Several biodegradable sustained-release (SR) device concepts, from drug-eluting contact lenses to lacrimal inserts and intracameral implants, have been put forward in recent years as a means of lowering intraocular pressure (IOP) in the treatment of glaucoma. To be successful, though, these devices must prove that they can achieve their proposed benefits — increasing compliance and potentially stabilizing IOP peaks and troughs — without posing any significant additional risks. One such device has now met these criteria.
In March 2020, the US Food and Drug Administration approved the first intracameral biodegradable SR implant, the bimatoprost implant (Durysta), which will be commercially available this June.
Approval was based on published phase 1/2 trials and two phase 3 trials (known as ARTEMIS) that have yet to release data in the peer-reviewed literature. According to a press release describing the phase 3 results, however, the implant demonstrated an approximately 30% decrease in IOP from baseline over the 12-week primary efficacy period, meeting the predefined criteria for non-inferiority to the study comparator.
The published phase 1/2 data included 75 patients with open-angle glaucoma and a history of a minimum of 20% IOP-lowering response to a topical prostaglandin analog. Four doses of the bimatoprost SR implant (6, 10, 15, or 20 µg) were studied; the fellow eye was treated with topical bimatoprost 0.03% once daily. If additional medication was needed, either a topical rescue medication or a single repeat implant was permitted.
At 24 months, all four doses of the SR implant demonstrated a mean pressure reduction in the range of 7.3-8.9 mm Hg vs 8.2 mm Hg in the topically treated fellow eye. Rescue or re-treatment was necessary in 32% of implant eyes by 6 months, 60% by 12 months, and 72% by 24 months.
Adverse events occurring in the study eyes within 2 days of the procedure were transient. Thereafter, the incidence of adverse events was similar in both study and fellow eyes, demonstrating the very low risk posed by injecting the small implant into the anterior chamber via a 28-gauge delivery system.
These data reveal the considerable promise of this implant, with all tested doses achieving IOP lowering equal to that of topical bimatoprost and minimal IOP fluctuation on diurnal testing. The implant appears to pose no increased patient risk and even lowers long-term cosmetic side effects compared with topical administration. And, of course, the implant eliminates the need for patients to remember daily doses of a medication, thus improving quality of life and compliance.
There are several important questions surrounding this implant that will require answers. Most important is that the efficacy and duration of this implant remain unclear.
It is marketed to last 3-6 months. However, the phase 1/2 study data indicate that > 50% of eyes had sustained IOP lowering for at least 6 months post implant, and in a small percentage of patients the effect was sustained up to 24 months. This was a surprising finding given that in vitro the drug is released over 90 days, and in vivo studies revealed nondetectable levels by 4.5 months.
The implant degradation (estimated by a percentage of the original size) can similarly vary anywhere from 76% to 125% at month 6. By month 12, the majority had totally degraded or become less than 25% of their initial size. In the eyes that did not have to be rescued or re-treated, 28.6% had no visible implant at 24 months, yet IOP nonetheless remained controlled. Before we can determine the appropriate follow-up for IOP checks or repeat implantation schedule, the true degradation rate in humans needs to be clarified.
This fluctuating degradation rate may be dependent on multiple factors, such as age, race, gender, or even previous topical medication usage. It may be necessary to elucidate these factors to properly counsel individual patients on how long their implant may last before they consent to undergo this procedure.
As suggested by the authors of the phase 1/2 study, the mechanism of sustained IOP lowering even after implant degradation in some patients may be due to its ability to achieve higher target tissue drug concentrations than topical administration, which can result in durable tissue remodeling of the trabecular meshwork. If this proves to be the case, it will certainly influence how physicians counsel their patients regarding the frequency at which they may need another implant. The implant is currently approved for only one administration, but further studies will hopefully encourage the approval of repeated implantations.
We also require additional research to determine the ideal concentration of medication in the implant. The current release is for 10 mg, but if it can be determined that a higher concentration is more likely to stimulate long-term changes to the trabecular meshwork, then the benefit of the implant would be twofold.
The surprising results regarding this implant's duration of effect leave many unanswered questions. What is clear, however, is that this implant is an exciting new option for lowering IOP in the treatment of glaucoma and a step in the right direction to reducing blindness related to this common disease.
Shuchi B. Patel, MD, is director of glaucoma services in the department of ophthalmology at West Palm Beach VA Medical Center in Florida. She explores the ever-changing glaucoma space for Medscape, including advances in diagnostics and treatments.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Shuchi B. Patel. Bimatoprost Implant a Promising Weapon in Fight Against Glaucoma - Medscape - Jun 26, 2020.
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