Shares of Alkermes, the Dublin-based developer of brain drugs, have surged nearly 50% in the last month, in good part because of positive clinical data for the company’s most talked about research program.

The data, released in mid-June, showed Alkermes’ experimental pill “alixorexton” was significantly better than a placebo at keeping patients with the more common, “Type 2” form of narcolepsy awake and alert. Patients also tolerated the drug well, as there were no serious “treatment-emergent adverse events.” Alkermes has since initiated a global, Phase 3 program that will evaluate its pill in patients with Type 2 as well as Type 1 narcolepsy, which is hallmarked by a specific kind of loss in muscle control.

On Wall Street, analysts see a multibillion-dollar opportunity in a new class of drugs that includes alixorexton as well as medicines from Takeda Pharmaceutical, Eli Lilly and Eisai. These therapies stimulate certain proteins, “orexins,” that are found through the circuits of the brain and regulate key functions like stress, energy, mood, learning and attention. As such, developers expect that orexin-targeting agents will be valuable treatments not only for narcolepsy, but for conditions like ADHD as well as other sleep disorders like idiopathic hypersomnia.

Blair Jackson, Alkermes’ chief operating officer and soon-to-be CEO, spoke to BioPharma Dive about his company’s strategy to compete against much larger rivals and how he, in his new role, will navigate what’s poised to be the most important 12-month period in Alkermes’ history.

The following conversation has been edited and condensed for clarity.

BIOPHARMA DIVE: The narcolepsy Type 2 data Alkermes just disclosed, how closely did they match with the company’s expectations? Were there any findings that surprised you?

JACKSON: When you move from an NT1 group, which has no orexin, and you go into an orexin-adequate person, you expect to see an even more tolerable profile. We actually saw that, and I think that was a surprise for a number of people, a number of investors, and the community as a whole. What a lot of people missed is: that bodes really well for these orexin agonists moving outside of idiopathic hypersomnia and narcolepsy and into other, bigger indications like ADHD and fatigue. So that was very validating for us and consistent with our investment hypothesis.

Where we saw a couple surprises had to do with the heterogeneity of the population. The NT1 group, that population performed similarly along the way. They were very responsive to orexin agonism. What we found with NT2 is the disease is a little more heterogeneous; different patients needed different doses. They also had different responses to treatment overall, depending on what lane they were put in. Some would respond, some wouldn't. But when we moved them into the open-label, where they could select their appropriate dose, we saw a movement to the normal range.

So there are always learnings through these studies, and this was one of them. The other was just being really fastidious in standardizing measurements. We saw some variability in how some of the treatment centers and physicians would enact some of the tests, and we spent a long time thinking about that as we started our Phase 3 planning. You have 100 sites around the world — they need to be doing it the same way so you can maintain statistical power.

I remember there was a lot of discussion among analysts about your drug potentially causing visual impairments in some patients. Is that still a big concern?

JACKSON: That was pretty much a Wall Street phenomenon. We started to see early in the program a few patients would get a visual disturbance. It was typically something like they're in a dark room and we turn the lights on, and they go, “The lights look brighter.” That's a visual disturbance. And it goes away really, really quickly.

We had a handful of those, and Wall Street started to lose it. They were all over the place about it, and that was being sort of prodded on by some of our competition. What was interesting is when you talk to the treating physicians, to the sleep community, no one really cared. It wasn't going to impact their treatment. But, out of an abundance of caution, we put visual testing into our Phase 2 program just to make sure if someone had a visual disturbance, we could follow up.

In the intervening time, I think people have started to recognize that [if the adverse event] is not impacting the patient's outcome, if it's not impacting their lives, then it’s nothing to worry about. Really, the prominent things you see related to this class are [more frequent urination], a bit of transient insomnia and some dizziness.

How important is narcolepsy Type 2 to the commercial success of alixorexton?

JACKSON: Very important. Not from a market [perspective], because the markets individually are very, very large. But when you look at this patient group as a whole, whether you're talking about NT1, NT2 or IH, the diagnosis between them can sometimes be blurred.

You can imagine a situation where, when Takeda enters the marketplace with their drug, it can only be used in NT1. When that happens, payers are going to say to the doctors, "You must prove this patient has NT1.” And you can do that in only a few ways. One is a lumbar puncture, which nobody does. The other is to look at a genetic marker in the gene HLA1. A lot of people don't get that done either. So you put this hurdle up in front of the physician to prove this patient has NT1.

