Will the Entry of Adalimumab Biosimilars to the US Market Successfully Lower Spending?

In a review article, researchers from Brigham and Women’s Hospital and Harvard University speculated on whether the availability of adalimumab biosimilars in the United States, which began in January 2023, will lead to cost savings for patients. Although it is too early to know, they said, “there are already some concerning signs.”

The reviewers called the adalimumab reference product (Humira) “the world’s biggest blockbuster drug.” Sales have been more than $200 billion since it was approved by the US FDA more than 20 years ago. They also noted that AbbVie, the manufacturer of Humira, has raised the price of the drug 27 times since it was released. The current price is 470% more than when it was introduced.

Adalimumab is a monoclonal antibody targeting tumor necrosis factor (TNF) alpha. TNF inhibitors have become mainstays of treatment in inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease.

The different approval pathways for generic drugs and biosimilars are one reason cited by authors to explain why, overall, biosimilars have not resulted in the price reductions that generics typically do.

Generics are approved by the FDA via an abbreviated regulatory pathway set by the Hatch-Waxman Act of 1984, which requires evidence of equivalence to the original product. All 50 states allow pharmacists to substitute a generic for a brand name drug. In contrast, the Biologics Price Competition and Innovation Act of 2010 requires additional evidence beyond equivalence to the reference product. Additional head-to-head studies of the biosimilar and the originator, including a comparative clinical trial in a relevant indication, are required. Most US states “make pharmacist substitution of biosimilars more complicated than for generics,” the reviewers added.

Biosimilars were introduced in the United States in 2015 but, according to the authors, “price competition in this market has not been as vigorous as expected.” They attributed this in part to “patent thickets” secured by the manufacturers of originator biologics. Indeed, the first adalimumab biosimilars were approved by the FDA in 2016, but patent litigation kept them off the market until 2023.

Another factor cited for the limited cost savings for patients is that biosimilars are typically priced “only marginally lower” than originator drugs and “perverse financial incentives” for intermediaries. The authors wrote that pharmacy benefit managers (PBMs), hospitals, and clinics “can all financially benefit by steering patients toward higher-priced biologics instead of less expensive biosimilars.”

New Version of Humira “Might Complicate Biosimilar Competition”

AbbVie in 2018 released an updated version of Humira designed to make injections more comfortable for patients. The new, more concentrated version of Humira requires a smaller volume to be injected, uses a smaller gauge needle, does not contain citrate in the buffer solution, and is priced the same as the original version. Uptake of this new version has been “rapid,” and as of 2021, it accounted for 85% of adalimumab use among Medicaid recipients.

The authors expressed concern that this new version of the reference product “might complicate biosimilar competition.” Of the 9 approved adalimumab biosimilar products, 8 contain the lower concentration of the original Humira product, 2 included citrate, and 3 used the larger-gauge needle. Therefore, switching to a biosimilar might entail a less comfortable injection, which could “pose a major barrier to biosimilar adoption.”

Another concern is how the new biosimilars will be covered by insurers and PBMs. Although formulary tiers typically encourage patients to use lower-cost drugs, some PBMs have announced they will cover Humira on the same formulary tier as the new biosimilars. As a result, the reviewers wrote, “at least in 2023, insurers and PBMs will not nudge patients or clinicians toward use of biosimilars, and some patients will face the same out-of-pocket costs whether they use Humira or a biosimilar.”

Two-Price Strategy for the First Adalimumab Biosimilar

Amgen, the manufacturer of the first adalimumab biosimilar, plans to sell 2 versions of their biosimilar at 2 different prices, 5% and 55% lower than Humira. According to the authors, the two-price strategy is “problematic” because it may incentivize PBMs to cover the higher-priced version “so that they can negotiate rebates in exchange for formulary position.” But they added that even if the rebates lead to a net price equal to the lower-price version, “this could lead to higher out-of-pocket costs for patients, because deductibles and coinsurance are calculated based on the drug’s list price.”They added that in similar two-price strategies for biosimilar insulin products, “PBMs overwhelmingly preferred the higher-priced versions.”

Since the number of competitors is directly related to price reduction for generics, the authors said it is likely that more competition among adalimumab biosimilars will also result in additional cost savings.

Recommendations: “Policymakers Should Act Now”

Market entry of adalimumab biosimilars in the United States “is a critically important moment for the fate of biosimilars,” and the authors suggested policy changes might be necessary to ensure that biosimilars successfully provide savings for patients and the health care system.

They recommended the FDA should provide more clarity about achieving interchangeable status, “and work with biosimilar manufacturers to ensure that more of such products emerge.”

States should permit pharmacists to easily substitute an interchangeable biosimilar for its reference product, as “substitution by pharmacists has been critically important to the success of generic competition.” The reviewers also recommended that state and federal legislators consider restricting confidential manufacturer rebates for biologics once biosimilars become available, to “promote transparent price competition that would benefit patients.”

Finally, the authors recommended the FDA and professional societies should better educate prescribers and patients about biosimilars to increase uptake, “in particular the fact that biosimilars are subject to stringent testing to prove that they are just as safe and effective as the original drug.”

Reference

Rome BN, Kesselheim AS. Biosimilar competition for Humira is here: signs of hope despite early hiccups. Arthritis Rheumatol. Published online April 7, 2023. Accessed July 14, 2023. doi: 10.1002/art.42520.