Eptinezumab Endeavors to Maintain Migraine Prevention Progress

Bob Azelby, MBA, chief executive officer of Alder Biopharmaceuticals

Bob Azelby, MBA

If all goes according to the plans of Alder Biopharmaceuticals, its anti-calcitonin gene-related peptide (CGRP) migraine treatment, eptinezumab, will be entering commercialization in early 2020. However, the market it will be entering has become increasingly crowded, with 3 other CGRP-focused inhibitors—erenumab (Aimovig, Amgen/Novartis), galcanezumab (Emgality, Eli Lilly), and fremanezumab (Ajovy, Teva)—granted FDA approval already.

Bob Azelby, MBA, chief executive officer of Alder, has expressed the company’s confidence in eptinezumab’s ability to provide patients advantages over its competing products. Studies of the antibody have shown that its bioavailability is 100% by the end of its half-hour infusion. Most notably, in a number of statements, Azelby has touted eptinezumab’s design as focused specifically for “rapid, effective, and sustained suppression of migraine.”

To find out more about the quarterly intravenous (IV) therapy, where it fits in the marketplace, and its potential to provide advantages to patients with migraine, NeurologyLive^® spoke with Azelby in an interview.

NeurologyLive^®: Where does eptinezumab fit into the marketplace in a broad sense?

Bob Azelby, MBA: Obviously, it’s an investigational product and we’re hoping for it to be on the market Q1 of 2020. But before we jump into the clinical data, I think it’s really important that we step back and think about what a chronic migraine patient actually goes through. For example, in our PROMISE-2 data are patients averaging 16 migraines a month—that’s 4 per week—and what’s really important is that we have to do a better job of making sure we educate society that this is not just this devastating pain. It’s impacting their light sensitivity, their sound sensitivity, these people are nauseous, and they’re vomiting. In fact, when you get into the chronic migraine setting with multiple migraines a week, it starts to impact your sleep, anxiety, depression—you’re living with migraine every day, it’s not just the day of the attacks.

The reason why I highlight that as a backdrop is that this is a serious neurological disease, so it’s about the efficacy of the products. When we jump into our PROMISE-2 data, for example, where the patients are having 16 migraines per month, we were able to take roughly 6 out of 10 patients from 16 migraine days a month to less than 8, and about one-third of patients from 16 migraines a month to less than 4.

When you look at that magnitude of effect with clinicians who treat these types of patients, as well as share this data with the patients themselves, they get really, really excited with the efficacy component of eptinezumab. It’s not only that you’re getting a tremendous magnitude of the effect, you actually start getting it within 24 hours of the 30-minute quarterly infusion. You’re getting that depth of response that starts early, and when you think about the patient that is struggling every day to manage through their disease, the effectiveness and also the rapidity of which the prevention starts is really important. We don’t think we’re going to be niche, we think that their primary agent for patients that are suffering from migraine impacting their lives.

What does it offer to the physicians treating migraine?

From a targeting perspective, because we’re an IV delivery—again a quarterly IV infusion—we’re going to be targeting roughly 3000 doctors—3000 neurologists and headache specialists. These particular physicians are seeing between 150 to 200 migraine patients. These are the folks who are seeing the most impact.

Then, when we look at the current sales of the anti-CGRPs, these roughly 3000 doctors are writing about 80% of the anti-CGRPs today. So that’s going to be our target market, we see it as our specialty market. As it relates to the question and how does it fit in with that particular clinician’s practice, when we look at those 3000 doctors, about 2/3 of them have IV capabilities in their offices or their hospital outpatient clinic. We see this product fitting really well into their workflow, and they like the fact that they can ensure compliance for the next 90 days. Once you infuse the product, the patient’s going to be covered, and for many of these clinicians, they have a business model that’s operating from a procedure perspective which eptinezumab would fit well into in terms of executing procedures, such as infusions and buying and billing products.

What’s the pricing going to look like for patients? Do you anticipate any challenges for physicians to get it to patients?

Two key points here: We’re not in the pharmacy benefit like the subcutaneous IVs are. They’re managed by pharmacy benefit provider; we’re going to be under the medical benefit. There are 2 different systems in the payers that operate the reimbursement level, but we’ve been very active with payers, and payers what they’ve said to us hey we really like the depth of response and the speed of response, as I’ve articulated, but they also like the fact they only have to pay for the product once it’s in the veins of the patients.

The payers enjoy the compliance element and the fact that they’re paying for a product that’s in the system, so we don’t anticipate a lot of hiccups in terms of getting reimbursed or having the clinician reimbursed for the product. In fact, we’re excited about that particular end point as it relates to the price. We’re still 10 months out or so of a potential approval, and so obviously we’re studying the market in terms of how the subcutaneous products are priced and that will be a benchmark for us. But we’re working through our health economic data as we speak to really be able to articulate the value proposition that eptinezumab not only brings to payers, but to the practice as well as to the patient.

Are there any unique characteristics of its mechanism of action or delivery?

One of our founders, John Latham, PhD, started the designing of this molecule over a decade ago because of his wife, who’s a chronic migraine sufferer. Two key elements are its binding affinity—when you attach it to the ligands, you’re encapsulating it so that it can’t interact with the receptor—and the other, which I think really makes the difference, is the 100% bio-availability of eptinezumab.

A patient goes in and sits down for a 30-minute infusion. Once that infusion is over, 100% of eptinezumab is available in the system to engage with CGRP, which is known as the root cause of the migraine cascade. That not only allows for that depth of response that I spoke about earlier, but it talks about the rapidity of the prevention. The ability to start preventing migraines within 24 hours—that, to us, is a really critical component and differentiation. Additionally, the fact that it’s done on a quarterly basis allows it to match up to when patients actually go to see their clinician.

Were there any subgroup findings or analyses for eptinezumab that were surprising or unexpected?

What we found surprising is when we did all that subanalysis, the surprising analysis was that eptinezumab worked across the whole spectrum of patients. The interesting thing was we didn’t find anything. The fact that it was consistent across all patients, whether it be age, weight, works in MOA (medication overuse patients)—we’re really pleased in the consistency of the data, not only in terms of the efficacy in general but in the subpopulations.

Anything to add that the physician community should know?

First of all—and the doctors would know—but what we hear anecdotally is about the way the current CGRP therapies are working in a very similar way to trials in clinical practice. One-third of patients are getting great benefit, one-third of patients are getting pretty good benefit or some benefit, and one-third are not. What I would say is, obviously, there are opportunities for new innovative therapies to enter the marketplace.

And not only with eptinezumab coming into the marketplace in terms of its unique clinical profile, but we’re also really excited about ALD1910, which is focused on the PACAP-38 pathway, which is separate and distinct to the CGRP pathway. We expect to be first-in-human with ALD1910 by the end of 2019—the end of this year. We’re excited that that may be another opportunity because as excited as we are about eptinezumab and its unique clinical profile, we’re helping out about 6 out of 10 patients. That means 4 out of 10 patients are not getting relief. We see ALD1910 as an opportunity to help those patients, and it’s just reiterating that we’re early on in this migraine disease and understanding it, so there’s still a lot of opportunity for innovation.