Humira exclusivity expires in 2023: Will biosimilar boom benefit patients or industry?
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In 2021, Humira — the blockbuster biologic that has for years been the highest grossing drug in the world — accomplished something that no drug had previously achieved when its global revenues topped $20 billion.
More precisely, Humira (adalimumab) earned $20.7 billion in revenue in 2021 — including $17.3 billion just from U.S. sales — for its manufacturer AbbVie after coming just a few hundred million short of the $20 billion benchmark for three years in a row. However, while this news was no-doubt greeted warmly by the company, AbbVie’s fourth-quarter 2021 financial report included another figure that may have somewhat dampened any board-room festivities.
However, for those without insurance, the out-of-pocket cost for a months worth of Humira can be as high as $7,000. Hanauer noted that this is where newly available biosimilars may make a difference.
Source: Stephen B. Hanauer, MD.
It turns out that Humira’s net revenues from outside of the United States — totaling $3.4 billion for the year — had decreased 9.6% on a reported basis or 12.8% on an operational basis, compared with 2020. According to the financial report, this decrease was due to “biosimilar competition.”
And the situation is unlikely to get any easier for the company come 2023.
The reason: That biosimilar competition, long kept at bay and limited to European and other overseas markets by AbbVie’s use of patent litigation, is coming for Humira in the United States, and it is coming soon. Following a series of legal settlements between AbbVie and various biosimilar manufacturers, at least eight — but possibly as many as 10 — adalimumab biosimilars will be hitting the U.S. marketplace for the first time in 2023.
Meanwhile, AbbVie’s newly arrived exclusive drugs that treat many of the same indications as Humira — Skyrizi (risankizumab) and Rinvoq (upadacitinib) — netted downright paltry revenues of $2.9 billion and $1.7 billion in 2021, respectively.
However, whether or when that influx of competing agents will fundamentally alter the treatment landscape in gastroenterology and offer a much-needed shot in the arm for biosimilar uptake in the U.S. is far from certain.
“On an individual patient basis, when all of these adalimumab biosimilars hit the market, it is not likely to make a difference — at least not immediately,” Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern Medicine and professor of medicine at the Feinberg School of Medicine, told Healio Gastroenterology. “Patients with commercial insurance now pay around $5 a month for Humira. I can’t imagine the pricing of biosimilars competing with that.”
However, for those without insurance, the out-of-pocket cost for a month’s worth of Humira can be as high as $7,000. According to Hanauer, this is where newly available biosimilars may make a difference.
“They could have more options at a lesser cost,” he said. “Those who fall into the donut hole of Medicare may also have a lower cost.”
Still, experts like Steven Newmark, director of policy and chief legal officer at the Global Healthy Living Foundation (GHLF), are much more skeptical about the cost savings that may result from several new biosimilars.
“It depends on whose wallet you are talking about,” he said.
2023 Release Dates
A total of eight FDA-approved adalimumab biosimilars are now cleared for a 2023 release in the United States. For some of these drugs, it has been nearly a decade since they were first approved for use.
First out of the floodgates will be Amgen’s Amjevita (adalimumab-atto), with a settlement-enforced launch date of no earlier than Jan. 31. Then will come Hadlima (adalimumab-bwwd, Organon), no earlier than June 30; Cyltezo (adalimumab-adbm, Boehringer Ingelheim) and Yusimry (adalimumab-aqvh, Coherus), both starting on July 1; Hulio (adalimumab-fkjp, Mylan), no earlier than July 31; Hyrimoz (adalimumab-adaz, Novartis Sandoz), starting on Sept. 30; and Abrilada (adalimumab-afzb, Pfizer), no earlier than Nov. 23.
Additionally, two companies have inked deals with AbbVie to allow the U.S. release of their own biosimilars in 2023 pending FDA approval: Celltrion, which is eyeing July for its Yuflyma (CT-P17), and Alvotech/Teva, which will be able to legally release AVT02 on July 1 following FDA approval.
Fresenius Kabi’s Idacio (adalimumab-aacf) received FDA approval in December 2022 and is set to be available in July. Celltrion, as of the time of this writing, is still expecting an FDA decision by the end of 2022. Meanwhile, an FDA decision regarding Alvotech’s Humira biosimilar is on hold until the company can address “certain deficiencies” the administration found during a March inspection of its manufacturing facility in Reykjavik, Iceland.
In a perfect world, multiple new drugs would lead to competition that would lower the burden of copays, deductibles and premiums for patients.
However, Newmark fears that pharmaceutical companies, insurance carriers and pharmacy benefit managers (PBMs) are more likely than patients to benefit from the expanded number of treatment options.
