FDA Approves Sobi’s Gamifant as the First and Only Treatment Primary HLH

Rare Daily Staff
The U.S. Food and Drug Administration approved Gamifant, an interferon gamma blocking antibody for the treatment primary hemophagocytic lymphohistiocytosis (HLH), an ultra-rare syndrome of hyper-inflammation with high morbidity and mortality and for which there was previously no approved drug.

The approval covers primary HLH with refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy.

In primary HLH the immune system attacks the body’s tissues and organs. Symptoms usually appear within the first year of life and can rapidly become lethal if left untreated, with median survival of less than two months. The immediate goal of treatment is to quickly bring the hyperinflammatory emergency under control and to prepare for hematopoietic stem cell transplant, which is the only cure. It is estimated that fewer than 100 cases of primary HLH are diagnosed each year in the United States.

Gamifant is a monoclonal antibody that binds to and neutralizes interferon gamma, which nonclinical data suggest plays a pivotal role in HLH. Gamifant is indicated for the treatment of adult and pediatric patients with primary HLH. It is the first and only medicine approved for primary HLH. Gamifant is indicated to be administered in combination with the steroid therapy dexamethasone, through intravenous (IV) infusion over one hour twice per week until hematopoietic stem cell transplant.

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

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.

Gamifant was administered concomitantly with dexamethasone, which could be tapered during the study. The primary endpoint was achieved, with 63 percent 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 percent of patients proceeded to hematopoietic stem cell transplant. Of the 27 refractory patients treated in the study, 82 percent had a genetically confirmed primary HLH diagnosis.

The most common adverse reactions reported during the study were infections (56 percent), hypertension (41 percent), infusion-related reactions (27 percent), and fever (24 percent).

“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.

Gamifant is expected to be available for administration in treatment centers across the United States in the first quarter of 2019.

November 20, 2018
Photo: Rami Levin, president of Sobi in North America