Clearside Biomedical to report key milestones in 2018
Clearside Biomedical (NASDAQ:CLSD) is expected to report several key milestones in 2018 in its programs of developing potential treatments for back of the eye diseases with its corticosteroid therapy, CLS-TA, administered through the suprachoroidal space (SCS) to readily access the retina and choroid and thereby target disease pathology.
CLS-TA is Clearside’s suspension formulation of the corticosteroid, triamcinolone acetonide, for suprachoroidal administration.
“There are several key milestones in 2018 that are important inflection points for our potential treatments of eye diseases with our SCS platform,” Charlie Deignan, CFO, says in an interview with BioTuesdays.
Clearside’s upcoming milestones include top line data from a pivotal Phase 3 trial in non-infectious uveitis in the first quarter and top line data from a Phase 2 study in diabetic macular edema (DME) in the second quarter.
And in the first quarter of 2019, the company expects to release top line results from a first Phase 3 trial in patients with retinal vein occlusion (RVO).
Mr. Deignan explains that precise access to the back of the eye through the SCS for CLS-TA has the benefit of potentially resulting in high drug concentrations at the sites of disease in the retina and choroid, and away from the anterior chamber and lens where side effects occur, such as cataracts and the elevation of intraocular pressure.
“Our extensive patent estate includes proprietary access to the suprachoroidal space and for treatments of eye diseases through this 17-square cm area of the eye,” he adds.
In addition to RVO, uveitis and DME, Clearside also is collaborating with multiple companies in preclinical programs, evaluating potential pharamacologic candidates for treatments of diseases through the SCS. These studies include approaches to treat retinal vascular diseases and gene therapy.
“The objectives of our clinical programs are improved benefit-to-risk ratios, rapid vision gains, consistent patient response and sustained vision improvement,” Mr. Deignan points out.
A good example is in Clearside’s program in RVO, the second most common cause of blindness from retinal vascular disease after diabetic retinopathy. RVO is a blockage of the veins that carry blood away from the retina, which converts light images to nerve signals and sends them to the brain. RVO affects 16 million people worldwide, with an estimated U.S. prevalence of 2.2 million people.
According to Mr. Deignan, anti-VEGF agents are currently first-line therapy for macular edema secondary to RVO, and are used monthly initially before attempting to extend the interval between treatments. Phase 3 trials of anti-VEGF agents used six monthly injections.
Intravitreal corticosteroids are generally used as second-line treatment in patients with RVO when there is persistence of edema after a long course of injections of a VEGF-neutralizing protein, or when there appears to be an inability to substantially extend the period between anti-VEGF injections without recurrent edema. “There is a clear need here to improve this high treatment burden on RVO patients,” he suggests.
Clearside’s Phase 2 RVO trial, where outcomes from patients receiving a single suprachoroidal CLS-TA injection plus a single intravitreal Eylea injection were compared with outcomes from those receiving a single intravitreal Eylea injection only in treatment of naïve RVO patients, showed potential patient advantages in the combination arm.
Patients in each arm could receive as needed intravitreal Eylea at each monthly visit. In the trial, patients in the combination arm showed greater improvement of vision starting at the first month, compared with those in the Eylea alone arm.
In addition, the clinical benefit, both in terms of vision and retinal thickness, was sustained over the three-month trial period and there were significantly fewer additional Eylea treatments through the three-month trial.
“Faster improvement in vision is very important to doctors in the care of their patients because the earlier visual acuity gains in patients could not only result in earlier resolution of disease complications, but also could lead to better longer- term visual outcomes,” Mr. Deignan points out.
In addition, there were no serious adverse events in the combination arm in the Phase 2 study and no adverse events that led to patients discontinuing treatment.
In an extension study, Clearside found that 74% of patients who received combination therapy at baseline in the Phase 2 trial did not receive additional treatment through a minimum of a nine-month observation period.
Clearside’s first Phase 3 RVO trial is a yearlong study, and is currently enrolling 460 patients worldwide at 150 clinical sites, with 230 patients receiving the combination of CLS-TA plus Eylea, and 230 patients Eylea alone. Patients in the combination treatment arm will receive suprachoroidal CLS-TA together with intravitreal Eylea at the beginning of the trial, Eylea alone at week 4, and CLS-TA together with Eylea at weeks 12 and 24.
Patients in the control arm will receive intravitreal Eylea alone at the beginning of the trial and follow-up treatments of Eylea alone every four weeks through week 24.
After 24 weeks, patients will be followed for approximately an additional six months, with as needed treatments in each arm. The primary endpoint is superiority of best-corrected visual acuity after two months.
Last August, Clearside completed enrollment of 160 patients in a pivotal Phase 3 trial of suprachoroidal CLS-TA for the treatment of macular edema associated with non-infectious uveitis. Patient follow-up in the trial is six months, leading to data readout in the current quarter.
“This is our most advanced clinical development program and the data readout will be our first key milestone in 2018,” Mr. Deignan says.
The primary efficacy outcome measure in the Phase 3 trial is based on improvement in best-corrected visual acuity over the six-month duration of the study. Safety will be assessed by analyzing the occurrence of adverse events and changes in key safety parameters over the course of the trial.
Based on feedback from an end-of-Phase 2 meeting with the FDA, Clearside believes that the current pivotal trial in non-infectious uveitis will be sufficient to support a potential new drug application filing at the end of 2018.
Uveitis is a set of inflammatory conditions affecting the eye and is one the world’s leading causes of blindness. Uveitis occurs in about 350,000 patients in the U.S. and is typically found in both eyes. Macular edema occurs in approximately one-third of all non-infectious uveitis cases and is a major contributor to vision loss in these patients.
Administration of corticosteroids is the most common treatment for all forms of uveitis, including macular edema. “Corticosteroids show reasonable efficacy but 35% to 40% of patients develop elevated intraocular pressure, and similar numbers of patients have cataract formation or worsening,” Mr. Deignan notes.
In an earlier Phase 2 uveitis study, CLS-TA demonstrated substantial improvements in efficacy with a statistically significant reduction in retinal thickness and a statistically significant mean nine-letter eye chart improvement in best-corrected visual acuity. In addition, there were no corticosteroid-related increases in intraocular pressure, which was very important, Mr. Deignan adds.
A third Clearside program is in diabetic eye disease. DME is an accumulation of fluid in the macula caused by leaky blood vessels as a consequence of diabetes. DME is the most common complication of diabetes in patients with diabetic retinopathy. It may cause images to appear blurry or wavy and colors that seem washed out.
There are an estimated 29.1 million people with diabetes in the U.S., of which 1.1 million have DME. In Europe, there are some 55 million people with diabetes, of which 5.8 million have DME.
Current treatments for DME include anti-VEGF injections, with Eylea providing the greatest benefit in patients with poorer vision; corticosteroids, such as Iluvien and Ozurdex; and lasers to cauterize leaky blood vessels. Similar to the treatment of RVO, anti-VEGF agents appear to be first-line therapy in patients with DME.
A Phase 2 DME study has completed enrollment, with preliminary data expected in the second quarter this year. Patients will be evaluated on a monthly basis through the six-month trial period, with best-corrected visual acuity as the primary outcome measure.
“While the results of the exploratory Phase 2 remain to be seen, if suprachoroidal CLA-TA can provide a potential for the treatment of DME, this will represent an additional large market opportunity,” Mr. Deignan suggests.
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