Verisome (TM) a New Injectable Sustained Release and Biodegradable Intraocular Drug Delivery System

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Verisome Presented at the American Society of Retina Specialists Annual Meeting, October 11-15, 2008, Maui, HI

Verisome Presented at the American Society of Retina Specialists Annual Meeting, October 11-15, 2008, Maui, HI

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  • Good morning – on behalf of my coauthors, I would like to introduce to you the Verisome. A new, injectable sustained release and biodegradable drug delivery system.
  • I do not have an equity interest in ICON, but do receive research funding.
  • With the FDA approval of Macugen and Lucentis, medical therapies for ocular disease are exceptionally promising. But, the frequency of these invasive treatments or hardware inside the eye are a drawback. This leads us to the question of whether a versatile, effective biodegradable delivery platform can be developed.
  • ICON Bioscience has developed the Verisome Drug Delivery Technology that is injectable through a standard 30g needle. This verisome is biodegradable and versatile for different drugs including steroids, NSAIDS, and biologic materials. The duration is determined by the volume adminstered and can range from 1 day to one year.
  • Here we can see an in vitro image of triamcinolone with this verisome technology. it is being tested in two forms – one 6 month and one 12 month dose. This is a linear system that provides the same concentration of drug on a daily basis with the duration dependent on the volume of drug administered.
  • In a rabbit model, No initial burst or spike in the drug concentration was seen and a linear volume related duration was observed.
  • Today, I will be presenting preliminary results of the first Phase I of the verisome technology in humans. Triamcinolone for cystoid macular edema due to retinal vein occlusion or pseudophakia was selected for this study.
  • As this is a Phase I study, Safety is the primary endpoint. Secondary endpoints are systemic safety and changes in vision and OCT at day 180.
  • Patients with a diagnosis of CME due to RVO with vision better than 20/200 and CRT greater than 250um were included. Patients with a diagnosis of glaucoma, on any glaucoma medications or who were known steroid responders were excluded.
  • After IRB approval and written consent were obtained, Patients received one injection at baseline and are being followed though the course of one year. Cohort two was started once all patients in the shorter group cleared the primary safety endpoint at day 60.
  • 10 patients have been enrolled at 3 sites between October 2007 and July 2008. Patients have a mean age of 73 years and are predominantly female. All patients have CME due to RVO. Mean Baseline vision was 48 letters and mean OCT CRT was 508um. The study is ongoing and I will be presenting data as of August 1 st .
  • The primary endpoint is safety. One patient in each group had an increase in IOP but all patients have been managed with topical anti-glaucoma medications. One vitreous hemorrhage was observed in the longer duration group, but it is unknown whether this is treatment related. No endophthalmitiis, cataract, retinal detachment, or other drug related adverse events have been reported.
  • A secondary endpoint is change in OCT CRT. This is a graph of patients in the longer acting group. This reduction in retinal thickness demonstrates a controlled release efficacy through 120 days. Data collection is ongoing.
  • At baseline, retinal edema is seen on the macular map and radial line scans. The cysts are absent by day 7 and remain so.
  • Here is a slit lamp photo of the verisome immediately after injection before it has settled down in the vitreous. And here is a fundus photo of it inside the eye. The verisome sits below the visual axis.
  • On ultrasound imaging, we can see the verisome in the vitreous cavity of a rabbit model and then in our patient.
  • In conclusion, this Phase I study of triamcinolone with the verisome technology has not shown any unexpected safety issues to date and controlled release efficacy has been confirmed. We look forward to starting enrollment in Phase II in the fourth quarter.

