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fenfluramine

Trade name: Pondimin

Small moleculeapprovedOrphan Drug FDA

Approved

Jun 1, 1973

Fenfluramine (former brand names Pondimin, Ponderax and Adifax), also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is no longer marketed. In combination with phentermine, it was part of the anti-obesity medication Fen-phen. Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997. It is the racemic mixture of two enantiomers, dexfenfluramine, and levofenfluramine. The drug increases the level of serotonin, a neurotransmitter that regulates mood, appetite and other functions. Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter and reversing serotonin transporter function. The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. In this small exploratory and retrospective study, remarkably good results were reported on the use of fenfluramine as an add-on medication for controlling seizures in patients with the Dravet syndrome. The side effects were rare and nonserious and did not result in termination of the treatment. It is possible that this drug may have anticonvulsive effects for other severe epilepsy syndromes, especially in those characterized by photosensitive or induced seizures. — NCATS

Clinical trial activity

25 trials · 18 clinical orgs · 3 marketing orgs

Phase 1
4
Phase 2
17
Phase 3
11
Phase 4
3

Earliest trial started May 1, 1983 (NCT00000506)

Timeline

1970s

  1. Jun 1, 1973

    AH Robins — Earliest FDA Approval

  2. Jun 1, 1973

    AH Robins — NDA Organization

1980s

  1. Jan 1, 1983

    Earliest Phase 2 Sponsor(trial)

1990s

  1. Jan 1, 1999

    Earliest Phase 1 Sponsor(trial)

2010s

  1. Dec 20, 2013

    Orphan Drug Designation

  2. Jan 1, 2016

    Zogenix, Inc. — Earliest Phase 3 Sponsor(trial)

2020s

  1. Jun 25, 2020

    Zogenix, Inc. — Marketing Organization

  2. Jun 25, 2020

    UCB — Marketing Organization

  3. Jun 25, 2020

    UCB — NDA Secondary Org

Indications

Approved for

Studied for

Mechanism of action

  • Serotonin 1d (5-HT1d) receptorAGONIST

    HTR1D agonist

    Fenfluramine (FA) reduces epileptiform activity by stimulating 5-HT2C and 5-HT1D receptors, leading to enhanced GABAergic neurotransmission, and by a ¿1-antagonistic action that can reduce the excitatory neurotransmission by modulating N-methyl-D-aspartate (NMDA) responses. In addition, FA also significantly decreases the noradrenaline (NAD) brain content that might contribute to its anti-epileptic effects. Fenfluramine causes the release of serotonin (5-HT) by disrupting vesicular storage of the neurotransmitter and inhibiting its reuptake. The increased 5-HT availability in the brain results in a loss of appetite.

  • Serotonin 2c (5-HT2c) receptorAGONIST

    HTR2C agonist

    Fenfluramine (FA) reduces epileptiform activity by stimulating 5-HT2C and 5-HT1D receptors, leading to enhanced GABAergic neurotransmission, and by a ¿1-antagonistic action that can reduce the excitatory neurotransmission by modulating N-methyl-D-aspartate (NMDA) responses. In addition, FA also significantly decreases the noradrenaline (NAD) brain content that might contribute to its anti-epileptic effects. Fenfluramine causes the release of serotonin (5-HT) by disrupting vesicular storage of the neurotransmitter and inhibiting its reuptake. The increased 5-HT availability in the brain results in a loss of appetite.

  • Sigma opioid receptorANTAGONIST

    SIGMAR1 antagonist

    Fenfluramine (FA) reduces epileptiform activity by stimulating 5-HT2C and 5-HT1D receptors, leading to enhanced GABAergic neurotransmission, and by a ¿1-antagonistic action that can reduce the excitatory neurotransmission by modulating N-methyl-D-aspartate (NMDA) responses. In addition, FA also significantly decreases the noradrenaline (NAD) brain content that might contribute to its anti-epileptic effects. Fenfluramine causes the release of serotonin (5-HT) by disrupting vesicular storage of the neurotransmitter and inhibiting its reuptake. The increased 5-HT availability in the brain results in a loss of appetite.

