Explore a selection of our essential drug information below, or:
Identification
- Summary
Corifollitropin alfa is a FSH analogue indicated for Controlled Ovarian Stimulation (COS) in combination with a GnRH antagonist for the development of multiple follicles in women participating in an Assisted Reproductive Technology (ART) program.
- Brand Names
- Elonva
- Generic Name
- Corifollitropin alfa
- DrugBank Accession Number
- DB09066
- Background
Corifollitropin alfa, also known as Elonva is used in women undergoing fertility treatment to stimulate the development of more than one mature egg (oocyte) at a time in the ovaries. This drug used together with a gonadotropin-releasing hormone (GnRH) antagonist, a type of medicine also used in fertility treatments. Elonva is available only by prescription 6.
In July 2014, Merck announced the receipt of a Complete Response Letter (CRL) from the U.S. FDA for its New Drug Application for this drug. Corifollitropin alfa is marketed as Elonva in more than 75 countries 8.
Corifollitropin alfa is produced by a method known as ‘recombinant DNA technology’. This means that it is made by cells into which a DNA has been introduced that makes them able to produce corifollitropin alfa 6.
Multiple studies and a meta-analysis suggest that corifollitropin alfa is as efficacious as recombinant FSH in terms of live birth rate, ongoing pregnancy rate, as well as clinical pregnancy rate. The increased in the number of eggs retrieved under corifollitropin alfa regimen represents the elevated effectiveness of this drug, however, warns at the same time against the possibility of an increased risk of ovarian hyperstimulation in the high responder study group of women 12, 4.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 25398.0389 Da
- Sequences
- Not Available
- Synonyms
- Corifolitropina alfa
- Corifollitropin alfa
- FSH-CTP
- External IDs
- MK-8962
- ORG 36286
- ORG-36286
- SCH 900962
- SCH-900962
Pharmacology
- Indication
Controlled ovarian stimulation 9 in cases of women who are undergoing fertility treatment to stimulate the development of more than one mature egg simultaneously in the ovaries in combination with a gonadotrophin-releasing hormone (GnRH) antagonist (a type of medicine also used in fertility treatments)6.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
A single dose of corifollitropin alfa could initiate and sustain multi-follicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection 10.
This drug is structurally similar to follicle stimulating hormone (FSH), a hormone naturally present in females. FSH stimulates the production of eggs (ova) in the ovaries. In corifollitropin alfa, a peptide is attached to the FSH to prolong its activity. As a result, one single dose of the medicine can be administered to stimulate egg production for seven days, replacing daily injections that are normally needed with other FSH medicines 6.
In phase III clinical trials, the number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment 10.
- Mechanism of action
Corifollitropin alfa is a long-lasting single injection fusion protein which lacks luteinizing hormone (LH) activity. Only one injection is needed for the first 7 days, which replaces the first 7 daily injections of traditional follicle stimulating hormone (FSH). It is a follicle-stimulation hormone (human α-subunit reduced), a combination of follicle stimulation hormone (human β-subunit reduced) fusion protein with 118-145-chorionic gonadotropin (human β-subunit) 6. Frequent, repetitive injections increase stress and error rates, and are often a burden for women, leading to therapy noncompliance 13.
The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH 1.
Corifollitropin alfa serves as a sustained follicle stimulant that has similar pharmacological effects to recombinant follicle stimulating hormone (rFSH), however, with a relatively long elimination half-life, resulting in a longer duration of action. This is achieved using site-directed mutagenesis and gene transfer techniques to create a glycoprotein that consists of an α-subunit that is identical to human follicle stimulating hormone (FSH) noncovalently bound to a β-subunit comprised of a complete β-chain of human FSH elongated by the carboxyterminal peptide of the β-subunit of human chorionic gonadotrophin (hCG) 7. This unit interacts with the FSH receptor 1 to stimulate the release of oocytes.
