may be accessed by calling 1-833-597-6530.

Gamifant was developed and submitted for approval to the FDA by Novimmune SA. Sobi acquired the global rights to Gamifant from Novimmune SA through an exclusive licensing agreement announced in July 2018 and closed in August 2018. In the U.S., Gamifant was reviewed under Priority Review and received Orphan Drug Designation, Breakthrough Therapy Designation and Rare Pediatric Disease Designation from the FDA.