Russell D. Cohen, MD, FACG, AGAF, director of the Inflammatory Bowel Disease Center and co-director of the Advanced IBD Fellowship Program at University of Chicago Medicine, told Healio Gastroenterology that the incentive for patients should be that they agree to switch to a biosimilar in return for having no copay.
“That is what should happen,” he said. “That is what all providers think should happen. I doubt that will happen, because, in our opinion as providers, PBMs are just interested in making more money for themselves rather than providing better access and lower cost medicines to their patients.”
These financial ramifications are just one component of the biosimilar discussion. There are also clinical considerations pertaining to their safety, efficacy and interchangeability with their bio-originator reference products. The clinical trial process leading to FDA approval of biosimilars is as rigorous as it is for any drug and far more demanding than the process for generic small-molecule drugs. This process has been widely documented at conferences and in peer-reviewed literature.
For patients, though, it is a different story. Whether they are familiar with biosimilars or understand the concepts at hand — for example, interchangeability and the difference between a biosimilar and a generic drug — is much less clear. In fact, for some patients, the distinction may not even matter.
“Patients just want to know two things,” Hanauer said. “Is the drug going to work the same? And will it have the same side effects?”
That said, 2023 will likely be the beginning of some shift in the GI pharmaceutical marketplace. The size and nature of that shift will depend on several factors that are, unfortunately, largely beyond the control of both doctors and patients.
Will PBMs Share Savings With Patients?
In a paper published in Inflammatory Bowel Diseases, Patil and colleagues summed up a response to the question of whether more biosimilars would lead to lower prices for patients. They reported the use of biosimilars has been predicted to decrease direct spending on biologics by $54 billion from 2017 to 2026.
“The financial impact of biosimilars will be greatly determined by market share and competition,” they wrote. “In several European countries with low biologic consumption, the entry of biosimilars into the market has resulted in significantly increased access due to competitive prices of biosimilars or reactive reduction in originator product prices. The projected range of spending reduction with biologics is $24 to $150 billion, with the actual savings dependent upon industry, regulatory, insurer, provider and patient decisions, as well as policy evolution.”
They added, “Several unique roadblocks to increased use of biosimilars exist in the United States, including considerations in the areas of patents, reimbursement, rebates and intellectual property.”
According to Amelia Bond, PhD, of Weill Cornell Medical College in New York, early experience with other biosimilars in the United States indicates that prices may “decline modestly” at initial entry of the cluster of adalimumab biosimilar products. Other experts have similarly pointed to the advent of generic medications as a predictor of how new biologics will perform.
“Historically, when a new generic enters the market, the cost savings for patients is typically 80% to 85% lower than the originator,” Newmark said. “The same should be true for biosimilars, but for this to happen, the insurers and PBMs have to put a crowbar in their wallet and share the savings with patients.”
Cohen pointed out that thus far there has not been evidence that PBMs intend to offer savings to patients for biosimilars. “I think that the promise of the idea behind biosimilars is to bring down the cost of these drugs and to make them more widely available,” he said.
“I am pro biosimilar, but you have to do it responsibly,” Cohen continued. “And patients should be getting the break — not the billion-dollar profit insurance companies.”
Advocacy organizations like GHLF and the Alliance for Transparent and Affordable Prescriptions have been urging lawmakers to consider PBMs and the opacity of the U.S. health care market for years, with varying degrees of success. The message is beginning to have some impact, with legislation targeting the role of PBMs in the health care system recently being introduced in Congress. However, it remains uncertain whether that legislation will even make it to the floor for debate, given the current institutional gridlock in the legislative bodies.
In the meantime, there are some aspects of Humira, and its biosimilars, that may influence their uptake that need to be carefully considered.
A Unique Biosimilar
Humira and its biosimilars are unique for a few reasons, according to Bond.
“First, Humira is primarily a medication prescribed in the retail setting,” she said. “Patients pick it up from a traditional pharmacy and self-administer it.”
Cohen voiced his fear regarding who will educate and train staff and patients on how to use the adalimumab biosimilars, which are a self-injectable agent with a different delivery device.
Other biosimilar launches, meanwhile, were for drugs administered by a provider in the physician office or hospital outpatient setting, Bond added. The self-administered nature of adalimumab may impact use and, consequently, pricing.
“The second point is that there are at least seven biosimilars launching, which is many more than we have seen for previous reference products,” Bond said. “Theoretically, additional biosimilars should exert more pressure to decrease prices.”
