Biotech Values

[DewDiligence]

PTLA reports phase-2 top-line data of Andexanet Alfa as Lovenox antidote:

http://finance.yahoo.com/news/portola-pharmaceuticals-announces-positive-phase-120000662.html

In the randomized, double-blind, placebo-controlled, dose-escalation, Phase 2 proof-of-concept study, 27 healthy volunteers were administered enoxaparin 40 mg subcutaneously once daily for six days and then randomized in a 2:1 ratio to andexanet alfa administered as an IV bolus (210 mg or 420 mg) or to placebo.

Enoxaparin is an indirect inhibitor of Factor Xa, and results showed that anti-Factor Xa activity was reduced within two minutes to a level below the established enoxaparin therapeutic anticoagulation threshold. Inhibition of thrombin generation was also restored to normal baseline levels immediately following completion of the bolus dose. The reversal of anti-Factor Xa activity was maintained for two to three hours after the single bolus administration as was the normalization of thrombin generation.

Andexanet alfa was well tolerated with no thrombotic events or serious adverse events reported. No antibodies to andexanet alfa, Factor Xa or Factor X were observed.

Protamine sulfate, the standard reversal agent for (unfractionated) heparin, only partially reverses the anticoagulation effect of Lovenox; hence, there’s an unmet medical need for a Lovenox antidote, but the commercial opportunity is modest, IMO.

Andexanet Alfa probably has a better chance to garner sales as an antidote to the oral FXa inhibitors (Xarelto, Eliquis, Lixiana); however, absent a major marketing effort by a large pharma company, I’m not convinced that this market is a large opportunity either.

Andexanet Alfa was previously known as PRT4445. Detailed data on the phase-2 trial described above will be presented at the ISTH conference in late June.