PBM Moves Spur Humira Biosimilar Uptake but Raise Questions

Reprinted with AIS Health permission from the May 2024 issue of Radar on Specialty Pharmacy.

The FDA has approved 10 biosimilars of AbbVie Inc.’s Humira (adalimumab), with nine of them launching in the U.S. since last year, but uptake of them has been relatively slow. Recently, though, a formulary change by CVS Health Corp. seems to have spurred uptake of the agents, and an upcoming change by The Cigna Group should increase their use again. However, some industry experts question whether those changes were made with an eye on increasing biosimilar access — or boosting their own profits.

On April 25, Evernorth Health Services, a subsidiary of Cigna, revealed that it will have a high- and low-concentration interchangeable Humira biosimilar for zero out-of-pocket costs for “eligible patients” of its specialty pharmacy, Accredo, starting in June. The product, according to a press release, “will be produced for Evernorth’s affiliate private label pharmaceutical distributor, Quallent Pharmaceuticals, through agreements with multiple manufacturers.”

Scott Halperin, Pharm.D., senior pharmacy benefit clinical consultant for employer groups at Pharmaceutical Strategies Group, an EPIC company, says Quallent “has experience ‘commercializing’ or ‘private labeling’ generic products from several manufacturers, which is especially leveraged through its home delivery dispensing channel.”

The biosimilar will be available through Quallent’s copay assistance program. Evernorth said it expects an annual savings of $3,500 per person. The price of the biosimilar will be approximately 85% lower than Humira’s list price. “For many employers, unions, municipalities and other health plan sponsors that choose to work with Accredo as part of their specialty pharmacy network offering, this represents an opportunity for significant savings,” said the company, which noted that more than 100,000 Accredo patients use Humira or one of its biosimilars.

At the time of the announcement, only one interchangeable Humira biosimilar with both low- and high-concentration formulations had been approved by the FDA: Alvotech and Teva Pharmaceutical Industries Ltd. affiliate Teva Pharmaceuticals’ Simlandi (adalimumab-ryvk), which was approved Feb. 23 for nine of the reference drug’s indications.

But less than a week after the Evernorth announcement, on April 30, the FDA approved a high-concentration version of another interchangeable biosimilar, Boehringer Ingelheim Pharmaceuticals, Inc’s Cyltezo (adalimumab-adbm), which also is indicated for nine Humira indications. That latter agent launched as an interchangeable low-concentration formulation in July 2023.

Humira was first approved Dec. 31, 2002, in a low-concentration version, but it gained approval for a high-concentration version in November 2015. AbbVie did not make that version available until July 2018, meaning that when potential competitors began developing their biosimilars, they were developing low-concentration versions. The high-concentration formulation now has around 90% of Humira prescribing.

“We expect interchangeability on high-concentration Humira biosimilars will lead to an increase in market share, especially given that Cigna has stated this to be an important factor in their decision,” says Halperin. “We would note that formulary strategy still seems to be the driving force behind changes in market share, and policymakers are proposing changes to the interchangeability designation for biosimilars as early as 2025.”

Presumably, Evernorth has an arrangement for Simlandi. On April 19, Alvotech and Teva revealed that they had signed a “long-term agreement with a strategic partner to further enhance access to adalimumab-ryvk in the U.S. market.”

Then on April 30, Alvotech said that under the strategic partnership, it would manufacture its high-concentration interchangeable biosimilar for Quallent Pharmaceuticals and would offer the agent via a copay assistance program.

An Evernorth spokesperson did not respond to an AIS Health request for comment.

During a May 2 call to discuss first-quarter 2024 earnings, David Cordani, Cigna chairman and CEO, said that the company has agreements with “multiple manufacturers who will produce biosimilars for Evernorth’s private label pharmaceutical distributor, Quallent Pharmaceuticals, which we launched back in 2021.”

The agents will be available to not only Accredo patients but also the company’s pharmacy benefit service clients and patients.

“Importantly, the biosimilar opportunity goes well beyond Humira,” stated Cordani, adding that Cigna expects to see biosimilars or generics available for almost half of the top 25 specialty drugs in the U.S. by 2030. “This translates to over $100 billion in annual spend, subject to additional choice and competition. The introduction of biosimilars creates a multiyear tailwind that enables us to continue to drive growth and value creation for the benefit of those we serve.”