Our goal is to come in and get approval across all three indications, so doctors don't have to justify their diagnosis. They could just say, “I think the patient is NT1, start them on a dose.” And if they need to move them around, they can easily do that. It gives a lot of flexibility and a lot of treatment options for those patients without having to deal with the payer every time you turn around.

The way things are going, you’ll likely be competing against two much larger, more resourced competitors in Takeda and Eli Lilly. How, specifically, will you win there?

JACKSON: When you look at this space, you're talking about a rare disease with a limited number of doctors, which minimizes the advantage that [those bigger players] have. This isn't like going after obesity, where we're going to see commercials everywhere and have to go to thousands of doctors and spend a ton of money. In fact, you're limited in how much you can really spend and do there.

Takeda, I've heard them throw around something like maybe 120, 160 reps; that's about the size of our Vivitrol sales force. That's a small sales force in the scheme of things, so the way you compete in a smaller set like this is with the best asset. Creating the best clinical profile, the best outcomes, the best label, that helps.

It becomes more difficult moving into these bigger markets, where Lilly can then start to push a
lot of their weight into the DTC and all that stuff. There, we take a different strategy.

Stifel analysts recently spoke to a couple key opinion leaders, one of whom believed there isn’t much differentiating the profiles of the leading orexin programs, which puts added weight on first-mover advantage. How much do you agree or disagree with that idea?

JACKSON: It’s true in one context, and maybe not in another.

In some of the endpoints, you might see that we have similar results or are all highly efficacious. As you look at the way the market stacks up, we see that Takeda's drug is really good, but it's limited in its ability to be dosed higher. So there's going to be one dose for each of these patients, and it's going to be limited. If it works for you, great. If you need more, or if you want to go later in the day and get later coverage, you're kind of out of luck.

I think it's going to launch really well, but I think it's going to leave a lot of room for improvement. And that's where we'll be able to come in with multiple doses across every different indication — NT1, NT2 and IH — and the ability to flex your dosing into the evening with our split-dose option. Differentiation is coming from the embodiment of the drug, the flexibility of the drug, the ability to give the doctors and patients what they need.

As it then comes to Lilly, we don't know what Lilly has. We haven't seen their data. At best, we think they could be similar to us. But our goal is to try to minimize their ability to differentiate as much as possible, so that our second-mover advantage is really providing a barrier for them to get market share later.

When Takeda presented data last year, at least some analysts described Alkermes as firmly planted in the No. 2 position. Do you think that perception is fair or creates any kind of impediment for you?

JACKSON: We are going to be second to market, not second in preference.

So I actually don't think that at all. Our data is being appreciated more and more. Physicians are really getting behind us.

Doctors and analysts see huge opportunities for orexin drugs outside of sleep. How much is Alkermes willing to invest to probe those opportunities?

We're leaders in the space of taking this mechanism and trying to understand where it works outside of narcolepsy. We've identified upwards of 19 different areas just within neuroscience; that's not looking at inflammation and metabolism.

We started moving drugs forward a number of years ago. Our two programs now are in the clinic — ‘7290 and ‘4510 — we're gonna have data on ADHD by the end of the year for ‘7290. So we’re at the front edge of that.

Having Lilly and others in the space is actually a benefit to us, because it means they're also going to be looking at a number of areas. We can then focus on the ones we know and can do really well in, and if they hit a really interesting spot, we could go there as well while not having to spend as much money as you would if you're the only one trying to see where this works.

You’re transitioning into the CEO role later this summer. What are one or two concrete, top-of-mind things you will be focused on achieving in the first few months after you take the reins?

JACKSON: In the next 12 months, we have a number of different clinical programs coming out with data. So the amount of execution needed over the next year is going to be higher than we've seen here in a really long time. I want to focus on that. I want to make sure we are delivering.

The other thing I really want to do is focus a lot on our commercial organization preparation for the launch of alixorexton, but also the build out of the oxybate class. This acquisition of Avadel and bringing in the Lumryz business [means] we've got a commercial business that’s going to deliver north of $1.7 billion this year. It's anchored by our legacy business, but the addition of Lumryz is very important within the sleep space.

Now that we can have both the night treatment with the oxybate and the morning treatment with the orexin agonists, we're getting a lot of interest from patients and physicians. So bolstering up that clinical data set so we can show the benefits of each of these drugs and how they can best be used, these are the things that I'm going to be spending a lot of time on over the next little while.