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Where Should These New Glaucoma Treatments Fit in Your Practice?

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With 3 new second-line treatments for glaucoma now on the market, all dosed once daily at bedtime, where should each one fit into your practice? Jonathan Myers, MD, chief of the Glaucoma Service at Wills Eye Hospital in Philadelphia, recently reviewed trial results and other key factors for these new options. In addition to which of the 3 offers the most strength, Dr Myers pointed out the nuances of picking the right drug at the right price point for the patient. He also weighed in on the value of these new medications for pediatric patients, low tension glaucoma, and as first-line therapies.

Efficacy and Safety

Latanoprostene bunod (LBN). The medication combines latanoprost, a prostaglandin that increases uveoscleral outflow to reduce intraocular pressure (IOP) with butanediol mononitrate, which can increase trabecular outflow. LBN was compared to latanoprost in the Voyager study, a randomized, investigator-masked, parallel-group, dose-ranging study involving 413 individuals. The commercially-available formulation of LBN (0.024%) lowered IOP by ~9 mmHg, vs 7.8 mmHg in those taking latanoprost (0.005%). Moreover, ~two-thirds of LBN patients achieved consistent pressure reduction to 18 mmHg or below, compared with half of latanoprost patients. “So that extra 1.23 mmHg meant that more people achieved goal pressure…on one medication dosed daily,” said Dr. Myers. Treatment-related adverse events comprised mainly ocular irritation and stinging, which occurred in ~19% of LBN patients, vs ~12% of those taking latanoprost.

LBN has also been compared with timolol, in the Apollo study, a phase 3 randomized, controlled, multicenter, double-masked, parallel-group study involving nearly 400 individuals. LBN once-daily lowered the average IOP to between 17.8 and 18.7 mmHg, vs 19.1 to 19.8 mmHg in those taking timolol 0.5% BID. “This difference in pressure reduction resulted in 22% vs 11% of patients consistently achieving a goal pressure” in favor of LBN, noted Dr. Myers. Adverse events were similar in both groups.

Netarsudil. This rho-kinase inhibitor and norepinephrine transporter inhibitor acts by separating and relaxing trabecular beams, reduces episcleral venous pressure, and lower aqueous production. It was evaluated in two trials involving a total of nearly 1,200 individuals. Netarsudil 0.02% once a day was compared with timolol 0.5% BID in one study. The second study also looked at netarsudil BID. In both, netarsudil at both doses was found to scientifically lower IOP, and was noninferior to timolol. It is important to note that BID is not the indicated dosage for netarsudil; however, explained Dr. Myers, it “lowered pressure slightly better at the afternoon time point, though it comes at the expense of greater side effects.”

Speaking of which, incidence conjunctival hyperemia was reported to be 50 to 53% for netarsudil once daily; nearly 60% for the BID dose; and 8% for timolol. Hyperemia “was mild and intermittent” in about 90% of patients who reported it, said Dr. Myers. The remaining 10% had more than a mild case, making the adverse event “an uncommon cause of discontinuation.” Two other points about adverse events, he noted:

  • Conjunctival hemorrhages were observed in ~15% of those taking netarsudil, vs a zero incidence for timolol patients. Often, “they’re very small and at the limbus. In rare cases, they can be large,” but over time go away.
  • Corneal deposits were reported more frequently with netarsudil than timolol. Most cases were mild, but in rare instances when it is more than mild, it resolves when the drug is discontinued.

BAK-free latanoprost. This prostaglandin analog contains potassium sorbate, rather than benzalkonium chloride (BAK). Dr. Myers was not at liberty to discuss the phase 3 trial data, which has yet to be published. The most important factors to note at this point:

  • It is supplied as a 2.5 mL emulsion filled in a 5-mL clear low-density polyethylene bottle that does not require refrigeration.
  • The prescriber information shows a 6 to 8 mmHg pressure reduction from a baseline of ~23 to 26 mmHg.
  • The most common side effects observed are hyperemia, seen in ~45 to 50% of patients, as well as stinging in ~40%.

Where They Fit in Practice

Dr. Myers answered a number of questions about what these three new medications mean at the practice level.

If you had to pick one as a second-line therapy, do you have a preference? While the answer is not clear cut, given how different patients respond to different dosages, not to mention cost considerations, “of the three, the strongest is latanoprostene bunod, because [it contains] both latanoprost and nitric oxide donor.” He also likes netarsudil because of its different mechanism of action. “I am using it a lot as a second-line therapy.” In the end, though, if looking at strength, LBN “gives people an extra push” when needed.

Do any of these medications offer benefit in pediatric patients? “My partner has used netarsudil in pediatric patients with Sturge-Weber related increased eye pressure [and has seen] surprisingly good pressure reduction.”

Do you see value in any of these therapies as first-line treatment? “The challenge I find is that price point where I [practice] matter[s] a lot. This doesn’t mean that they shouldn’t be considered as first-line agents, but [you also have to consider] what patients can achieve with other ones daily generic formulations.”

Can any of the new medications play a role in low tension glaucoma? Netarsudil appears to have value given its effect on scleral venous pressure, as well as an ability to reduce pressure in those with lower levels of elevated pressure. “Anecdotally, my colleagues and I have seen some surprisingly good responses in patients whose pressures are less than 20 mmHg, with pressure reductions of 4 mmHg or more.”



Myers J. Newly-approved glaucoma medications. Talk presented at: AAO 2018 annual meeting; October, 26-30, 2018; Chicago.

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