ICER Publishes Final Report and Policy Recommendations for Targeted Immune Modulator Therapies for Ulcerative Colitis

— Independent appraisal committee votes that evidence is adequate to demonstrate clinical superiority of vedolizumab over adalimumab —

— Due to competition introduced with biosimilars, the price for infliximab has dropped substantially in recent years; although prices are still marginally above traditional cost-effectiveness thresholds, the majority of independent appraisal committee members votes that infliximab and its biosimilars represent “intermediate” long-term value for money given their impact on patient benefits beyond health, such as improved work and educational opportunities —

— Recommendations arising from policy roundtable discussion urge structural changes to achieve lower drug prices that align with patient benefit, call for insurance benefits that eliminate financial pressure on patients to choose surgical treatment over medications, and delineate the requirements needed for appropriate design of step therapy and medication switching coverage policies —

BOSTON, October 16, 2020 – 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 the following targeted immune modulators (TIMs) that treat moderate-to-severe ulcerative colitis:

• Adalimumab (Humira®, AbbVie)
• Golimumab (Simponi®, Janssen)
• Infliximab (Remicade®, Janssen)
• Infliximab-abda (Renflexis®, Merck)
• Infliximab-dyyb (Inflectra®, Pfizer)
• Tofacitinib (Xeljanz®, Pfizer)
• Ustekinumab (Stelara®, Janssen)
• Vedolizumab (Entyvio®, Takeda)

ICER’s report on these therapies was reviewed at the September 2020 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s three independent evidence appraisal committees.

“Ulcerative colitis can create a lot of suffering for patients and their families and caregivers,” said Pamela Bradt, MD, MPH, ICER’s Chief Scientific Officer. “Fortunately, for patients not receiving adequate response to conventional immune modulator treatment, the evidence clearly demonstrates that targeted immune modulators often produce durable periods of clinical remission of ulcerative colitis symptoms, allowing patients to resume normal activities. However, there is very little head-to-head data comparing treatment options in this increasingly crowded, and expensive, therapy class. Prices are generally too high, even for the significant clinical benefits obtained, but the advent of biosimilars for infliximab has led to dramatic price decreases for this one agent and its biosimilars, displaying the potential cost savings that biosimilars may be able to deliver more broadly in the US. In the meantime, insurers use prior authorization, step therapy, and switching policies to try to manage the inappropriate pricing in this area, but they need to take specific actions to ensure that these policies do not prevent patients from being able to get appropriate care at a price they can afford.”

Voting on Clinical Effectiveness and Contextual Considerations

All agents in this review had evidence clearly demonstrating their superiority to placebo. The evidence was quite limited in helping to distinguish among the different treatments, but in one head-to-head trial, supported by indirect network meta-analysis, vedolizumab was found to produce greater rates of clinical response and remission over adalimumab, the market leader, in both biologic-naïve and biologic-experienced patients. All the other TIMs were found to produce net health benefits at least comparable to adalimumab, with no clear differences among them.

During the public meeting, CTAF members voted 12-2 that the evidence was adequate to demonstrate clinical superiority of vedolizumab compared to adalimumab, but they concluded unanimously that evidence was inadequate to demonstrate the clinical superiority of ustekinumab. The majority of panelists (14-1) also found the evidence inadequate to distinguish between the benefits of tofacitinib, ustekinumab, and vedolizumab.

During their deliberation, panel members also weighed the treatments’ other potential benefits and contextual considerations. While noting significant uncertainty in the treatments’ long-term side effects and durability of benefit, panelists emphasized that these interventions are intended for the care of individuals with a condition of particularly high severity in terms of quality of life and a high lifetime burden of illness. In addition, they acknowledged that, when compared to conventional therapy, TIMs offer a novel approach that will allow successful treatment of many patients, which would significantly improve patients’ ability to achieve work and educational objectives while reducing caregiver burden.

Cost-Effectiveness Findings and Voting on Long-Term Value for Money

Given the available evidence on comparative effectiveness and incremental cost-effectiveness, and considering all other benefits, disadvantages, and contextual considerations, a majority of CTAF panelists at the public meeting voted that the current pricing of infliximab and its biosimilars represented an intermediate long-term value for money when used to treat ulcerative colitis. Consistent with ICER’s methodology, the CTAF did not vote on long-term value for money of the other TIMs because, at their current prices and for this indication, they all far exceed commonly cited thresholds for cost-effectiveness.

For the indication of ulcerative colitis, ICER’s recommended health-benefit price benchmark (HBPB) ranges are $5,800-$6,900 per year for adalimumab; $6,300-$7,600 for golimumab; $8,800-$10,900 for infliximab and its biosimilars; $12,600-$15,300 for tofacitinib; $9,000-$17,200 for ustekinumab; and $9,200-$12,000 for vedolizumab. Among these therapies, the prices net of rebates for infliximab and its biosimilars come the closest to meeting its HBPB, requiring an additional 25% discount to reach the top end of the recommended price range. The other TIMs require much deeper discounts in addition to their current estimated rebates to reach their respective HBPB ranges (e.g., 85% for adalimumab and 82% for ustekinumab). The relatively better cost-effectiveness for infliximab and its biosimilars reflects reductions in net pricing for infliximab seen over the past several years due to the effects of biosimilar competition.

The HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

Key Policy Recommendations  

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

• The significantly lower prices seen for infliximab and its biosimilars speaks to the important potential for improved value with broader availability and uptake of biosimilar treatment options. All stakeholders should collaborate to ensure that TIM biosimilars have an increasing and comprehensive role in the ulcerative colitis treatment landscape.
• Manufacturers should lower their prices to align more reasonably with the added benefits their drugs provide. Structural changes to the rebate system are also needed to achieve lower drug prices. In particular, the “bundled rebate” approach, in which rebates are provided at the drug level across all of its possible indications, should be abolished and replaced with an indication- and value-based pricing approach.
• Insurance coverage should be structured to prevent situations in which patients are forced to choose a treatment approach on the basis of cost.
• Because there are no clear biomarkers or predictors of the success for any given treatment in ulcerative colitis, it is not unreasonable to consider prior authorization criteria in order to manage the costs of expensive medications and negotiate prices for TIMs priced beyond a fair range. However, prior authorization criteria should be based on clinical evidence, specialty society guidelines, and input from clinical experts and patient groups. Specific requirements for appropriate design and implementation of step therapy and medication switching policies are provided in the full report.
• Given the maturity and longstanding use of several of the TIMs of focus in this review, the FDA should require the inclusion of active control arms in Phase III clinical trials of ulcerative colitis treatments.

ICER’s detailed set of policy recommendations 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.