ISPOR Europe 2019, Copenhagen, Denmark, 2-6 November, 2019 BUDGET IMPACT 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 human growth receptor antagonist, which leads to normalization of serum insulin-like growth factor-I (IGF-I) concentrations in most patients with acromegaly 1,2 • Pegvisomant became available in Russia starting from 2018 3, but currently only few patients receive this treatment. OBJECTIVES • The aim of this study is to estimate budget impact of using pegvisomant in its target patient population in Russia during 2020–2022. METHODS • Since pegvisomant is indicated for patients with acromegaly, who have had an inadequate response to surgery, radiation therapy or treatment with somatostatin analogues in Russia 4, we proposed a Markov model of patient flows between these types of therapies, as well as treatment with dopamine receptor agonists and pegvisomant itself (Figure 1). CONCLUSION Using pegvisomant for acromegaly treatment would result into US$8.82 million (+28%) budget expenditure increase over 3 years 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. State Register of Medicines. https://grls.rosminzdrav.ru/GRLS.aspx?RegNumber= &MnnR=Пэгвисомант &lf=&TradeNmR=&OwnerName=&MnfOrg=&MnfOrgCountry=&isfs=0&isND=-1®type=&pageSize=10&or der=RegDate&orderType= desc&pageNum=1 4. Pegvisomant medical label in Russia. https://grls.rosminzdrav.ru/Grls_View_v2.aspx? routingGuid=dab2d0a3- a1fc-4530-a941-184a8cba6d12&t= 5. Registry of patients with tumors in hypothalamic-pituitary region, june 2016. • The Russian healthcare system perspective was used, time horizon of the model was 3 years and the length of modelling cycle was 3 months. • Initial distribution of patients among treatment options was based on Russian hypothalamic and pituitary tumours registry. According to registry data, 44.9% of new patients receive surgery and/or radiotherapy and 55.1% start treatment with somatostatin analogues 5 • After failure of surgery/radiotherapy patients start somatostatin analogues therapy (2 nd line treatment). • If there is no response, patients start 3 rd line treatment: dopamine receptor agonist therapy ± surgery ± radiotherapy (in scenario without pegvisomant) or pegvisomant therapy (in scenario with pegvisomant). • In case of pegvisomant therapy failure, patients start dopamine receptor agonist therapy ± surgery ± radiotherapy. If this therapy fails no further active treatment is assumed in base case, but in scenario analysis a fraction of such patients can start pegvisomant treatment during each cycle. • Efficacy of pegvisomant was based on Trainer et al. data 1 and for other therapy options was derived from the survey of 5 practicing physicians, who have experience in acromegaly treatment in Russia. Quarterly transition probabilities are presented on Figure 1. • We validated the model by adding 120 patients to the model every cycle (average number of new acromegaly cases in Russia quarterly), until there were approximately 3 430 living patients. This number was achieved by the 129 th cycle that was dated as Q2 2016, since 3 428 living patients with acromegaly were registered in Russia at that time 5. Cycles 144–155 corresponded to Q1 2020 – Q4 2022, respectively. • Direct medical costs of treating acromegaly were considered, including: 1. Medications: – somatostatin analogues (lanreotide 120 mg every 28 days first 3 months and 120 mg every 42 days after; octreotide 20 mg every 28 days); – dopamine receptor agonists (cabergoline 0,5 mg daily; bromocriptine 10 mg daily); – pegvisomant (40 mg at the first day of treatment, then 15 mg daily); 2. Monitoring; 3. Surgery; 4. Radiotherapy. • Budget impact was defined as the difference between direct medical costs associated with acromegaly with or without using pegvisomant in its target patient population in 2020–2022. RESULTS • Around 60 patients are eligible for initiation of pegvisomant treatment each year. 133 patients will be on pegvisomant treatment by the end of 2022. • Using pegvisomant will increase budget expenditure on acromegaly treatment by US$1.28 million (+12%) in 2020, US$3.00 million (+29%) in 2021 and US$4.54 million (+44%) in 2022 (Table 1). • Sensitivity analysis showed that results were robust to variations in model assumptions (Figure 2). Table 1. Budget impact, mln US$ Cost per patient groups Before including pegvisomant into VEDL, mln US$ After including pegvisomant into VEDL, mln US$ Budget impact, mln US$ 2020 2021 2022 Tota for 3 years 2020 2021 2022 Total for 3 years 2020 2021 2022 Total for 3 years Surgery and/or radiotherapy 0.19 0.18 0.17 0.55 0.19 0.18 0.17 0.55 – – – – Somatostatin analogues 10.05 9.80 9.55 29.40 10.05 9.80 9.55 29.40 – – – – Dopamine receptor agonists ± surgery ± radiotherapy 0.53 0.51 0.50 1.54 0.47 0.45 0.42 1.34 –0.06 –0.07 –0.07 –0.20 Pegvisomant – – – – 1.34 3.07 4.61 9.02 1.34 3.07 4.61 9.02 Total 10.77 10.50 10.22 31.49 12.05 13.50 14.76 40.31 1.28 3.00 4.54 8.82 Figure 2. One-way sensitivity analysis of budget impact 0% 14% 28% 42% 56% 70% 84% Proportion of patients recieving pegvisomant therapy after lack of remission on dopamine receptor agonists, 0 ... 2% Pegvisomant dosage, 10 ... 20 mg daily Proportion of patients, who has no response to somatostatin analogues therapy, 52.2% ... 72.2% Price of pegvisomant +/-15% Price of somatostatin analogues +/-15% Patient age, 36 ... 56 Positi ve budget i mpact N egative budget impact C os t s aving C os t increas e PDB 88 Figure 1. Mathematical model Note: doted lines reflect model states and transitions between them when using pegvisomant. Key limitations of the analysis were the following : • Patients distribution between the model states (treatment options of acromegaly) were dervied from the registry data that was published in 2016, which may not fully reflect current or future practice. • If there were no response 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. 2) suggests that results are robust, at least unless pegvisomant dose is ≤ 20 mg daily for all patients.