Approval history

  • approvedPriority reviewJun 1, 1973

Chemistry & pharmacology

Loading structure…

SMILES

CCNC(C)Cc1cccc(C(F)(F)F)c1
Mol. weight
231.26 g/mol
Lipinski Ro5
Pass
Rule of 3
No
Chirality
Racemic Mixture
Inorganic
No
Polymer
No
Delivery
Oral
Availability
Prescription Only

Oral

Yes

Parenteral

No

Topical

No

Black box warning

Sources

Also known as

  • ahr-3002
  • ahr-3002
  • dl-fenfluramine
  • fenfluramina
  • fenfluramina
  • fenfluramine
  • fenfluramine
  • fenfluramine
  • fenfluramine
  • fenfluramine
  • fenfluramine
  • fenfluramine
  • fenfluramine
  • fenfluramine hcl
  • fenfluramine hcl
  • fenfluramine hcl
  • fenfluramine hydrochloride
  • fenfluramine hydrochloride
  • fenfluramine hydrochloride
  • fenfluraminum
  • fenfluraminum
  • ponderax
  • ponderax
  • ponderax pacaps
  • pondimin
  • pondimin
  • pondimin

Clinical trials

NCT IDPhaseStart dateSponsor(s)
NCT06679413Phase 1Dec 6, 2024UCB
NCT06598449Phase 4Oct 31, 2024Mayo Clinic, UCB, University of California, San Francisco, University of Colorado, University of Colorado, Denver
NCT06118255Phase 3Dec 31, 2023UCB
NCT05560282Phase 3Dec 10, 2022University of Toronto, Zogenix, Inc.
NCT05232630Phase 4Oct 20, 2022Hospital Ruber Internacional, Zogenix, Inc.
NCT05064878Phase 3Oct 31, 2021Zogenix, Inc.
NCT05026398Phase 4Apr 12, 2021National Institute for Health Research, United Kingdom, University of Oxford, Zogenix, Inc.
NCT04289467Phase 2Apr 1, 2020University of California, Irvine
NCT03861871Phase 2Apr 30, 2019New York University
NCT03936777Phase 3Apr 22, 2019Zogenix, Inc.
NCT03790137Phase 3Feb 28, 2019Harvard University, Zogenix, Inc.
NCT03467113Phase 1/Phase 2 (Phase 2)Jan 19, 2018Zogenix, Inc.
NCT03355209Phase 3Nov 27, 2017Zogenix, Inc.
NCT03299842Phase 3Aug 23, 2017Zogenix, Inc.
NCT02926898Phase 3Sep 1, 2016Zogenix, Inc.
NCT02823145Phase 3Jul 1, 2016Zogenix, Inc.
NCT02826863Phase 3Jun 1, 2016Zogenix, Inc.
NCT02682927Phase 3Jan 1, 2016University of California, San Francisco, Zogenix, Inc.
NCT02655198Phase 2Jan 1, 2016Katholieke Universiteit Leuven, Zogenix, Inc.
NCT00000312Phase 1Sep 20, 1999Department of Veteran Affairs, National Institute on Drug Abuse (NIDA)
Showing 20 of 25 trials
Page 1 / 2

Organizations

Research & Development (18)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
Zogenix, Inc.For profit151042016
Department of Veteran AffairsGovernment3021994
National Institute on Drug Abuse (NIDA)Government3321994
UCBFor profit3232023
University of California, San FranciscoAcademic/Hospital2022016
Harvard UniversityAcademic/Hospital1112019
Hospital Ruber InternacionalAcademic/Hospital1112022
Katholieke Universiteit LeuvenAcademic/Hospital1112016
Mayo ClinicAcademic/Hospital1012024
National Heart, Lung, and Blood Institute (NHLBI)Government1111983
National Institute for Health Research, United KingdomGovernment1012021
New York UniversityAcademic/Hospital1112019
University of California, IrvineAcademic/Hospital1112020
University of California, Los AngelesAcademic/Hospital111—
University of ColoradoAcademic/Hospital1012024
University of Colorado, DenverAcademic/Hospital1112024
University of OxfordAcademic/Hospital1112021
University of TorontoAcademic/Hospital1112022
18 organizations
Page 1 / 1

Marketing (4)

OrganizationOrg typeRelationshipDate
AH RobinsFor profitNDAJun 1, 1973
UCBFor profitMKTGJun 25, 2020
UCBFor profitNDA2Jun 25, 2020
Zogenix, Inc.For profitMKTGJun 25, 2020