Focus is on the performance of targeted immune modulators relative to conventional anti-rheumatic drugs, and if they met certain cost-effectiveness thresholds. But over the long term, biosimilars may be the real game-changer for patients choosing between meals and medicine.
Rheumatoid arthritis (RA) is the latest high-profile disease for which the Institute for Clinical and Economic Review (ICER) has constructed a “value framework” for assessing and comparing available drug treatments. In April, ICER issued a comprehensive, 529-page report on targeted immune modulators (TIMs) for RA that covers 14 medicines—all but two biologics, and none biosimilars.
Among the report’s key findings are that:
- Cost of the drugs, based on the discounted wholesale acquisition (WAC) price, ranges from about $22,000 to $42,000 annually
- There is strong evidence that TIMs substantially improve patient outcomes
- All of the TIMs evaluated failed to reach cost-effectiveness thresholds generally accepted as “reasonable” ($50,000-$150,000 per additional quality-adjusted life year), although eight TIMs were found to be less costly and more effective than market leader adalimumab (AbbVie’s Humira); unknown were the price points on two new treatments for moderate-to-severe RA patients, sarilumab (Sanofi/Regeneron’s Kevzara) and baricitinib (Eli Lilly’s Olumiant), which have both been rejected by the FDA since the report’s writing
- By consensus vote of the New England Comparative Effectiveness Public Advisory Council, current evidence is adequate to demonstrate only that the net health benefits of toclizumab monotherapy (Genetech’s Actemra) and Kevzara monotherapy (FDA-rejected over deficiencies found at a French plant) are superior when compared to adalimumab monotherapy
In the ICER report, public policymakers are asked to consider regulatory intervention to ensure that drug prices do not continue to increase. California has in fact tried this price-control tactic, without luck. Perhaps the best we can do is to continue pressuring drug companies to be more transparent about how pricing gets calculated, and encourage development of biosimilars. The more competition you have in a free market, the lower prices fall—in theory at least.
In its recommendations aimed at clinical societies, the report states that clinical guidelines should be developed that align with evidence on patient outcomes. The challenge here is the shortage of head-to-head comparisons of medicines in the same drug class, which would be more telling—but riskier for drug makers if they don’t get the results they want. The comparator in clinical trials is typically standard of therapy. For RA, that has generally meant proving the new drug is as good as or better than the conventional disease-modifying anti-rheumatic drug methotrexate.
Overall, the ICER report will be most beneficial to payers, the target audience for the majority of the recommendations. RA is a disease state typically managed by a rheumatologist in the outpatient setting and treated with injectable drugs that patients self-administer. The drugs utilized reflect the coverage policies of insurance companies and pharmacy benefits managers.
But provider organizations will want to pay attention to reports like these, particularly with so many hospitals opening specialty and mail-order pharmacies, and buying up physician practices. Reimbursement practices in the outpatient setting are different than on the inpatient side and can be fairly complicated—particularly when biosimilars are involved. The care experience will surely be better if providers understands the out-of-pocket realities of patients and connect them to a financial assistance program.
As communities move toward population health, providers across the continuum of care will also have a vested interest in catching RA early and treating it appropriately so patients have a better quality of life and lower risk of comorbidities related to being in pain and therefore sedentary.
Biosimilars could be game-changers … eventually
Two biosimilars are now FDA-approved for RA, but too recently to be included in the ICER report. Pfizer’s Inflectra (infliximab) made its commercial launch last November, and offers a roughly 19 percent discount off the price of Janssen Biotech’s Remicade (based on a WAC-to-WAC price comparison). A second infliximab biosimilar, manufactured by Samsung Bioepis, was approved for marketing at the end of April, but its patent dance with Amgen is delaying its market availability.
Patent litigation is but one of a host of factors tempering initial expectations that biosimilars launched in the U.S. would be priced 30-40 percent below their originator product, as typically happens with generics of small-molecule drugs. For starters, there’s the R&D costs. Drug makers have to prove to the FDA that their biosimilar product has a high degree of similarity in terms of pharmacokinetic (PK) and pharmacodynamic (PD) outcomes with the originator drug—but again, no head-to-head comparative effectiveness studies required within a drug class such as TNFa inhibitors (e.g., Remicade vs. Enbrel). Companies also need to obtain an “interchangeability designation” allowing pharmacists to make the substitution without the approval of the prescribing physician. Patient safety is the overriding concern—not only is the biosimilars market very new in the U.S., but biologics come with a risk of immunogenicity reactions whereby patients develop antidrug antibodies and no longer respond to therapy. Additionally, drugs are not backed by large studies because the affected patient population is relatively small.
The cost of manufacturing biosimilars is also quite expensive. It’s just not cheap to produce medicines from living cells that are highly sensitive to their environment. Plus, companies have to find a way to coax these cells to produce an identical outcome to an existing treatment.
For RA patients having good clinical results on Remicade, but having a difficult time affording the $28,906 average annual cost, switching them to a biosimilar like Inflectra with the same PK/PD profile sounds reasonable. The problem is that Inflectra does not yet have that interchangeability designation, which some state pharmacy laws require before retail pharmacists can start making the swap when Remicade is prescribed. Even in states where such swapping is allowed, doing so without the interchangeability designation involves extra paperwork and provider approval, potentially delaying the start of therapy.
Between litigation and patent extensions, most companies manufacturing biologics for RA have in any case pushed back their patent cliff another five to seven years, stalling the uptake of biosimilars. Humira, whose patent was initially to sunset last year will now do so in 2022. The patents on Actemra and Janssen’s Simponi (golimumab) don’t expire until 2024; Enbrel’s is good until 2028. Remicade, the only biologic facing an imminent patent cliff, is now contesting its deadline in court.
Members of HealthTrust have access to an online portal containing a growing library of information about biosimilars (interchangeability, naming conventions, etc.), as well as related webinars with CE credits. Physicians and nurses, as well as pharmacists, need to be helping patients understand the differences between RA medicines, including biosimilars, amidst growing direct-to-consumer marketplace noise.