Advancing Ocular Health
Advancing Ocular Health
Episode 1

Alleviate with ZERVIATE™ – First New Molecule for Allergic Conjunctivitis in Over 10 Years!

In the first installment, Ranjan P. Malhotra, MD, FACS, and Eric T. Brooker, OD, FAAO, discuss safety and phase 3 data of ZERVIATE™, the first topical ocular formulation of cetirizine. ZERVIATE™ formulated with Hydrella is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Please see the Full Prescribing Information.

Intro Voiceover: Welcome to the first episode of Advancing Ocular Health, a podcast mini-series in which ophthalmologists and optometrists discuss the latest innovations in eye care pharmaceuticals. Today, Dr. Ranjan P. Malhotra from Ophthalmology Associates in St. Louis, and Dr. Eric T. Brooker from the Advanced Vision Institute in Las Vegas, discuss the safety and efficacy of ZERVIATE, the first new molecule for allergic conjunctivitis in over 10 years. Let’s get started.

Dr. Brooker: Hi, I'm Dr. Brooker from Las Vegas, and I'm here with Dr. Malhotra from St. Louis. Welcome Dr. Malhotra.

Dr. Malhotra: Thank you, Dr. Brooker.

Dr. Brooker: Well, we're really excited to be here today to talk about a brand-new product from a company called Eyevance, for allergic conjunctivitis known as ZERVIATE, which they were able to isolate the molecule from a product that's been used for, for several years in Zyrtec. And off of that, an ophthalmic solution. Uh, Dr. Malhotra, have you had a chance to use this in your practice?

Dr. Malhotra: I have. Um, I started using it uh, soon after it was released. Um, and I've been very familiar with products, other products from Eyevance uh, because they're very prominent in anterior segment including TobraDex ST and Flarex. But I was very happy when uh, ZERVIATE came out and I'm excited to talk about it.

Dr. Brooker: That's good. We've had the same experience in our practice as well. Eyevance, although they're a new company, all of their product offerings are very high quality and we've had great patient outcomes with all of them. Um, not just clinically on our end, but patients reporting improvements in their symptoms uh, and they come back happy. And uh, that's the most important thing for us.

Dr. Brooker: Here, in Las Vegas uh, we've had a really high resurgence recently of allergic conjunctivitis, so we've had a really nice opportunity to test out ZERVIATE. Um, how're things out in St. Louis? Have you had a lot of uh, cases similar?

Dr. Malhotra: Yeah. We've seen a lot of allergic conjunctivitis cases uh, since it's big allergy season right now. Uh, we saw a lot during our telemedicine during the shutdown. And then especially after opening up about a month ago, we're continuing to see a big resurgence of ocular allergies.

Dr. Brooker: Absolutely. And, and, and in fact we understand that almost 40% of patients in North America actually suffer from some form of allergic conjunctivitis, and allergic conjunctivitis just happens to be the most common conjunctivitis that, that optometrists and ophthalmologists see and encounter in their practices. Interesting enough, interestingly enough, uh, 30% to 70% of patients that have allergic rhinitis also uh, suffer from allergic conjunctivitis, but we've been finding that a lot of those patients go undiagnosed and sometimes untreated. Have you noticed that as well?

Dr. Malhotra: Yeah. I, I definitely have noticed that. And sometimes patients come in and, you know, they usually could self um, diagnose their allergic rhinitis, but sometimes they don't realize that their ocular surface symptoms are related to allergies. They may think it's dry eye or other conditions. And so, um, so coming in for the diagnosis, we're educating them on it's really allergic rhinitis. So, I agree, it is definitely under-, under-diagnosed and even undertreated.

Dr. Brooker: Yeah. And the interesting impact, and I saw a study on this in The Journal of Allergy and Immunology, is that many patients uh, report that it really has an adverse effect on their quality of life, whether that's them not being able to be as efficient at work or enjoy the activities that they do most commonly. Um, when you're using it with your patients, how often are you recommending the dosing of the medication for ZERVIATE?

Dr. Malhotra: Um, so I'm, I'm recommending it uh, twice a day, you know, on label using it morning and evening. Um, you know, and many times patients will ask me, “Do I need to use this year-round, or?” You know, and then I tell them they could use it as needed after ... Once they ... Once their symptoms improve.

Dr. Brooker: Oh, that's excellent.

