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Potential presbyopia treatment coming
Gretchyn Bailey, NCLC, FAAO: I am Gretchyn Bailey with Optometry Times® and today I have the pleasure of speaking with Michael Robinson from Allergan. He is global therapeutic area head of ophthalmology. Michael, thank you so much for joining me today.
Michael Robinson, MD: Thank you very much for the invite.
Bailey: Well, you have some exciting news happening there in your neck of the woods. There has been a new drug submission for AGN-19584, which is a mouthful, for the presbyopia or reading drops. Can you tell me a little bit about how this came about and what the next steps are?
Allergan’s new presbyopia drop
Dr. Robinson: Yeah, absolutely. Let me first start with some background on the condition that the new eyedrop is treating. That is presbyopia and, in general, presbyopia starts after the age of 40 and results from a gradual stiffening of the lens in the eye. So, people have difficulty focusing on near objects or intermediate distance objects such as a laptop computer. Presbyopic symptoms can significantly disrupt a lot of routine, everyday activities such as reading, looking at a smartphone, and cooking. Those who have presbyopia know what I am talking about.
While individuals currently have a number of different options to help manage this, including glasses, contact lenses, and even surgery of the eye, we have done market research which has shown that the majority of presbyopic individuals are frustrated with the use of contact lenses and glasses. They are inconvenient, and the vision quality is not quite ideal. So, we see a significant opportunity for therapeutic eyedrops to be a first-line treatment, especially for newly diagnosed, mild-to-moderate presbyopic patients, or as an adjunct to reading glasses for those who desire more flexibility and convenience.
For example, laser-assisted in situ keratomileusis (LASIK) patients, or those who wear contact lenses, would be especially interested in the eye drop, in order to stay glasses-free as they get into their 40s and are having difficulty reading. We have a development at Allegan, now, AbbVie, a new formulation of pilocarpine eyedrops, which is currently an investigational treatment for presbyopia. We met the primary endpoint in 2 pivotal phase 3 studies involving 750 patients. And we submitted a new drug application to the FDA last week. We expect that they will act on this by the by the end of the year.
Bailey: A couple of quick questions. You mentioned that this drug would be appropriate for emerging presbyopes, mild to moderate. Do you have a power range there like from going from a +0.50 D to a +1.00 D? Anybody over +2.00 D? Maybe not?
Dr. Robinson: The results with theeyedropp show there can be an improvement of vision. We enrolled patients who had visual acuity between 20/40 and 20/100. These are for the mild-to-moderate presbyopes. What we found is that the majority of patients after they have put in the eye drop can see 20/40 or better. So, 20/40 is Jaeger 3; it is very similar to very fine print, like newspaper print. In a starting range between 20/40 to 20/100, a majority of patients are able to read newspaper print, just to give you an example of what they would be able to do.
Bailey: Sure. You also mentioned that this therapy might be appropriate for post-LASIK patients. Did you include post-LASIK patients in your study?
Dr. Robinson: Yes, we did. We included post-LASIK. Two-thirds of the patients were actually emmetropes. One-third were not emmetropes. So, we wanted to have a balance of patients. We tested 40 to 55 years of age, 20/40 to 20/100 vision, including patients who have had prior refractive surgery. So, we did include those in the clinical trial to be somewhat representative of the population here. It was a US-based study.
Bailey: Gotcha. Well, let's talk a little bit about how this drop works and what patients should expect in terms of lasting effects.
Dr. Robinson: Sure, so the mechanism of action of the eyedropper is interesting. The mechanism of the eyedrop goes through what we call dynamic pupil modulation. It is an effect in which the iris sphincter is contracted to achieve a pupil-sized reduction in an optimal range. We determined this optimal range through phase 2 studies. We have been at this for a number of years, developing our reading eyedrops.
The goal of this pupil size reduction is to increase the depth of focus, so that without wearing glasses you have a greater range of uninterrupted near and intermediate vision. This is similar to adjusting the aperture size of a camera. A large F stop number, say an F 16, results in a smaller, narrower aperture size, and therefore a deeper depth of field. That is basically how it works—through a pinhole effect that we call dynamic pupil modulation. And if it is too small, it might affect the distance vision. The FDA is concerned about that. So, part of the regulatory approval required for efficacy would be at least a 3-line gain in visual acuity and also no more than 1 line loss of distance vision. So that is how the eyedrop works.
Bailey: So let’s talk about how optometrists might be involved in prescribing this drop. Do you see this drop being targeted mainly to ophthalmologist, or do you see optometry playing a role as well?
