WILL SUSTAINED RELEASE OCULAR FORMULATIONS REVOLUTIONISE THE RETINAL THERAPEUTICS MARKET? GROUP 12 DARA BELL ARRON COLEMAN LARA GIBNEY MIKEY O’CONNOR
WILL SUSTAINED RELEASE OCULAR FORMULATIONS REVOLUTIONISE THE
RETINAL THERAPEUTICS MARKET?
GROUP 12
DARA BELL
ARRON COLEMAN
LARA GIBNEY
MIKEY O’CONNOR
RETINAL THERAPEUTICS MARKET VALUED AT OVER $3 BILLION IN 2013.
DIABETIC RETINOPATHY (DR)/ DIABETIC MACULAR EDEMA (DME)
• Leading cause of blindness in working-aged population affecting over 8 million
people living in the U.S.
• Abnormal growth of blood vessels in attempt to restore normal bloodflow to
ischemic retina.
• Leads to development of diabetic macular edema (DME).
• Poorly developed blood vessels cause leakage of water, blood cells and proteins
into surrounding retinal tissue.
• Results in dysfunction of macula and decreased vision.
AGE RELATED MACULAR DEGENERATION (AMD)
• Degenerative retinal disease causing progressive loss of central vision.
• Leading cause of irreversible vision loss in individuals over the age of 50
affecting 11 million people in the U.S.
• Promotes the growth of new, weak blood vessels behind the retina that leak lipids
and serum into macular cells
• Leads to progressive death of macular cells.
CURRENT PHARMACOLOGICAL TREATMENTS
• Growth of immature endothelial blood vessel in DR and AMD promoted by
vascular endothelial growth factor (VEGF).
• Current treatments aimed at inhibiting VEGF and reducing blood vessel formation.
• All current anti-VEGF treatments are in the form of intra-vitreal injections.
PROBLEMS WITH CURRENT PRODUCTS ON THE MARKET ?
• Risks associated with intra-vitreal injections.
• Administration requires an opthalmologist.
• Dosage frequency.
• Cost effectiveness.
CANDIDATES FOR SRDF:
• Have neither a very long (>8 hours) nor a very
short half life (<2 hours)
• Possess a therapeutic index
• Contain desirable absorption and solubility
characteristics
• Administered in relatively small doses
• Used for treating chronic instead of acute
conditions.
POSTERIOR SOLUTIONS:
Figure1. Intra-vitreal implants, biodegradable
or non-biodegradable
Figure 2. Sustained Release of an Anti-
Glaucoma Drug: Demonstration of Efficacy of
a Liposomal Formulation in the Rabbit Eye
ADVANTAGES OF SRDF OVER OTHER CONVENTIONAL
FORMS:
• Decreased local and systemic side effects which results in reduced gastrointestinal irritation
• Reduction in cost
• Reduction in dosing frequency
• Reduction of fluctuations in circulating drug levels
• Improvement in patient compliance and reduced patient care time
Figure 1. Plasma Drug Concentration Profile for Conventional Release, a Sustained Release and Zero Order Controlled Release
DISADVANTAGES OF SRDF:
• Dose dumping.
• Poor systemic availability in
general.
• Reduction in the potential for
dosage adjustment.
• It is unpredictable for in-vitro
and in-vivo correlation.
CURRENT SUSTAIN RELEASE THERAPIES FOR DME/ AMD
OZURDEX (DEXAMETHASONE IMPLANT)
• A sustain release biodegradable implant
• FDA approved since 2014
• A corticosteroid that blocks chemical pathways which leads to inflammation, leakage from the
retinal blood vessels and swelling of the retina.
• Advantages: long duration (4-6 months)
Small injection, no stitches needed
• Disadvantages: can cause increased I.O.P, therefore regular monitoring is necessary.
Can potentially result in cataracts
OZURDEX: HOW IT WORKS?
• Ozurdex is an implant which gets injected into the
vitreous humour of the eye.
• The biodegradable material of the implant mixes
with the dexamethasone (the active drug) forming
the rod shaped implant.
• Once injected into the eye, the vitreous gel causes
the implant to slowly dissolve, releasing the drug
dexamethasone.