Dr. Malhotra: I’ll say, as you know Dr. Brooker, there's been a lot of treatment options for allergies out there, um, and some of them, you know, even though um, they work, um, there's been some side effects that patients complain about including dysgeusia or an altered taste from using them. And sometimes it exacerbates some of their ocular surface problems and makes their dry eye worse, so I was really excited with ZERVIATE coming out because it addresses these issues without having many of those side effects.

Dr. Brooker: Absolutely. And I noticed the comfort level with ZERVIATE is much better compared to some of the more recent uh, allergy eyedrops that have come into the marketplace that do cause a lot of stinging. And I've found that patients have a hard time uh, committing themselves to using a drop if they don't find comfort on initial application as well.

Dr. Malhotra: Yeah. And as you mentioned just earlier that ZERVIATE is the first ocular formulation of cetirizine, which is a common oral antihistamine, one of the most common oral antihistamines prescribed by allergists. And most patients are familiar with uh, it as Zyrtec. Um, it is one of the first new topical ophthalmic antihistamines released in the last 10 years.

Dr. Malhotra: And um, I've definitely had um, you know, when I bring it up to patients and ask them um, if they're ... As I diagnose them with ocular allergies, and I um, ask them, “What's ... Are you using anything for your allergies right now?” And they commonly say Zyrtec, but they, they say, “Gosh, with Zyrtec I sometimes get sleepy from it, so I don't like taking it.” And when I tell them, “Look, you can use it now as an eye drop,” they're excited to be able to use an eye drop uh, and not have the side effects of causing any drowsiness with it.

Dr. Brooker: Yeah. That's, that's exactly been my experience as well. You don't get ... because it's an H1 receptor antagonist, we see that it uh, quenches ocular itching, which is one of the on-labels for the FDA approval. And because it's an H1 receptor antagonist, it's selective, and we found it also helps stabilize the mast cells because it's preventing histamine uh, from bonding back onto mast cells and re-stimulating uh, this allergic type reaction and degranulation of the mast cells. Um, it's similar to some other products that are out there. It has the same effect of mast cell stabilization, as well as the selective uh, H1 receptor antagonist.

Dr. Malhotra: Yeah. Like you said, as a compound, cetirizine is known to be a very potent H1 receptor antagonist, and it's also known to be a mast cell stabilizer. Um, but one really positive effect is that it doesn't have any effects on the muscarinic receptors, because a lot of antihistamines are really potent muscarinic antagonists. And uh, cetirizine or Zyrtec or ZERVIATE isn't a muscarinic antagonist, and so because of this, this anti-muscarinic activity is not really uh, desirable uh, because it causes a lot of drying effects, especially on the ocular surface. So, the fact that it's a very potent H1 antagonist and it has no effect on the muscarinic receptors, is a big advantage to cetirizine or ZERVIATE.

Dr. Brooker: Absolutely. And I think we've seen that in practice. And I've had some patients that have come in on um, all these other selective uh, H1 antagonists in oral forms and they're suffering from dryness and they still have the conjunctivitis as well. And in some cases, I've actually taken them off the oral medications and just put them on the topical cetirizine. And sometimes we end up adding in another um, like a spray, a nasal spray, but those tend to be very, very effective. So, I think what, you know, the label that ... And the things that they're telling us from my Eyevance of how this medication works, I fully agree that it's a very effective treatment.

Ad Voiceover: Our program will continue after a short break.

Ad Voiceover: This podcast is brought to you by Eyevance Pharmaceuticals. At Eyevance, we are Advancing Ocular Health by investing in vision through ophthalmic therapies. Our mission is to ensure optimal vision and better quality of life for all patients. To learn more, visit Eyevance.com. That’s E-Y-E-V-A-N-C-E dot com.

Dr. Malhotra: So Dr. Brooker, I'm sure you're familiar with the phase three trials um, in uh, for ZERVIATE. And as you know, any allergy medication that's approved in the United States, the gold standard for studying these and approving these in the U.S. is doing a Conjunctival Antigen Challenge model. And uh, we're involved in a lot of FDA trials in our practice. And uh, when I first started in our practice 20 years ago, being the little man on the totem pole, I was there on Saturdays doing these Conjunctival Antigen Challenges.

Dr. Malhotra: And um, one thing I learned is that uh, patients will do almost anything for money, because they'd get paid to be in these studies and after I saw what these patients sometimes had to go through, um, we would, if you're familiar with this, we would actually do skin testing to see if they're allergic to uh, to what we're testing. And then once we found out what they're most allergic to, we would actually with a pipette put it in their eyes and challenge them.

