(Heavy chain)
EVQLVESGGG VIQPGGSLRL SCAASGFTFD DYAMNWVRQG PGKGLEWVSA ISGDGGSTYY
ADSVKGRFTI SRDNSKNSLY LQMNSLRAED TAFFYCAKDL RNTIFGVVIP DAFDIWGQGT
MVTVSSASTK GPSVFPLAPC SRSTSESTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP
AVLQSSGLYS LSSVVTVPSS SLGTKTYTCN VDHKPSNTKV DKRVESKYGP PCPPCPAPEF
LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSQEDPEVQ FNWYVDGVEV HNAKTKPREE
QFNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKGLPSSIEK TISKAKGQPR EPQVYTLPPS
QEEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSRLTVDK
SRWQEGNVFS CSVMHEALHN HYTQKSLSLS LGK
(Light chain)
DIQMTQSPST LSASVGDRVT ITCRASQSIR SWLAWYQQKP GKAPKLLIYK ASSLESGVPS
RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSYTFGQ GTKLEIKRTV AAPSVFIFPP
SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT
LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC
(Disulfide bridge: H22-H96, H140-L214, H153-H209, H232-H’232, H235-H’235, H267-H327, H373-H431, H’22-H’96, H’140-L’214, H’153-H’209, H’267-H’327, H’373-H’431, L23-L88, L134-L194, L’23-L’88, L’134-L’194)
Evinacumab
エビナクマブ (遺伝子組換え)
Immunoglobulin G4, anti-(human protein ANGPTL3 (angiopoietin-like 3)) (human monoclonal REGN1500 heavy chain), disulfide with human monoclonal REGN1500 light chain, dimer
Formula |
C6480H9992N1716O2042S46
|
---|---|
CAS |
1446419-85-7
|
Mol weight |
146081.9345
|
Protein Sequence
Sequence Length: 1334, 453, 453, 214, 214multichain; modified (modifications unspecified)
FDA APPROVED, 2021/2/11, EVKEEZA
Antihyperlipidemic, Anti-angiopietin like 3
Monoclonal antibody
Treatment of dyslipidemia
- REGN 1500
- REGN-1500
- REGN1500
Sequence:
Sequence:
Sequence:
Sequence:
Sequence Modifications
Type | Location | Description |
---|---|---|
bridge | Cys-22 – Cys-96 | disulfide bridge |
bridge | Cys-140 – Cys-214” | disulfide bridge |
bridge | Cys-153 – Cys-209 | disulfide bridge |
bridge | Cys-232 – Cys-232′ | disulfide bridge |
bridge | Cys-235 – Cys-235′ | disulfide bridge |
bridge | Cys-267 – Cys-327 | disulfide bridge |
bridge | Cys-373 – Cys-431 | disulfide bridge |
bridge | Cys-22′ – Cys-96′ | disulfide bridge |
bridge | Cys-140′ – Cys-214”’ | disulfide bridge |
bridge | Cys-153′ – Cys-209′ | disulfide bridge |
bridge | Cys-267′ – Cys-327′ | disulfide bridge |
bridge | Cys-373′ – Cys-431′ | disulfide bridge |
bridge | Cys-23” – Cys-88” | disulfide bridge |
bridge | Cys-134” – Cys-194” | disulfide bridge |
bridge | Cys-23”’ – Cys-88”’ | disulfide bridge |
bridge | Cys-134”’ – Cys-194”’ | disulfide bridge |
PATENTS
WO 2017024062
US 20170305999
Evinacumab, sold under the brand name Evkeeza, is a monoclonal antibody medication for the treatment of homozygous familial hypercholesterolemia (HoFH).[1][2]
Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions – including involvement in the regulation of lipid metabolism – which have made them desirable therapeutic targets in recent years.2 Loss-of-function mutations in ANGPTL3 have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.3
In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name “Evkeeza”.8 Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH.
Common side effects include nasopharyngitis (cold), influenza-like illness, dizziness, rhinorrhea (runny nose), and nausea. Serious hypersensitivity (allergic) reactions have occurred in the Evkeeza clinical trials.[2]
Evinacumab binds to the angiopoietin-like protein 3 (ANGPTL3).[2] ANGPTL3 slows the function of certain enzymes that break down fats in the body.[2] Evinacumab blocks ANGPTL3, allowing faster break down of fats that lead to high cholesterol.[2] Evinacumab was approved for medical use in the United States in February 2021.[2][3]
NAME | DOSAGE | STRENGTH | ROUTE | LABELLER | MARKETING START | MARKETING END | ||
---|---|---|---|---|---|---|---|---|
Evkeeza | Injection, solution, concentrate | 150 mg/1mL | Intravenous | Regeneron Pharmaceuticals, Inc. | 2021-02-11 | Not applicable | ||
Evkeeza | Injection, solution, concentrate | 150 mg/1mL | Intravenous | Regeneron Pharmaceuticals, Inc. | 2021-02-11 | Not applicable |
History
The effectiveness and safety of evinacumab were evaluated in a double-blind, randomized, placebo-controlled, 24-week trial enrolling 65 participants with homozygous familial hypercholesterolemia (HoFH).[2] In the trial, 43 participants received 15 mg/kg of evinacumab every four weeks and 22 participants received the placebo.[2] Participants were taking other lipid-lowering therapies as well.[2]
The primary measure of effectiveness was the percent change in low-density lipoprotein (LDL-C) from the beginning of treatment to week 24.[2] At week 24, participants receiving evinacumab had an average 47% decrease in LDL-C while participants on the placebo had an average 2% increase.[2]
The U.S. Food and Drug Administration (FDA) granted the application for evinacumab orphan drug, breakthrough therapy, and priority review designations.[2] The FDA granted approval of Evkeeza to Regeneron Pharmaceuticals, Inc.[2]
References
- ^ Jump up to:a b https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761181s000lbl.pdf
- ^ Jump up to:a b c d e f g h i j k l m n “FDA approves add-on therapy for patients with genetic form of severely”. U.S. Food and Drug Administration (FDA). 11 February 2021. Retrieved 12 February 2021. This article incorporates text from this source, which is in the public domain.
- ^ “FDA Approves First-in-class Evkeeza (evinacumab-dgnb) for Patients with Ultra-rare Inherited Form of High Cholesterol” (Press release). Regeneron Pharmaceuticals. 11 February 2021. Retrieved 12 February 2021 – via PR Newswire.
Further reading
- Dewey FE, Gusarova V, Dunbar RL, O’Dushlaine C, Schurmann C, Gottesman O, et al. (July 2017). “Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease”. N Engl J Med. 377 (3): 211–221. doi:10.1056/NEJMoa1612790. PMC 5800308. PMID 28538136.
External links
- “Evinacumab”. Drug Information Portal. U.S. National Library of Medicine.
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Human |
Target | Angiopoietin-like 3 (ANGPTL3) |
Clinical data | |
Trade names | Evkeeza |
Other names | REGN1500, evinacumab-dgnb |
License data |
|
Routes of administration |
Intravenous |
ATC code |
|
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6480H9992N1716O2042S46 |
Molar mass | 146083.95 g·mol−1 |
//////////////Evinacumab, Peptide, APPROVALS 2021, FDA 2021, Monoclonal antibody, dyslipidemia, エビナクマブ (遺伝子組換え) , REGN 1500, REGN-1500, REGN1500,