“We’ve got the maximum number of available dosages [of interchangeable biosimilar adalimumab in both concentrations] in the market,” said Eric Palmer, Cigna’s executive vice president for enterprise strategy and Evernorth’s president and CEO, during the Q&A.

CVS CAREMARK CHANGE HAS HELPED BOOST HYRIMOZ UPTAKE

In August 2023, CVS Health launched the wholly owned subsidiary Cordavis to commercialize and/or co-produce biosimilars. The first collaboration was with Sandoz and its Hyrimoz (adalimumab-adaz), which Cordavis said it would offer at a list price more than 80% off Humira’s.

AbbVie also is providing Cordavis with a “committed volume of co-branded Humira,” which will be available in the second quarter of this year, CVS revealed in January.

On April 1, CVS Caremark removed Humira from its national commercial template formularies and replaced it with three Sandoz biosimilars: Hyrimoz, Cordavis-branded Hyrimoz and adalimumab-adaz, the unbranded Hyrimoz. Since then, Hyrimoz uptake has exploded.

According to an April 15 research note from Evercore ISI, new Hyrimoz prescriptions rose from 643 for the week ending March 29 to 8,294 for the week ending April 5. That increase boosted new prescriptions of Humira biosimilars from 5% to 36% of the market, with Hyrimoz accounting for 93% of that total.

For the week ending April 26, just over four weeks after CVS removed Humira from its national commercial template formularies, growth of new prescriptions for Hyrimoz had slowed to 6,569, compared with 7,595 for the prior week and 10,266 for the week before that. But even with that decline, wrote Evercore ISI analyst Elizabeth Anderson in a May 3 research note, “Hyrimoz has seen a major inflection point since the Cordavis formulary change,” representing approximately 91% of Humira biosimilars.

In the most recent data, biosimilar adalimumabs made up about 15% of the total Humira market. “Past experience suggests ~90% of the biosimilars erosion happens within the first 2-3 weeks after formulary changes — we think this would also likely be the case for Humira/Hyrimoz but will continue to monitor the prescription data to see where the trend goes,” said Anderson.

Madelaine A. Feldman, M.D., FACR, a clinical assistant professor of medicine at Tulane University School of Medicine and provider with The Rheumatology Group in New Orleans, tells AIS Health, an MMIT company, that her patients “are being nonmedically switched from Humira to Hyrimoz if they are to stay on an adalimumab product. So, of course, the trajectory of growth of Hyrimoz is steep with CVS.”

And Halperin says that PSG saw an increase in Hyrimoz prescriptions in March, based on its book of business data, “as prescriber outreach was initiated. We also saw a large increase in April due to CVS excluding branded Humira from their major commercial formularies. It is a reminder that the formulary strategy of large PBMs has a great impact on biosimilar uptake in the U.S.”

He also points out that co-branding Humira “will help CVS customers within the noncommercial lines of business grow comfortable with the Cordavis branding. There may be some members who seek medical exceptions to remain on branded Humira within the commercial population.”

But while formularies trump prescribing, physicians seem to be open to the idea of using Humira biosimilars.

In a March 25 research note, Deutsche Bank shared prescribing patterns from a FirstWord Pharma poll of 126 U.S. providers — 42 dermatologists, 56 gastroenterologists and 28 rheumatologists — according to AlphaSense, Inc. Sixty-two percent of the dermatologists said they had prescribed Humira biosimilars, while 84% of gastroenterologists and 93% of rheumatologists said the same. When asked what had prevented them from prescribing the biosimilars, the top response was payer/insurance, cited by 43%, followed by physician/patient preference for Humira, claimed by 39%.

When they were asked if they consider the biosimilars inferior, superior or comparable to Humira, 69% of dermatologists and 82% of both gastroenterologists and rheumatologists said they believed them to be comparable.

PBM FORMULARIES HAVE PLAYED ROLE IN UPTAKE

The first Humira biosimilar, Amgen Inc.’s Amjevita (adalimumab-atto), launched Jan. 31, 2023, and numerous others became available later in the year. But so far, observes Halperin, “traction has been limited, mainly due to PBM formulary strategies, which have not maximized the opportunity for competition within adalimumab products. A strategy that endeavors to convert members to a lower cost and clinically effective biosimilar option for Humira is a positive. While the [Cigna] announcement addresses member affordability, it does not address the impact on cost to payers, which continues to be a concern.”

