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Annual anti-inflammatory review
There was activity in the ocular surface arena, but most of the developments were unexpected.
Summer is over. Sunrise comes later, sunset too early to celebrate. Only the empty nesters can be found on the beaches of Cape Cod. Like so many migratory birds, all of the children have returned to school. Ophthalmologists turn their eyes toward the annual American Academy of Ophthalmology meeting, their focus on securing a hotel room within three zip codes of the convention center.
For AAO 2021. Sigh.
That means that September is here and with it the annual dry eye disease anti-inflammatory review courtesy of your humble scribe. It has been quite a crazy 12 months since our last review, eh? As I predicted last year, steroids were big for all kinds of indications related to the ocular surface, just not necessarily the ones we were expecting. Indeed, this past year has been more extraordinary for all of the things that did not happen rather than those that did. I have to admit that I was surprised by that.
We should probably begin with the events at the corporate level because it is likely that these will set the stage for what is to come. Xiidra (lifitegrast ophthalmic solution 5%) managed to get itself sold not once but twice since our last review. Shire was purchased by the Japanese pharma giant Takeda, which promptly turned around and disgorged both Xiidra and all 400+ folks who worked in the ophthalmic business unit. Swiss giant Novartis, owner of all pharma things Alcon, scooped up Xiidra for a kingly sum. As I write this column, Novartis is in the process of weaning its combined sales force; in the process, it is shedding the entire management team that brought Xiidra to market.
Restasis maker Allergan was gobbled up by AbbVie. As predicted, the combined company will retain the Allergan name. AbbVie did not have any ophthalmic products. At the moment, it appears that the entire eye care business unit remains intact, including the salesforce. The only management movement of any consequence for our world is that Allergan chairman and CEO Brent Saunders has accepted a position on the board of the new company but is no longer involved in day-to-day decisions.
These two events are large; they will likely have a significant impact on our daily lives as DED doctors, albeit for different reasons. For more than a decade, Mr. Saunders has had an outsized impact on eye care. As CEO of Bausch + Lomb and Allergan, he led two of the most important companies in our world. Overall his contributions at both have left eye care much better than it was before his arrival. If he does indeed withdraw from active daily management, we will have lost a valuable voice for our industry. At the moment, it seems that Allergan is on cruise control when it comes to Restasis (cyclosporine ophthalmic emulsion 0.05%). Like the rest of us, it appears to be waiting to see who will compete for the cyclosporine segment before it commits resources in our direction.
Novartis, on the other hand, is a big old mystery. It has acquired an asset, Xiidra, which is literally a case study in how to build a business in health care from scratch (Takeda’s return on investment was more than 2,000%, according to Bloomberg). Already in possession of a traditional portfolio of ophthalmic drugs (glaucoma, steroid, NSAID, antibiotic and antihistamine), Novartis represents an “old guard” of the ophthalmic industry. Will it retain the aggressive, outside-the-box approach to building market share that the original Xiidra managers (and salesforce) used so successfully? Or will it instead resort to something that looks like a 1990s Alcon, selling from the executive suite rather than the field? More than any other medicine I have prescribed in nearly 30 years of practice, Xiidra has a definite “culture” that extends throughout the community of managers, sales reps, office staff and doctors who embraced the challenge of getting it to DED patients. Can a large pharmaceutical company steeped in traditional structure and practice maintain sales momentum and continue to increase access for our patients?
Lots will likely have happened at Novartis between the time I write this and the time you get to read it.
It turns out I was spot-on when it came to calling 2019 the year of steroids in DED, just not necessarily for the reasons I thought. I was sure that we would have an on-label steroid to prescribe for DED by now. For whatever reason, the FDA has delayed approval of Kala’s low-concentration loteprednol for the treatment of acute DED symptoms. Aware that this might occur, Kala had already begun enrolling another phase 3 study. Topline results are reportedly arriving at the end of the year.
The ASCRS Starr Chamber gave us a protocol to diagnose DED in the perioperative period. Once DED is diagnosed, the ASCRS protocol encourages aggressive, rapid-acting treatment that includes the use of steroids on the ocular surface. All kinds of loteprednol should see a bump in prescriptions written because of this. Nothing could have been more fortuitous for Bausch + Lomb and its launch of Lotemax SM (loteprednol etabonate ophthalmic gel 0.38%) or for Kala and Inveltys (loteprednol etabonate ophthalmic suspension 1%). Both of these medications work beautifully for all things DED.
I would be severely remiss if I did not point out that 2019 did see some innovation with the introduction of two truly new steroids for the treatment of perioperative inflammation associated with cataract surgery. Dextenza (Ocular Therapeutix) is a slow-release dexamethasone in a punctal plug and Dexycu (EyePoint Pharmaceuticals) an extended-release dexamethasone contained in a small spherule injected into the space just behind the iris. Both replace steroid drop use (and exposure to preservatives, which protects the ocular surface), and both are instilled at the end of the case. At the moment, both are pass-through medications with unique J codes for billing. As an aside, I am sure that your Allergan rep has visited you with the news that Allergan is reintroducing and aggressively supporting Pred Forte (prednisolone acetate ophthalmic suspension), especially in the cataract space. How interesting that the Year of the Steroid brings back the ultimate steroid OG.
The year’s biggest surprise was the discovery that fluorometholone upregulates the activity of mucin-producing genes in ocular surface tissues. You now have ammunition to lob at pharmacy benefit managers if you choose to prescribe this for DED. Beware. You will doubtless run up against a litany of formulary barriers if you do. Keep your eye on another “blast from the past” here. Eyevance has acquired Flarex, a thoroughly effective version of fluorometholone. Jerry St. Peter was the marketing force at Inspire behind the original launch of AzaSite (azithromycin ophthalmic solution). Will he create the same marketplace magic for Flarex and DED?
It was a really weird year. Anticipating not one, not two, but three generic competitors for Restasis, we got none. Bupkis. Nada. Frankly, I cannot figure out if we do or do not have a compounded option. Imprimis lost a lawsuit to Allergan but was forced to pay damages of only 17 squirrel pelts and a mercury head nickel. Is it allowed to sell its stuff? No clue. Despite excellent phase 3 results and what surely sounded like an approval, Sun’s cyclosporine, Cequa, has been held up by the FDA. Some kind of kerfuffle over labeling. Smart money had it on the market by June. Kinda like smart money had Mylan and Teva serving up their generics by now. Hopefully we will see at least Cequa by year’s end.
You are waiting for a prediction now, right? OK, here goes: 2020 is the year that nothing happens. Nobody steps up. At best, the DED market for anti-inflammatory medicines is flat, with little or no movement in market share by anyone. Nobody makes any aggressive moves. Marketing and practice support dry up (with the possible exception of a Cequa launch), including pre-authorization assistance. With less help from industry, more responsibility falls on you and your staff to do more uncompensated work, which makes it harder to treat DED. Despite Washington promises to the contrary, the insurance/PBM industry becomes still more powerful. All of this happens while more and more DED patients come through your door as the multiscreen lifestyle and systemic nutritional deficiencies create more disease.
Please. Somebody. Anybody. Prove me wrong.
- 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.