Last Word: Eptinezumab on the Horizon

Tell Us About Alder, Please?

Alder was founded 15 years ago by 4 researchers who wanted to bring their science to the marketplace and has since grown to a company of more than 200 people. The culture is unbelievable in the sense of the commitment to science and passion for having monoclonal antibodies make a difference to people living with migraine. I would also call Alder courageous and resilient, having learned all the lessons that a small firm must to weather the ups and downs of the last 15 years. Ultimately, the culture is one of getting it done—whether that means everyone setting their own projects aside briefly so we could all work on the biologics license application (BLA) submitted in February 2019, or just the way people pursue their own projects on a day-to-day basis.

With the positive results we’ve seen for eptinezumab in clinical trials and the BLA submitted, we look forward to working with the FDA to seek approval for eptinezumab. We also plan to expand our operations, actively going from a research and development organization to a firm bringing a treatment to market. This means growth not only from adding a sales force but also from all the positions needed to create a commercial infrastructure—from finance, to human resources, to marketing, and more.

What Makes Alder Unique?

We feel very fortunate to have been able to submit a BLA and to have had strong science and good fortune when there are so many companies working so hard to create solutions for people with migraine. We share an advantage with other small firms in that we are nimble. Another key strength is that we have an absolute focus on migraine and giving people with migraine their lives back, which is to say, making it possible for them to live their daily lives without the interruption of disabling pain.

What’s Most Exciting About Eptinezumab?

We feel really good about the safety and efficacy data seen in the trials with great consistency between the trials. I’ll focus more on the results for chronic migraine, because that’s where there is the most disability and therefore, greatest impact. In the PROMISE-2 trial, the average participant had 16 monthly migraine days (MMD)—4 migraine days per week. For approximately 6 of 10 people treated with eptinezumab, that was reduced to less than 8 MMD, and approximately 3 of 10 people had a reduction to less than 4 MMD. After a second quarterly dose, on average, 1 in 5 individuals treated had freedom from pain for each month of the following 3 months. That depth of response is especially exciting.

We are also excited because we believe we’ve achieved 2 of the key goals set when Alder was founded. The first was to have a treatment that could be dosed quarterly to match the typical frequency of physician visits a person with migraine has. The second was to have a product that was 100% bioavailable as quickly as possible. This all goes back to our mission of helping individuals with migraine get their lives back with treatments that fit into their lifestyles and are fully available to reduce a known effector of migraine, calcitonin gene-related peptide (CGRP), as soon as the 30-minute infusion of the antibody is complete. That bioavailability has allowed us to begin analysis and see effects of prevention as early as 24 hours after infusion.

Like any drug, there were some side effects. The most common side effect observed in the trial (those with incidence at least 2% and at least 2% greater than placebo) was nasopharyngitis.

What Makes Eptinezumab Unique?

It’s not possible to answer that question exactly because no head-to-head comparisons with other migraine treatments have been done. What I can say is that when we share the data with clinicians and people affected by migraine, we see a lot of excitement around the high responder rate, relatively rapid onset of prevention, quarterly dosing schedule, and ability to fit a 30-minute infusion that doesn’t require pretreatment into clinical care and day-to-day living.

Where Will Alder Go Next?

As optimistic as we are about eptinezumab potentially bringing relief to people with migraine, we haven’t stopped thinking about the people in our trials who didn’t respond as well as others. We are exploring expanded use of eptinezumab, focusing on the depth of response and the rapid onset of prevention.

We are also developing a monoclonal antibody antagonist, ALD1910, that binds pituitary adenylate cyclase-activating peptide (PACAP). Similar to CGRP, if you infuse PACAP in a person with migraine, an attack will occur. A CGRP antagonist, however, does not improve symptoms of an attack induced with PACAP (nor does a PACAP antagonist improve a CGRP-induced attack). The attack induced with PACAP is also clinically different in that it tends to have more aura and somewhat slower onset.

Our antibody targets the ligand, which is important because we now know there are 3 PACAP receptors, rather than 1 as initially thought. In our preclinical trials, we use a proprietary animal model of rats or mice predisposed to have photophobia in response to PACAP infusion. When we treated the animals with PACAP-induced attacks with antibodies to the PACAP receptor, they did not return to lighted areas after treatment. In contrast, when we treated them with ALD1910, the antibody to the ligand, they returned to the lighted area.

Preclinical studies have been positive, and we expect to initiate first-in-human phase 1 clinical trials of ALD1910 by the end of 2019.

What Else Would You Like to Share With Practical Neurology Readers?

At Alder, we are committed not only to providing treatments that help people with migraine reclaim their daily lives, but also to educating people about migraine. We want everyone to understand that migraine isn’t just a bad headache—both episodic and chronic migraine are chronic conditions—it is the number 1 cause of disability for people under age 50 worldwide. Improving understanding will increase access to treatments and access to treatment can improve understanding.