MODELING THERAPEUTIC PERSISTENCE IN OCULAR THERAPIES: A REVIEW OF HTA SUBMISSIONS
Author(s)
Pushkar Narvilkar, MSc1, Sandra Milev, MSc2, Anadi Mahajan, PharmD3, Anshul Shah, B.pharm, MSc4, Benjamin White, MSc2, Monique Martin, MSc, MBA3.
1Red Nucleus, Dombivali, India, 2Red Nucleus, Yardley, PA, USA, 3Red Nucleus, London, United Kingdom, 4Red Nucleus, yardley, PA, USA.
1Red Nucleus, Dombivali, India, 2Red Nucleus, Yardley, PA, USA, 3Red Nucleus, London, United Kingdom, 4Red Nucleus, yardley, PA, USA.
OBJECTIVES: Therapeutic persistence is a key driver of cost-effectiveness uncertainty in ocular disease HTA. We evaluated how persistence assumptions are modeled and scrutinized across ocular classes and jurisdictions.
METHODS: HTA appraisals across three product classes were identified: inherited retinal and optic nerve diseases (voretigene neparvovec, idebenone; n=7), extended-interval anti-VEGFs (faricimab, brolucizumab, aflibercept 8 mg; n=13), and standard anti-VEGFs (aflibercept 2 mg, ranibizumab, bevacizumab gamma; n=4) across NICE, CADTH, ICER, SMC, HAS, G-BA, and PBAC (2008-2025). Five persistence domains were assessed: durability/waning, injection burden, treat-and-extend (T&E) modeling, visual acuity (VA) extrapolation, and discontinuation.
RESULTS: Persistence-related uncertainty differed by therapeutic class. Durability/waning and VA extrapolation were the key drivers in inherited retinal and optic nerve disease submissions, while injection burden and T&E modeling governed extended-interval anti-VEGF appraisals. Scrutiny of the same domain varied across HTAs: conservative durability assumptions raised voretigene neparvovec ICERs. NICE shortened treatment-effect duration; CADTH applied broader conservative assumptions; HAS modeled 10-year stabilization followed by 10-year waning; SMC varied duration, residual effect, and waning period. Idebenone in Leber's hereditary optic neuropathy (LHON) relied on extrapolation of short-term trial data using observational follow-up. For extended-interval anti-VEGFs, T&E maintenance was pivotal: CADTH’s re-analysis, assuming equal injection frequency, required price reductions up to 98%; G-BA rejected claims because aflibercept was not dosed per its T&E label. VA extrapolation was less impactful, as the committees accepted non-inferior outcomes and scrutiny fell on dosing frequency. Discontinuation was not a key driver.
CONCLUSIONS: Ocular HTA scrutiny differed by persistence domain and therapeutic class: durability and VA extrapolation dominated when there was no strong evidence on extended benefit, while T&E maintenance and injection frequency dominated in interval-extension paradigms. As gene therapies and sustained-release treatments enter ocular markets, durability and extrapolation scrutiny will likely remain central.
METHODS: HTA appraisals across three product classes were identified: inherited retinal and optic nerve diseases (voretigene neparvovec, idebenone; n=7), extended-interval anti-VEGFs (faricimab, brolucizumab, aflibercept 8 mg; n=13), and standard anti-VEGFs (aflibercept 2 mg, ranibizumab, bevacizumab gamma; n=4) across NICE, CADTH, ICER, SMC, HAS, G-BA, and PBAC (2008-2025). Five persistence domains were assessed: durability/waning, injection burden, treat-and-extend (T&E) modeling, visual acuity (VA) extrapolation, and discontinuation.
RESULTS: Persistence-related uncertainty differed by therapeutic class. Durability/waning and VA extrapolation were the key drivers in inherited retinal and optic nerve disease submissions, while injection burden and T&E modeling governed extended-interval anti-VEGF appraisals. Scrutiny of the same domain varied across HTAs: conservative durability assumptions raised voretigene neparvovec ICERs. NICE shortened treatment-effect duration; CADTH applied broader conservative assumptions; HAS modeled 10-year stabilization followed by 10-year waning; SMC varied duration, residual effect, and waning period. Idebenone in Leber's hereditary optic neuropathy (LHON) relied on extrapolation of short-term trial data using observational follow-up. For extended-interval anti-VEGFs, T&E maintenance was pivotal: CADTH’s re-analysis, assuming equal injection frequency, required price reductions up to 98%; G-BA rejected claims because aflibercept was not dosed per its T&E label. VA extrapolation was less impactful, as the committees accepted non-inferior outcomes and scrutiny fell on dosing frequency. Discontinuation was not a key driver.
CONCLUSIONS: Ocular HTA scrutiny differed by persistence domain and therapeutic class: durability and VA extrapolation dominated when there was no strong evidence on extended benefit, while T&E maintenance and injection frequency dominated in interval-extension paradigms. As gene therapies and sustained-release treatments enter ocular markets, durability and extrapolation scrutiny will likely remain central.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE582
Topic
Economic Evaluation, Health Technology Assessment
Disease
Sensory System Disorders (Ear, Eye, Dental, Skin)