New Topical Medications Sunita Radhakrishnan, M.D. Glaucoma Center - - PDF document

▶
new topical medications
SMART_READER_LITE
LIVE PREVIEW

New Topical Medications Sunita Radhakrishnan, M.D. Glaucoma Center - - PDF document

Mar 14, 2024 229 likes •446 views

New Topical Medications Sunita Radhakrishnan, M.D. Glaucoma Center of San Francisco, Glaucoma Research and Education Group Financial Disclosure Consultant: Netra Systems, Inc Latanoprostene bunod Netarsudil FDA approval Nov 2017 Dec 2017

slide-1
SLIDE 1

Sunita Radhakrishnan, M.D.

Glaucoma Center of San Francisco, Glaucoma Research and Education Group

New Topical Medications

Financial Disclosure Consultant: Netra Systems, Inc

slide-2
SLIDE 2

Latanoprostene bunod Netarsudil

FDA approval Nov 2017 Dec 2017

Uveoscleral outflow

  • Prostaglandins
  • Alpha agonists

Trabecular outflow

  • Pilocarpine
  • Latanoprostene

bunod

  • Netarsudil

Aqueous inflow

  • Beta blockers
  • Alpha agonists
  • CAIs

Rudkin et al. Recognizing congenital glaucoma. Med J Aust 2009; 191: 466-467

NEW

slide-3
SLIDE 3

Netarsudil and latanoprost fixed combination

New Medications

Latanoprost with potassium sorbate (non BAK) FDA approval Sept 2018 Mar 2019

Latanoprostene bunod

  • Latanoprost + Nitric oxide donating component

(butanediol mononitrate)

  • Dual mechanism of action

– Latanoprost increases uveoscleral flow – NO relaxes TM and increases trabecular outflow

slide-4
SLIDE 4

Latanoprostene bunod

  • Efficacy:

– IOP reduction of 8-9 mm Hg (30 to 33%) in OAG/OHTN with mean baseline IOP of ~27mm Hg.

(pooled phase-3 studies APOLLO, LUNAR; Weinreb et al. J Glaucoma 2018)

– IOP reduction of at least 22% (4.3 mm Hg) in Japanese patients with mean baseline IOP of 19.6 mm Hg (JUPITER study, Kawase et al. Adv Ther. 2016; 12 month follow-up)

Latanoprostene bunod

  • Side effects

– Similar to latanoprost – Stinging

slide-5
SLIDE 5

Netarsudil

  • RhoKinase inhibitor
  • Multiple mechanisms of action

– Increases trabecular outflow by relaxing TM – Reduces episcleral venous pressure – Reduces aqueous production

Netarsudil

  • Efficacy:

– IOP reduction of 3.3 to 5.1 mm Hg (15 to 22%) in 3 phase 3 trials (ROCKET-1, 2, 4) with mean baseline IOP 20.7 to 23.4)

– In ROCKET-4, netarsudil demonstrated non-inferiority to timolol across various IOP ranges (<25, <27, <30)

Serle et al, ROCKET 1,2 AJO 2018, Khour et al. ROCKET 4, AJO Aug 2019

slide-6
SLIDE 6

Netarsudil

  • Side effects reported in ROCKET -4 study

with 6 month follow-up – Hyperemia: 48%, mostly mild – Subconjunctival hemorrhages: 16% – Instillation site pain: 24% – Cornea verticillata: 25%

  • Onset at ~ 3 months
  • Mild, no visual consequence
  • Resolved upon discontinuation in 60%

www.aeriepharma.com

Netarsudil

  • Discontinuation rate:

– From all adverse events (mostly ocular): 19% – Due to conjunctival hyperemia: 4%

ROCKET-4, Khouri et al. AJO, Aug 2019

slide-7
SLIDE 7

Latanoprost emulsion with potassium sorbate (Xelpros)

  • Efficacy:

– In one Phase 3 trial, IOP reduction was 5.0 – 6.2 mm Hg (22 – 25%) in Xelpros group versus 5.7 – 6.6 m Hg (25-

26%) in Xalatan group.

