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New report finds critical flaws in drug pricing math used to deny patient care Traditional cost-effectiveness math omits quantifiable values recommended by leading health economists WASHINGTON, Sept. 06, 2023 (GLOBE NEWSWIRE) -- A new report released today by the nonprofit group No Patient Left Behind revealed critical flaws in a key metric used by U.S. insurance companies and foreign governments to determine whether to cover prescribed treatments at low out-of-pocket costs. The report found that the methodology used by the Institute for Clinical and Economic Review (ICER) for analyzing the cost-effectiveness of drugs has been incorrectly claiming a number of medications offer insufficient value to patients and society. “It’s time to get cost-effectiveness math right and stop using flawed math to undervalue the patient and societal benefits of new medicines,” said Peter Rubin, Executive Director of No Patient Left Behind (NPLB). “This report quantifies how society derives tremendous value from the net prices of new medicines and debunks the math used by insurers and foreign governments to justify that prescribed treatments are not worth covering at low out-of-pocket costs to premium-paying members.” The new study incorporates improvements long recommended by leading health economists and ISPOR to correct how traditional cost-effectiveness models determine the value of a drug. The report reviewed 20 medications that had previously been assessed by ICER using their traditional methodology. Under ICER’s approach, only eight of the 20 medications in the study were deemed at or before launch to have sufficient value to patients to justify their prices — a finding that insurance companies use to deny coverage. However, when the math is updated to model just some of the additional elements of value that medicines offer to society, the study found that at least 17 of the drugs provided good value for money. “Today’s price negotiations determine the focus of tomorrow’s innovations,” said Darius Lakdawalla, co-founder and Chief Scientific Officer of EntityRisk. “When prices accurately reflect value to society, they encourage innovation that benefits patients and their families the most. However, current approaches to computing value leave out known benefits that have been identified by scientific research. Our study demonstrates how to use cutting-edge methods and robust software tools to compute societal value efficiently and accurately so that prices can reflect real value and encourage the right kinds of innovation.” Making Cost-Effectiveness Math Better: Three Improvements The improved generalized cost-effectiveness analysis (GCEA) in the new study, conducted by a group of health economists with EntityRisk, made three key updates to the ICER cost-effectiveness model to bring it more in line with real-world patient experiences and market-pricing dynamics. One critical improvement involved the methods used to calculate the potential benefits that severely ill or disabled patients could receive from a particular treatment. The legacy approach to cost-effectiveness analysis (CEA) devalues medications given to people with severe illnesses or disabilities because they are judged to have a lower baseline quality of life. While the Inflation Reduction Act (IRA) explicitly forbids the government from placing a lower value on extending the lives of these patients, this disparity remains part of ICER’s formula. Traditional CEA also fails to account for the greater value that sicker patients might receive from a drug as compared to healthier patients. The updated analysis released by NPLB rejected this approach, adopting a methodology that ensures that the lives and health gains of disabled and severely ill patients are not undervalued. The ICER formula also assumes that a drug will always cost whatever its list price was during the first year it became available, disregarding negotiated rebates, how prices change over time, and how future patients might pay much less. The updated analysis adds two new factors to the equation: “dynamic pricing,” reflecting that drug prices typically fall sharply after generic versions become available, and “stacked cohorts,” accounting for the reality that people will start treatment in future years when the medicine is closer to going generic or already generic. Remember Lipitor? The new study included a re-analysis of atorvastatin, which was known as Lipitor when it first launched. Each year, millions of people diagnosed with high cholesterol start on generic statins, long after that class of medicines went generic, and are kept out of hospitals at low cost. Yet that quantifiable value doesn’t factor into how ICER or others practicing traditional cost-effectiveness math calculate the value of medicines when they first launch. Implications for IRA Implementation: The Cost of Bad Math The findings are especially significant as the federal