ICER Issues Final Report and Policy Recommendations for Add-on Therapies to Treat Type 2 Diabetes

— Oral GLP-1 semaglutide achieves commonly cited thresholds for cost-effectiveness but is less cost-effective than SGLT-2 competitor empagliflozin —

— Independent appraisal committee votes that oral semaglutide provides a superior net health benefit over background therapy alone, achieves intermediate long-term value for money, and may be an attractive alternative for patients who would prefer an oral treatment; however, the large potential short-term budget impact associated with treating even a small percentage of eligible US patients leads ICER to issue an Access and Affordability Alert —

BOSTON, December 9, 2019 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report and Report-at-a-Glance assessing the comparative clinical effectiveness and value of oral semaglutide (Rybelsus®, Novo Nordisk), a GLP-1 receptor agonist for the treatment of Type 2 diabetes mellitus (T2DM). This new therapy is an oral version of the injectable Ozempic® (Novo Nordisk), which was approved by the FDA in 2017. For this analysis, adding oral semaglutide was compared to background therapy with metformin alone, and to three competitors for add-on therapy: liraglutide (Victoza®, Novo Nordisk), sitagliptin (Januvia®, Merck), and empagliflozin (Jardiance®, Boehringer Ingelheim). ICER’s report on these therapies was reviewed at the November 2019 public meeting of the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), one of ICER’s three independent evidence appraisal committees.

“People with Type 2 diabetes who would like to use a GLP-1 receptor agonist have had no oral options until oral semaglutide, which appears to have similar efficacy to that of the injectable GLP-1s,” said David Rind, MD, ICER’s Chief Medical Officer. “However, oral semaglutide’s estimated net price is much higher than that of the oral SGLT-2 inhibitors like empagliflozin that appear to have similar benefits with fewer common side effects, making SGLT-2 inhibitors a more cost-effective ‘next’ therapy for many people with T2DM. Many patients may require multiple therapies, and clinical experts at our public meeting felt that a large percentage of the eligible patient population that could have benefited from GLP-1 therapy but avoided it because of the need for injections would be interested in trying an oral GLP-1; this could potentially create short-term budgetary challenges for the US health care system.”

During the meeting, CEPAC members unanimously voted that the evidence was adequate to demonstrate that adding oral semaglutide to ongoing background therapy provides a positive net health benefit, and that this benefit is superior to that provided by adding sitagliptin. However, a majority of the CEPAC found that the evidence did not adequately demonstrate that the net health benefit of adding oral semaglutide was superior to that of adding liraglutide, nor did the evidence adequately distinguish the net health benefit of adding oral semaglutide from that provided by adding empagliflozin.

During their deliberation, panel members also weighed the therapies’ other benefits and contextual considerations. Noting that diabetes represents a particularly high lifetime burden of illness, the panel members voted that the oral version of semaglutide offers reduced complexity compared to injectable liraglutide, and this reduced complexity may significantly improve patient outcomes.

Given the available evidence on comparative effectiveness and incremental cost-effectiveness, and considering other benefits, disadvantages, and contextual considerations, the CEPAC panel voted that oral semaglutide provides “intermediate” long-term value for money. When compared to background therapy alone, oral semaglutide’s annual estimated net price of $6,103 falls within ICER’s value-based price benchmark range of $6,000-$6,400 per year. However, oral semaglutide is unlikely to reach commonly cited thresholds compared with empagliflozin.

ICER’s value-based price benchmarks suggest a price range, net of any discounts and rebates, that aligns fairly with a treatment’s added benefits for patients over their lifetime. The ranges reflect commonly cited cost-effectiveness thresholds between $100,000 and $150,000 per Quality-Adjusted Life Year (QALY) gained. Prices at or below these thresholds help ensure that the health benefits gained by patients using new treatments are not outweighed by health losses due to long-term cost pressures that lead individuals to abandon care or lose health insurance. To reach thresholds of between $100,000 and $150,000 per life year gained, oral semaglutide would need to be priced between $6,400-$7,100 per year.

Access and Affordability Alert

ICER is issuing an Access and Affordability Alert for oral semaglutide. At the public meeting, clinical experts stated their belief that, because primary care providers are often uncomfortable prescribing injectable GLP-1 receptor agonists, oral semaglutide would be an attractive alternative for up to 50% of the eligible patient population. However, at oral semaglutide’s estimated net price, despite meeting common lifetime cost-effectiveness thresholds, only approximately 7% to 14% of eligible US patients could be treated in a given year before crossing ICER’s potential budget impact threshold of $819 million.

The purpose of an ICER Access and Affordability Alert is to signal to stakeholders and policy makers that the amount of added health care costs associated with a new service may be difficult for the health system to absorb over the short term without displacing other needed services or contributing to rapid growth in health care insurance costs that threaten sustainable access to high-value care for all patients.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts — including clinicians, patient advocates, and representatives from manufacturers and payers — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

• Manufacturers with new diabetes agents should seize the opportunity to come to market with a lower list price to benefit patients.
• To provide high quality head-to-head evidence on the comparative effectiveness of emerging treatment options for patients with diabetes, manufacturers should look to the example set by the PIONEER trials of oral semaglutide.
• As the treatment options for T2DM continue to evolve, primary care providers should make themselves aware of the updated clinical guidelines to ensure that all treating clinicians know how to identify the varying risks and benefits of different agents for particular subpopulations.
• Given the high rate of gastrointestinal side effects with oral semaglutide, real-world evidence on adherence should be studied and reported.

ICER’s detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

About ICER 

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.