by April Ingram
In managing glaucoma, lowering the intraocular pressure (IOP) and preserving vision are always top priorities. If we can achieve these and, at the same time, support a good quality of life for the patient, then it’s a win-win situation.
The go-to, first-line therapy for glaucoma treatment is almost always topical prostaglandin analog (PGA) medication. PGAs are the first choice due to their trusted and favorable efficacy and safety profiles, not to mention the added benefit of a once-a-day dosing that patients appreciate and can easily adhere to. However, no matter how easy the medication instructions, compliance can be a challenge for patients. Several studies have shown that patients are not motivated to administer their medication as directed, especially when their glaucoma is still asymptomatic. Some of the reasons given for non-adherence include forgetfulness, difficulty of administration, medication cost and undesirable side effects. Non-compliance and non-adherence can be harmful to the patient and frustrating to the physician.
A Possible Answer to Patients’ Non-Adherence Issues
In a perfect world, we could take a page from our vitreoretinal colleagues and deliver a sustained release product and be assured that even our most noncompliant, no-show patient is taken care of. This perfect world may be on the horizon as sustained-release formulations are already in development – which hold the promise of prolonged drug exposure and specifically targeting intended tissues. This could be the answer to adherence and compliance issues of daily dosing and perhaps even the occurrence of surface and periocular adverse events.
Bimatoprost SR is a sustained-release, biodegradable implant currently in clinical development. This tiny, rod-shaped implant has a solid reservoir of bimatoprost, held within the biodegradable NOVADUR (Allergan, Dublin, Ireland) drug delivery platform. NOVADUR underwent some modification to ensure a steady-state, non-pulsatile slow release of bimatoprost after it has been placed intracamerally, using a prefilled, single-use applicator.
Backed by Scientific Studies
The promise of slow, controlled release of bimatoprost, which quietly and consistently lowers IOP in glaucoma patients for four to six months after administration, sounds pretty perfect. But what do the studies have to say?
Lewis and colleagues published their phase 1/2 study results in the American Journal of Ophthalmology in 2017, comparing the IOP-lowering effects of Bimatoprost SR to topical bimatoprost 0.03% over six months. They found the IOP-lowering efficacy to be similar1.
Jennifer Seal and colleagues recently explored the potential added benefit to intracameral implanted bimatoprost targeted drug delivery. By delivering the drug directly to the iris-ciliary body (ICB), the key site of PGA drug action, and limiting exposure to the conjunctiva and periocular tissues, they hypothesized a reduced occurrence of adverse effects that are typically associated with topical application. Their 2019 publication in the Journal of Ocular Pharmacology and Therapeutics describes the distribution of bimatoprost in ocular tissues of beagle dogs, quantified using liquid chromatography and tandem mass spectrometry following bilateral administration of either a topical bimatoprost 0.03% ophthalmic solution or Bimatoprost SR 15 mg2.
Seal et al., confirmed that administration of Bimatoprost SR provided targeted drug delivery to the ICB compared to topical bimatoprost, and drug distribution to surrounding ocular tissues, typically associated with PGA side effects (i.e., conjunctiva, eyelid margins and periorbital fat) were low or undetectable. The group concluded that by targeting bimatoprost delivery to the ICB, and reducing or eliminating exposure to non-target ocular tissues, that the incidence of adverse events typically associated with topical PGAs would be substantially reduced.
Presentation at the ASCRS 2019 Annual Meeting
At the recent American Society of Cataract and Refractive Surgery (ASCRS) 2019 annual meeting, Dr. E Randy Craven presented the 24-month results of the phase 1/2 study of Bimatoprost SR in glaucoma patients, which was previously published by Lewis3. In this presentation, they specifically looked at the relationship between implant degradation and IOP lowering over time.
They collected data related to whether patients required additional IOP-lowering treatment, and if so, at what time point after Bimatoprost SR implantation and what medications were used.
“IOP was controlled without rescue/retreatment in 68%, 40% and 28% of Bimatoprost SR-treated eyes up to six, 12 and 24 months, respectively,” explained Dr. Craven. More than 25% of patients did not require any additional treatment two years after Bimatoprost SR administration.
Dr. Craven presented a case that had a baseline IOP of 24.5 mmHg and received the 6 µg implant. At 24 months, the implant was no longer visible in the intracameral space, but the IOP was maintained at 15.5 mmHg. The second case received a 15 µg implant and had a baseline IOP of 22.0 mmHg. At 24 months the implant was barely visible and the IOP remained at 11.0 mmHg. These cases demonstrated reductions in IOP of 9.0 and 11.0 mmHg, without any added intervention, two years after Bimatoprost SR.
When the researchers looked at the rate of implant degradation, they found that at months 12 and 24, the implants were either totally biodegraded or most commonly ≤25% of their initial size at assessment. They concluded that the Bimatoprost SR implant, as expected, effectively reduced IOP, and slow biodegradation of implants was observed over 24 months.
The Future is Clear
“The sustained IOP lowering through month 24, when residual implant was small or no longer visible, was seen in some eyes and potentially may be explained by durable remodeling of aqueous outflow pathways,” shared Dr. Craven.
“Drop free medical therapy is on the horizon,” said Dr. Craven, summing it up perfectly. Data from two phase 3 trials showed a reduction in IOP of 30% over 12 weeks, and more than 80% of glaucoma patients were treatment-free after receiving three Bimatroprost SR treatments and did not require any additional treatment to control their IOP for at least a year. This data was used to support a recently accepted new drug application (NDA) by the United States Food and Drug Administration (US FDA).
Action on the NDA is expected in early 2020 ̶ very exciting news for the industry, and that this promising advancement in open-angle glaucoma or ocular hypertension treatment is one step closer to being available in practice.
REFERENCES:
1. Lewis RA, Christie WC, Day DG, et al. Bimatoprost sustained-release implants for glaucoma therapy: 6-month results from a phase I/II clinical trial. Am J Ophthalmol.
2017;175:137-147.
2. Seal JR, Robinson MR, Burke J, Bejanian M, Coote M, Attar M. Intracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues. J Ocul Pharmacol Ther. 2019;35(1):50-57.
3. Craven ER, Chen M, Zhang J, Robinson MR, Rhee DJ. Biodegradation of Intracameral Bimatoprost Sustained-Release Implant (Bimatoprost SR) in a 24-Month, Phase 1/2 Study in Glaucoma Patients. Presentation, ASCRS 2019.
