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October 27, 2023
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BLOG: Immunomodulator mayhem: Battles in the marketplace

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Key takeaways:

  • The anti-inflammatory market in dry eye disease is heating up.
  • Cyclosporine brands will battle with each other, while cyclosporine also takes on lifitegrast.

Well now, it seems as though I ruffled more than a few feathers with my annual anti-inflammatory review last month.

With the emergence of two new therapies, Xdemvy (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals) for Demodex blepharitis and Miebo (perfluorohexyloctane ophthalmic solution, Bausch + Lomb) to treat evaporative dry eye disease (DED) (shameless plug: read my November column!), one might think that anti-inflammatories are no longer all that interesting. Heck, with the latest news about reproxalap and the FDA, you might think that the end is nigh.

Darrell E. White, MD

Nothing could be further from the truth!

All things reproxalap aside, the immunomodulator part of the anti-inflammatory market is gonna continue to be a blast to watch. Think about it: We have two great battles that have just gone from smoldering conflicts to the brink of full-on flaming hot business war. I’ve said for several years that this space would eventually break down into a civil war between all the cyclosporine (CsA) cousins and a “DED world” war between CsA and lifitegrast. It has taken all this time to ignite because of the delay in the effective rollout of generic CsA options and the lack of effective market support for Xiidra (Bausch + Lomb). More on that in a bit.

The first salvos in the CsA family feud were fired in court. Mylan (now part of Viatris) finally obtained the right to make and market CsA 0.05%; it was immediately joined by three companies selling “generic” Restasis actually manufactured by Allergan. Sun pecked around the perimeter of the battlefield by offering a cash option for its Cequa brand, effectively bypassing the moat that Allergan built around insurance company formularies. It’s been mostly a numbers battle until recently as “the cousins” maneuvered for an advantage based on price/cost/access.

Remember when the most important thing a drug company had to demonstrate with a new entrant into a disease space was greater efficacy? Vevye, developed by Novaliq and now owned by Harrow, would like to make the case that it is the bestest, but in an openly competitive world, nothing is better than a head-to-head cage fight. At the recent American Academy of Optometry convention, Sun and Cequa went toe-to-toe with Restasis — that’s right, an old-school brand-on-brand battle — and Cequa walked away with the belt.

In a phase 4 study, 124 patients treated with Restasis with continued signs and symptoms of active DED were switched to Cequa. To mimic “real-world” circumstances, trial subjects were allowed to use artificial tears. Total corneal fluorescein staining (tCFS) and a modified SANDE/DED visual analog symptom scale (VAS) were analyzed. The mean pre-switch tCFS score was 5.67 at onset and improved to 4 at 4 weeks and 2.7 at 12 weeks. Mean VAS symptom score was 67.1 at the time of the switch and decreased to 48.4 and 38.3 at weeks 4 and 12, respectively. Cequa was well tolerated with side effects consistent with its phase 3 FDA trial data. Round 1 in the CsA civil war goes to Cequa.

What about the DED worldwide war between CsA and lifitegrast? For the first time since Shire handed over the reins for Xiidra to Takeda, Xiidra is no longer adrift on the battlefield. Acquired by Bausch + Lomb, a company that paid $1.75 billion (with milestone payments that may reach $750 million) and is now led by Brent Saunders, Xiidra finally has the backing it will need to compete against the CsA Nostra. Without the need to battle its own family, Saunders and B+L can simply battle CsA without regard to brand. Remember, Saunders built the Restasis juggernaut.

Immunomodulators still matter. The CsA civil and the worldwide CsA vs. lifitegrast wars have begun.

References:

Sources/Disclosures

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Disclosures: White reports consulting for Aldeyra, Avellino, Bausch + Lomb, Johnson & Johnson, Novartis, Orasis, Rendia, Santen, Sight Sciences, Sun, Tarsus and Trukera Medical; speaking for Novartis, Santen and Sun; and having ownership interest in Orasis.