Emapalumab

Emapalumab
Monoclonal antibody
Type	Whole antibody
Source	Human
Target	IFN-gamma
Clinical data
Pronunciation	/ˈɛməpəlˌuməb/ EM-a-PAL-eu-mab
Trade names	Gamifant
Other names	NI-0501, emapalumab-lzsg
AHFS/Drugs.com	Monograph
MedlinePlus	a619024
License data	US DailyMed: Emapalumab;
Routes of; administration	Intravenous
ATC code	L04AG09 (WHO) ;
Legal status
Legal status	US: ℞-only;
Identifiers
CAS Number	1709815-23-5;
DrugBank	DB14724;
ChemSpider	none;
UNII	3S252O2Z4X;
KEGG	D11120;
Chemical and physical data
Formula	C6430H9898N1718O2038S46
Molar mass	145352.66 g·mol−1

Emapalumab, sold under the brand name Gamifant, is an anti-interferon-gamma (IFNγ) antibody medication used for the treatment of hemophagocytic lymphohistiocytosis (HLH),^[3]^[4]^[5] which has no cure.^[6]

The most common side effects include infections, hypertension, infusion-related reactions, and pyrexia.^[3]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[7]

Medical uses

Emapalumab is used to treat primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.^[3]

Adverse effects

In the clinical trials that lead to emapalumab's FDA approval, the most commonly reported adverse effects were infections (56%), high blood pressure (41%), infusion reactions (27%), and fever (24%).^[2]^[8] Serious adverse effects occurred in about half of the subjects studied in the clinical trial that led to its FDA approval.^[8]

Pharmacology

Mechanism of action

In the setting of HLH, over-secretion of IFN-γ is thought to contribute to the pathogenesis of the disease.^[2] Emapalumab binds and neutralizes IFN-γ, preventing it from inducing pathological effects.^[2]

Pharmacokinetics

Like other antibody-based medications, which are made of amino acid chains called polypeptides, emapalumab is broken down into smaller peptides via the body's normal catabolism.^[2]

Society and culture

Legal status

The U.S. Food and Drug Administration (FDA) granted orphan drug designations in 2010 and 2020,^[9]^[10] and breakthrough therapy designation in 2016, on the basis of preliminary data from the phase II trial.^[11]

In July 2020, and again in November 2020, the European Medicines Agency (EMA) recommended the refusal of the marketing authorization for emapalumab.^[12]^[13]

Research

The research name of emapalumab was NI-0501.^[1] A phase II/III trial began in 2013 and is ongoing as of August 2018^[update].^[14] The trial targets patients under the age of 18 who have failed to improve on conventional treatments.^[15] This study was realised in the context of an EU-funded FP7 project, named FIGHT-HLH (306124).^{[citation needed]}

References

^ ^a ^b "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL" (PDF). Retrieved 21 November 2018.
^ ^a ^b ^c ^d ^e "Gamifant (- emapalumab-lzsg injection". DailyMed. 30 June 2020. Retrieved 7 October 2020.
^ ^a ^b ^c "FDA approves emapalumab for hemophagocytic lymphohistiocytosis". U.S. Food and Drug Administration (FDA). 20 November 2018. Retrieved 19 March 2021. This article incorporates text from this source, which is in the public domain.
^ "FDA Approves Gamifant (emapalumab-lzsg), the First and Only Treatment Indicated for Primary Hemophagocytic Lymphohistiocytosis (HLH)" (Press release). Sobi. 20 November 2018. Retrieved 21 November 2018 – via Business Wire.
^ Cheloff AZ, Al-Samkari H (July 2020). "Emapalumab for the treatment of hemophagocytic lymphohistiocytosis". Drugs of Today. 56 (7): 439–446. doi:10.1358/dot.2020.56.7.3145359. PMID 32648854. S2CID 220473902.
^ Clinical trial number NCT02069899 for "Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody" at ClinicalTrials.gov
^ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.
^ ^a ^b "Emapalumab Approved for Rare Primary Hemophagocytic Lymphohistiocytosis". Rare Disease Report. Archived from the original on 22 November 2018. Retrieved 22 November 2018.
^ "Emapalumab Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 25 September 2020. Retrieved 19 March 2021.
^ "Emapalumab Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 26 March 2010. Retrieved 19 March 2021.
^ "Novimmune's NI-0501 Granted Breakthrough Therapy Designation by US FDA for Treatment of Patients With Primary Hemophagocytic Lymphohistiocytosis (HLH) - FierceBiotech". www.fiercebiotech.com. 16 March 2016.
^ "Gamifant: Pending EC decision". European Medicines Agency. 24 July 2020. Retrieved 21 September 2020.
^ "Gamifant EPAR". European Medicines Agency (EMA). 21 July 2020. Retrieved 19 March 2021.
^ Clinical trial number NCT01818492 for "A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis" at ClinicalTrials.gov
^ "NI-0501: A Study to Investigate the Safety and Efficacy of an Anti-IFN? mAb in Children Affected by Primary Hemophagocytic Lymphohistiocytosis". www.cincinnatichildrens.org.

External links

Clinical trial number NCT01818492 for "A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis" at ClinicalTrials.gov

[SearchUSAN-1] "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL" (PDF). Retrieved 21 November 2018.

[Gamifant_FDA_label-2] "Gamifant (- emapalumab-lzsg injection". DailyMed. 30 June 2020. Retrieved 7 October 2020.

[FDA_emapalumab-3] "FDA approves emapalumab for hemophagocytic lymphohistiocytosis". U.S. Food and Drug Administration (FDA). 20 November 2018. Retrieved 19 March 2021. This article incorporates text from this source, which is in the public domain.

[BW_Gamifant-4] "FDA Approves Gamifant (emapalumab-lzsg), the First and Only Treatment Indicated for Primary Hemophagocytic Lymphohistiocytosis (HLH)" (Press release). Sobi. 20 November 2018. Retrieved 21 November 2018 – via Business Wire.

[pmid32648854-5] Cheloff AZ, Al-Samkari H (July 2020). "Emapalumab for the treatment of hemophagocytic lymphohistiocytosis". Drugs of Today. 56 (7): 439–446. doi:10.1358/dot.2020.56.7.3145359. PMID 32648854. S2CID 220473902.

[6] Clinical trial number NCT02069899 for "Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody" at ClinicalTrials.gov

[7] New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.

[RDR-8] "Emapalumab Approved for Rare Primary Hemophagocytic Lymphohistiocytosis". Rare Disease Report. Archived from the original on 22 November 2018. Retrieved 22 November 2018.

[9] "Emapalumab Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 25 September 2020. Retrieved 19 March 2021.

[10] "Emapalumab Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 26 March 2010. Retrieved 19 March 2021.

[11] "Novimmune's NI-0501 Granted Breakthrough Therapy Designation by US FDA for Treatment of Patients With Primary Hemophagocytic Lymphohistiocytosis (HLH) - FierceBiotech". www.fiercebiotech.com. 16 March 2016.

[12] "Gamifant: Pending EC decision". European Medicines Agency. 24 July 2020. Retrieved 21 September 2020.

[13] "Gamifant EPAR". European Medicines Agency (EMA). 21 July 2020. Retrieved 19 March 2021.

[14] Clinical trial number NCT01818492 for "A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis" at ClinicalTrials.gov

[15] "NI-0501: A Study to Investigate the Safety and Efficacy of an Anti-IFN? mAb in Children Affected by Primary Hemophagocytic Lymphohistiocytosis". www.cincinnatichildrens.org.

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