{"id":3650,"date":"2020-10-01T12:08:02","date_gmt":"2020-10-01T10:08:02","guid":{"rendered":"https:\/\/www.ab-science.com\/ab8939-leucemie-myeloide-aigue\/"},"modified":"2026-09-29T10:41:38","modified_gmt":"2026-09-29T08:41:38","slug":"ab8939-leucemie-myeloide-aigue","status":"publish","type":"page","link":"https:\/\/ab-science.excalibra.com\/fr\/pipeline\/ab8939-leucemie-myeloide-aigue\/","title":{"rendered":"AB8939 \u2013 Leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb"},"content":{"rendered":"

[vc_row][vc_column]

<\/span>\u00c0 propos de la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb<\/span><\/div><\/div>
<\/div>[vc_column_text]La leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb (LMA) est un cancer de la lign\u00e9e my\u00e9lo\u00efde des cellules sanguines, caract\u00e9ris\u00e9 par la croissance rapide de cellules anormales qui s’accumulent dans la moelle osseuse et le sang et qui interf\u00e8rent avec la production normale de cellules sanguines.<\/p>\n

Chez les patients inaptes \u00e0 une chimioth\u00e9rapie intensive de rattrapage, les options de traitement efficaces font d\u00e9faut avec des taux de r\u00e9ponse compl\u00e8te typiques de 20\u00a0% et une survie globale m\u00e9diane d’environ 8 mois seulement.[\/vc_column_text]

<\/span>Positionnement de la mol\u00e9cule AB8939 dans la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb<\/span><\/div><\/div>
<\/div>[vc_column_text]AB8939 est initialement d\u00e9velopp\u00e9 dans la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb (LMA) car les cellules canc\u00e9reuses prolif\u00e8rent rapidement dans cette maladie. AB8939 est 100 fois plus puissant que la doxorubicine (adriamycine), qui est un m\u00e9dicament de r\u00e9f\u00e9rence dans la LMA. De plus, AB8939 n’est pas d\u00e9sactiv\u00e9 par l’enzyme my\u00e9loperoxydase, ce qui est un avantage par rapport aux vinca alcalo\u00efdes (vincristine ou vinblastine)123<\/sup>.<\/p>\n

AB Science \u00e9value AB8939 dans un premier essai clinique chez l\u2019humain portant sur sa tol\u00e9rance et son efficacit\u00e9 chez les patients atteints de leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb en traitement de deuxi\u00e8me ou troisi\u00e8me intention et qui ne sont pas aptes \u00e0 recevoir une chimioth\u00e9rapie intensive. La strat\u00e9gie consiste \u00e0 positionner AB8939 chez les patients pr\u00e9sentant une cytog\u00e9n\u00e9tique anormale les rendant non r\u00e9pondeurs au traitement de premi\u00e8re intention.<\/p>\n

En reconnaissance du besoin critique de nouveaux traitements, AB8939 a re\u00e7u la d\u00e9signation de m\u00e9dicament orphelin pour la LMA de la Food and Drug Administration (FDA) des \u00c9tats-Unis et de l\u2019Agence europ\u00e9enne des m\u00e9dicaments (EMA).[\/vc_column_text]

<\/span>Etude clinique de phase 1\/2 en cours dans la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb<\/span><\/div><\/div>
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Sur la base de ces r\u00e9sultats pr\u00e9cliniques prometteurs, AB Science a initi\u00e9 une \u00e9tude de phase 1\/2 dans la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb r\u00e9fractaire ou en rechute avec la mol\u00e9cule AB8939.<\/p>\n

La premi\u00e8re partie est une \u00e9tude d\u2019escalade de dose visant \u00e0 d\u00e9terminer la s\u00e9curit\u00e9 et la tol\u00e9rance d\u2019AB8939 et \u00e0 \u00e9tablir la dose recommand\u00e9e pour l\u2019\u00e9tude d\u2019extension de la deuxi\u00e8me phase.<\/p>\n

