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Uveitis eye

Uveitis
(Macular Edema associated with non-infectious uveitis)

  • Uveitis is a collection of inflammatory conditions affecting the eye. Roughly 30 diseases causing inflammation in the eye fall under the classification of uveitis.
  • Uveitis is classified as noninfectious (NIU) (approximately 80% of cases) or infectious (approximately 20% of cases). 1
  • Uveitis is further identified by the dominant (geographic) location of the inflammation in the eye as anterior, intermediate, posterior, or pan uveitis.
  • Over 350,000 adults in the U.S. have uveitis. Most patients are aged 20-50 years. 2
  • Uveitis does not cause mortality, but morbidity results from chronic swelling in the retina, called macular edema, which may lead to vision loss.
  • Macular edema may be found with any geographic location of uveitis,3 and affects approximately 30-40% of all uveitis patients. 4
  • Even though macular edema is the dominant cause of vision loss in uveitis patients, there are no approved treatments for macular edema associated with uveitis.

1. Miserocchi, E., Fogliato, G., Modorati, G. & Bandello, F. Review on the worldwide epidemiology of uveitis. European Journal of Ophthalmology 2013;23:705-717.

2. Thorne, J. E., Suhler, E., Skup, M., Tari, S., Macaulay, D., Chao, J., & Ganguli, A. Prevalence of noninfectious uveitis in the United States: A claims-based analysis. JAMA Ophthalmology 2016;134, 1237–1245.

3. Karim, R., Sykakis, E., Lightman, S. & Fraser-Bell, S. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis. Clinical ophthalmology (Auckland, N.Z.) 2013;7, 1109–44.

4. Lardenoye, C. W. T. A., van Kooij, B. & Rothova, A. Impact of Macular Edema on Visual Acuity in Uveitis. Ophthalmology 2006;113, 1446–1449.

Current Treatments for Noninfectious Uveitis

Current treatments for NIU are systemic or local to the eye, if not both.

  • Systemic treatments include corticosteroids and other immunomodulatory therapies.
  • Local therapies are most commonly corticosteroids that are used in and around the eye, either topically as drops or injected peri-ocularly (sub-Tenons) or intra-ocularly (intravitreal injections or implants). 1

The Unmet Need

There are no approved treatments for vision impairment associated with uveitic macular edema, even though macular edema is the dominant cause of vision loss in uveitis patients.

1. Jabs, D. a et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. American journal of ophthalmology 130, 492–513 (2000).

Uveitis Phase 3: PEACHTREE Trial

  • Two-armed randomized, controlled, double-masked, multi-center trial at ~60 clinical sites
  • 3:2 randomization of suprachoroidal CLS-TA vs. sham injection; 160 patients total
  • Primary endpoint at week 24: superiority of best corrected visual acuity from treatment

Peachtree

Design for Pivotal Phase 3 Clinical Trial

Peachtree Graph

Primary Endpoint

Proportion of patients in each arm gaining ≥ 15 ETDRS letters in BCVA from baseline at Week 24

Secondary Endpoint

Mean change from baseline in CRT at week 24 in microns

Secondary Endpoint

Secondary Endpoint

Mean change from baseline in BCVA in ETDRS letters by visit

BCVA and ME

Summary of Best Corrected Visual Acuity by Visit, Study Eye (LOCF Method); ITT population

Safety Summary

safety summary

Uveitis Phase 2: DOGWOOD Trial

  • Single suprachoroidal injection of CLS-TA 4.0 mg or 0.8 mg
  • Randomized, controlled, masked, multi-center trial
  • 22 subjects with macular edema associated with noninfectious uveitis
  • Primary endpoint: reduction in retinal thickness at 2 months

Primary Endpoint

Reduction in CST1 From Baseline – ITT Population N=17

Primary Endpoint

1CST is the central retinal thickness measured using optical coherence tomography (OCT)
* One patient was not included in this measurement

Secondary Endpoint

Best Corrected Visual Acuity - ITT Population1

Secondary Endpoint

1N = 17

2Eylea®, Lucentis®, Ozurdex® Prescribing Information

BCVA and ME Improvements at Month 2

Percent of Patients with BCVA Improvement

BCVA Chart

Macular Edema Outcomes  Percentage
20% reduction in retinal thickness 69%
Retinal thickness ≤ 310 microns 56%

Anterior Chamber (AC) Cells, AC Flare and Vitreous Haze – Reduced From Baseline to Month 2 (4.0 mg group; ITT)

Anterior Chamber

AC cells, AC flare and vitreous haze are signs of inflammation of the eye

  • Each of these signs shows favorable changes from baseline
  • The average in each case shows trend toward improvement; a majority of individual patients either improve or maintain low levels

Phase 1/2 study in non-infectious uvetis (NIU)

Study design

Phase 1/2 Study

Open label, multi-center study

  • Subjects with noninfectious uveitis
  • Single suprachoroidal injection of TA
    • 8 subjects received a single unilateral suprachoroidal injection of TA
    • Followed for 26 weeks

Phase 1/2 Study - Change in retinal thickness from baseline

change in retinal thickness

The data shown are descriptive; no imputations have been performed on the data. Information for subjects at a time point is shown for subjects who remain on study medication at time of evaluation

Phase 1/2 Study - Change in visual acuity from baseline

change in visual acuity

The data shown are descriptive; no imputations have been performed on the data. Information for subjects at a time point is shown for subjects who remain on study medication at time of evaluation

Uveitis Phase 2 & Phase 1/2 Safety Summary

  • No serious adverse events related to treatment
  • No adverse events leading to discontinuation
  • No steroid-related increase in IOP
  • Only adverse events related to treatment in more than 5% of dosed patients were cystoid macular edema, blurred or decreased vision, and eye pain

Retinal Vein Occlusion (RVO)

  • Retinal vein occlusion is blockage of the veins that drain the retina.
  • RVO is a common cause of vision loss, affecting 16 million people (5.20 per 1000) world wide.
  • It is the leading cause of blindness from retinal vascular disease after diabetic retinopathy.
  • RVO is most often caused by atherosclerosis and the formation of a blood clot. It can lead to further eye problems including glaucoma and macular edema.

