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Monday, June 29, 2009 7:45:43 PM
MNTA: M118 Refresher Course
M118 is a proprietary anticoagulant for acute coronary syndromes (ACS) that consists of a mixture of short- and long-chain heparins. It was designed by MNTA from the ground up:
• to retain the same binding affinity to Factor-IIa (thrombin) and Factor-Xa as unfractionated heparin (UFH);
• to be fully reversible; and
• to retain the predictability of response that is the hallmark of LMWH’s (low-molecular-weight heparins) such as Lovenox.
No existing drug—and no drug in development other than M118—has all of these attributes.
The following chart summarizes the features of M118 compared to UFH, LMWH (Lovenox), and Angiomax (a direct thrombin inhibitor widely used in ACS):
(For readers with a more technical bent, the graphic in #msg-26897966 depicts the human clotting cascade and shows where FXa and FIIa fit into the cascade. The graphic in #msg-26898084 shows how the short and long chains of UFH and LMWH bind to ATIII [antithrombin] in order to enable anticoagulation.)
Let’s comment in a little more detail on the deficiencies of the existing anticoagulants for ACS.
Factor-Xa inhibition with Lovenox or oral FXa inhibitors such as Xarelto* works well for preventing venous thrombosis (a/k/a/ DVT, VTE); however, FXa inhibition without comparable FIIa inhibition is ineffective against arterial thrombosis. Moreover, Lovenox and oral FXa inhibitors are not reversible, which is a substantial practical drawback in acute-care settings.
FIIa inhibition via Angiomax works well for preventing arterial thrombosis, and hence Angiomax is widely used in the cath lab. However, Angiomax does not inhibit FXa, which makes its anticoagulation effect less predictable than what is seen with Lovenox and M118. Moreover, Angiomax is non-reversible.
Unfractionated heparin, the old hospital standby, inhibits FXa and FIIa equally well and is reversible; however, UFH is unpredictable with respect to dose response and requires close monitoring to prevent life-threatening bleeding episodes.
In other words, if M118 continues to perform as advertised, it could be the Holy Grail for anticoagulation in ACS, which is a very large commercial indication.
--
*Xarelto is not included in the table above because it is not yet approved.
M118 is a proprietary anticoagulant for acute coronary syndromes (ACS) that consists of a mixture of short- and long-chain heparins. It was designed by MNTA from the ground up:
• to retain the same binding affinity to Factor-IIa (thrombin) and Factor-Xa as unfractionated heparin (UFH);
• to be fully reversible; and
• to retain the predictability of response that is the hallmark of LMWH’s (low-molecular-weight heparins) such as Lovenox.
No existing drug—and no drug in development other than M118—has all of these attributes.
The following chart summarizes the features of M118 compared to UFH, LMWH (Lovenox), and Angiomax (a direct thrombin inhibitor widely used in ACS):
(For readers with a more technical bent, the graphic in #msg-26897966 depicts the human clotting cascade and shows where FXa and FIIa fit into the cascade. The graphic in #msg-26898084 shows how the short and long chains of UFH and LMWH bind to ATIII [antithrombin] in order to enable anticoagulation.)
Let’s comment in a little more detail on the deficiencies of the existing anticoagulants for ACS.
Factor-Xa inhibition with Lovenox or oral FXa inhibitors such as Xarelto* works well for preventing venous thrombosis (a/k/a/ DVT, VTE); however, FXa inhibition without comparable FIIa inhibition is ineffective against arterial thrombosis. Moreover, Lovenox and oral FXa inhibitors are not reversible, which is a substantial practical drawback in acute-care settings.
FIIa inhibition via Angiomax works well for preventing arterial thrombosis, and hence Angiomax is widely used in the cath lab. However, Angiomax does not inhibit FXa, which makes its anticoagulation effect less predictable than what is seen with Lovenox and M118. Moreover, Angiomax is non-reversible.
Unfractionated heparin, the old hospital standby, inhibits FXa and FIIa equally well and is reversible; however, UFH is unpredictable with respect to dose response and requires close monitoring to prevent life-threatening bleeding episodes.
In other words, if M118 continues to perform as advertised, it could be the Holy Grail for anticoagulation in ACS, which is a very large commercial indication.
--
*Xarelto is not included in the table above because it is not yet approved.
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