Elafibranor

Last updated

Elafibranor
Elafibranor.svg
Clinical data
Trade names Iqirvo
Other namesGFT505, SureCN815512
AHFS/Drugs.com Iqirvo
License data
Routes of
administration
By mouth
Drug class Antihyperlipidemic
ATC code
Legal status
Legal status
Identifiers
  • 2-[2,6 Dimethyl-4-[3-[4-(methylthio)phenyl]-3-oxo-1(E)-propenyl]phenoxyl]-2-methylpropanoic acid [2]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
Formula C22H24O4S
Molar mass 384.49 g·mol−1
3D model (JSmol)
  • O=C(O)C(Oc1c(cc(cc1C)\C=C\C(=O)c2ccc(SC)cc2)C)(C)C
  • InChI=1S/C22H24O4S/c1-14-12-16(13-15(2)20(14)26-22(3,4)21(24)25)6-11-19(23)17-7-9-18(27-5)10-8-17/h6-13H,1-5H3,(H,24,25)/b11-6+
  • Key:AFLFKFHDSCQHOL-IZZDOVSWSA-N

Elafibranor (INN [3] ), sold under the brand name Iqirvo, is a medication used for the treatement of primary biliary cholangitis. [1] [4]

Contents

Elafibranor is a dual PPARα/δ agonist. [5] [6] Elafibranor and its main active metabolite GFT1007 are peroxisome proliferator-activated receptor (PPAR) agonists, both of which activate PPAR-alpha, PPAR-gamma, and PPAR-delta in vitro. [1]

In June 2024, the US Food and Drug Administration (FDA) granted accelerated approval to elafibranor. [1] [7] [4]

Medical uses

Elafibranor is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults who have an inadequate response to ursodeoxycholic acid, or as monotherapy in people unable to tolerate ursodeoxycholic acid. [1] [4] [8]

Adverse effects

The most common adverse reactions include weight gain, diarrhea, abdominal pain, nausea, vomiting, arthralgia, constipation, muscle injury, fracture, gastroesophageal reflux disease, dry mouth, weight loss, and rash. [1]

History

In 2019, the US Food and Drug Administration (FDA) granted elafibranor breakthrough therapy designation, based on phase II data, for the treatment of primary biliary cholangitis in adults 18 and older with inadequate response to ursodeoxycholic acid (UDCA). [9] The designation was granted to Genfit. [9]

In June 2024, the US FDA granted accelerated approval to elafibranor. The approval was based on positive phase III ELATIVE trial data. [10] The designation was granted to Ipsen. [11]

Society and culture

In July 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Iqirvo, intended for the treatment of primary biliary cholangitis (PBC). [12] The applicant for this medicinal product is Ipsen Pharma. [12]

Research

This chemical compound is also being studied and developed by Genfit for the treatment of endocrine and metabolic diseases such as type 2 diabetes, dyslipidemia, and MASH. [13] [14] [15]

Related Research Articles

<span class="mw-page-title-main">Primary biliary cholangitis</span> Autoimmune disease of the liver

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.

<span class="mw-page-title-main">Ursodeoxycholic acid</span> Medication and metabolite of cholesterol

Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile of bears of genus Ursus, from which its name derived. In purified form, it has been used to treat or prevent several diseases of the liver or bile ducts.

<span class="mw-page-title-main">Cholestasis</span> Medical condition

Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:

Ipsen is a French biopharmaceutical company headquartered in Paris, France, with a focus on drug development and commercialization in three therapeutic areas: oncology, rare diseases and neuroscience. Ipsen is one of the world's top 15 biopharmaceutical companies in terms of oncology sales.

<span class="mw-page-title-main">PPAR agonist</span> Drug

PPAR agonists are drugs which act upon the peroxisome proliferator-activated receptor. They are used for the treatment of symptoms of the metabolic syndrome, mainly for lowering triglycerides and blood sugar.

Pitolisant, sold under the brand name Wakix among others, is a medication used for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist (an antihistamine drug specific to that kind of receptors). It represents the first commercially available medication in its class, so that the US Food and Drug Administration (FDA) declares it a first-in-class medication. Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness. It was approved by the European Medicines Agency (EMA) in March 2016 for narcolepsy with or without cataplexy, and for excessive daytime sleepiness by the FDA in August 2019. The most common side effects include difficulty sleeping, nausea, and feeling worried.

<span class="mw-page-title-main">Seladelpar</span> Chemical compound

Seladelpar, sold under the brand name Livdelzi, is a medication used for the treatment of primary biliary cholangitis. It is used as the lysine dihydrate salt. It is a PPARδ receptor agonist. The compound was licensed from Janssen Pharmaceutica NV.