Treatment Goal

The goal of treatment is to reduce morbidity and prevent complications

Current Treatments

Anti-VEGF agents - Eylea, Lucentis and Avastin Corticosteroids - Dexamethasone and Triamcinolone Acetonide Lasers
Anti-VEGF agents are most commonly used as first line therapy. Please see Eylea PI or Lucentis PI for their use in the treatment of RVO

Treating Ocular Inflammation

Retinal Vein Occlusion Phase 2: TANZANITE Trial

  • Single suprachoroidal injection of CLS-TA plus intravitreal Eylea® versus intravitreal Eylea only in treatment naïve RVO patients
  • 1:1 controlled, randomized, masked, multi-center trial
  • 46 subjects with macular edema associated with Retinal Vein Occlusion
  • Treatment naïve patients randomized to treatment first day and evaluated monthly
  • Primary endpoint: the number of times patients met the criteria for additional intravitreal Eylea treatments over the three-month trial duration

Eylea is a registered trademark of Regeneron®

60% Fewer Additional Intravitreal Eylea Injections in the Suprachoroidal CLS-TA + Intravitreal Eylea Arm Versus Control Over 3 Months

Number of Additional Intravitreal Eylea Injections

60% Fewer Additional Eylea Injections

Intent to treat (ITT) population N = 46 (23:23)

69% Fewer Patients Required Additional Eylea® Treatments

60% Fewer Additional Eylea Injections

Intent-to-treat (ITT) population: N = 46 (23:23)


1 Based on post-hoc analysis

Suprachoroidal CLS-TA + Intravitreal Eylea Resulted In Improved Visual Acuity at Months 1, 2, 3 vs. Intravitreal Eylea Alone

suprachoroidal cls-ta

Proportion of patients

M1 = Month 1; M2 = Month 2; M3 = Month 3

Suprachoroidal CLS-TA + Intravitreal Eylea Resulted in Sustained Retinal Thickness Reductions at Months 1, 2, 3 vs. Intravitreal Eylea Alone

Sustained Retinal Thickness Reductions

Post-TANZANITE Evaluation: 74% of Patients who Received Combination Therapy Did Not Receive Additional Treatment Through a Minimum Nine Months

Post Tanzanite Evaluation

RVO Phase 2 & Post-TANZANITE Evaluation Summary

Suprachoroidal CLS-TA + Intravitreal Eylea vs. Intravitreal Eylea alone

  • Greater improvement of vision compared with Intravitreal Eylea alone in phase 2 trial
  • Sustained clinical benefit over the 3-month trial period
  • Significantly fewer additional Intravitreal Eylea treatments

Safety Summary

  • No serious adverse events
  • No adverse events leading to discontinuation
  • Only adverse events observed in more than 5% of patients in the suprachoroidal CLS-TA + intravitreal Eylea arm were conjunctival hyperemia, eye pain, ocular hypertension and increased IOP

Extension Study

  • Conducted an extended evaluation to better assess the duration of effect of the combination treatment and the potential to reduce the burden of therapy
  • Patients who completed TANZANITE and did not receive first re-treatment during TANZANITE
  • Patients managed according to treating physician’s discretion without a prospective protocol
  • Records were obtained retrospectively
  • Main efficacy outcome: time to first RVO re-treatment

Diabetic Macular Edema (DME)

Diabetic Macular Edema (DME) is an accumulation of fluid in the macula caused by leaky blood vessels as a consequence of diabetes mellitus. It is defined as retinal thickening within 2 disc diameters of the macula center. DME is the most common complication of Diabetes in patient with Diabetes Retinopathy, affecting more than 150 million people worldwide. It may cause images to appear blurry or wavy and colors that seem “washed out”.

Treatment Goal

Prevention of vision loss is important, visual improvement would be preferable.

Current Treatments

  • Corticosteroid Implants
  • Intravitreal injections corticosteroid Implants
  • Anti-VEGF Therapy used off label
  • Laser treatments or pars plana vitrectomy

Clinical Trial Design

Phase 1/2 Study

  • Single suprachoroidal injection of CLS-TA alone and in combination with intravitreal Eylea
  • 10 treatment naïve subjects and 10 subjects treatment non-naïve
  • Safety and efficacy information will be collected through the entire time period

enrolling patients

Focused Pipeline of SCS Treatments for Multiple Blinding Eye Disease

Indication

Study drug

Current Status

Uveitis
(macular edema associated with non-infectious uveitis)
Suprachoroidal CLS-TA
(corticosteroid triamcinolone acetonide)
row1
RVO
(retinal vein occlusion)
Suprachoroidal
CLS-TA with anti-VEGF (Intravitreal Eylea®)
row2
DME
(diabetic macular edema)
Suprachoroidal CLS-TA
alone or with anti-VEGF (Intravitreal Eylea)
row3
Retinal Vasular Disease Proprietary Compound(s) row4
Orphan Diseases Gene Therapy row5

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