Gamifant (emapalumab-lzsg) is the first therapy approved by the U.S. Food and Drug Administration for children (including newborns) and adults with primary hemophagocytic lymphohistiocytosis (HLH), who have failed to respond to therapy, or whose disease continued to progress despite conventional treatment.
Gamifant, initially developed by Novimmune and later by Sobi, is an antibody against interferon (IFN)-gamma. Primary HLH is a rare, inherited condition, characterized by an overactivated immune system causing too much inflammation. As a result, the immune system damages the person’s own tissues and organs. IFN-gamma has been shown to promote the progression of HLH.
Approved in 2018, Gamifant is “the first and only FDA-approved treatment for primary HLH,” Rami Levin, president of Sobi in North America, said in a news release.
Typically, treatment for HLH aims to halt the immune system’s response, and conventional therapies include corticosteroids and chemotherapy. However, this approach is not specific for HLH, and can have severe immunosuppressive side effects. A transplant of hematopoietic (blood-forming) stem cells is considered the cure for HLH, but prior to the transplant, patients need to undergo treatment with corticosteroids and/or chemotherapy to destroy excess immune cells.
“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 at Cincinnati Children’s Hospital Medical Center-HLH Center of Excellence.
Gamifant was developed to be administered in combination with the corticosteroid dexamethasone, through intravenous (into the vein) infusion, twice per week, until the patient undergoes an hematopoietic stem cell transplant.
The FDA’s approval of Gamifant was based on results from a multicenter, open-label, single-arm Phase 2/3 clinical trial. The study (NCT01818492) investigated the efficacy of Gamifant plus dexamethasone in a cohort of 34 patients (up to 18 years old), of which 27 were intolerant or failed to respond to conventional HLH therapy.
Patients were given Gamifant, every three to four days, at a dose of 1 mg/kg, and increasing as needed up to 10 mg/kg. The therapy was given with dexamethasone, which could be tapered during the study. Patients were treated for eight weeks on average.
The trial achieved its primary endpoint, with results showing that 63% of the patients had either a complete or partial response, or HLH improvement.
Moreover, 64.7% of all patients and 70.4% (19 of 27) of those who had previously failed to respond to prior conventional HLH therapy went on to receive a hematopoietic stem cell transplant, with a success rate of more than 89%.
The most common adverse reactions reported during the study were infections (56%), hypertension (41%), infusion-related reactions (27%), and fever (24%).
“Emapalumab represents an entirely new approach to treating primary HLH and helping these very sick patients reach hematopoietic stem cell transplant,” said Jordan, the trial’s lead researcher.
Richard Pazdur, MD, a director at the FDA, said in an agency news release: “Primary HLH is a rare and life-threatening condition typically affecting children, and this approval fills an unmet medical need for these patients. We are committed to continuing to expedite the development and review of therapies that offer meaningful treatment options for patients with rare conditions.”
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