Dextenza Implant Effective as Standard Topical Steroid Regimen
Dextenza implant is effective as a standard topical steroid regimen for the prevention of post-op pain and inflammation in cataract and cataract/MIGS surgical patients
In 2019, Ocular Therapeutix, Inc received FDA approval of a supplemental new drug application (sNDA) for Dextenza to include the treatment of ocular inflammation following ophthalmic surgery as an additional indication. Previously in 2018, Dextenza received marketing clearance for the treatment of ocular pain following ophthalmic surgery.
Dextenza is the first FDA-approved intracanalicular insert that delivers drug to the surface of the eye without the need for eye drops. A single corticosteroid intracanalicular insert, which is placed in the punctum and into the canaliculus, releases a 0.4-mg dose of dexamethasone to the ocular surface for up to 30 days without preservatives following insertion. After treatment, DEXTENZA resorbs and exits the nasolacrimal system without the need for removal. If necessary, saline irrigation or manual expression can be performed to remove the insert.
The approval of the sNDA is supported by 3 phase 3 randomized, vehicle-controlled trials support in which patients received the insert or a vehicle immediately upon completion of cataract surgery. In all 3 trials, Dextenza (n=567) had a statistically significant higher proportion of patients than the vehicle group who were pain-free on post-op Day 8. On postop Day 14, in 2 of the 3 studies, the insert group had a higher proportion of patients than the vehicle group, at a statistically significant level, who had an absence of anterior chamber cells. Safety was assessed from the 3 phase 3 clinical trials and a phase 2 clinical trial. The most common ocular adverse reactions were anterior chamber inflammation including iritis and iridocyclitis (10%), increased IOP (6%), reduced visual acuity (2%), cystoid macular edema (1%), corneal edema (1%), eye pain (1%), and conjunctival hyperemia (1%). Headache was the most common non-ocular adverse event (1%).
Surgeons report ease of use with the insert. “Surgeons appreciate that Dextenza solves compliance issues, by helping take the most complex drop regimen post-surgery out of the picture, and does so preservative-free and hands-free, providing a better experience for all involved—surgeon, staff, patients,” said Michael H. Goldstein, MD MBA; president, ophthalmology and chief medical officer at Ocular Therapeutix, Inc.
Dextenza addresses the unmet need for compliance in the ophthalmic space. “People are notoriously noncompliant with prescribed medications, and this is especially true with eye drops,” he explained. “Many patients have physical limitations (such as arthritis or a tremor) or memory issues (such as dementia) which makes it hard to take eye drops. Even if a patient successfully places an eye drop, there is only about 5% bioavailability to the eye from an eye drop. Surgeons can have peace of mind knowing drug is on board as Dextenza eliminates concerns about patient compliance and the difficulties associated with the self-administration of eye drops.”
Therapy also is simplified because DEXTENZA delivers a self-tapering dose of dexamethasone, while being preservative free, Dr Goldstein added.
Numerous studies presented at the ASCRS 2021 Annual Meeting in Las Vegas, Nevada, demonstrated the expanded options for insert use, which offers surgeons and patients additional flexibility in developing perioperative pain and inflammation control strategies:
- A study by Raju1 concluded that the Dextenza intracanalicular insert can be efficiently inserted in an office setting and it provides sufficient steroid medication for 4 weeks postoperatively. The insert was placed in the office 3 days before cataract surgery. Breakthrough medication was not necessary for any of the 10 patients in the first month postoperatively. No cases of extrusion or irritation were reported.
- A study by Shafer2 found that in patients undergoing bilateral PRK, at Month 3, 70% of patients preferred the dexamethasone insert, 20% preferred prednisolone acetate, and 10% expressed no preference for the postop steroid treatment. No statistical or clinically significant differences were observed between the cohorts in healing time, postop pain, or visual outcomes. Twenty patients participated in the study, in which one eye received Dextenza and the second eye received prednisolone acetate 1% QID 1 week, BID 1 week following bilateral PRK surgery. All eyes received topical moxifloxacin QID for one week.
- A study by Singh3 demonstrated that the real-world use of Dextenza implant is safe and effective as standard topical steroid regimens for the prevention of postoperative pain and inflammation in cataract and cataract/MIGS surgical patients. The retrospective study evaluated 82 patients (132 eyes) from 4 groups: those who underwent cataract only (with and without the implant), and cataract-MIGS (with and without the implant). Standard topical steroid regimen was given to those without the implant; those with the implant did not receive topical steroids. No statistical differences in inflammation or pain were observed between all 4 groups. No IOP spikes were reported in any of the groups, and there was no difference in glaucoma medication burden reduction.
