PTLA Part 2: Andexanet Alfa

In Part 1, I took a look at Portola [$PTLA, currently around $40] and their drug betrixaban. In this, part 2, I’m going to look at PTLA’s other main drug candidate, andexanet alfa. Andexanet is a drug designed to reverse the effects of factor Xa inhibitors like betrixaban.

As you may recall from Part 1, factor Xa inhibitors are anticoagulants, a class of drug extremely useful for preventing dangerous blood clots. The trick, of course, is that anticoagulants prevent all blood clots; a patient on anticoagulants runs the risk of bleeding to death from even a minor injury. Imagine a small cut on your finger that just kept bleeding and bleeding, no matter what you tried to do.

Enter andexanet. PTLA calls andexanet alfa an “antidote” to factor Xa inhibitors, and in several senses, this really is the best description. As we’ll see, andexanet works rapidly, doesn’t seem to cause harmful effects, and (probably) effectively countered the factor Xa inhibitors it was deployed against. However, some concerns about the lack of a control group prevent me from recommending $PTLA as an investment.

The Data

I took the graph below from the first Phase 3 study of andexanet. It shows two groups of patients, both of which were using a factor Xa inhibitor. The “800mg bolus” group was given a large injection and IV drip of andexanet alfa, while the placebo group was not given any. The left side of the graph measures the effectiveness of the factor Xa inhibitors (anticoagulants). As you can see, the anticoagulants rapidly stopped working in the group given andexanet alfa, and stayed “off” until the end of the IV drip. There were no safety issues.

This graph shows andexanet's efficacy
Andexanet works rapidly on injection and can be sustained via an IV drip.

At this point, $PTLA asked the FDA for approval of the drug… and were denied. The FDA wanted additional data for two of the four Factor Xa inhibitors tested. As such, the researchers began a second phase 3 study which tested andexanet alfa in bleeding patients. This study is still ongoing, but in September 2016 researchers posted interim data: of 47 bleeding patients who received andexanet, 37 (79%) saw a clear clinical benefit.

This seems good, but there’s a snag – the study had no control group. Ultimately, it’s impossible to tell whether the andexanet stopped the patients from bleeding or whether it would have happened anyway.  In and of itself, this isn’t a show-stopper. I have seen drugs without control groups get FDA approval in the past. However, given that the FDA has already rejected $PTLA’s drug once, this study design makes me wonder.

Will andexanet get approved?

Given the data, I would say yes, it is likely that the application for andexanet alfa will be approved by the FDA. The lack of a control group is worrisome, but andexanet is addressing a completely unmet clinical need. Ultimately, andexanet appears to be almost entirely without side-effects, and I think that the FDA will approve the application, even given the somewhat marginal phase 3 study formulation.

That said, I cannot recommend buying stock in $PTLA at this juncture. As I mentioned in part 1 of my look at Portola, I think that the betrixaban study is going to fail. If I’m right, the share price of $PTLA could drop precipitously, and I can’t predict how much a successful application for andexanet might boost it.

Prediction: FDA Approval – but don’t invest at this time.

The unmet clinical need and safety data make me think this drug will probably receive FDA approval, but the issue with Betrixaban should keep you from investing at this time.

 

Portola, part 1: the new drug application for betrixaban

Two readers emailed in to point out that I misinterpreted the meaning of the net clinical benefit figure. As much as I hate being wrong, I hate misleading people even more  – so I’ve pulled the piece until I get a chance to take another look at the data.

A word of thanks for the readers who wrote in with their disagreements.