Dr. Malhotra: And then in these studies, they'd either be randomized the vehicle or the drug, and then once we found out what they're allergic to, prove that they reacted to it in their eyes, we'd actually basically with a pipette put it at a titration in their eye and 15 minutes later start evaluating whether they uh, how they're reacting, or even as soon as three minutes later, how they're ... How the vehicle and the drug is uh, working against this patient that's being challenged with what they're allergic to.

Dr. Malhotra: And we even put, we ... Some of the worst allergies we saw was to cats and grasses, and that we were actually putting cat dander or grasses straight in their eyes. So, when I saw patients go through this, I thought, “Oh my gosh.” You know, these patients are getting paid. I don't know if it's worth the five hundred dollars they're getting paid to be in these studies.

Dr. Malhotra: But, then when ZERVIATE came out, we were actually involved in these studies, so we looked at uh, and they even segregated these trials through moderate patients and severe patients with allergies. And uh, so what patients were done is they were ... Once they were proved they were allergic to what they're allergic to on the skin testing and even on conjunctival testing, then patients were randomized either through vehicle or to ZERVIATE and um, 15 minutes after they were uh, exposed to the drug or given the drug, then they were challenged. And they were challenged with uh, the antigen. And then immediately in the ZERVIATE group, we started seeing results that were statistically significant where they had less itching compared to vehicle. So, we saw an onset of action in just three minutes after the challenge.

Dr. Brooker: Wow.

Dr. Malhotra: And then, we also looked at patients to look at duration of action to see how long the drug was working, so we would give them the drug and then eight hours later, challenge them. And then again, three minutes after the challenge we started seeing a statistical, significant improvement and less itching in the patients that got ZERVIATE versus the vehicle. So, I learned early on in my career, because we do like St. Louis is a hotbed for allergies, that uh, how these studies like ... So, when you see a drug that's approved for allergies, uh, you see they have to go through this challenge model to prove that it actually works.

Dr. Brooker: Well Dr. Malhotra, the studies you presented are really uh, profound in that it looks like Eyevance really did their due diligence here in these studies. And that the medication really helped patients with their, with their allergies and most notably, the ocular itching in both the studies, and not only the moderate, but the severe cases.

Dr. Brooker: The statistics that you mentioned are based on them having the drops and then 15 minutes later having the allergies induced into their eyes and seeing how, how much they responded to it. And one thing that I noted that you said, is that they still had um, less uh, less itching even after they had taken the drop eight hours ago, and then you put allergens into their eye. Is that correct?

Dr. Malhotra: That's absolutely correct. So that, that ... They had to do that to prove the duration of action. That's why it did get a BID indication, uh, because it lasted eight hours. So eight hours after giving them the medication, and one thing like I said, and these poor patients that got vehicle, it was obvious because, you know, once you put some, put this antigen in a patient that didn't get anything, uh, they needed to be rescued. So, you know, so um, and usually these patients did pretty miserable, the patients that got vehicle, but um, but you could see a marked difference between the vehicle patients and the drug patients. And of course, as investigators, we're masked as to what the patient's getting.

Dr. Malhotra: We know a lot of uh, allergy patients have concomitant, as a comorbid condition uh, dry eye. So, having antihistamine, you now, mast cell stabilizing drug like cetirizine um, in addition to having a lubricant like an artificial tear with some, two good artificial tear components mixed in one drop is very synergistic.

Dr. Malhotra: So I think that's why it really leads to a lot of the safety and a lot of the uh, comfort of this drug. And looking at the FDA trial results, if you look at any of the adverse events that's listed on label, uh, the ocular hyperemia was similar between the drug group and the vehicle group, which was at 6.7%. Um, the installation site pain was very low at 3.6% on the ZERVIATE group versus 0.9% in the vehicle group. And uh, really there was uh, very little, no visual acuity loss, which was actually less than cetirizine group or the ZERVIATE group versus 2.1% in the vehicle group.

Dr. Malhotra: So, one big differentiating factor is in all the patients in the FDA trial, of all the 511 patients that were on the treatment of cetirizine or ZERVIATE, only one patient reported a dry eye event, which is a really low percent.

Dr. Malhotra: So it was a very well tolerated drug. And no patients, I was going to point out, complained of any dysgeusia. So, there was not any altered taste uh, like we see with some of the other products that are out there.

Dr. Brooker: Yeah, that's excellent. And I noticed that some of the patients that were enrolled in the study were, you know, two years old, two-year-olds. Um, so young, young patients and, and I think that's excellent that we know that it's safe to use in children because many children do have a lot of allergic conjunctivitis and allergic symptoms.