- A study by Foster4 showed the dexamethasone intracanalicular insert placed either immediatel postoperatively or the next day achieves similar inflammation and pain control after phacoemulsification. The retrospective analysis included data from 17 eyes (17 subjects): 8 received the insert immediately postoperative and 9 in the office the next day. All eyes were free of pain and inflammation preoperatively, and no eyes experienced intraoperative adverse events. Trace cell was present, and flare was absent in all 17 eyes on Day 1; cell was present in 22% of eyes seen at Day 7 (one in each group); and by Day 30, trace cell was present in a 6% of eyes (one eye). Pain was absent in all 17 eyes on Day 1, present in 11% of eyes seen at Day 7, and absent in all 17 eyes at Day 30. No insert-related adverse events were observed.
- A pooled efficacy analysis by Rubin5 from 4 randomized, vehicle-controlled studies demonstrated that Dextenza (DEX) is superior to placebo (PV) for the treatment of both ocular itching and conjunctival redness due to allergic conjunctivitis. Safety data exhibit the insert is generally safe and well tolerated with a low risk of increased IOP. The pooled analysis included data of the prospective, multicenter, double-masked, placebo-controlled clinical trials evaluating efficacy (3 phase 3; DEX/PV: n=127/128) and safety (1 phase 2, 3 phase 3; DEX/PV: n=154/161). On Day 8, DEX achieved a statistically significant decrease in mean ocular itching scores compared to PV at 3-, 5-, and 7-minutes post-Conjunctival Allergen Challenge (CAC). Mean conjunctival redness scores were significantly lower with DEX relative to PV at 7-, 15-, and 20-minutes post-CAC on Day 8. A lower proportion of DEX-treated subjects reported adverse events (AEs) and treatment-related AEs compared to PV.
- An ongoing study by Ilyas6 is evaluating the postoperative symptom control with the intracanalicular dexamethasone insert to topical steroid drops following bilateral pterygium surgery. The prospective, open label, randomized, controlled clinical trial includes 20 adult patients undergoing surgery that are randomized 1:1 to receive either 3 sequential monthly dexamethasone inserts (following surgery, Month 1, Month 2) or prednisolone topical drops for 3 months in one eye. Fellow eye receives the alternate therapy. During follow up, pain, inflammation and clinical outcomes such as pterygium recurrence, visual acuity, IOP, adverse events, rescue therapy, patient callbacks are being assessed. A modified COMTOL questionnaire at Month 3 will also be used to determine patient preference.
Research with Dextenza was well represented at ASCRS, noted Dr. Goldstein. “This is proof positive that the ophthalmic community is embracing Dextenza as a value-add product addressing unmet need. The presented data continue to support the use of Dextenza to treat post-operative ocular inflammation and pain following cataract surgery and beyond, following a variety of ophthalmic surgeries including post-refractive surgery, glaucoma surgery etc. Dextenza is approved for all ophthalmic surgery and not just cataract surgery, this shows surgeons are starting to see a place for Dextenza as a therapeutic option following other ophthalmic surgeries also,” he said.
Ocular Therapeutix has filed a supplemental New Drug Application (sNDA) for the indication of ocular itching associated with allergic conjunctivitis, based on results from phase 3 trials evaluating safety and efficacy of Dextenza for treating subjects with the condition. “We are anticipating approval on the PDUFA target action date scheduled for October 18, 2021. Regardless of the indication, Dextenza can be used in an office or ASC setting,” he said.
- Raju L. Efficacy of Dextenza Insertion Preoperatively in the Office. Presented at: 2021 ASCRS Annual Meeting.
- Shafer BM, et al. The Restore Study: Safety and Efficacy of Dextenza for Post-Operative Inflammation and Pain Following PRK. Presented at: 2021 ASCRS Annual Meeting.
- Singh IP. A Retrospective Analysis of Outcomes Using an Intracanalicular Dexamethasone Implant in Post Cataract and/or Cataract-MIGS Surgery Patients. Presented at: 2021 ASCRS Annual Meeting.
- Foster BB. Immediate Postoperative Versus Next-Day Dexamethasone Intracanalicular Insert for Inflammation and Pain Control Following Cataract Surgery. Presented at: 2021 ASCRS Annual Meeting.
- Rubin JM, et al. Pooled Analysis Evaluating Efficacy and Safety of an Intracanalicular Dexamethasone Insert for the Treatment of Allergic Conjunctivitis. Presented at: 2021 ASCRS Annual Meeting.
- Ilyas H. Postoperative Symptom Control with an Intracanalicular Dexamethasone Insert Compared to Topical Steroid Drops Following Pterygium Surgery. Presented at: 2021 ASCRS Annual Meeting.