ISPOR Europe 2019, Copenhagen, Denmark, 2-6 November, 2019 COST-EFFECTIVENES ANALYSIS OF USING PEGVISOMANT FOR TREATMENT OF ACROMEGALY IN RUSSIA Nikolay A. Avxentyev 1, Maxim Y. Frolov 2 , Alexander S. Makarov 3 1 Research Institute of Finance and Russian Presidential Academy of National Economy and Public Administration, Moscow, Russia 2 Volgograd State Medical University and Volgograd Medical Scientific Center, Volgograd, Russia 3 Interregional Association of Clinical Pharmacologists, Volgograd, Russia BACKGROUND • Acromegaly is a neuroendocrine disease leading to chronic overproduction of growth hormone (somatotropin). • Pegvisomant is a genetically modified analogue of human growth hormone, which is an antagonist of its receptors. The suppression of the action of growth hormone under the influence of pegvisomant leads to a decrease in the concentration of insulin-like growth factor (IGF-I) in blood 1. • As of 2019 pegvisomant is not included in the Vital and Essential Drug List (VEDL) in Russia, which limits access to this therapy for patients with limited treatment options. OBJECTIVES • To perform a cost-effectiveness analysis (CEA) that compares pegvisomant with the best supportive care (BSC) from the Russian healthcare system perspective. METHODS • Following acromegaly therapy options for patients, who had no adequate response to surgical treatment and / or radiation therapy and / or somatostatin analogues therapy, were considered: 1. Pegvisomant (40 mg at the first day of treatment, then 15 mg daily, which is in line with average daily dose in the long-term study of pegvisomant 2 ); 2. BSC with no medical treatment, since patients usually do not receive medications in such clinical situation in Russia (according to survey of 5 practicing physicians, who have experience in acromegaly treatment in Russia). • We developed mathematical model of acromegaly progression on pegvisomant or BSC. The model includes the following sequential mutually exclusive health states (Figure 1): 1. Normal level of IGF-I concentration; 2. Elevated level of IGF-I concentration; 3. Death. CONCLUSION Pegvisomant is a cost-effective option for acromegaly treatment, compared to BSC, and should be recommended for inclusion into VEDL in Russia. FUNDING: This study was funded by Pfizer, Inc. (developer of pegvisomant). REFERENCES 1. Trainer, Peter J., et al. “Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.”New England Journal of Medicine 342.16 (2000): 1171–1177. 2. van der Lely, Aart Jan, et al. “Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.” The Lancet 358.9295 (2001): 1754–1759. 3. Holdaway, I.M., M.J. Bolland, and G.D. Gamble. “A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly.” European Journal of Endocrinology 159.2 (2008): 89–95. 4. Mortality rates by age and sex. Centre for Demographic Research at the New Economic School (CDR). http:// demogr.nes.ru/index.php/ru/demogr_indicat/data 5. Omelyanovskiy, V., et al. “PCN286-Incremental cost-effectiveness ratio for the antineoplastic drugs approved and rejected for the vital and essential drugs list in 2017 in Russia.” Value in Health 21 (2018): S62-S63. Figure 1. Mathematical model of acromegaly development • Transition probabilities between the first two states were derived from the 12-week randomized clinical trial that compared three pegvisomant regimens vs placebo 1. • After 12 weeks we assumed no transitions between normal and elevated IGF-I concentration states and only considered mortality, which was higher in the elevetad IGF-I concentration state, according to meta-analysis 3. • Probability of death was calculated using survival curve for Russian general population of 48- year olds (mean age of acromegaly diagnosis in Russia + 2 years) 4, which was adjusted by standardized mortality ratios for acromegaly patients with normal IGF-I (1.1) and with elevated IGF-I (2.5) 3 • The model was used to calculate direct medical costs associated with considered options that include: 1. Medications (pegvisomant); 2. Monitoring. • We used a lifetime horizon and calculated incremental cost-effectiveness ratio (ICER) as difference in costs of pegvisomant vs BSC derived by difference in life-years gained (LYG). RESULTS • Pegvisomant was associated with 26.65 LYG vs 21.60 LYG on BSC (Figure 2). • Annual medication costs of pegvisomant were US$44,524 per patient. • Lifetime medical costs associated with pegvisomant treatment were US$496,971 per patient (Table 1). • ICER for pegvisomant vs BSC was US$98 318 per one LYG. • This value is within the actual ICER range for antineoplastic drugs, approved for the VEDL in 2017 in Russia 5 (Table 2). Figure 2. Effecacy end-points in the model Table 1. Cost US$* per patient (1US$=64.5372 RUB on 22.05.2019) Option 1 (Pegvisomant) Option 2 (BSC) Differece Elevated IGF-I 10,442 164 10,278 Medication 10,394 0 10,394 Monitoring 48 164 –116 Normal IGF-I 486,529 21 486,508 Medication 486,368 0 486,368 Monitoring 161 21 140 Total 496,971 186 496,785 Table 2. ICERs of drugs approved for VEDL in 2017 in Russia, US$ (1US$=64.5372 RUB on 22.05.2019) Tumor localization ICER per LYG per Progres- sion-free LYG Breast cancer 69,702 173,549 Rectal and rectosigmoid junction cancer 71,555 76,535 Lung cancer 90,099 110,568 Urogenital cancer 103,102 221,629 Cancer of the lymphatic and hematopoietic tissue 239,077 112,283 Skin cancer – 170,573 Figure 3. One-way sensitivity analysis of incremental costs per LYG for pegvisomant vs BSC • Sensitivity analyses showed that results were robust to variations in model assumptions (Figure3). PDB 89 • Key limitations of the analysis were the following: • We assumed no change of response to treatment after week 12, i.e. after that time IGF-I level remains on the same level until death; • If there were no response on pegvisomant treatment by the end of week 12, we assumed pegvisomant discontinuation without any dose adjustments, which may not reflect the real- world practice. However, sensitivity analysis (fig. 3) suggests that results are robust, at least unless pegvisomant dose is ≤ 20 mg daily for all patients.