• It works by suppressing inflammation which inhibits
inflammatory cytokines and results in decreased
oedema, capillary leakage, fibrin deposition and
migration of inflammatory cells.
FLUOCINOLONE ACETONIDE (FA) INTRAVITREAL IMPLANT (ILUVIEN)
• A sustain released non-biodegradable implant
• FDA approved since 2014
• Advantages: long duration (up to 36 months)
• Disadvantages: eye infections, inflammation or
increased IOP and cataracts.
• How it works: iluvien is similar to ozurdex as it is
a small implant injected into the eye. The drug
released from the implant is fluocinolone
acetonide.
THE FUTURE OF THE RETINAL THERAPEUTICS MARKET
1. Future projected prevalence of key diseases
2. Factors affecting demand for retinal products
INCREASING DEMAND FOR OCULAR THERAPY AS A RESULT OF A GREYING POPULATION
PROJECTED NO. OF PEOPLE AGED OVER 60 (GLOBAL) UP TO 2050
The over 60 age group will rise from 750 million in 2010 to roughly 1 billion in 2020 and 2 billion in 2050 -
Retinal diseases such as macular degeneration, and Diabetic retinopathy occur at a rate of 7.6%, and 1.9%,
respectively, in populations over 40
RISE IN RETINAL DISEASE PROMINENCE
AMD - approx. 18 million in 2010-35 million in 2020
-More than 25 companies are currently working on developing sustained release drug delivery systems
Env1305, sustained release treatment of amd. -Long
term studies to assess pharm kinetics starting this year
RISE IN RETINAL DISEASE PROMINENCE
Diabetic Macular Edema
-Approx. 33 million people worldwide-
-ENV1105 treatment of DME , sustained release,
minimum of 6 months
retinal diseases market –$6500m in 2013 to $12,400m in 2019
Sustained ocular release market-2014 Market research study predicted The overall market is likely to be more
than USD 6 billion in the coming decade. [Smith- 2015].
38%
43; 43%
12%
7%
Retinal market 2013
DME AMD RVO Other
References1. http://jamanetwork.com/journals/jamaophthalmology/fullarticle/419278
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306122/
3. http://www.envisiatherapeutics.com/
4. https://www.slideshare.net/prashantmane01/sustained-release-drug-delivery-system?next_slideshow=1
5. "OZURDEX®". Ozurdex.com. N.p., 2017. Web. 18 Apr. 2017.
6. "ILUVIEN For Diabetic Macular Edema - Iluvien". Iluvien. N.p., 2017. Web. 19 Apr. 2017.
7. Schmit-Eilenberger, Vera. "A Novel Intravitreal Fluocinolone Acetonide Implant (Iluvien&Reg;) In The Treatment of Patients With Chronic
Diabetic Macular Edema That Is Insufficiently Responsive To Other Medical Treatment Options: A Case Series". Clinical Ophthalmology
(2015): 801. Web.
8. Dugel, Pravin U., Francisco Bandello, and Anat Loewenstein. "Dexamethasone Intravitreal Implant In The Treatment Of Diabetic Macular
Edema". Clinical Ophthalmology (2015): 1321. Web.
9. http://www.prnewswire.com/news-releases/sustained-release-ocular-drug-delivery-systems-2015---2025-2nd-edition-300158356.html
10. http://www.envisiatherapeutics.com/overview
References
11. https://www.reviewofophthalmology.com/article/systemic-drugs-with-ocular-side-effects
12. http://www.ncbiotech.org/article/envisia-raises-165m-advance-eye-therapies/168911
13. http://www.harriswilliams.com/sites/default/files/content/hwco_hcls_vision_industry_updatev2.pdf
14. https://eandv.biomedcentral.com/articles/10.1186/s40662-015-0026-2
15. https://www.visiongain.com/Press_Release/768/Retinal-Disease-Pharmaceutical-Sales-Will-Reach-12-5bn-In-2019-A-New-
Visiongain-Study-Predicts
16. Macular Degeneration (AMD) And Other Retinal Diseases: World Drug Industry And Market 2015-2025 [2015]