Mylan gets nod for ‘generic Restasis’
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They said it would never happen. We would never see it in our lifetimes. It was a dream held by millions, but sadly, naught but a pipe dream.
The Cubs winning the World Series? In comparison, that was a veritable lock. The Cincinnati Bungles, er, Bengals in the Super Bowl? As much of a sure thing as butterfly poop in Capistrano. This was as unlikely as seeing elephants fly. Well, let that murder of crows sing out loud. Godot is standing at the front desk of your office, and now he is waiting for you. Call your travel agent because it is officially this year in Jerusalem.
A generic version of Restasis was approved by the FDA.
Is this really that big a deal? Meh, who even knows. What can be said is that more ink has been spilled over this generic transition than anything else in eye care. We should be clear about what it is that we are talking about: This is not generic Restasis. What has been approved is the abbreviated new drug application submitted by Mylan for a topical non-preserved solution that contains 0.05% cyclosporine A (CsA) in a lipid emulsion, not the lipid emulsion of the brand. That, me droogies, is not Restasis. Call it “Fauxstasis.”
What we all know as Restasis is 0.05% CsA in the proprietary Allergan lipid emulsion that was once upon a time available as Endura (from what I can see, the European-available Endura is not the original). Allergan/AbbVie (heretofore just Allergan) reported $1.29 billion in 2021 sales for Restasis. No matter where you sit on whether or not this is a big deal clinically, a billion dollars almost got Austin Powers taken out by Dr. Evil.
In many ways, the story of dry eye disease (DED) began with the approval of Restasis in 2003, and the story of the business of DED is the story of Restasis. Remember, before 2000, you could literally count the number of eye doctors who looked at dry eye as a disease on the hands and feet of a single patient. Mike Lemp, Hank Perry and maybe Ken Kenyon; Darrell White and Mark Milner* hadn’t even been invented yet. While it was — and in some circles, remains — controversial, the science backing up the Allergan NDA legitimized the diagnosis and treatment of DED.
There were a couple of hiccups in the early days that stalled any real developmental progress. Bausch + Lomb drop-kicked Lotemax (loteprednol etabonate) as a DED treatment despite a label covering pretty much everything, and Alcon put Flarex (fluorometholone acetate ophthalmic suspension) in a closet and simply forgot it had it. Inspire may very well have blown the lid off the whole space if it had chosen the right regimen for diquafosol; can you imagine how delicious the battles with the FDA over AzaSite (azithromycin ophthalmic solution) would have been with younger versions of Jerry St. Peter, Kim Brazzell and Bob Dempsey?
It took more than 10 years for new therapeutics to make a mark, and the first ones to do so were devices, not drugs. LipiFlow (now Johnson & Johnson) and intense pulsed light (IPL) began to make inroads among the next generation of dry eye innovators such as Frank Bowden (LipiFlow) and Rolando Toyos (IPL) in the mid 20-teens. There was a 12-year gap between the approval of Restasis and the introduction of the next DED medication, Xiidra (lifitegrast ophthalmic solution 5%, Novartis). DED has been the “hot dot” in eye care since, attracting millions of research dollars and launching multiple startups.
With a big, old bull’s-eye on Restasis.
Do you remember the legal stuff around the Restasis patents in 2017? Allergan faced action in the federal courts and the U.S. Patent and Trademark Office as several companies sought to have patent protection stripped from Restasis so that generic versions could be made and marketed. This prompted either the most ingenious tactic or the one with the worst optics in eye care history when Allergan gifted the St. Regis Mohawk Tribe with the patent rights to Restasis. In so doing, all actions before the patent office were rendered moot; actions against sovereign nations cannot be taken. Brilliant or too slick by half, the sheer audacity of the maneuver was simply awesome.
This left Allergan vulnerable to an adverse ruling from the federal court in Texas. InnoPharma, the generic division of Pfizer at the time, brought suit seeking to declare the Restasis patents unenforceable. The outcome set the stage for the recent big approval news. InnoPharma and Allergan settled the suit in a manner that affirmed the validity of the Restasis patents until 2024 unless InnoPharma was able to obtain FDA approval for a generic. Mylan and InnoPharma were combined to form Viatris, the company that received FDA approval. Quick side note: Teva failed to achieve a similar outcome, losing a case in February 2019 and at the moment is still on the sidelines until 2024.**
Which brings us back to the blockbuster approval and Mylan’s declaration that it would launch its product “immediately.” What does that mean for us at the slit lamp? Will this have any effect on out-of-pocket costs for patients? How about our staff members and the uncompensated time we all spend dealing with the burdens hoisted upon us by insurance companies? Is this the end of Restasis as we know it?
Not all generics are equal. For every Xalatan/latanoprost, there are a dozen Acular/ketorolacs in which the generic is less effective, often due to side effects from nonactive ingredients that cause poor tolerance. One only needs to look at the various bromfenac and loteprednol products to see that vehicle technology can affect both efficacy and tolerance. There is nothing magical about 0.05% CsA. Whispers abound that Allergan knew that it had “underpowered” Restasis but was fearful that a higher concentration would be rejected by the FDA. It may very well be that both Cequa (0.09% CsA, Sun Pharma) and Verkazia (0.1% CsA, Santen) will prove more effective in treating inflammation-driven DED.
But the only reason that Cequa and Verkazia will even be in the game is because they went through the trouble of developing an effective and tolerable vehicle.*** Teva has been selling a generic version of CSA 0.05% in Canada for a few years now. Why hasn’t it knocked Restasis out of the game? According to the Canadian eye doctors with whom I have chatted, it is because the drop is poorly tolerated by patients, and clinical regression of DED is seen presumably due to poor absorption. Imprimis has been selling a non-0.05% version of CsA in the non-lipid Klarity moiety; its market share barely registers. A hydrophobic active ingredient that must be delivered in a hydrophilic is a challenge. Will the Mylan emulsion pass muster?
Sadly, none of that is going to save you or your patients from being forced to use 0.05% CsA in the Mylan emulsion. Remember, it ain’t Restasis, no matter what your friendly health insurance rep tells your patient. Prepare for step therapy; you will be forced to trial Fauxstasis for every new immunomodulator candidate, and every patient now on Restasis (or Cequa or Xiidra) will receive a letter saying that they must switch to Fauxstasis. Make sure you have data when it comes time to declare treatment failure. Schirmer scores, tear breakup time, SPEED and Ocular Surface Disease Index will all be requested. Our only hope is that Mylan came up with a better recipe than Teva and that Fauxstasis does turn out to be a generic Restasis.
Godot and I are boarding our flight for Jerusalem to visit the Western Wall and pray.
*OG Mark Milner appears in every Austin Powers movie.
**I am not a lawyer. This is my interpretation of analyses in the business media.
***Xiidra’s vehicle is buffered saline. When the lifitegrast patent expires, Xiidra is toast.
- 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.
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