L’objectif de l’\u00e9tude de phase 1 est de d\u00e9terminer la dose maximale tol\u00e9r\u00e9e (DMT) pour les diff\u00e9rentes \u00e9tapes de traitement par AB8939.<\/p>\n

    \n
  • Etape 1 : D\u00e9termination de la DMT apr\u00e8s 3 jours cons\u00e9cutifs de traitement par AB8939 seul.<\/li>\n
  • Etape 2 : D\u00e9termination de la DMT apr\u00e8s 14 jours cons\u00e9cutifs de traitement par AB8939 seul.<\/li>\n
  • Etape 3 : D\u00e9termination de la DMT apr\u00e8s 14 jours cons\u00e9cutifs de traitement par AB8939 en association avec le v\u00e9n\u00e9toclax.<\/li>\n
  • Etape 4 : D\u00e9termination de la DMT apr\u00e8s 14 jours cons\u00e9cutifs de traitement par AB8939 en association avec le v\u00e9n\u00e9toclax et l’azacitidine.<\/li>\n<\/ul>\n

    Les trois premi\u00e8res \u00e9tapes de l\u2019essai clinique de phase 1 avec AB8939 sont achev\u00e9es. Les deux premi\u00e8res \u00e9tapes ont consist\u00e9 \u00e0 d\u00e9terminer la dose maximale tol\u00e9r\u00e9e (DMT) apr\u00e8s 3 et 14 jours cons\u00e9cutifs de monoth\u00e9rapie. Dans les deux cas, la DMT \u00e9tait de 21,3 mg\/m\u00b2.<\/p>\n

    La troisi\u00e8me \u00e9tape, d\u00e9sormais achev\u00e9e, a \u00e9valu\u00e9 la combinaison d\u2019AB8939 et du v\u00e9n\u00e9toclax. Six patients ont \u00e9t\u00e9 trait\u00e9s \u00e0 deux niveaux de dose (AB8939 pendant 14 jours \u00e0 une dose de 16 mg\/m\u00b2 + v\u00e9n\u00e9toclax pendant 14 jours, puis AB8939 pendant 14 jours \u00e0 une dose de 21,3 mg\/m\u00b2 + v\u00e9n\u00e9toclax pendant 14 jours), sans toxicit\u00e9 limitant la dose ni toxicit\u00e9 h\u00e9matologique observ\u00e9e, ce qui conforte la s\u00e9lection de la dose recommand\u00e9e pour la phase 2. Quatre des six patients ont pr\u00e9sent\u00e9 une r\u00e9ponse objective (une r\u00e9mission compl\u00e8te avec r\u00e9cup\u00e9ration h\u00e9matologique incompl\u00e8te et trois r\u00e9ponses partielles), soit 67 % de r\u00e9ponse globale, les deux autres \u00e9tant en maladie stable, soit un contr\u00f4le de la maladie de 100 %, apr\u00e8s un seul cycle de traitement de 14 jours. La prochaine \u00e9tape (\u00e9tape 4) \u00e9valuera la triple combinaison AB8939 + v\u00e9n\u00e9toclax + azacitidine.<\/p>\n

    [\/vc_column_text][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]R\u00e9f\u00e9rences<\/strong><\/em><\/p>\n

      \n
    1. Humbert M, et al. (2019). Anticancer Activity of a Highly Potent Small Molecule Tubulin Polymerization Inhibitor, AB8939. Blood. 134. 2075-2075. 10.1182\/blood-2019-122540.<\/em><\/li>\n
    2. Goubard A, et al. (2019). In Vivo Assessment of the Next Generation Microtubule-Destabilizing Agent AB8939 in Patient-Derived Xenograft Models of Acute Myeloid Leukemia. Blood. 134. 5142-5142. 10.1182\/blood-2019-127143.<\/em><\/li>\n
    3. Goubard A, et al. (2019). AB8939, a Microtubule-Destabilizing Agent with Potential to Overcome Multidrug Resistance, Is Active across the Range (M0-M7) of Acute Myeloid Leukemia Subtypes. Blood. 134. 5154-5154. 10.1182\/blood-2019-127021.<\/em><\/li>\n<\/ol>\n

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