Dr. Malhotra: Right. And since this was a topical uh, drop, you know, not, it had very low systemic absorption, and so that way the patients, not only ... they didn't get any dysgeusia, no altered taste, but they didn't get any of the drowsiness that patients sometimes report with taking oral Zyrtec.

Dr. Brooker: That's excellent.

Ad Voiceover: Our program will continue after a short break.

Ad Voiceover: This podcast is brought to you by Eyevance Pharmaceuticals. At Eyevance, we are Advancing Ocular Health by investing in vision through ophthalmic therapies. Our mission is to ensure optimal vision and better quality of life for all patients. To learn more, visit Eyevance.com. That’s E-Y-E-V-A-N-C-E dot com.

Dr. Malhotra: So one big advantage of using ZERVIATE, is it’s very comfortable for our patients. And one unique feature of ZERVIATE, it has a component called Hydrella, which is a combination of glycerin and hydroxypropyl methylcellulose or HPMC, which are both two components found in many lubricant drops or artificial tears. Um, and this also, it's a very comfortable drop because it has a neutral page of 7.0.

Dr. Malhotra: And that makes it comfortable because a lot of children have allergies, it's safe in children in ages two and older. And so, obviously children don't like drops that sting, so this is a comfortable drop. It lubricates because a lot of patients that have uh, allergies can have concomitant dry eye, and this is a drop since it has a built-in glycerin and HPMC. Um, have you had a lot of uh, good experience with this also, Dr. Brooker?

Dr. Brooker: You know, absolutely. And I think, when I first started using it, um, I was very delighted to see how many patients came back and told me that their eyes felt much more comfortable. They had less itching. Um, and they just overall felt better. So, the compliance was very high uh, using this medication.

Dr. Brooker: And when I look back it made me curious, so I went back and looked at some of the studies, some of which you've mentioned, and I saw that um, in the studies, when patients used this, that they reported very good comfort scores. On a scale of one to 10, all patients were almost close to zero. They were between zero and one in their comfort score, which is telling us that, you know, patients in the studies also found the drop very, very comfortable. And that's what we've seen in the, in the real world um, in our clinic. What about with you?

Dr. Malhotra: Um, I've had a great um, a great experience with using it with patients. Patients, um, I haven't had patients complain of any altered taste like I've had with some of the other products that I've used. There's not any excessive sleepiness that patients uh, have complained about with even using oral medications. Um, and the other advantage that I like using with ZERVIATE is that it comes in individual single-use vials, which patients like because it's convenient to take uh, if they're using it uh, at work or if they're traveling. They have these vials individually ... They're used to using individual preservative-free uh, dry eye medications, but they like using these vials cause they're used to using them, just like their artificial tears.

Dr. Brooker: Right. And it, it, it ... That's been great. And because there is a lot of experience with uh, Zyrtec out on the market, which is the number one allergist recommended brand over the counter, uh, selective oral antihistamine, patients understand that they're, they're anxious to try it and the nice thing about that is that Eyevance has really been committed to stepping up and helping patients have access through their um, access program for patients. And we've been able to get patients copay cards and using different pharmacies, the most patients are paying is forty-five dollars. And so, uh, have you had good success with that out in St. Louis?

Dr. Malhotra: I have. And you know, and I know in the past a lot of allergy medicines aren't covered by insurance. They're, they're pretty much forced to use over the counters that don't work as well. And so, because of this copay card, it works with private insurances and it also works even in Medicare patients. And the patients are assured to pay no more than forty-five dollars for this product, which is really reasonable uh, for a product with this uh, with all these advantages.

Dr. Malhotra: And the other advantage being it has a really rapid onset of action as early as three minutes uh, after being exposed to something the patient's allergic to. And having a long duration of action, at least up to eight hours, uh, based on the FDA trials. And um, on top of that, it has the advantage of not exacerbating any type of dry eye because it has a low uh, incidence of dry eye side effects based on only one patient out of 511 patients in the trial have been reporting any type of dry eye.

Dr. Brooker: Yeah, I think that's why it's fit in so well in our, in our dry eye practice here in Las Vegas because we do have a lot of allergic patients as well uh, that suffer from allergic conjunctivitis. And I'm really excited about this new formulation, the Hydrella, that you mentioned earlier. Um, and I think that that has been part of our success with the medication, because patients have felt so comfortable with it. And I guess that correlates with the studies that we've seen. Um, and because that probably has to do with the, the, the vehicle that you mentioned, which HPMC and glycerin, that's known as Hydrella. Um, we didn't mention too much about the PH. What did you think about the PH of this medication?