  • Side effects:

– 67% reported eye pain with Xelpros versus 47% with Xalatan

  • Storage:

– No refrigeration required

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000MedR.pdf

Netarsudil and latanoprost fixed combination (Rocklatan)

  • Efficacy:

– IOP reduction of 6.8 to 9.2 mm Hg (31 to 37%) from

mean baseline IOP of 22.4 to 24.7 mm HG

– Additional IOP lowering IOP of

  • 1.8–3.3 mmHg vs netarsudil
  • 1.3–2.5 mm Hg vs latanoprost

Asrani et al, MERCURY-1, AJO June 2019; Walters et al, MERCURY – 2, Ophthalmolog Glaucoma 2019, In Press

slide-8
SLIDE 8
  • Side effects:

– 53 to 55% conjunctival hyperemia (similar to netarsudil) – 2.5 to 7% discontinuation rate (lower than netarsudil)

Asrani et al, MERCURY-1, AJO June 2019; Walters et al, MERCURY – 2, Ophthalmolog Glaucoma 2019, In Press

Netarsudil and latanoprost fixed combination (Rocklatan)

Frequency of administration

PGA

β- α2+

CAI-

α2+ α2+

CAI- CAI-

AM PM

PGA+NO

RhoK-

slide-9
SLIDE 9

PGA

CAI-

PGA+NO

RhoK-

Choosing first line therapy

  • Effective
  • Good side effect profile
  • Inexpensive
  • Once a day dosing
  • 24 hour IOP control
slide-10
SLIDE 10

Van der Walk R, et al. IOP lowering effects of all commonly used glaucoma drugs: a meta-analysis of RCTs. Ophthalmology. 2005;112:1177-85

Newer options for first line therapy

  • Latanoprostene bunod and Netarsudil

– Advantages:

  • May help maintain the physiological aqueous outflow pathways
  • Convenient dosing

– Disadvantages

  • Cost/Access
  • Netarsudil: Side effects
slide-11
SLIDE 11

Adjunctive treatment

  • Many glaucoma patients require more than one

medication to adequately lower IOP

– OHTS, 40% required 2 or more meds by year 5 – CIGTS, 75% required 2 or more meds after 2 years of treatment

  • With PGA monotherapy, consider trying a

different PGA before adding another medication

Choosing adjunctive therapy

  • Additional IOP lowering
  • Other factors

– Side effects – Impact on adherence

  • Dosing schedule
  • Cost
slide-12
SLIDE 12

Adjunctive therapy to PGAs

  • Beta blockers

– Easy once daily dosing schedule – Poor nocturnal IOP control

  • Rho Kinase inhibitor

– Easy qd dosing – Diurnal and nocturnal IOP control

  • Topical CAIs

– At least BID – Diurnal and nocturnal IOP control

  • Brimonidine

– At least BID – Poor nocturnal IOP control

New medications versus latanoprost

  • Netarsudil/latanoprost fixed dose combination

– Additional IOP lowering of 1.8mm – 2.5 mm Hg – Higher proportion of patients achieving IOP ≤ 15 mm Hg

  • 42 to 44% with netarsudil/latanoprost FDC versus 18-

25% with latanoprost alone

slide-13
SLIDE 13

First line and adjunctive therapy

  • No one-size-fits-all algorithm
  • Treatment has to be individualized for

each patient

Clinical experience - Early

  • Initially tried both Latanoprostene bunod and

Netarsudil in patients who were already on multiple medications

slide-14
SLIDE 14

Early experience

  • Cost:
  • Access:

– Prior authorization for almost every prescription – Created template statement about mechanism of action

  • f new meds
  • Side effects:

– Warned patients of hyperemia from netarsudil; tends to get better after first few days of use

Early experience

  • Efficacy of netarsudil:

– Greater than expected in some patients – Able to achieve single digit IOPs even in patients on multiple medications

slide-15
SLIDE 15
  • Side effects with netarsudil

– Follicular conjunctivitis and eyelid dermatitis similar to brimonidine induced reaction

  • Takes longer to resolve?

– Discontinuation rate higher than reported in trials

Early experience

Brimonidine induced follicular

  • conjunctivitis. Eyerounds.org

Initial survey

  • 64 patients started on netarsudil treatment
  • 25% discontinued due to side effects:

– Conjunctival hyperemia (n=6) – Follicular conjunctivitis (n=5) – Eyelid dermatitis (n=3) – Tearing, discomfort, or severe itching (n=2)

slide-16
SLIDE 16

New medications in 2019

  • More likely to consider latanoprostene bunod as

first line agent, especially in younger patients

– Good efficacy – Tolerated well – Potential advantage of maintaining trabecular pathways open

New medications in 2019

  • Netarsudil can be a good adjunct to PGA
  • Side effects are relatively more common but has

several advantages over other agents

– Once daily dosing – Night-time efficacy – May keep trabecular pathways open – May achieve very low IOPs in some patients

slide-17
SLIDE 17
  • Cost is still an issue for many patients

– Competing against very cheap generics

New medications in 2019

slide-18
SLIDE 18
slide-19
SLIDE 19
  • Access is improving

New medications in 2019

slide-20
SLIDE 20

Summary

  • New medications with novel mechanisms of

action are a welcome addition to our treatment portfolio

  • Cost and access is not optimal
  • Side effects/discontinuation rate with Rho Kinase

inhibitors is high but they can be very effective in some patients