The Dry Eye

On the horizon and over the rainbow

There is a lot of new stuff to look forward to in the treatment of dry eye disease.

Every time I think about “new and improved,” I think back to two of the biggest busts in the history of consumer goods, New Coke and New Tide. Both were indeed new, and New Tide was also advertised as “improved.” Said so right on the box/bottle. We all know how the New Coke story played out. Microscopic sales and universal ridicule led to a plummeting stock price and the eventual capitulation and removal from the market. New Tide may have been “improved” in the lab, but out in the wild all it turned out to be was more expensive. I think we can lay the “blame” for the rise of private label cleaners at the foot of New Tide.

Lesson: Sometimes you need to leave a good thing alone.

In our dry eye disease world, there has really not been anything that is truly new since the introduction of lifitegrast, now Xiidra (Takeda). One could make a case that even this was not so much new as it was different; ever since Bausch + Lomb dropkicked Lotemax (loteprednol etabonate) as a DED medicine in the ’90s and opened the door for Allergan and Restasis (cyclosporine ophthalmic emulsion 0.05%), DED meds have simply been a race to find the next anti-inflammatory drop. Much of what goes by “new” in the pharma world of DED care is more like adding angels to the head of the same pin. There is plenty of room on the pin, but it is awfully hard to stand out in that crowd.

Our nearest future looks like it will bring us a truly new vehicle to transport our old friend cyclosporine A (CsA) to the ocular surface. Cequa (Sun Pharma), with its micelle encapsulation that promises to deliver CsA in a highly effective manner, should see the light of the commercial day sometime later this year. We have spoken often about the imminent arrival of a “generic Restasis” from the likes of Mylan and Teva for more than a year. What does that mean, anyway? Unlike latanoprost, which seemingly can be delivered in any liquid that is less toxic than kerosene, CsA is really tough to carry to and through the outer layers of the ocular surface. There is no such thing as generic Restasis (unless Allergan sells or licenses its vehicle). What may be new is price competition for topical CsA, which like Tide would be the improvement.

Looking on from outside the kitchen, I am always curious as to why the “chef” chooses a particular ingredient and “dose.” Both B+L and Kala will likely debut products with an old ingredient (loteprednol) delivered in a new form (new and unique delivery systems). Kala will try to get the same amount of flavor (effect) by using less drug, treating acute symptomatic DED with low-dose steroid. B+L will reformulate its classic Lotemax (Alrex). Will it seek to return superficial punctate keratitis to the label? Even though there is nothing new about using topical steroids for DED, having that indication on the label would be new and improved. The chefs at Ocugen are in the DED kitchen, too, using a glaucoma medicine (0.2% brimonidine tartrate) to treat symptoms. Their results show an impressive reduction in SANDE score with a rapid onset of action.

While they do not necessarily constitute a new approach, there certainly is a bunch of new stuff in the device side of the DED world. 2019 brings us the approval and launch of iLux. On top of that, iLux brings Alcon into the DED arena (welcome to the Thunderdome, Adam!). Apparently, the patents protecting the LipiFlow (Johnson & Johnson Vision) intellectual property were not secure enough to keep another posterior thermal treatment off the market. iLux will bring more doctors and non-DED specialty centers into the arena of meibomian gland dysfunction, as will TearCare from Sight Sciences for the simple reason that the acquisition costs are low. In my opinion, each of these is inferior to LipiFlow, but their entry into the market must surely have influenced the J&J decision to lower the LipiFlow activator price to $100.

If you are looking for truly new stuff in the treatment of DED, pharma is where you need to look. At the moment, there are no drugs whose FDA approval is imminent, but a look just a tad deeper in the pipeline of several companies reveals some treasures. With more drugs coming before it, the FDA has become rather consistent in what it is asking of those medications. In order to be approved, meds must demonstrate an effect on both signs and symptoms of DED, and they must be at least as well tolerated as Restasis.

Three unique molecules from three new, smallish developmental companies are on track to at least see the finish line. CyclASol from Novaliq is a calcineurin inhibitor, a new class of medicine for the ocular surface. In its most recent phase 2/3 study, it met a primary endpoint for inferior corneal staining and secondary symptom endpoints. BRM421 (Brim Biotechnology) has a novel neurotrophic mechanism of action (MOA). Its most impressive finding thus far was a reduction in burning and dryness symptoms at the 2-week mark, and it appears to be effective in severe DED. RGN-259 (RegeneRx) was likewise found to be effective in reducing both signs and symptoms in a phase 2 trial. Word is that the company will launch a phase 3 trial with 700 subjects very soon.

All three of these have a new MOA that attacks a heretofore unaddressed target on the ocular surface. For something truly new, we have to leave the surface of the eye and once again follow Michael Ackermann into the nose. You remember him, right? He is the guy who brought us the treatment of DED with electrostimulation of the oculomotor nerve in the nose with TrueTear (Allergan). His new company, Oyster Point Pharma, is studying two nasal sprays to treat DED. In their respective phase 2 trials, intranasal application of both OC-01 and OC-02 produced an extraordinary increase in Schirmer scores (P < .001 compared with placebo for OC-01 0.1%). DED symptoms were also significantly reduced (P < .05) for OC-01. You have to hand it to Mr. Ackermann; he certainly seems to have — wait for it — a nose for treating DED.

After decades as the red-haired stepchild of eye care, DED continues to be one of the most dynamic development spaces in all of medicine. We have new, and we have improved. No unicorns as of yet, but there do appear to be quite a few rainbows out there.

