WO2012061060A1 - Utilisation de tériflunomide pour le traitement d'atrophie cérébrale - Google Patents

Utilisation de tériflunomide pour le traitement d'atrophie cérébrale Download PDF

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Publication number
WO2012061060A1
WO2012061060A1 PCT/US2011/057456 US2011057456W WO2012061060A1 WO 2012061060 A1 WO2012061060 A1 WO 2012061060A1 US 2011057456 W US2011057456 W US 2011057456W WO 2012061060 A1 WO2012061060 A1 WO 2012061060A1
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WO
WIPO (PCT)
Prior art keywords
teriflunomide
patient
brain
volume
reduction
Prior art date
Application number
PCT/US2011/057456
Other languages
English (en)
Inventor
Ross Rocklin
Original Assignee
Sanofi-Aventis U.S. Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi-Aventis U.S. Llc filed Critical Sanofi-Aventis U.S. Llc
Publication of WO2012061060A1 publication Critical patent/WO2012061060A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • This invention relates to use of teriflunomide for slowing the reduction of the volume of white matter in the brain, particularly in a patient having multiple sclerosis (MS).
  • MS multiple sclerosis
  • Teriflunomide is a novel oral disease-modifying therapy (DMT) in development for the treatment of relapsing-remitting multiple sclerosis (RMS).
  • DMT oral disease-modifying therapy
  • RMS multiple sclerosis
  • Teriflunomide blocks de novo pyrimidine synthesis, which inhibits the replication and function of activated (but not resting) lymphocytes.
  • This invention relates to a method for slowing the reduction of the volume of white matter in the brain, comprising administering to a patient in need thereof a
  • teriflunomide or a pharmaceutically acceptable salt thereof.
  • Figure I shows the change from baseline in volume of white matter over time of the three patient groups in the TEMSO study.
  • a compound that slows the reduction of the volume of grey matter in the brain means a compound that is already known for slowing the reduction of the volume of grey matter in the brain, such as fingolimod.
  • “Clinically proved effective” means that the results of clinical trial are statistically significant, i.e., the results of the clinical trial are not likely to be due to chance with an alpha level les than 0.05. "Patient” means humans.
  • “Pharmaceutically acceptable salt” refers to the relatively non-toxic, inorganic and organic acid addition salts, and base addition salts, of teriflunomide. "Pharmaceutically effective amount” means an amount of a compound/composition according to the present invention effective in producing the desired therapeutic effect.
  • Treating means to alleviate symptoms, eliminate the causation of the symptoms either on a temporary or permanent basis, or to slow the appearance of symptoms of the named disorder or condition.
  • One specific embodiment of the invention relates to a method for slowing the reduction of the volume of white matter in the brain, comprising administering to a patient having multiple sclerosis a pharmaceutically effective amount of teriflunomide or a pharmaceutically acceptable salt thereof.
  • Another specific embodiment of the invention relates to a method for slowing the reduction of the volume of white matter in the brain, comprising administering to a patient having multiple sclerosis a pharmaceutically effective amount of teriflunomide.
  • Another specific embodiment of the invention relates to a method for slowing the reduction of the volume of white matter in the brain, comprising administering to a patient having relapse-remitting form of multiple sclerosis a pharmaceutically effective amount of teriflunomide.
  • Another specific embodiment of the invention relates to a method for slowing the reduction of the volume of white matter in the brain, comprising administering to a patient having relapse-remitting multiple sclerosis about 7 mg or about 14 mg of teriflunomide daily.
  • Another specific embodiment of the invention relates to a method for slowing the reduction of the volume of white matter in the brain, comprising administering to a patient having relapse-remitting multiple sclerosis about 14 mg of teriflunomide daily, wherein the method is clinically proven effective.
  • Another specific embodiment of the invention relates to a method for treating brain atrophy, comprising administering to a patient having multiple sclerosis a
  • teriflunomide or a pharmaceutically acceptable salt thereof and a compound that slows the reduction of the volume of gray matter in the brain.
  • Another specific embodiment of the invention relates to teriflunomide for use in reducing the volume of white matter in brain in a patient having multiple sclerosis.
  • Another specific embodiment of the invention relates to teriflunomide for use in slowing the reduction of the volume of white matter in brain in a patient having relapse-remitting form of multiple sclerosis.
  • Another specific embodiment of the invention relates to teriflunomide for use in slowing the reduction of the volume of white matter in brain in a patient having relapse-remitting form of multiple sclerosis, wherein teriflunomide is administered to the patient about 7 mg or about 14 mg daily.
  • Another specific embodiment of the invention relates to teriflunomide for use in slowing the reduction of the volume of white matter in brain in a patient having relapse-remitting form of multiple sclerosis, wherein teriflunomide is administered to the patient about 14 mg daily, and wherein the use is clinically proved effective.
  • teriflunomide and a compound that slows the reduction of the volume of grey matter in the brain of a patient.
  • Another specific embodiment of the invention relates to a combination of teriflunomide and a compound that slows the reduction of the volume of grey matter in the brain of a patient for use in treating brain atrophy.
  • Example 1 is exemplary of the invention. They should in no way be construed, however, as limiting the broad scope of the invention.
  • Patients eligible for enrolment were aged 18-55 years, met McDonald's criteria for MS diagnosis, and exhibited a relapsing clinical course, with or without progression. They were required to have a score of no more than 5.5 on the Kurtzke Expanded Disability Status Scale (EDSS), a minimum of two clinical relapses in the previous 2 years or one relapse during the preceding year, but no relapses in the 60 days before randomization. During the 4 weeks prior to randomization, patients were required to be clinically stable and have signed both the informed consent form and informed consent for H IV testing .
  • EDSS Kurtzke Expanded Disability Status Scale
  • cladribine Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporine, methotrexate or mycophenolate
  • MRI Contraindication for MRI including presence of pacemaker, metallic implants in high-risk areas (e.g. artificial heart valves, aneurysm/vessel clips), presence of metallic material (e.g. shrapnel) in high-risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol-scheduled MRI visits; hip implants were not contraindicated
  • high-risk areas e.g. artificial heart valves, aneurysm/vessel clips
  • metallic material e.g. shrapnel
  • HlV Human immunodeficiency virus