government recently announced a list of ten drugs for which Medicare would begin “negotiating” with manufacturers to set their prices. Under the IRA, the government is required to negotiate “maximum fair prices” for drugs based on a range of factors that include, among others, values commonly used in CEA. Three of the drugs studied in the report were also included in CMS’ initial “negotiation” list: rivaroxaban (Xarelto), sitagliptin (Januvia), and empagliflozin (Jardiance). A fourth drug, Trikafta, was recently selected by the Colorado State Prescription Drug Affordability Board (PDAB) for potential price controls based on the ICER cost-effectiveness formula, a move that could lead to limited access and higher out-of-pocket costs for patients in the state. The traditional approach to cost-effectiveness math must be improved before it is adopted by the federal or state governments. CMS and state PDABs have the regulatory power to consult more comprehensive GCEA math when considering whether and how to set the prices of innovative medicines. “We are all patients — now or in the future,” Rubin continued. “This study suggests that US payors have been successful in securing cost-effective prices for their members. Payors have a responsibility to now pass along that value to patients without burdening them with high out-of-pocket costs." Read the full report released by No Patient Left Behind here: https://www.nopatientleftbehind.org/getting-the-math-right-when-valuing-new-medicines Watch this brief GCEA animation and read more about how to fix cost-effectiveness analysis to ensure that Americans have access to the medications they need at a low out-of-pocket cost. About NPLB: Our Goal is Affordable Innovation It’s not enough to just make today’s medicines affordable. NPLB is focused on achieving affordability and innovation because the continued development of new and better medicines is how we can reduce the suffering and cost of diseases that are not yet well addressed. NPLB has three guiding principles: 1) prescribed treatments should have low patient out-of-pocket costs; 2) drug prices should not stay high for too long; and 3) market- and patent-based incentives are effective at guiding investment to research and development that will solve the problems that most matter to society. NPLB previously commented on CMS’ proposed IRA guidance and 1,200 of its supporters sought improvements to IRA prior to its passage. When the price of medicine stays high for too long, NPLB supports government regulations to bring their prices down after a patent-based period of market-based pricing. The IRA approximates this for biologics by allowing them 13 years on the market and then having CMS force their prices down if there isn’t any biosimilar competition by that time. But the IRA overreaches in the case of small molecule drugs, price controlling them just nine years after their launch, creating a so-called “small molecule penalty” that has already driven shifts in investment away from the development of these highly valuable and cost-effective types of medicines. We want more Trikaftas and Lipitors, not fewer. Leaving diseases like Alzheimer’s untreated by discouraging the development of medicines to prevent dementia will not save money but rather drive up our healthcare costs because millions more people will be condemned to having their declining health managed in hospitals and nursing homes with significant burdens on caregivers. Biomedical innovation can be affordable. The right tool for that is insurance. When medicines turn out to be worth their prices to society, the right way to pay for them is as a society through premiums, not to burden with high out-of-pocket costs the few among us who happen to need treatment today. Just as the fire department doesn’t cover its costs by charging a family a copay before saving their burning home, neither should we do that with medicines that protect all of us, today or in the future, from the threat and cost of disease. Learn more at nopatientleftbehind.org. About EntityRisk EntityRisk was founded by Dana Goldman, PhD, Darius Lakdawalla PhD, and Neal Masia, PhD — three leading health economists bringing together decades of academic and industry experience to unlock financial innovation in the way new medicines are brought to patients. The company's data-driven solutions are helping large and small organizations across the healthcare ecosystem address the full spectrum of risk considerations ranging from the uncertainty of drug pricing and access to the uncertainty in real-world effectiveness, utilization, and value. Learn more here: EntityRisk.com. Contact: NPLBpress@nopatientleftbehind.org