Corifollitropin alfa does not demonstrate any intrinsic LH/hCG activity 6.
Target Actions Organism AFollicle-stimulating hormone receptor agonistHumans - Absorption
After one single subcutaneous injection of this drug, the maximal serum concentration is 4.24 ng/mL (2.49-7.21 ng/mL1) and is reached 44 hours (35-57 h) post-dose administration. Its absolute bioavailability is 58% (48-70%) 6.
- Volume of distribution
Distribution, metabolism and elimination of corifollitropin alfa are very similar to other gonadotropins, such as FSH, hCG and LH 9.
After absorption into the blood, corifollitropin alfa is distributed mainly to the ovaries and the kidneys. The steady-state volume of distribution is 9.2 L 9.
Exposure to corifollitropin alfa increases in a linear fashion with the dose within a range of 60 micrograms - 240 micrograms 6.
- Protein binding
Not Available
- Metabolism
The metabolic fate of corifollitropin alfa highly resembles that of endogenous glycoprotein hormones, which predominantly is comprised of kidney clearance and the urinary excretion of the intact protein in parallel to kidney catabolism 3.
- Route of elimination
Radioactivity labeling showed that the drug was mainly (86%) excreted in the urine. 90% of the radioactivity in serum was identified as [(125)I]corifollitropin alfa, but only 7-15% of the radioactivity in urine was identified as [(125)I]corifollitropin alfa and its dissociation products, the alpha- and beta-subunits (including its CTP part) 3.
Elimination of corifollitropin alfa mainly occurs via the kidneys. The elimination rate of this drug may be reduced in patients with renal insufficiency. Hepatic metabolism contributes to a minor extent to the elimination of corifollitropin alfa 6.
- Half-life
Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing 1.
Corifollitropin alfa has an elimination half-life of 70 hours (59-82 hours) 6.
- Clearance
0.13 L/h (0.10-0.18 L/h1) 6
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most common side effects with Elonva (seen in between 1 and 10 patients in 100) include a headache, nausea, fatigue, pelvic pain and/or discomfort, breast tenderness and ovarian hyperstimulation syndrome (OHSS). This syndrome occurs when the ovaries have a heightened response to therapy, leading to abdominal swelling and pain, nausea and diarrhea 6.
More than one injection of Elonva within one treatment cycle or an excessively high dose of Elonva and/or (rec)FSH can increase the risk of ovarian hyperstimulation syndrome 6, which may cause swollen or painful ovaries, abdominal bloating, nausea, and a weight gain of up to 3kg 11.
In severe cases, ovarian hyperstimulation syndrome may cause rapid weight gain ranging from 15 to 20 kilograms in 5-10 days. Severe abdominal pain, severe, persistent nausea, and vomiting, decreased urination, and abdominal bloating, as well as other generalized symptoms, may occur 11. About 1 - 2 % of women undergoing ovarian stimulation develop a severe form of ovarian hyperstimulation syndrome (OHSS). Severe OHSS can be life-threatening. Complications may include: ascites, pulmonary edema, electrolyte disturbances (sodium, potassium, others), thrombosis in large vessels, usually in the lower extremities, renal failure, ovarian torsion, rupture of ovarian cysts. Some of these conditions can lead to hemorrhage, respiratory failure, spontaneous miscarriage or pregnancy termination due to complications, resulting in death 6.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Corifollitropin alfa which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Corifollitropin alfa which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Elonva Injection, solution 150 micrograms Subcutaneous N.V. Organon 2016-09-08 Not applicable EU 
Elonva Injection, solution 100 micrograms Subcutaneous N.V. Organon 2016-09-08 Not applicable EU
Categories
- ATC Codes
- G03GA09 — Corifollitropin alfa
- Drug Categories