Whether this will translate into actual cost savings remains to be seen and will likely only be known after some time has passed with the products on the market.
The last point, according to Bond, is interchangeability. The FDA designated Cyltezo as the first interchangeable biosimilar to treat certain inflammatory diseases in 2021, allowing pharmacists to substitute it for Humira without the need for the prescriber to alter the prescription. It was, at the time, just the second interchangeable biosimilar product approved by the FDA and the first monoclonal antibody.
Since then, the FDA has accepted applications for interchangeability from Alvotech and Pfizer for their Humira biosimilars. Amgen and Samsung Bioepis have announced they are also seeking interchangeability status for their own Humira biosimilars.
“These will be the first launches with this designation,” Bond said. “The additional interchangeability designation allows the pharmacist to substitute the branded Humira with an interchangeable biosimilar. However, substitution can only occur in states that permit this.”
The dependence on state regulations is another unique aspect of the U.S. health care system that could significantly affect the biosimilar market.
Gastroenterologists, then, will be at the mercy of not only PBMs and insurance formularies, but of regulations in their individual state. Understanding physician attitudes and knowledge about biosimilars could also influence prescriptions and use moving forward.
Comfort and Concerns
In a paper published in TheAmerican Journal of Gastroenterology, Buchner and colleagues reviewed current data on the use of biosimilars for IBD, including efficacy and safety.
The paper highlighted a survey of U.S. physicians on nonmedical switching, with results indicating that more than 80% of physicians did not want patients to switch if they were stable and more than 50% anticipated a switch from originator to a biosimilar.
Other notable concerns included limited practice and monitoring guidelines, the potential for payer-initiated mandates to switch based solely on cost savings and possible traceability if safety issues arise. Additionally, the authors reported that nonmedical switching of biological medication may potentially lead to a “nocebo” effect, or an unexplained, negative therapeutic effect after switching.
“We have heard that some health care providers have concerns with prescribing biosimilars, while others are completely comfortable with using FDA-approved biosimilars,” Sarah Yim, MD, director of the FDA Office of Therapeutic Biologics and Biosimilars, told Healio Gastroenterology.
Consistent with findings from Buchner, Yim noted that most of the concerns she hears are related to switching stable patients from a reference product to a biosimilar or interchangeable drug.
“However, all FDA-approved biological products, including reference products and biosimilar products, undergo a thorough evaluation and meet FDA’s rigorous standards so that health care providers and their patients can be assured of the efficacy, safety and quality of these products,” she said.
That said, it is critical that insurance companies do not insist on switching a patient to a biosimilar simply to protect or increase profit, according to Newmark.
Cohen proposed another concern about switching to a biosimilar: If the patient were to become ill after switching, who would be responsible to pay?
“If [patients] are well, then changing can only result in staying well, or getting worse,” he said. “The adage, ‘If it ain’t broke, don’t fix it’ applies here. There is uncertainty. I can’t imagine any patient wanting to switch unless it directly benefitted them.”
According to Yim, much of the hesitancy regarding biosimilars in general is “simply expected” since these are relatively new products in the United States. “There is a lack of experience with prescribing these products,” she added.
However, that experience is growing. Biosimilars have been used in the U.S. since 2015 with no major safety or efficacy issues.
“They have been used in Europe for more than 15 years with great success,” Yim noted.
Patience may be the most essential factor when considering the impact that biosimilars will ultimately have in gastroenterology.
“If you take the field of cancer as an example, hematologists and oncologists do not pay much attention to biosimilars anymore because they have been accepted as part of the system for many years,” Hanauer said. “The newness is to the field of immune disease.”
Both gastroenterologists and their patients may eventually reach a point where biosimilars are as accepted as they are in the cancer field. In the meantime, it may be useful to explore patient attitudes surrounding biosimilars to predict how they may be perceived, and used, in the coming years.
The Promise of Real-World Data
According to Hanauer, there is a psychological component to a non-brand name medication that plays a significant role in how it is perceived. And a significant part of that perception is wrapped up in a drug’s price tag.
Although the cost of the adalimumab biosimilars coming to market is not yet known, it is likely that they will carry cheaper sticker prices than Humira.
“The idea of a new product that is perceived as generic can lead to cognitive dissonance,” Hanauer said. “If something costs more, it can be perceived as better, even if it is not better, or if it has been proven in clinical trials to be exactly the same.”
Fortunately, data on this topic are beginning to accrue, particularly in Europe. It may be possible to look to the European experience to see how patient attitudes could evolve in the United States.