CHICAGO--(BUSINESS WIRE)-- Xeris Biopharma, Inc. (Nasdaq: XERS), a growth-oriented biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies, today announced that the Food and Drug Administration (FDA) granted its subsidiary Xeris Pharmaceuticals, Inc., orphan-drug exclusivity (ODE) for Recorlev® (levoketoconazole) for the treatment of adult patients with endogenous Cushing’s syndrome for whom surgery is not an option or has not been curative. As the first approval of levoketoconazole (Recorlev) for Cushing’s syndrome, Xeris is entitled to seven years of orphan-drug market exclusivity from its FDA approval date of December 30, 2021. The FDA's Orphan Drug Designation program is designed to advance the development of drugs that treat a condition affecting 200,000 or fewer U.S. patients annually. This regulatory exclusivity is in addition to the patent exclusivity under Xeris’ U.S. patents covering Recorlev and its therapeutic use, which extends to at least March 2040. “Cushing’s syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options," said Paul R. Edick, Xeris’ Chairman and CEO. “We are excited to receive this important orphan-drug exclusivity approval for Recorlev on a new therapeutic option that can address symptoms while treating the root cause of the disease for this underserved Cushing’s patient community.” Mr. Edick continued, “Recorlev is an important and welcome therapeutic option for clinicians to help manage patients with endogenous Cushing's syndrome, a severe, potentially life-threatening rare disease. The approval of Recorlev was based upon data from two positive Phase 3 studies that evaluated a combined study population of 166 patients and was shown to be effective for reducing and normalizing cortisol.” In order to serve and support this community, Xeris is committed to ensuring everyone who needs access to their therapies will receive it. Xeris has created Xeris CareConnection™ to provide a comprehensive program for patients and their caregivers throughout the treatment journey, including financial assistance, one-on-one support, and educational resources. Xeris CareConnection also supports healthcare professionals and their teams through education on access and reimbursement. For more information visit our website ( ) or contact Xeris CareConnection (available Monday–Friday from 8 a.m–7 p.m ET) at 1-844-444-RCLV (7258). About Cushing’s Syndrome Endogenous Cushing’s syndrome is a rare, serious, and potentially fatal endocrine disease caused by chronic elevated cortisol exposure—often the result of a benign tumor of the pituitary gland. This benign tumor tells the body to overproduce high levels of cortisol for a sustained period of time, which often results in characteristic physical signs and symptoms that are distressing to patients. The disease is most common among adults between the ages of 30–50, and it affects women three times more often than men. Women with Cushing's syndrome may experience a variety of health issues, including menstrual problems, difficulty becoming pregnant, excess male hormones (androgens), primarily testosterone, which can cause hirsutism (growth of coarse body hair in a male pattern), oily skin, and acne.3 Additionally, the multisystem complications of the disease are potentially life threatening. These include metabolic changes such as high blood sugar or diabetes, high blood pressure, high cholesterol, fragility of various tissues, including blood vessels, skin, muscle, and bone, and psychological disturbances such as depression, anxiety, and insomnia.3 Untreated, the five-year survival rate is only approximately 50%.4 About Recorlev® Recorlev® (levoketoconazole) is a cortisol synthesis inhibitor for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.1 Endogenous Cushing’s syndrome is a rare but serious and potentially fatal endocrine disease caused by chronic elevated cortisol exposure.2 Recorlev is the pure 2S,4R enantiomer of ketoconazole, a steroidogenesis inhibitor.1 Recorlev has demonstrated in two successful Phase 3 studies to significantly reduce mean urinary free cortisol.1 The Phase 3 program for Recorlev included LOGICS and SONICS, two multinational studies designed to evaluate the safety and efficacy of Recorlev when used to treat endogenous Cushing’s syndrome. LOGICS, a double-blind, placebo-controlled, randomized-withdrawal study met its key endpoint of normalizing and maintaining therapeutic response compared with placebo.1 The supportive SONICS study met its primary and secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase.1,2 The ongoing open-label OPTICS study will gather further useful information related to the long-term use of Recorlev. Recorlev received orphan drug designation from the FDA and the European Medicines Agency for the treatment of endogenous Cushing's syndrome. Indication & Important Safety Information for Recorlev® BOXED WARNING: HEPATOTOXICITY AND QT PROLONGATION HEPATOTOXICITY Cases of hepatotoxicity with fatal outcome or requiring liver transplantation have been reported with oral ketoconazole. Some patients had no obvious risk factors for liver disease. Recorlev is associated with serious hepatotoxicity. Evaluate liver enzymes prior to and during treatment. QT PROLONGATION Recorlev is