IN SO MANY WORDS

Alimera’s Dan Myers

In So Many Words is a succinct, timely talk with a leading, ophthalmic industry KOL.

Dan Myers

Dan Myers still sounds a bit frustrated that Iluvien, the long-term, low-dose sustained release corticosteroid implant for DME, didn’t pass the FDA’s review in 2010, the first time the agency considered it for approval. It would be tough to blame Mr. Myers, Alimera’s CEO and co-founder, for that sentiment. After Alimera’s first NDA was rejected, the company reapplied in 2011 after more agency-requested data were collected and submitted. Approval was granted in fall 2014, just a few months after the FDA approved Allergan’s Ozurdex (dexamethasone). This short-term intravitreal implant’s indication for DME, while approved for other indications, was more limited (for a short time) than that of Iluvien’s.

Perhaps a less experienced individual would have sold what he could and walked away, but not Dan Myers, who helped bring the first retina drug, Novartis’ Visudyne (verteporfin) to market. “I had thought the approval process would be shorter,” he concedes. “It was frustrating, but what we have learned about DME and the role of steroids has helped us [better] position Iluvien today.”

OM: Before we talk about your better position, a brief description of Iluvien, please.

Dan Myers: In the United States, Iluvien is approved for patients with DME, who, after having been treated with a course of corticosteroids, did not experience a clinically significant rise in IOP. The 3.5-mm implant is injected into the back of the eye. The implant is filled with fluocinolone acetonide, with 0.2 mg of its contents released very slowly every day. One Iluvien injection is designed to last for 36 months. In the EU, where we first gained approval, Iluvien has a different indication. There, it is indicated for patients with chronic DME who are insufficiently responsive to available therapies.

OM: An adverse event is IOP. Why is that?

DM: It’s a class issue, it occurs with all steroids, not just Iluvien. We have managed this issue for years. We are not sure we totally understand why some patients are more prone to pressure rise. We do know there is a segment of population that is.

In our phase 2 trial (FAME) there were 38% of patients who had to be treated with topical IOP medications, and their IOP was managed. And there are similar numbers in other trials. We have over 3,000 implants in Europe where the real-life data are more like a 20% IOP response. In clinical trials you are taking all comers and not trying to vet those who are predisposed to IOP.

I don’t believe management of IOP will be a long-term impediment because we know more about DME today than when we were enrolling for FAME. We are treating patients more intelligently; we know who is more predisposed to an IOP rise.

OM: You learned about better patient selection with the delay?

DM: Absolutely. Now, doctors are more aware — they have a standard protocol — they can try a short-acting steroid to see if the patient does develop an elevated IOP. If not, then it begs the question why one would use a short-acting pulse therapy for a persistent disease like DME. We are selecting the right patient, and we are managing the IOP side effect in the small number of patients who experience IOP.

OM: What have you learned about the role of Iluvien?

DM: First, even though the approval took four years, (the FAME trial began in 2005), it was a good outcome because the indication does not preclude Iluvien from being used first line. Across the United States, doctors are still using anti-VEGF first. However, Protocol T has shown us that, depending on the arm, between 37% and 56% of patients required rescue therapy. We have learned that DME is a multifactorial disease that could require more than just anti-VEGF. Iluvien can be an adjunctive or combination therapy. With the early analysis of Protocol I, we have also learned that after three injections you know who the responders and non-responders are. Why keep patients on constant injections if they are not responding? There might be more to learn here.

OM: How did the idea of an implant come about?

DM: I started Alimera in 2003. We initially thought we would focus on the anterior segment. But we had tremendous success in our first two rounds of raising financing; we raised $57 million. At the same time, pSivida management had this control delivery system we now know as Iluvien, and it was looking for a development partner. I knew there were a lot of retinal diseases with unmet needs, and we had this capital looking to be deployed. They had the confidence that we had the experience with Novartis to get the device through the FDA and launch it commercially. We saw long-term value in the treatment. This wasn’t something to write into a business plan with a five-year strategy. You know it when you see it. If anything we were fortunate enough to see a unique opportunity.

OM: And the future of Alimera?

DM: In the immediate future, I think we have two key initiatives. First, we are seeing a strong effect of peer to peer meetings. We want to facilitate meetings where doctors who have had significant experience with Iluvien, here or in the EU, to share their case studies and outcomes. When you are changing a treatment paradigm, it requires more than just a sales person or a marketing campaign. Hearing doctors share their patient’s experience moving from a constant regimen of injections to Iluvien’s is powerful. Secondly, many patients and caregivers do not know that there is an alternative to frequent anti-VEGF injections. Patient education is a key.

Long term, we think additional indications are possible. We have had productive meetings with the FDA, and we want to begin studies for those indications.

Finally, there are 13 EU countries where we have marketing authorization but we have not launched commercially. I think you will see us expand our EU footprint in the coming months. OM