New Medicines

GamifantPrimary haemophagocytic lymphohistiocytosis (HLH) in children aged <18 years


New molecular entity
Swedish Orphan Biovitrum (Sobi)
Swedish Orphan Biovitrum (Sobi)

Development and Regulatory status

Mar 21EU/UK development was discontinued after the CHMP negative opinion [15].
Nov 20Further negative opinion recommending a refusal of the marketing authorisation for emapalumab for the treatment of primary haemophagocytic lymphohistiocytosis (pHLH) in children under 18 years of age. Company resolved some but not all of the concerns raised by EMA [14].
Sep 20SOBI has requested a re-examination of the Committee decision. Once the grounds for the request have been assessed, the data originally presented will be re-examined and a final opinion delivered [13].
Jul 20Not recommended for EU approval by CHMP (Negative opinion). The Committee considered that that due to multiple issues it was not possible to determine effectiveness and safety; therefore the benefits were not considered to outweigh the risks. The company may appeal this decision and ask for a re-examination of the opinion within 15 days, but cannot present new data at this stage [12].
Oct 19Sobi expect a regulatory decision by the end of 2019 [10].
Aug 19Still filed with EMA and under assessment [9].
Dec 18Launched in the US [8]
Nov 18Approved in the US [7]
Oct 18Oct 18: Now reported as not being evaluated in the EU using the accelerated assessment programme [6].
Aug 18filed in EU with accelerated assessment, for treatment of patients with primary Haemophagocytic Lymphohistiocytosis (HLH). Accelerated assessment cuts 60 days from the standard CHMP timeline, with the potential for a CHMP opinion in less than five months from submission [5].
Mar 18Filed in US for treatment of patients with primary HLH [3].


Monoclonal antibody, targeting anti-interferon-γ IFNγ
Primary HLH is a clinical syndrome of hyperinflammation, driven by high interferon gamma production and characterised by severe hyperferritinemia, fever, severe cytopenia, coagulation defects and organomegaly. Approximately 1 per 200 000 children become unwell with HLH each year; most (70-80%) become unwell in the first year of life [1].
Primary haemophagocytic lymphohistiocytosis (HLH) in children aged <18 years

Further information


Trial or other data

May 20The single-group, PII/III study (n=34; NCT01818492 and NCT02069899) found a response rate of 63% and 65% for emapalumab infusion in those previously treated with other agents, and treatment naïve respectively. This was significantly, more than the prespecified null hypothesis of 40% (p<0.05 for both) [11].
Dec 18Data from the pivotal PII/III study (n=34) presented at the annual meeting of the American Society of Hematology (ASH). The trial achieved its primary endpoint, with 64.7% of all patients treated (22 of 34; p=0.0031) and 63% of the patients who had failed prior conventional HLH therapy (17 of 27; p=0.0134) demonstrating an overall response at the end of treatment, defined as achievement of either a complete or partial response, or HLH improvement. Across both cohorts, the overall response rate (ORR) was significantly higher than the pre-specified null hypothesis of 40%. The median time to response was 8 days, and patients remained in response for a median of 75% of the time.The majority of all patients treated – 64.7% (22 of 34) of the full patient group and 70.4% (19 of 27) of the patients who had failed prior conventional HLH therapy – proceeded to haematopoietic stem cell transplantation (HSCT), with 90.9% (20 of 22) of the full group and 89.5% (17 of 19) of the subgroup surviving post HSCT. The most common adverse reactions reported during the study were infections (56%), hypertension (41%), infusion-related reactions (27%) and fever (24%) [8].
Mar 18PII/III study (NCT01818492) is still recruiting [4].
Jan 13PII/III study (NCT01818492) to assess the safety, tolerability and efficacy of NI-0501 aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment. 32 children aged up to 18 years will be recruited in the US, Germany, Italy, Spain, Sweden and the UK. Collection of primary outcome data (overall response rate) is due to complete Jun 18 [4].

Evidence based evaluations