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.

Every time I think about “new and improved,” I think back to two of the biggest busts in the history of consumer goods, New Coke and New Tide. Both were indeed new, and New Tide was also advertised as “improved.” Said so right on the box/bottle. We all know how the New Coke story played out. Microscopic sales and universal ridicule led to a plummeting stock price and the eventual capitulation and removal from the market. New Tide may have been “improved” in the lab, but out in the wild all it turned out to be was more expensive. I think we can lay the “blame” for the rise of private label cleaners at the foot of New Tide.

Lesson: Sometimes you need to leave a good thing alone.

In our dry eye disease world, there has really not been anything that is truly new since the introduction of lifitegrast, now Xiidra (Takeda). One could make a case that even this was not so much new as it was different; ever since Bausch + Lomb dropkicked Lotemax (loteprednol etabonate) as a DED medicine in the ’90s and opened the door for Allergan and Restasis (cyclosporine ophthalmic emulsion 0.05%), DED meds have simply been a race to find the next anti-inflammatory drop. Much of what goes by “new” in the pharma world of DED care is more like adding angels to the head of the same pin. There is plenty of room on the pin, but it is awfully hard to stand out in that crowd.

Our nearest future looks like it will bring us a truly new vehicle to transport our old friend cyclosporine A (CsA) to the ocular surface. Cequa (Sun Pharma), with its micelle encapsulation that promises to deliver CsA in a highly effective manner, should see the light of the commercial day sometime later this year. We have spoken often about the imminent arrival of a “generic Restasis” from the likes of Mylan and Teva for more than a year. What does that mean, anyway? Unlike latanoprost, which seemingly can be delivered in any liquid that is less toxic than kerosene, CsA is really tough to carry to and through the outer layers of the ocular surface. There is no such thing as generic Restasis (unless Allergan sells or licenses its vehicle). What may be new is price competition for topical CsA, which like Tide would be the improvement.

Looking on from outside the kitchen, I am always curious as to why the “chef” chooses a particular ingredient and “dose.” Both B+L and Kala will likely debut products with an old ingredient (loteprednol) delivered in a new form (new and unique delivery systems). Kala will try to get the same amount of flavor (effect) by using less drug, treating acute symptomatic DED with low-dose steroid. B+L will reformulate its classic Lotemax (Alrex). Will it seek to return superficial punctate keratitis to the label? Even though there is nothing new about using topical steroids for DED, having that indication on the label would be new and improved. The chefs at Ocugen are in the DED kitchen, too, using a glaucoma medicine (0.2% brimonidine tartrate) to treat symptoms. Their results show an impressive reduction in SANDE score with a rapid onset of action.

PAGE BREAK

While they do not necessarily constitute a new approach, there certainly is a bunch of new stuff in the device side of the DED world. 2019 brings us the approval and launch of iLux. On top of that, iLux brings Alcon into the DED arena (welcome to the Thunderdome, Adam!). Apparently, the patents protecting the LipiFlow (Johnson & Johnson Vision) intellectual property were not secure enough to keep another posterior thermal treatment off the market. iLux will bring more doctors and non-DED specialty centers into the arena of meibomian gland dysfunction, as will TearCare from Sight Sciences for the simple reason that the acquisition costs are low. In my opinion, each of these is inferior to LipiFlow, but their entry into the market must surely have influenced the J&J decision to lower the LipiFlow activator price to $100.

If you are looking for truly new stuff in the treatment of DED, pharma is where you need to look. At the moment, there are no drugs whose FDA approval is imminent, but a look just a tad deeper in the pipeline of several companies reveals some treasures. With more drugs coming before it, the FDA has become rather consistent in what it is asking of those medications. In order to be approved, meds must demonstrate an effect on both signs and symptoms of DED, and they must be at least as well tolerated as Restasis.

Three unique molecules from three new, smallish developmental companies are on track to at least see the finish line. CyclASol from Novaliq is a calcineurin inhibitor, a new class of medicine for the ocular surface. In its most recent phase 2/3 study, it met a primary endpoint for inferior corneal staining and secondary symptom endpoints. BRM421 (Brim Biotechnology) has a novel neurotrophic mechanism of action (MOA). Its most impressive finding thus far was a reduction in burning and dryness symptoms at the 2-week mark, and it appears to be effective in severe DED. RGN-259 (RegeneRx) was likewise found to be effective in reducing both signs and symptoms in a phase 2 trial. Word is that the company will launch a phase 3 trial with 700 subjects very soon.

All three of these have a new MOA that attacks a heretofore unaddressed target on the ocular surface. For something truly new, we have to leave the surface of the eye and once again follow Michael Ackermann into the nose. You remember him, right? He is the guy who brought us the treatment of DED with electrostimulation of the oculomotor nerve in the nose with TrueTear (Allergan). His new company, Oyster Point Pharma, is studying two nasal sprays to treat DED. In their respective phase 2 trials, intranasal application of both OC-01 and OC-02 produced an extraordinary increase in Schirmer scores (P < .001 compared with placebo for OC-01 0.1%). DED symptoms were also significantly reduced (P < .05) for OC-01. You have to hand it to Mr. Ackermann; he certainly seems to have — wait for it — a nose for treating DED.

PAGE BREAK

After decades as the red-haired stepchild of eye care, DED continues to be one of the most dynamic development spaces in all of medicine. We have new, and we have improved. No unicorns as of yet, but there do appear to be quite a few rainbows out there.

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.