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Third annual anti-inflammatory report: What is and what shall be
An expert takes a look at the current and soon-to-be-available dry eye treatments.
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At the moment I am gazing out over the white caps that litter the surface of my inland ocean as I contemplate the state of anti-inflammatory treatment of dry eye disease. By the time you read this, my third annual installment, Labor Day will have come and gone. Only empty nesters like yours truly are free to believe that summer is still upon us. What kind of summer was it here in Dry Eye Land? Was it the endless summer of so many Beach Boys songs or a summer of discontent?
Pretty much depends on whether your glass of rosé is half full or half empty, I’d say.
How about a recap of the year just past? 2018 brought us the Texas court defeat of Allergan’s bid to retain patent protection of the entire Restasis (cyclosporine ophthalmic emulsion 0.05%) franchise. Not only did this bring an immediate write-off of the value of Restasis by Allergan, it resulted in the Black Thursday purge of roughly half of the ophthalmic sales force built up over the Restasis years. Coupled with an equally dramatic decrease in marketing and the message from Allergan is clear: Generic competition for Restasis-like cyclosporine A treatments for dry eye will drive prices below the level at which previous marketing efforts make economic sense.
This is the biggest and most important story of 2018. Yes, I know, Xiidra (lifitegrast ophthalmic solution 5%) has continued its impressive growth in our market, and Shire has reacted by expanding its efforts both in the U.S. and internationally. But the Big Dawg has spoken, and all of us in the prescribing community should be paying attention. Cyclosporine A in a traditional solution is now a competition with only two metrics: price and comfort. Two giant generic manufacturers, Mylan and Teva, are likely set to enter the space with products that look an awful lot like “Classic Restasis.” They will come unpreserved in dropperettes (with fill levels similar to Xiidra). Insurance companies and our BFFs, the pharmacy benefit managers (PBMs), will force us to go through generics trials for our patients.
Anyone who has been at this game for longer than 15 years is now steeling themselves for the inevitable disappointment of using a traditional drop without the Endura vehicle. Ask Mark Milner about mixing cyclosporine A in peanut oil in the pre-Restasis days; it is brutally difficult to make an effective topical version that is comfortable enough to use. As I have written in the past, I am a classic inflammatory DED sufferer; I try pretty much everything that comes for my own dry eye. I have found the affordable “generic equivalent” compounded version of cyclosporine A from Imprimis rather uncomfortable. Of course, your mileage may vary.
What should we make of the news that Sun has received approval to market its unique form of cyclosporine A, Cequa? The vehicle makes the medicine, and here it appears that Cequa fits the bill. In the FDA trials, the number and degree of side effects are no greater than Restasis, and if you look closely at the reported data, you will notice that like Endura the vehicle has a nice little effect on dry eye, too. I think Sun has a winner in Cequa. How will the new team running the Sun eye care business unit bring their fully branded product to a market with as many as four direct competitors? We shall see.
Which brings us to the other anti-inflammatory medication now on the market to treat DED, Xiidra from Shire/Takeda. Xiidra seems to be more unique the more we use it. Remember, in a world in which the original DED medicine is highly dependent on the vehicle in which it is carried, lifitegrast is delivered in buffered saline. No help there, I am afraid. Pretty much the entire effect from Xiidra is from its active ingredient. Since its release, Xiidra in the wild has performed pretty much as expected. Like so many new products, we have learned more as we have used it. For instance, it behooves us all to be forthcoming about possible side effects; they happen a bit less frequently than expected, but when they do arise, they are sometimes more of an issue than anticipated.
All in all, Xiidra has performed at least as well as I had hoped. Increased use of this medicine is justified.
With all of this competition about to get started, 2019 is likely to look like, well, 2018. Sorry, but I don’t see anything different when it comes to the bane of our existence, the need to find a medication that not only works but can also be had for less than the dowry of a Mesopotamian princess. 2019 insurance contracts are being negotiated right now. It is anyone’s guess as to whether Mylan will leverage what looks like a full approval from the FDA into a place on the big carriers’ formularies. Sun can look to 2017 and Xiidra for a peek at what it faces in its effort to have PBMs bless Cequa. Perhaps we will see creative specialty pharmacy programs, and hopefully someone will find a way to make a coupon program that does not require a PhD and 40 hours of work per prescription.
How about a little bit of daydreaming and then a prediction? Medicare is an absolute crap show. Pop some corn and pull up a chair as Shire and Allergan go at it in court over their versions of how and why it is that Xiidra is not covered by any Medicare medication program. Of course, the easiest way to resolve that would be for Allergan to buy Shire/Takeda’s eye care business unit if Takeda leaves the space. That would be pretty slick, although it would be way better theater if Alcon picked off Xiidra and the Shire/Takeda pipeline. Back to the future with Allergan and Alcon at each other’s throats like in the good old days!
What will happen with “Classic Restasis” now that Allergan is only supporting its “multidose” version (covered by Medicare, by the way)? Allergan shed its generic division as part of the Actavis deal. Will it keep what is effectively a generic Restasis? Will it continue to produce Restasis in dropperettes? Can Allergan sell that product and keep the multidose version? Heck if I know.
And that prediction? This column is about the state of anti-inflammatory treatment of DED. The original and still most effective treatment for pretty much all things dry eye is topical steroids. Kala is now enrolling subjects in an FDA-requested phase 3 trial of its uniquely delivered loteprednol product. It is rumored that Bausch + Lomb is retooling the original Lotemax (loteprednol etabonate ophthalmic suspension 0.5%). You may recall that it has an on-label indication for the treatment of superficial punctate keratopathy, a ubiquitous clinical sign in DED. If the Kala product is approved or B+L pulls off a Besivance-level resurrection of Lotemax, we will have two steroid products with on-label dry eye indications.
I predict that 2019 is year 1 in the Age of Steroids in DED.
- For more information:
- Darrell E. White, MD, can be reached at SkyVision Centers, 2237 Crocker Road, Suite 100, Westlake, OH 44145; email: dwhite@healio.com.
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.