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BLOG: Cequa enters, stage left — let the cyclosporine battles begin
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Ladieeeees annnnnd gentlemen, in this corner (points to the right), the reigning champion, RESTASIS! And to my left, from the spunky upstart Sun Pharmaceuticals, the Kid, CEQUA! Let’s get ready to RUMbllllllllllle!
Too much?
I dunno. Maybe. But then again, maybe not. It’s been 15 years or so since Restasis (Allergan) embarked on its thus far triumphant reign as the only cyclosporine A (CsA) in the market. That’s an incredibly long run for a medication whose active ingredient was already off patent when it first came out. You could say that Restasis was as integral to the growth of the dry eye disease market as Jean-Claude Van Damme was to UFC, except that unlike JC Van D, Restasis was actually in the ring and fighting. Restasis the drug (CsA + Endura) was such a good solution to the problem of making CsA useful topically that no one even entered the ring to challenge it. The continued absence of a generic CsA in the U.S. (and the apparent lack of enthusiasm for the product on the market in Canada) only goes to prove this.
Cequa is the result of research undertaken to create a wholly new vehicle to deliver CsA to the ocular surface. The essential problem is that CsA is hydrophobic, limiting its aqueous solubility in traditional formulations and therefore its transit into ocular surface tissues. Restasis solves this by putting CsA in a lipid emulsion. Cequa is a novel solution in which CsA is entrapped within micelle structures that present a hydrophilic outer layer surrounding a hydrophobic core. Once though the hydrophilic gauntlet, the CsA is released, producing high tissue levels in both the cornea and conjunctiva.
The phase 3 study for Cequa (OTX-101 in premarket lingo) was just published in Ophthalmology. In and of itself, that’s a pretty big deal; ’twas a time not too very long ago that the mere mention of DED was a straight shot to the circular file at the venerable Blue Journal. Because the original approval for Restasis hinged on showing an increase in Schirmer scores, this was the primary endpoint; it was met quite handily. Significant improvements relative to vehicle were also seen in corneal (as early as 28 days) and conjunctival staining. Corneal clearing is particularly relevant when one is contemplating cataract and other surgeries that require a healthy ocular surface for a successful outcome.
Cequa must now prove its chops with DED docs accustomed to using Restasis. I predict challenges in which head-to-head comparisons of the two branded CsA medications take place. Expect to hear about increased tissue concentrations of CsA when 0.09% preparations are compared with 0.05%. Whether or not there is a clear victor in these round-robin matches, the knock-out rounds will feature two battle lines in the clinic and the boardrooms of insurance companies, one between CsA formulas and another between CsA and lifitegrast. Maybe the CsA opponents will team up against lifitegrast. You know, like “tag team” in WWE. Restasis and Cequa take on those “double i’s” in Xiidra (Novartis).
Pull up a chair. Pop some corn. The rumble is coming.
Reference:
Goldberg DF, et al. Ophthalmology. 2019;doi:10.1016/j.ophtha.2019.03.050.
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.