“A zero-copay incentive saving the typical patient $3,500 per year is a powerful incentive to move to the biosimilar, so a similar or higher jump in Humira biosimilar market share as following CVS’s change would likely follow Evernorth’s action,” says Elan Rubinstein, Pharm.D., principal at EB Rubinstein Associates. AbbVie, he adds, “may be positioning (with prescribers and patients) its newer products Skyrizi and Rinvoq to replace Humira, effectively ceding the latter biologic’s market to biosimilars.”

“Cigna owns every step of the supply chain for Simlandi and will make money on every step,” remarks Feldman. “Most likely if there is a copay card or other form of patient assistance through Quallent, it will be attached to some process where the assistance doesn’t count towards the patient’s deductible or OOP [out-of-pocket] max.” 

Feldman, who is also vice president of advocacy and government affairs of the Coalition of State Rheumatology Organizations, maintains that the Cigna arrangement is similar to that of Cordavis/CVS. “There is a black box that somehow has the formulary constructor and the manufacturer with ties to each other — exactly what the FTC [Federal Trade Commission] put the kibosh on in the 1990s,” when manufacturers owned PBMs that they had to divest.

“The FTC was not happy with the conflict of interest” in that situation, she explained in a previous article about Cordavis, because manufacturers “could make the drug and then prefer it on the formulary. So one of the controls was that the formulary created, for example, by Medco (owned by Merck) would have to be ‘open,’ meaning that all competitors would have to be included on the formulary. This certainly would make the formulary less profitable and disincentivizes ownership. Merck eventually divested itself from Medco.”

“Effectively the strategies employed by CVS Caremark and Express Scripts preserve elements of the oft-criticized rebate system, though not with rebates per se but rather with co-branded licensing fees and acquisition cost discounts,” wrote Joshua Cohen in a Forbes article. “It’s doubtful that this is what policymakers envisioned biosimilar competition would look like, namely a web of vertically integrated stakeholders, including health insurers, pharmacies, PBMs and manufacturers, all operating under corporate umbrellas.”

WILL OTHER PAYERS FOLLOW?

Asked if other PBMs may take similar approaches to biosimilars, Feldman remarks that UnitedHealth Group’s UnitedHealthcare is the only company with the “clout of CVS and Cigna,” but that company is dealing with the fallout from the cyberattack on its subsidiary Change Healthcare.

“I think that other PBMs will follow CVS’s and Cigna’s lead on this, because patients needing these biologics will be aware of major copay discrepancies,” Rubinstein states.

“Not all PBMs have the scale of operations to replicate the Cigna/CVS strategy to commercialize and/or co-produce biosimilars, but those that do may be likely to follow with a similar strategy for biosimilars,” Halperin says. “These announcements will likely create demand within the market for more proactive measures by PBMs to optimize the opportunity for cost savings within adalimumab products.”

As far as biosimilars’ anticipated use in the U.S., “we expect uptake to continue to grow throughout 2024 and into 2025, but the complexities of drug rebates may lead to slower uptake of pharmacy benefit biosimilars vs. some physician-administered biosimilars. Our State of Specialty Spend and Trend reports confirm this,” he comments.

Feldman says she also thinks the U.S. is seeing a turnaround in the uptake of biosimilars — “but only because the ‘payers’ are figuring out ways to make more money on them.”

And while provider-administered biosimilars have pulled a decent amount of market share from their reference products, she says there is an issue in the space with certain manufacturers, particularly those of Remicade (infliximab) biosimilars, giving payers “huge rebates and fees…to [get] ‘fail-first’ placement on the formulary. Because those rebates are reported to the government, they artificially bring down the ASP [average sales price] very quickly. Unfortunately, physicians cannot purchase it for less than the ASP, so we cannot afford to give the biosimilars mandated by the payers. We are underwater because their reimbursement is lower than the price we acquire the drugs at because of the high rebates they received. This delays care, and sometimes patients lose access to their original infliximab when they are forced to switch to biosimilars that doctors and freestanding infusion centers and even some hospitals will not infuse.”

On the pharmacy side, however, “no rebates are reported on a drug-by-drug basis to the government. There really is no ASP on the pharmacy side — it’s the wild, wild West when it comes to drug pricing.”

Looking ahead, Halperin notes that multiple biosimilars of Johnson & Johnson Innovative Medicine’s Stelara (ustekinumab) are set to launch in early 2025, making that the “next major self-administered biosimilar event.…Payers should be proactively engaging their vendors for potential Stelara biosimilar formulary strategies much earlier to ensure alignment with a lowest net cost strategy.”

By Angela Maas