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Specialty Pharmacy Continuum • May/June 2022
CLINICAL
Predicting the Cost of NASH Therapies desaturase-1 (SCD1) inhibitors; pegylated fibroblast growth factor-21 analogs; apoptosis signal–regulating kinase-1 (ASK1) inhibitors; and galectin-3 inhibitors (Nat Rev Gastroenterol Hepatol 2021;18:373-392). Some drugs that have failed as monotherapy for NASH are still being studied as part of dual or triple therapies, Dr. Lugo noted. For example, selonsertib (Gilead), an ASK1 inhibitor, and elafibranor, a PPAR agonist, are being continued in trials as part of combination therapies. Phase 2 trials are being conducted in many additional agents, Dr. Lugo said, including the first potential triplecombination therapy of semaglutide (Ozempic, Novo Nordisk), a subcutaneous GLP-1 receptor agonist, with the FXR agonist cilofexor and the ACC inhibitor firsocostat (Gilead) (box).
Belapectin (Galectin): An IV galectin-3 inhibitor
with NAFLD (61,332 individuals) and NASH (13,645 individuals) diagnoses. They also reviewed usage of medications for diabetes such as dapagliflozin (Farxiga, AstraZeneca), obeticholic acid (Ocaliva, Intercept), odevixibat (Bylvay, Albireo), pioglitazone and semaglutide. Rates were fairly low, ranging from 0% to 1.3% of beneficiaries with NAFLD and 0% to 2.8% of those with NASH. Next, Dr. Palmrose’s team incorporated cost estimates from the Institute for Clinical and Economic Review (ICER) on the long-term cost-effectiveness of obeticholic acid for NASH. The estimated cost is $219.96 per dose for federal agencies, or $80,340 per year. The published ICER model posted prices for a quality-adjusted life-year (QALY) threshold of $50,000, $100,000 or $150,000 per year, treating an estimated 3 million patients over five years, and with a budget impact threshold of $819 million per year for new drugs used. In this model, ICER estimated that only 4.2% of patients could be treated before reaching the QALY threshold of $50,000 if the annual per-patient cost was $11,800. At an annual per-patient cost of $16,000, only 3% of beneficiaries could be treated before reaching the QALY threshold of $150,000. Payors can use data points such as these as starting points to estimate budget impact and try to determine the level at which it would be difficult for the health system to absorb without displacing other needed services, Dr. Palmrose said. Building on the ICER analyses, TRICARE estimated it could treat 10.8% of beneficiaries receiving dapagliflozin at a yearly cost per patient of $4,752 before reaching their impact threshold, or 100% of beneficiaries receiving pioglitazone at a yearly cost per patient of $84 before reaching their impact threshold, he said, citing some examples. Payors can evaluate their potential patient populations for NASH medications based on risk factors among their beneficiaries such as age, obesity, diabetes and dyslipidemia, Dr. Lugo added, and be prepared to expect “a significant cost to the health system.” Work with pharmacoeconomics specialists to put together models, evaluate the potential budget impact, develop any prior authorization criteria focusing on criteria in the clinical trials and “come up with a good definition of response to ensure you’re getting the most bang for your buck out of these products,” she advised.
Cenicriviroc (Allergan): An oral CCR2/5 dual antagonist being studied in combination with the FXR agonist tropifexor (Novartis) in a phase 2b study
Dr. Lugo reported no relevant financial disclosures. Dr. Palmrose reported holding stock in Walgreens Boots Alliance.
By Karen Blum
Chicago—The race continues for pharmaceutical companies to gain FDA approval for a drug for nonalcoholic steatohepatitis (NASH), speakers said during the AMCP 2022 annual meeting. Payors should plan ahead to estimate the effects on their budgets. “There’s so many people with their hands in the pot trying to get a product approved,” said Amy Lugo, PharmD, BCPS, a clinical pharmacy specialist and formulary manager for the Defense Health Agency Pharmacy Operations Division. “It’s important to stay vigilant, focusing on ClinicalTrials.gov, with how many different sponsors are in the game.” As of January 2022, there were 86 drug-related trials for NASH in phases 2 and 3 from 62 sponsors, Dr. Lugo said, as well as 11 phase 4 studies of currently marketed products. An estimated 22% of the gastroenterology drug pipeline is for liver disease therapies, she said, citing April 2019 data from IQVIA. “Eventually, something is going to get FDA approved, and likely it’s going to have an orphan designation, which oftentimes allows for the manufacturer to charge a higher price,” she added. NASH is a subset of nonalcoholic fatty liver disease (NAFLD), a condition of excess fat buildup in the liver, Dr. Lugo said. It is marked by inflammation, liver fibrosis and sometimes cirrhosis. About one-fourth of U.S. adults, 75% of obese individuals and 10% of children aged 2 to 19 years have NAFLD (Hepatology 2016;64[1]:73-84). This represents the potential patient pool that could progress to NASH, she said. An estimated 5% to
6.5% of U.S. adults have NASH, and 20% of those patients will develop cirrhosis. Risk factors include age (40-60 years), obesity, diabetes, high cholesterol and ethnicity, with Hispanics having the highest prevalence (Cochrane Database Syst Rev 2017;3[3]:CD011640), Dr. Lugo said. “Given the high prevalence of NASH risk factors in the U.S. population, one could assume the patient pool for a NASH drug to be tremendous,” she said. With no currently approved therapies, the mainstays of treatment include lifestyle modifications such as dietary changes and exercise, weight loss and control of diabetes, high cholesterol, and cardiovascular health. The three main targets among NASH drugs in development are to treat fibrosis, the metabolic pathway or inflammation, Dr. Lugo said. A variety of agents are being studied, she said, including farnesoid X receptor (FXR) agonists; peroxisome proliferator–activated receptor (PPAR) agonists; glucagon-like peptide-1 (GLP-1) receptor agonists and sodium– glucose cotransporter-2 (SGLT2) inhibitors; ileal bile acid transporter (IBAT) inhibitors; acetyl coenzyme A carboxylase (ACC) inhibitors; dual C-C chemokine receptor types 2 and 5 (CCR2/5) antagonists; thyroid hormone receptorbeta (THR-beta) agonists; stearoyl-CoA
Phase 3 Trials to Watch Odevixibat: An oral IBAT inhibitor approved for progressive familial intrahepatic cholestasis, a rare progressive liver disease Obeticholic acid: An oral FXR agonist approved for the treatment of primary biliary cholangitis Dapagliflozin: An oral SGLT2 inhibitor approved for the treatment of type 2 diabetes, heart failure and chronic kidney disease Arachidyl amido cholanoic acid (Aramchol, Galmed): An oral SCD1 inhibitor MGL-3196 (Resmetirom, Madrigal): An oral THR-beta agonist Selonsertib: An oral ASK1 inhibitor being studied in combination with the FXR agonist cilofexor and the ACC inhibitor firsocostat Oltipraz (PharmaKing): An oral liver X receptoralpha inhibitor
Data for Payors It’s difficult to estimate what the budget impact will be of any approved drugs, said Gregory Palmrose, PharmD, PhD, BCACP, the chief of enterprise integrated analytic solutions for the Defense Health Agency Pharmacy Operations Division. But there are some limited data available payors can use to conduct forecasts. TRICARE, the military’s health plan, has some 9.6 million beneficiaries, Dr. Palmrose said, 71% of whom used the pharmacy benefit in fiscal year 2021. To estimate the impact of NASH agents once approved, his team looked at their demographics of beneficiaries