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne l'utilisation de tériflunomide pour ralentir la réduction du volume de la matière blanche dans le cerveau, en particulier chez un patient atteint de sclérose en plaques.
PCT/US2011/057456 2010-10-25 2011-10-24 Utilisation de tériflunomide pour le traitement d'atrophie cérébrale WO2012061060A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US40629110P 2010-10-25 2010-10-25
US61/406,291 2010-10-25
US201161487998P 2011-05-19 2011-05-19
US61/487,998 2011-05-19

Publications (1)

Publication Number Publication Date
WO2012061060A1 true WO2012061060A1 (fr) 2012-05-10

Family

ID=44913414

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/057456 WO2012061060A1 (fr) 2010-10-25 2011-10-24 Utilisation de tériflunomide pour le traitement d'atrophie cérébrale

Country Status (1)

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WO (1) WO2012061060A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021176070A1 (fr) * 2020-03-06 2021-09-10 Actelion Pharmaceuticals Ltd Procédés de ralentissement de la perte de volume cérébral
US11951097B2 (en) 2021-10-11 2024-04-09 Vanda Pharmaceuticals Inc. Methods of treating multiple sclerosis

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5679709A (en) 1985-09-27 1997-10-21 Hoechst Aktiengesellschaft Medicaments to combat autoimmune diseases
US6794410B2 (en) 2001-04-05 2004-09-21 Aventis Pharmaceuticals Inc. Use of (Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4′-trifluoromethylphenyl)-amide for treating multiple sclerosis

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5679709A (en) 1985-09-27 1997-10-21 Hoechst Aktiengesellschaft Medicaments to combat autoimmune diseases
US6794410B2 (en) 2001-04-05 2004-09-21 Aventis Pharmaceuticals Inc. Use of (Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4′-trifluoromethylphenyl)-amide for treating multiple sclerosis

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BERMEL ET AL.: "The measurement and clinical relevance of brain atrophy in multiple sclerosis", LANCET NEUROL, vol. 5, 2006, pages 158 - 70, XP024968905, DOI: doi:10.1016/S1474-4422(06)70349-0
LOSSEFF N A ET AL: "Progressive cerebral atrophy in multiple sclerosis: A serial MRI study", BRAIN, vol. 119, no. 6, 1996, pages 2009 - 2019, XP002665107, ISSN: 0006-8950 *
O'CONNOR P W ET AL: "A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses", NEUROLOGY, LIPPINCOTT WILLIAMS & WILKINS, PHILADELPHIA, US, vol. 66, no. 6, 28 March 2006 (2006-03-28), pages 894 - 900, XP002556504, ISSN: 0028-3878, DOI: 10.1212/01.WNL.0000203121.04509.31 *
SIMON JH: "Brain atrophy in multiple sclerosis: what we know and would like to know", MULTIPLE SCLEROSIS, vol. 12, 2006, pages 679 - 687, XP009154478, DOI: doi:10.1177/1352458506070823
TEDESCHI G ET AL: "Brain atrophy and lesion load in a large population of patients with multiple sclerosis", NEUROLOGY, vol. 65, no. 2, July 2005 (2005-07-01), pages 280 - 285, XP002665108, ISSN: 0028-3878 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021176070A1 (fr) * 2020-03-06 2021-09-10 Actelion Pharmaceuticals Ltd Procédés de ralentissement de la perte de volume cérébral
US11951097B2 (en) 2021-10-11 2024-04-09 Vanda Pharmaceuticals Inc. Methods of treating multiple sclerosis

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