Details of the Drug

General Information of Drug (ID: DMOGNXY)

• Drug Name: Sarilumab
• Synonyms: Kevzara

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Approved	[1]

• Drug Type: Monoclonal antibody
• Sequence:
  >heavy chain
  EVQLVESGGGLVQPGRSLRLSCAASRFTFDDYAMHWVRQAPGKGLEWVSGISWNSGRIGY
  ADSVKGRFTISRDNAENSLFLQMNGLRAEDTALYYCAKGRDSFDIWGQGTMVTVSSASTK
  GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
  LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF
  LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
  VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN
  QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
  VFSCSVMHEALHNHYTQKSLSLSPGK
  >light chain
  DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLESGVPS
  RFSGSGSGTDFTLTISSLQPEDFASYYCQQANSFPYTFGQGTKLEIKRTVAAPSVFIFPP
  SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
  LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 202 +/- 120 mgday/L [2]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 20.0 +/- 9.20 mg/L [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 10 days (in patients with RA at 200 mg dose every 2 weeks) [3]
  Vd: The volume of distribution (Vd) of drug is 7.3 L [2]
• Cross-matching ID:
  DrugBank ID: DB11767
  TTD ID: D0Z8CQ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Interleukin 6 receptor (IL6R)	TT0E5SK	IL6RA_HUMAN; IL6RB_HUMAN	Modulator	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Rheumatoid arthritis
• ICD Disease Classification: FA20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Interleukin 6 receptor (IL6R)	DTT	IL6R; IL6ST	5.77E-01	-0.24	-0.47

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Sarilumab

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Upadacitinib	DM32B5U	Major	Additive immunosuppressive effects by the combination of Sarilumab and Upadacitinib.	Rheumatoid arthritis [FA20]	[13]

Coadministration of a Drug Treating the Disease Different from Sarilumab (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Sarilumab and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[14]
Oliceridine	DM6MDCF	Moderate	Altered metabolism of Sarilumab due to Oliceridine alters the formation of CYP450 enzymes.	Acute pain [MG31]	[13]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Sarilumab and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[15]
Lurbinectedin	DMEFRTZ	Moderate	Additive myelosuppressive effects by the combination of Sarilumab and Lurbinectedin.	Lung cancer [2C25]	[13]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Sarilumab and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[16]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Sarilumab and Siponimod.	Multiple sclerosis [8A40]	[14]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Sarilumab and Ocrelizumab.	Multiple sclerosis [8A40]	[17]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Sarilumab and Ozanimod.	Multiple sclerosis [8A40]	[13]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
• [2] Kevzara product monograph
• [3] ema.europa
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2310).
• [7] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [8] IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics International Conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA. MAbs. 2013 March 1; 5(2): 178-201.
• [9] Clinical pipeline report, company report or official report of Ablynx.
• [10] The preclinical pharmacology of the high affinity anti-IL-6R Nanobody ALX-0061 supports its clinical development in rheumatoid arthritis. Arthritis Res Ther. 2015 May 20;17:135.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [13] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [14] Cerner Multum, Inc. "Australian Product Information.".
• [15] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [16] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
• [17] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.