Dr. Robinson: Yeah, that is a very good question. There are about 128 million presbyopes in the United States, and about 60 million are between 40 to 55 years of age who are in a mild-to-moderate category. That population is quite large. Every 5 years, we are adding 10 million patients over age 42 to the U.S. population, so every year you have more patients who are afflicted with presbyopia. Some 70% of mild-to-moderate presbyopes are already being treated by optometry. If approved, this is expected to be the first eyedrop to treat presbyopia and may be an alternative or compliment to glasses and contact lenses for loss of near vision and a non-surgical option.
A drop would be an ideal treatment to bring more patients into the optometry offices. Patients frequently go to optometrists for their refraction and eyeglass needs. But this is a way of bringing more traffic into the office. Once they get into the office, then they can also be treated for their other eye conditions, if they have any. It is better than a patient going to the drugstore and just trying out reading glasses and never having an eye exam. It really could be a gateway product to better eye health.
Bailey: Absolutely. And you mentioned an interesting point that if approved, this drug would be the first therapy for presbyopia. That is pretty significant.
Dr. Robinson: Right. The first medical therapy for presbyopia. Yeah, that is significant. We are very happy to be the first to submit a new drug application (NDA). Obviously, it has to be approved. Nevertheless, it would be the first therapy, medical therapy, available to treat presbyopia.
Bailey: Do you have any suggestions on how doctors should start positioning this potential new therapy to their patients? If they come in asking questions, wondering how it works, how long it will last? “Am I a good candidate?” What should doctors be telling their patients who are asking?
Dr. Robinson: Right, so, from our internal patient journey research—and we have done quite a bit of this—currently 80% of conversations about presbyopia are initiated by patients, so it is important to spend time with patients to discuss their conditions. It is also suggested to introduce the term presbyopia because, compared to other eye-related conditions, there is a much lower awareness of presbyopia by name, and the eyedrops will be referred to the treatment of presbyopia. So, it is important to link the two.
Consider asking the patient about how the condition is affecting their day-to-day activities so they can get a better idea of the best treatment option to fit their needs. For example, store-bought readers provide a single focal plane to read. So, moving material closer or farther away causes the reading material to become blurry. Progressive lenses allow a greater range of near vision. This is limited by a narrow field of vision, especially at intermediate distances. With the mechanism of action of closing the pupil down—reduction—then you are able to get a better depth of focus and a better range of visual acuity. Depending on a patient’s needs, and how their daily activities at near intermediate are affected, the doctor can make suggestions such as, ”You need glasses.” Plus, patients can intermittently use the reading eyedrop, or a reading eyedrop would be sufficient for your needs at this point. I think it is very important for optometrists to be familiar with the eyedrop, assuming it becomes approved.
Bailey: What is the dosing regimen?
Dr. Robinson: Initially, what we used in the clinical trial is once a day, and once a day will give you an onset of near vision improvement that starts at around 15 minutes. We measured the visual acuity in the clinic ,and it would last 6 to 8 hours. Now, we have also been planning a clinical trial looking at twice a day because if it lasts 6 to 8 hours in patients, they may want to have a longer duration. For those patients, it would be used potentially twice a day. Those clinical trialsare currently in planning.
Bailey: It all sounds very exciting, and I can’t wait to hear more, especially about this twice-daily dosing. If we are looking at a timeframe, you said that you anticipate the FDA getting back to you on this approval by the end of 2021. If we assume that that is an approval, when do you think patients could have these drops in their hands?
Dr. Robinson: You know, theoretically, if the approval is in December, the launch would be at the end of December, or January, February of next year. So, it would be very soon after the PDUFA [Prescription Drug User Fee Act]date, which is10 months from last week, when we submitted the NDA. And as you know, the FDA is very particular on meeting these timelines. We look forward to the FDA’s review, and we will work with them for whatever other information is required for the application.
Bailey: So, if all the stars align, it could be in about a year from now we would have the eyedrop available on the market for patients to use.
Dr. Robinson: That is correct. It would be a prescription product that you would have to go to the optometrist’s office or the ophthalmologist’s office for. I see that the optometrist will have a very big role with this. And just because they see these patients, ophthalmologists’focus is surgery, treating other medical conditions. This would definitely fall into the realm of the optometry practice. We certainly look forward to working with optometrists to help introduce this product into their practices.
Bailey: Well, this is all very exciting news. And we will stay tuned to see what is coming and in 10 months we will find out. So, thank you very much for joining me today, Michael. And we will stay tuned to hear more. Thank you.
Dr. Robinson: Thanks very much, Gretchyn. I appreciate the invitation.