<span class="mw-page-title-main">Saroglitazar</span> Chemical compound

Saroglitazar is a drug for the treatment of type 2 diabetes mellitus, dyslipidemia, NASH and NAFLD It is approved for use in India by the Drug Controller General of India. Saroglitazar is indicated for the treatment of diabetic dyslipidemia and hypertriglyceridemia with type 2 diabetes mellitus not controlled by statin therapy. In clinical studies, saroglitazar has demonstrated reduction of triglycerides (TG), LDL cholesterol, VLDL cholesterol, non-HDL cholesterol and an increase in HDL cholesterol a characteristic hallmark of atherogenic diabetic dyslipidemia (ADD). It has also shown anti-diabetic medication properties by reducing the fasting plasma glucose and HBA1c in diabetes patients.

<span class="mw-page-title-main">Selexipag</span> Chemical compound

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<span class="mw-page-title-main">Obeticholic acid</span> Chemical compound

Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.

<span class="mw-page-title-main">Palovarotene</span> Chemical compound

Palovarotene, sold under the brand name Sohonos, is a medication used for the treatment of heterotopic ossification and fibrodysplasia ossificans progressiva. It is a highly selective retinoic acid receptor gamma (RARγ) agonist. It is taken by mouth.

Intercept Pharmaceuticals, Inc. is an American biopharmaceutical company incorporated in 2002, focusing on the development of novel synthetic bile acid analogs to treat chronic liver diseases, such as primary biliary cirrhosis (PBC) now called primary biliary cholangitis, non-alcoholic fatty liver disease, cirrhosis, portal hypertension, primary sclerosing cholangitis and also the intestinal disorder, bile acid diarrhea.

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Semaglutide is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management. It is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1), modified with a side chain. It can be administered by subcutaneous injection or taken orally. It is sold under the brand names Ozempic and Rybelsus for diabetes, and under the brand name Wegovy for weight loss.

<span class="mw-page-title-main">Setanaxib</span> Chemical compound

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References

  1. 1 2 3 4 5 6 "Iqirvo- elafibranor tablet, film coated". DailyMed. 10 June 2024. Archived from the original on 16 June 2024. Retrieved 16 June 2024.
  2. Cariou B, Zaïr Y, Staels B, Bruckert E (September 2011). "Effects of the new dual PPAR α/δ agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism". Diabetes Care. 34 (9): 2008–14. doi:10.2337/dc11-0093. PMC   3161281 . PMID   21816979.
  3. World Health Organization (2015). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 74". WHO Drug Information. 29 (3). hdl: 10665/331070 .
  4. 1 2 3 "Ipsen's Iqirvo receives U.S. FDA accelerated approval as a first-in-class PPAR treatment for primary biliary cholangitis". Ipsen (Press release). 10 June 2024. Archived from the original on 16 June 2024. Retrieved 11 June 2024.
  5. US Patent No. 7655641 "96 dpi image of original patent USPTO 7655641" (PDF). Retrieved 31 March 2013.[ dead link ]
  6. Vázquez-Carrera M (2012). "GFT-505" (PDF). Drugs of the Future. 37 (8): 555–559. doi:10.1358/dof.2012.037.08.1835977. S2CID   258323049.[ permanent dead link ]
  7. "FDA Roundup: June 11, 2024". U.S. Food and Drug Administration (FDA) (Press release). 11 June 2024. Archived from the original on 11 June 2024. Retrieved 12 June 2024.
  8. "Historic Milestone Achieved with U.S. FDA Accelerated Approval of Ipsen's Iqirvo for Primary Biliary Cholangitis". wallstreet-online.de (in German). 10 June 2024. Archived from the original on 16 June 2024. Retrieved 11 June 2024.
  9. 1 2 "Genfit announces FDA Grant of Breakthrough Therapy Designation to Elafibranor for the Treatment of PBC". Genfit (Press release). 18 April 2019. Archived from the original on 5 June 2024. Retrieved 11 June 2024.
  10. Ipsen (9 May 2024). A Double-blind, Randomized, Placebo-Controlled Study and Open-label Long Term Extension to Evaluate the Efficacy and Safety of Elafibranor 80 mg in Patients With Primary Biliary Cholangitis With Inadequate Response or Intolerance to Ursodeoxycholic Acid (Report). clinicaltrials.gov. Archived from the original on 2 May 2024. Retrieved 11 June 2024.
  11. "Historic Milestone Achieved with U.S. FDA Accelerated Approval of Ipsen's Iqirvo for Primary Biliary Cholangitis". wallstreet-online.de (in German). 10 June 2024. Archived from the original on 11 June 2024. Retrieved 11 June 2024.
  12. 1 2 "Iqirvo EPAR". European Medicines Agency. 25 July 2024. Retrieved 27 July 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. "Advanced Compound Status" (Press release). Genfit. Archived from the original on 11 April 2013.
  14. "GFT505 Broadens Its Therapeutic Potential" (PDF) (Press release). Archived (PDF) from the original on 10 July 2021. Retrieved 31 March 2013.
  15. Cariou B, Staels B (October 2014). "GFT505 for the treatment of nonalcoholic steatohepatitis and type 2 diabetes". Expert Opinion on Investigational Drugs. 23 (10): 1441–8. doi:10.1517/13543784.2014.954034. PMID   25164277. S2CID   3190253.