Transcript

  • 1. Verisome ™ a New Injectable Sustained Release and Biodegradable Intraocular Drug Delivery System Anne Fung MD Mark Wieland MD, Vernon Wong MD, Mae Hu PhD Glenn Huang MS, Faina Karasina PhD
  • 2. Financial Disclosures
    • Research Support
      • Genentech
      • Icon Bioscience
      • CoMentis
    • Advisor
      • Genentech
      • Santen
      • Oraya
    • Speaker
      • Genentech
    Funding for this study provided by ICON Bioscience. The speaker has no equity interest in these companies.
  • 3. Background
    • Medical ocular therapies promising
    • Frequency of injections a drawback
    • Implanted devices a drawback
    • Could a biodegradable, injectable, self-forming sphere be developed?
  • 4. Verisome ™ Drug Delivery Technology
    • Standard 30g intravitreal injection
    • Biodegradable
      • Drug and carrier fully degraded as drug is released
    • Versatile for different drugs
      • Small molecules – steroids, NSAIDS, antibiotics
      • Monoclonal antibodies
      • Proteins
      • Nucleic Acids
    • Duration determined by volume administered
      • Can tailor to individual patients from 1 week to 1 year+
  • 5. Investigational Product
    • Designation: IBI 20089
    • Active Ingredient: Triamcinolone Acetonide, USP
    • 2 Dosage Forms:
      • ~ 6 month duration 20089 6.9 mg/25 ul
      • ~ 12 month duration 20089 13.8 mg/50 ul
      • Both should provide same concentrations of drug ( ~ 1.75ug/ml) with duration dependent on volume given.
    14 October 2008 26th Annual Meeting of the American Society of Retina Specialists
  • 6. IBI 20089: Rabbit Model
  • 7. A Phase I Open-Label, Dose Escalation Study of the Safety and Tolerability of 20089 (Triamcinolone Acetonide Intravitreal Injection) in the Treatment of Patients with Cystoid Macular Edema Associated with Retinal Vein Occlusion or Pseudophakia Purpose
  • 8. Study endpoints
    • Primary endpoint: Ocular safety (hemorrhage, infection, glaucoma, cataract, RD)
    • Secondary endpoints:
      • Systemic safety
      • Change in BCVA through day 180
      • Change in OCT CRT through day 180
  • 9. Patients
    • Inclusion criteria
      • Diagnosis: CME due to RVO or Pseudophakia
      • Baseline vision 20/40 – 20/200
      • OCT with CRT > 250um
    • Exclusion criteria
      • Glaucoma or any glaucoma medications
      • Known steroid responders
      • Previous vitrectomy
      • Previous laser, steroid, anti-VEGF within 90 days
  • 10. Methods
    • IRB approval of the protocol and written informed consent obtained
    • Single intravitreal injection at Baseline
      • 5 patients in cohort 1 – 6 month duration
      • If OK, then cohort 2 enrolled – 12 month duration
    • Visits at
      • Screening and Baseline
      • Days 1, 7
      • Months 1, 2, 4, 6, 9 and 12
    • Primary safety endpoint at Day 60
  • 11. Results Patient Baseline Characteristics
    • 10 patients enrolled at 3 sites
      • Baseline visits October 2007 - July 2008
      • 5 per group (6 and 12 month doses)
    • Women 9, Men 1
    • Mean age 73 years (range 55-88)
    • All CME associated with RVO
    • Baseline ETDRS vision: Mean 48, (range 5-70)
    • Baseline OCT CRT: Mean 508 (range 299-673)
    • Range of Duration in Trial: 1 to 8 Months
    • Current Trial Status: Ongoing
    • Data as of August 1, 2008
  • 12. Results Ocular Safety
    • All patients managed with topical glaucoma meds
    • No other drug related adverse reactions reported (no endophthalmitis, cataract, RD)
    1 0 Patients with >10 mmHg IOP rise Patients with < 10 mmHg IOP rise Vitreous hemorrhage 6.9 mg (shorter duration) 1 0 13.8mg (longer duration) 0 1
  • 13. Results OCT Central Retinal Thickness 13.8 mg 14 October 2008 26th Annual Meeting of the American Society of Retina Specialists
  • 14. Case 02-204 74yo woman, CRVO with recurrence of macular edema after bevacizumab injections
  • 15. Baseline Day 1 Day 7 Day 30 Day 60 Day 90 Day 120 20/125 20/160 20/125 20/100 20/100 20/400 20/320
  • 16. Results – In vivo IBI 20089 immediately after injection in human eye
  • 17. Results B scan Ultrasound Rabbit Human – Patient 02-204
  • 18. Triamcinolone Verisome™ Conclusions
    • Phase I in progress
    • No significant safety signals to date
    • Controlled-release efficacy confirmed
    • Phase II to begin Q4 2008
    • This and future products developed using Verisome™ Technology may offer clinical advantages
      • Standard intravitreal injection technique
      • Biodegradable as drug released
      • Ability to tailor duration to individual patients
      • Lack of hardware allows repeat dosing
  • 19. Phase I 20089 Study Group
    • Anne Fung MD
    • San Francisco CA
    • Mark Wieland MD
    • San Jose CA
    • Jenny Lim MD
    • Chicago IL