In a prospective observational analysis published in the European Journal of Hospital Pharmacy, Barbosa and colleagues queried 134 patients about their experience with an etanercept biosimilar. Results demonstrated that most patients were satisfied with the administration method of the biosimilar product. Overall satisfaction was also high.
Another reason patients under the GI disease umbrella may ultimately accept biosimilars pertains to the chronic nature of their conditions. It is for this reason that Bond is anxiously awaiting the first wave of data from the adalimumab biosimilars in real-world settings, as opposed to clinical trials.
“This will determine whether these medications are taken up at a faster rate and whether prices decline more than modestly as in early biosimilar launches,” she said.
Cohen noted that most GI patients are familiar with navigating the health care system, which includes specialty pharmacies and patient assistance programs. That said, not every patient is going to be as savvy about drug acquisition and use as, for example, a patient with IBD who has been on biologics for a decade.
“Many new patients are still unfamiliar with biosimilars and confused by the many terms that come along with biosimilars, like interchangeability or extrapolation,” Newmark said. “Further, we know patients go through trial and error to find the right medication, which carries an emotional and physical burden.”
Cohen added, “Based on the experience with infliximab biosimilars, patients are very confused as to why they are being changed and the communication from the insurance company or PBM can be confusing and upsetting.”
With that in mind, being switched to a biosimilar may be intimidating for patients, according to Newmark.
“That is why our organization is publishing educational content to inform patients about biosimilars and alleviate stress, so when the time comes that they are faced with a biosimilar option, they can have an informed conversation with their doctor and care team,” he said.
Signaling for a ‘Sea Change’
Hanauer noted that, after some initial uncertainty, societies like the AGA have been on board with biosimilar uptake, creating patient-facing materials as well as informational sessions at conferences and meetings. The same is true for other organizations.
“I have done a number of presentations for the American Gastroenterological Association and other organizations to educate people about biosimilars,” he added. “One of the concepts I discuss is that they will lower costs.”
However, Hanauer stressed that the issue keeps coming back to one fundamental problem — how long it will take for patients to benefit.
“It does not seem likely that they will lower the cost for the patient immediately,” he said. “It may take 10 years because most patients do not pay for their drugs.”
Organizations like the GHLF are engaged in similar efforts at patient and provider education. The Crohn’s and Colitis Foundation also offers resources to health professionals on biosimilars and has written extensively about biosimilars in their IBDVisible blog.
“The Global Healthy Living Foundation recently launched a new podcast called Breaking Down Biosimilars, to help patients and providers become more comfortable with biosimilars,” Newmark said. “Our goal is to educate patients on what biosimilars are, how they get approved, their potential savings, and what promise they hold.”
GHLF has also published the free, downloadable “Patient Guide to Biosimilars,” and regularly publishes articles that deal with all aspects of the topic, from health insurance to specialty pharmacies.
It seems encouraging that the FDA, societies like the AGA, Crohn’s and Colitis Foundation and advocacy organizations are all on the same page when it comes to making biosimilar products available for patients with GI diseases. The main question, then, is when.
“With so many biosimilars coming on to the market, we hope it signals a sea change that biosimilars will finally live up to their intended purpose of providing effective, safe treatment at a more affordable cost in the coming years,” Newmark said. “If so, this could lead to large savings for both patients, and in the case of Medicare, the national health care system.”
- References:
- Barbosa CMM, et al. Eur J Hosp Pharm. 2021;doi:10.1136/ejhpharm-2019-001999.
- Biosimilars: What you should know. www.crohnscolitisfoundation.org/what-is-ibd/medication/biosimilars. Accessed Dec. 13, 2022.
- Buchner AM, et al. Am J Gastroenterol. 2021;doi:10.14309/ajg.0000000000000844.
- Patil SA, et al. Inflamm Bowel Dis. 2022;doi:10.1093/ibd/izac048.
- For more information:
- Amelia Bond, PhD, can be reached at 402 E. 67th St., Room LA 220, New York, NY 10065; email: amb2036@med.cornell.edu.
- Russell D. Cohen, MD, FACG, AGAF, can be reached at 5841 S. Maryland Ave., Chicago, IL 60637; email: rcohen@bsd.uchicago.edu.
- Stephen B. Hanauer, MD, can be reached at 16th Floor, Clinic: 259 E Erie St., Chicago, IL 60611; email: shanauer@northwestern.edu.
- Steven Newmark can be reached at 15 N Midland Ave., Nyack, NY 10960; email: jdaitch@ghlf.org.
- Sarah Yim, MD, can be reached at 10903 New Hampshire Ave., Silver Spring, MD 20993-0002; email: cdertradepress@fda.hhs.gov.
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