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AHA Scientific Sessions 2019. L’acido bempedoico riduce il colesterolo senza influenzare negativamente il controllo glicemico. I risultati di analisi combinate presentati al Congresso AHA

L’acido bempedoico, in aggiunta a terapie ipolipemizzanti di background, riduce significativamente il colesterolo senza tuttavia influenzare negativamente il controllo glicemico. Daiichi Sankyo ha presentato al Congresso AHA, in corso a Philadelphia, due analisi combinate di dati provenienti da 4 trial di Fase III che hanno arruolato più di 3.600 pazienti. L’Acido Bempedoico, un inibitore orale dell’adenosina trifosfato (ATP) citrato liasi (ACL) che riduce la sintesi del colesterolo nel fegato, è attualmente in fase di valutazione regolatoria da parte dell’EMA e dell’FDA

Philadelphia, 18 novembre 2019 –  L’acido bempedoico, in aggiunta a terapie ipolipemizzanti di background, riduce significativamente il colesterolo senza tuttavia influenzare negativamente il controllo glicemico. E’ quanto emerge da due analisi combinate di quattro trial clinici di Fase III sull’acido bempedoico che hanno coinvolto un totale di oltre 3.600 pazienti,  e sono state presentate da Daiichi Sankyo all’American Heart Association (AHA) Scientific Sessions in corso a Philadelphia.

Una delle analisi ha mostrato che l’acido bempedoico ha ridotto l’emoglobina A1c (HbA1c) dello 0.19% rispetto al placebo in pazienti diabetici trattati per 12 settimane.[i] L’HbA1 è un parametro di valutazione standard del controllo glicemico, usato nella gestione del diabete. L’analisi ha inoltre dimostrato che i pazienti trattati con acido bempedoico hanno sperimentato un numero minore di nuovi casi di diabete così come di episodi di iperglicemia, rispetto a quelli trattati con placebo.2 L’analisi combinata suggerisce che l’acido bempedoico non ha un impatto negativo sul controllo glicemico in pazienti con e senza diabete, se aggiunto a una terapia ipolipemizzante stabile di background.2

“Molti pazienti ad alto o altissimo rischio di ipercolesterolemia combattono anche per mantenere sotto controllo i valori glicemici, siano essi soggetti già affetti da diabete o a rischio di svilupparlo. Il colesterolo elevato e la glicemia elevata sono entrambi fattori di rischio importanti per malattie cardiovascolari ed eventi quali infarto e ictus. - Ha dichiarato Wolfgang Zierhut, MD, responsabile del dipartimento Antithrombotic and Cardiovascular Medical Affairs di Daiichi Sankyo Europa – Ci sono evidenze che dimostrano che alcuni trattamenti ipolipemizzanti possano aumentare il rischio di diabete, quindi è incoraggiante per noi osservare che l’acido bempedoico, in aggiunta a terapie preesistenti, riduce il colesterolo senza tuttavia influenzare negativamente il controllo glicemico.”

Un’altra analisi ha dimostrato che in tutti e quattro gli studi di fase III, l’acido bempedoico riduce significativamente il colesterolo a bassa densità (C-LDL) nei pazienti con ipercolesterolemia, se aggiunto ad una terapia con statine alla massima dose tollerata.[ii] Nei soggetti trattati con terapia di background, l’acido bempedoico ha ridotto il C-LDL del 18% rispetto al placebo.3 Nei soggetti non trattati con terapia di background, l’acido bempedoico ha ridotto il C-LDL del 25% rispetto al placebo.3

L’acido bempedoico è in fase di sviluppo come trattamento addizionale in monosomministrazione giornaliera per quelle persone con ipercolesterolemia che non riescono a raggiungere i loro target di C-LDL e restano al alto rischio di eventi cardiovascolari come infarto o ictus, nonostante assumano terapie ipolipemizzanti orali ottimizzate.

La richiesta di autorizzazione all’immissione in commercio dell’acido bempedoico, è attualmente sottoposta a valutazione da parte dell’Agenzia Europea per i Medicinali (EMA) e della Food and Drug Administration (FDA).

 

Acido Bempedoico

L'acido bempedoico è un inibitore orale dell’ATP citrato liasi (ACL) che, con un meccanismo d'azione mirato, riduce la biosintesi del colesterolo nel fegato, riducendo i livelli di C-LDL in circolo.[iii],[iv] Utilizzato in monosomministrazione giornaliera, è destinato a pazienti affetti da ipercolesterolemia e/o ad alto rischio di malattia cardiovascolare aterosclerotica (ASCVD) che necessitano di una ulteriore riduzione di C-LDL, nonostante abbiano ricevuto statine alla massima dose tollerata.

L'acido bempedoico ha una modalità d'azione unica e innovativa, complementare a quella di altre terapie ipolipemizzanti come le statine.[v] Grazie alla sua specifica modalità d'azione sul fegato, l'acido bempedoico ha una ridotta potenzialità di indurre gli effetti collaterali a carico dell’apparato muscolare associati all’uso delle statine, e determina una riduzione ulteriore del C-LDL rispetto alla monoterapia con statine nei trial clinici.2

Con l’acido bempedoico si è osservata una riduzione della proteina C-reattiva ad alta sensibilità, un marker chiave dell’infiammazione associata a malattia cardiovascolare.5L'acido bempedoico in monoterapia (180 mg) e l’associazione fissa di acido bempedoico/ezetimibe (180 mg/10 mg) in compresse, sono attualmente in corso di valutazione da parte dell'Agenzia Europea per i Medicinali (EMA) e della Food and Drug Administration (FDA) statunitense per la riduzione del colesterolo LDL nei pazienti che non hanno raggiunto i loro livelli ottimali di C-LDL. Daiichi Sankyo Europa ha ottenuto da Esperion la licenza esclusiva per la commercializzazione di questi prodotti nell’area economica europea e in Svizzera. Le decisioni in merito all’approvazione sono attese per la prima metà del 2020.

Riferimenti

[I] Abstract. Bempedoic acid and glycemic control: A pooled analysis of 4 phase 3 clinical trials. Presented at the American Heart Association 2019 Scientific Sessions.

[II] Abstract. Efficacy of bempedoic acid: A pooled analysis of 4 pivotal phase 3 clinical trials. Presented at the American Heart Association 2019 Scientific Sessions.

[III] Ray KK, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019;380:1022–32.

[IV] Ballantyne CM, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis.2018;277:195–203.

[V] Laufs U, et al. Efficacy and Safety of Bempedoic Acid in Patients with Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc. 2019;8(7):e011662.