The European Committee for Medicinal Products for Human Use (CHMP) has recommended the denial of market authorization for Gamifant (emapalumab) for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in children younger than 18 in Europe.
The opinion follows a re-examination requested by Sobi, Gamifant’s developer, after CHMP’s initial negative opinion in July.
“This recommendation by the CHMP is disappointing given the significant unmet medical need which exists for patients with [primary] HLH who have no approved therapies in Europe,” Ravi Rao, head of R&D and chief medical officer at Sobi, said in a press release.
“During the re-examination we worked extensively with physicians and patients and were able to resolve some but not all of the concerns raised by EMA,” the European Medicines Agency, Rao added.
Rao said the CHMP decision will shift the company’s focus in terms of marketing the medication.
“We are confident about the clinical profile of emapalumab and our focus is now on increasing access for patients in other regions and developing new indications for this medicine,” Rao said.
Primary HLH is caused by mutations in genes that regulate immune system functions, resulting in excessive inflammation and overactive immune responses. The main treatment for HLH is the administration of anti-inflammatories that reduce immune activity, allowing the patient to receive an allogeneic hematopoietic stem cell transplant. Such a bone marrow transplant, from a matched, unrelated donor, is currently the only cure for HLH.
An antibody that binds to and blocks the activity of interferon gamma, Gamifant is a pro-inflammatory molecule that is elevated in HLH and plays an important role in immune system overactivity. The therapy is administrated twice-weekly, in combination with the steroid dexamethasone, by intravenous (into-the-vein) infusion until the patient can receive a transplant.
Gamifant was approved by the U.S. Food and Drug Administration (FDA) in 2018 for the treatment of adults and children, newborn and older, with recurrent or progressive HLH and those who have not responded to conventional HLH therapies.
The therapy’s FDA approval in the U.S. was based on data from Phase 2/3 clinical studies assessing the safety and efficacy of Gamifant in children with HLH (NCT01818492) and an ongoing longitudinal study of its long-term effects (NCT02069899). Results confirming the safety of Gamifant use in children were published in a study in the New England Journal of Medicine earlier this year.
According to Sobi, more than 100 patients in the U.S. have been treated with Gamifant with favorable results.
Gamifant has been granted orphan drug, breakthrough therapy, and rare pediatric disease designations by the FDA, all of which convey financial and regulatory incentives for the clinical development, approval, and commercial distribution of the treatment. The therapy was initially developed by Novimmune before its acquisition by Sobi.