Dexamethasone implant a first for macular edema after retinal vein occlusion - Benefits possible from drug delivery, effect on inflammation

Dexamethasone implant a first for macular edema after retinal vein occlusion - Benefits possible from drug delivery, effect on inflammation - Ophthalmology Times

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Dexamethasone implant a first for macular edema after retinal vein occlusion

Benefits possible from drug delivery, effect on inflammation

Jul 15, 2009
By: Nancy Groves
Ophthalmology Times

The recently approved dexamethasone 0.7 mg intravitreal implant (Ozurdex, Allergan) for the treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion first delivers the drug in a high dose and then in a lower, sustained dose. This delivery may allow better control of the disease while minimizing corticosteroid side effects.
The drug also reduces inflammation, which may play an important role in RVO.
The most common adverse reaction was increased IOP, which was reported in 25% of patients. This effect was temporary.
Doctors may choose to use this new treatment by itself or in combination with currently used laser therapies.
In the future, additional agents may be approved and considered for monotherapy or multimodality therapy against RVO.

Dr. Blumenkranz

The FDA has approved the dexamethasone 0.7 mg intravitreal implant (Ozurdex, Allergan) as the first drug therapy indicated for the treatment of macular edema (ME) following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).

The announcement was made in late June. The implant is expected to be available in the third quarter.

The implant contains a biodegradable, injectable steroid with extended drug release. It is administered by intravitreal injection via a proprietary solid polymer delivery system (Novadur, Allergan) designed to guide implantation in the vitreous cavity in the back of the eye, where it can treat ME and improve visual acuity.

In two multicenter, double-masked, randomized parallel studies involving approximately 1,300 patients, 20% to 30% of subjects treated with the implant experienced a three-line improvement in best-corrected visual acuity (BCVA). The onset of effect occurred within the first 2 months following therapy, and the duration of effect persisted an additional 1 to 3 months after onset, said Scott M. Whitcup, MD, executive vice president, research and development, and chief scientific officer at Allergan.

In the individual studies and a pooled analysis, the time to achieve a three-line improvement in BCVA cumulative response rate curves was significantly faster with the dexamethasone implant compared with sham (p < 0.01). Patients treated with the implant had the three-line improvement in BCVA earlier than the sham-treated patients.

Options expanding

The steroid implant is a welcome addition to the therapeutic options for both forms of RVO, according to Mark S. Blumenkranz, MD, professor and chairman, Department of Ophthalmology, Stanford University, Palo Alto, CA, said in an interview with Ophthalmology Times. Dr. Blumenkranz was a member of the study design team for the implant but was not an investigator in the clinical trials.

Between 140,000 and 150,000 new cases of RVO are diagnosed each year in the United States, he said; BRVO cases occur two to three times as frequently as those of CRVO, but both are associated with significant visual morbidity.

"One of the distinguishing features of this drug is that it is delivered in a very slow, precise way, which results in modest bioavailable dose of drug at any one point. As a result, we think that may have a beneficial effect on its side effect profile compared with a bolus injection," Dr. Blumenkranz said.

Data from earlier phase II studies of the implant suggested that the rates of adverse events often encountered with other steroids might be reduced by extended delivery of relatively low doses for moderate time periods. When the full data set from the most recent studies is released, clinicians should be in a position to evaluate this important issue critically.

According to Dr. Whitcup, pre-clinical pharmacokinetic studies show that the implant releases a high dose of dexamethasone over the first 2 months, followed by a lower, sustained release of the drug out to 6 months as the implant biodegrades. This initial pulse of dexamethasone followed by a sustained lower dose of the drug may allow better control of the disease and minimize corticosteroid side effects, he said.

The dexamethasone implant was extremely well-tolerated in the clinical studies, Dr. Whitcup added. The most common adverse reaction in patients receiving the implant was increased IOP, which was reported in 25% of patients. This effect was temporary, however. The occurrence of increased IOP peaked at day 60 but returned to baseline levels by day 180. Cataract was reported in 4% of patients receiving the implant and in 1% of patients receiving sham.