Dr. Malhotra: Yeah. It's a ... It's a very neutral PH. And so that's why I think that also leads to the comfort. So not only the Hydrella like you mentioned, but the actual neutral PH makes it comfortable. And again, it's approved uh, in children two and older so that's also a big advantage that you have a comfortable drop that's approved in kids. And again, it comes in these individual single-use vials, which is the only allergy product available in these single-use vials. So, I think I'm excited about that, also.

Dr. Brooker: Yeah. And we've seen that exactly in our practice, we actually dose patients uh, when they're in the office. And we've seen that they've had a great response uh, quickly even within just a few minutes. Um, and they leave our office happy. (laughs) That's great. Well, thanks Dr. Malhotra, I'm glad we had the time to uh, get together and talk about ZERVIATE and Eyevance and um, the opportunities for optometry and ophthalmology uh, for treating allergic conjunctivitis.

Dr. Malhotra: Yeah. Thank you, Dr. Brooker. So, hope to maybe see you soon in Las Vegas sometime.

Dr. Brooker: That sounds good.

Outro Voiceover: Thank you for joining us on this episode of Advancing Ocular Health. Subscribe to the podcast on Apple Podcasts or wherever you stream your content. If you enjoyed the experience, leave us a review. Join us next episode when we’ll discuss the latest innovations in ocular steroids by focusing on TobraDex ST.

7/16/2020 | 22:48

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INDICATIONS AND USAGE

ZERVIATE™ (cetirizine ophthalmic solution) 0.24% is a histamine-1 (H1) receptor antagonist indicated for treatment of ocular itching associated with allergic conjunctivitis.

DOSAGE AND ADMINISTRATION
Instill one drop of ZERVIATE in each affected eye twice daily (approximately 8 hours apart).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Contamination of Tip and Solution: As with any eye drop, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle or tip of the single-use container to avoid injury to the eye and to prevent contaminating the tip and solution. Keep the multi-dose bottle closed when not in use. Discard the single-use container after using in each eye.

Contact Lens Wear: Patients should be advised not to wear a contact lens if their eye is red. ZERVIATE should not be instilled while wearing contact lenses. Remove contact lenses prior to instillation of ZERVIATE. The preservative in ZERVIATE, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted 10 minutes following administration of ZERVIATE.

ADVERSE REACTIONS

The most commonly reported adverse reactions occurred in approximately 1%–7% of patients treated with either ZERVIATE or vehicle. These reactions were ocular hyperemia, instillation site pain, and visual acuity reduced.

Please see the Full Prescribing Information.

ZER-20-WB-67-00


INDICATIONS AND USAGE

For steroid responsive inflammatory ocular conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe and chronic anterior uveitis, corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies for which a corticosteroid is indicated and where the risk of superficial bacterial ocular infection is high or where there is an expectation that potentially dangerous numbers of bacteria will be present in the eye.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

Most viral disease of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal disease of ocular structures. Hypersensitivity to any components of the medication.

WARNINGS & PRECAUTIONS:

  • IOP increase – Prolonged use may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. IOP should be monitored.
  • Aminoglycoside sensitivity – Sensitivity to topically applied aminoglycosides may occur.
  • Cataracts – Posterior subcapsular cataract formation may occur.
  • Delayed healing – May delay healing and increase the incidence of bleb formation. Perforations of the cornea or sclera have occurred. Slit lamp biomicroscopy, and fluorescein staining should be conducted.
  • Bacterial infections – May suppress host response and increase secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated.
  • Viral infections – Use with history of herpes simplex requires great caution. The course and severity of many viral infections of the eye (including herpes simplex) may be exacerbated.
  • Fungal infections – Fungal infections of the cornea may occur and should be considered in any persistent corneal ulceration.
  • Use with systemic aminoglycosides – Total serum concentration of tobramycin should be monitored.

ADVERSE REACTIONS:

The most frequent adverse reactions (<4%) to topical ocular tobramycin are hypersensitivity and localized ocular toxicity, including eye pain, eyelid pruritus, eyelid edema, and conjunctival hyperemia.

The reactions due to the steroid component are increased intraocular pressure with possible development of glaucoma, and infrequent optic nerve disorder; subcapsular cataract; and impaired healing.

The development of secondary infection has occurred. Fungal infections of the cornea may occur. Secondary bacterial ocular infection following suppression of host responses also occurs.

Non-ocular adverse events (0.5% to 1%) included headache and increased blood pressure.

TST-20-WB-18-00