associated with dose-related QT interval prolongation. QT interval prolongation may result in life-threatening ventricular dysrhythmias such as torsades de pointes. Perform ECG and correct hypokalemia and hypomagnesemia prior to and during treatment. INDICATION Recorlev is a cortisol synthesis inhibitor indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative. Limitations of Use Recorlev is not approved for the treatment of fungal infections. CONTRAINDICATIONS Cirrhosis, acute liver disease or poorly controlled chronic liver disease, baseline AST or ALT > 3 times the upper limit of normal, recurrent symptomatic cholelithiasis, a prior history of drug induced liver injury due to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease. Taking drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes. Prolonged QTcF interval > 470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or prolonged QT syndrome. Known hypersensitivity to levoketoconazole, ketoconazole or any excipient in Recorlev. Taking certain drugs that are sensitive substrates of CYP3A4 or CYP3A4 and P-gp. WARNINGS AND PRECAUTIONS Hepatotoxicity Serious hepatotoxicity has been reported in patients receiving Recorlev, irrespective of the dosages used or the treatment duration. Drug-induced liver injury (peak ALT or AST greater than 3 times upper limit of normal) occurred in patients using Recorlev. Avoid concomitant use of Recorlev with hepatotoxic drugs. Advise patient to avoid excessive alcohol consumption while on treatment with Recorlev. Routinely monitor liver enzymes and bilirubin during treatment. QT Prolongation Use Recorlev with caution in patients with other risk factors for QT prolongation, such as congestive heart failure, bradyarrhythmias, and uncorrected electrolyte abnormalities, with more frequent ECG monitoring considered. Routinely monitor ECG and blood potassium and magnesium levels during treatment. Hypocortisolism Recorlev lowers cortisol levels and may lead to hypocortisolism with a potential for life-threatening adrenal insufficiency. Lowering of cortisol levels can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, and dizziness. Significant lowering of serum cortisol levels may result in adrenal insufficiency that can be manifested by hypotension, abnormal electrolyte levels, and hypoglycemia. Routinely monitor 24-hour urine free cortisol, morning serum or plasma cortisol, and patient’s signs and symptoms for hypocortisolism during treatment. Hypersensitivity Reactions Hypersensitivity to Recorlev has been reported. Anaphylaxis and other hypersensitivity reactions including urticaria have been reported with oral ketoconazole. Risks Related to Decreased Testosterone Recorlev may lower serum testosterone in men and women. Potential clinical manifestations of decreased testosterone concentrations in men may include gynecomastia, impotence, and oligospermia. Potential clinical manifestations of decreased testosterone concentrations in women include decreased libido and mood changes. ADVERSE REACTIONS Most common adverse reactions (incidence > 20%) are nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema. DRUG INTERACTIONS Consult approved product labeling for drugs that are substrates of CYP3A4, P-gp, OCT2, and MATE prior to initiating Recorlev.Sensitive CYP3A4 or CYP3A4 and P-gp Substrates: Concomitant use of Recorlev with these substrates is contraindicated or not recommended.Atorvastatin: Use lowest atorvastatin dose possible and monitor for adverse reactions for dosages exceeding 20 mg daily.Metformin: Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed.Strong CYP3A4 Inhibitors or Inducers: Avoid use of these drugs 2 weeks before and during Recorlev treatment.Gastric Acid Modulators: See Full Prescribing Information for recommendations regarding concomitant use with Recorlev. USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed during treatment and for one day after final dose. To report SUSPECTED ADVERSE REACTIONS, contact Xeris Pharmaceuticals, Inc. at 1-877-937-4737 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see Full Prescribing Information, including Boxed Warning. About Xeris Xeris (Nasdaq: XERS) is a growth-oriented biopharmaceutical company committed to improving patients’ lives by developing and commercializing innovative products across a range of therapies. Xeris has three commercially available products; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia, Keveyis®, the first FDA-approved therapy for primary periodic paralysis, and Recorlev® for the treatment of endogenous Cushing’s syndrome. Xeris also has an increasingly diverse pipeline of development and partnered programs using its proprietary formulation technology platforms, XeriSol™ and XeriJect™, bringing new products forward for the company as well as its partners Xeris Biopharma Holdings is headquartered in Chicago, IL. For more information, visit www.xerispharma.com, or follow us on Twitter, LinkedIn, or Instagram.