Replies to post #84115 on Biotech Values

[DewDiligence]

Musings on M118 differentiation:

If the relative efficacy of M118 (and by use of the term efficacy I mean that it works and works with fewer adverse events and can be reversed quicker and with less hassles) remains as established in M118, it appears to me that we can expect to see a much larger advantage of M118 if utilized in patients who are followed for longer periods of time. Is this an accurate expectation going forward into further clinical trials? Not necessarily as presently designed, but it appears that it would be a very telling trial to demonstrate the relative results in a study following patients over a longer duration.

You have two questions: one on the duration of treatment and follow-up and one on M118’s reversibility. Let me take them separately.

In the upcoming M118 phase-2b trial in ACS, the duration of treatment and follow-up will presumably be much longer than the 30-day post-PCI period in the EMINENCE trial. For instance, in the phase-2 Xarelto trial called ATLAS ACS TIMI described in #msg-33517140, patients were treated for six months.

It’s important to bear in mind that MNTA conducted the phase-2a M118 trial in PCI because practicing cardiologists demanded such a trial before they would agree to enroll patients in a full-fledged ACS trial (#msg-37693105). ACS per se—rather than just the PCI component—has always been MNTA’s target indication for M118.

In short, the answer to your first question is yes — the upcoming phase-2b trials in ACS will provide an opportunity for M118 to distinguish itself from the competition. These trials will also be large and expensive, which is why MNTA needs to ink a partnership deal for M118 before the trials can begin.

The answer to your question about M118’s differentiation due to reversibility depends on what the comparator drugs will be in the phase-2b trials. Unfractionated heparin (the comparator in the phase-2a trial) is reversible, but Angiomax, Lovenox, and placebo* are not. The table in #msg-39146357 is a handy reference for this—reversibility is shown in the third row. Regards, Dew

*In an ACS trial, the “placebo” treatment generally consists of Plavix+aspirin or a comparable mix. This regimen can serve as the control arm because patients in the other trial arms receive it in addition to the drug being tested.