- Drugs that are Mainly Renally Excreted
- Follicle Stimulating Hormone
- Genito Urinary System and Sex Hormones
- Gonadotropins
- Gonadotropins, Pituitary
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Peptide Hormones
- Pituitary Hormones
- Pituitary Hormones, Anterior
- Recombinant Proteins
- Sex Hormones and Modulators of the Genital System
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- T7K20Y2GWY
- CAS number
- 195962-23-3
References
- General References
- Loutradis D, Drakakis P, Vlismas A, Antsaklis A: Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility. Curr Opin Investig Drugs. 2009 Apr;10(4):372-80. [Article]
- de Lartigue J: Corifollitropin alfa: a new option to treat female infertility. Drugs Today (Barc). 2011 Aug;47(8):583-90. doi: 10.1358/dot.2011.47.8.1635872. [Article]
- van Schanke A, van de Wetering-Krebbers SF, Bos E, Sloot WN: Absorption, distribution, metabolism and excretion of corifollitropin alfa, a recombinant hormone with a sustained follicle-stimulating activity. Pharmacology. 2010;85(2):77-87. doi: 10.1159/000276546. Epub 2010 Jan 21. [Article]
- Benchabane M, Santulli P, Maignien C, Bourdon M, De Ziegler D, Chapron C, Gayet V: [Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for oocyte donors]. Gynecol Obstet Fertil Senol. 2017 Feb;45(2):83-88. doi: 10.1016/j.gofs.2016.12.022. Epub 2017 Feb 16. [Article]
- Corifollitropin alfa vs recombinant FSH for controlled ovarian stimulation in women aged 35–42 years with a body weight ≥50 kg: a randomized controlled trial [Link]
- EMA label [Link]
- Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation [Link]
- Corifollitropin alfa approval [Link]
- Australian APA report document, corifollitropin alfa [Link]
- Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility. [Link]
- Ovarian hyperstimulation syndrome [Link]
- Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for in vitro fertilization: a meta-analysis [Link]
- Gonadotrophins: The future [Link]
- External Links
- Wikipedia
- Gonadotropin_preparations
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Pregnancy 1 somestatus stop reason just information to hide 4 Completed Prevention Infertility 1 somestatus stop reason just information to hide 4 Completed Treatment Female Infertility 1 somestatus stop reason just information to hide 4 Completed Treatment Improving Ovarian Stimulation; Suboptimal Responders 1 somestatus stop reason just information to hide 4 Completed Treatment Infertility 4 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 100 MCG Injection, solution Parenteral; Subcutaneous 150 MCG Injection, solution Subcutaneous 100 micrograms Injection, solution Subcutaneous 150 micrograms Injection 100 mcg/0.5ml Injection, solution 100 mcg/0.5ml Injection, solution 150 mcg/0.5ml Injection, solution Subcutaneous 0.100 mg Injection, solution Subcutaneous 0.150 mg Solution Subcutaneous 100 mcg Solution Subcutaneous 33 cg Solution Subcutaneous Solution Subcutaneous 900 IU Solution Subcutaneous 100 mcg/0.5ml Solution Subcutaneous 150 mcg/0.5ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- G protein-coupled receptor for follitropin, the follicle-stimulating hormone (PubMed:11847099, PubMed:24058690, PubMed:24692546). Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways (PubMed:24058690)
- Specific Function
- Follicle-stimulating hormone receptor activity
- Gene Name
- FSHR
- Uniprot ID
- P23945
- Uniprot Name
- Follicle-stimulating hormone receptor
- Molecular Weight
- 78237.04 Da
References
- Loutradis D, Drakakis P, Vlismas A, Antsaklis A: Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility. Curr Opin Investig Drugs. 2009 Apr;10(4):372-80. [Article]
- de Lartigue J: Corifollitropin alfa: a new option to treat female infertility. Drugs Today (Barc). 2011 Aug;47(8):583-90. doi: 10.1358/dot.2011.47.8.1635872. [Article]
Drug created at May 11, 2015 22:42 / Updated at April 30, 2021 13:07