Since the FDA approved the first biosimilar — Zarxio (filgrastim-sndz) from Sandoz, then a division of Novartis Pharmaceuticals Corp. — on March 6, 2015, the agency has approved more than 40 additional agents via the 351(k) pathway established under the Biologics Price Competition and Innovation Act (BPCIA), itself part of the Affordable Care Act (ACA). This past year has been especially busy in the space, with highlights including the launch of nine biosimilars of AbbVie Inc.’s Humira (adalimumab) and approvals of the first biosimilars of three different biologics: Biogen’s Tysabri (natalizumab), Actemra (tocilizumab) from Genentech USA, Inc., a member of the Roche Group and Stelara (ustekinumab) from the Janssen Pharmaceutical Companies of Johnson & Johnson. As the FDA approves more biosimilars, uptake of these agents will continue to increase, say industry experts.
“2023 was a banner year for the biosimilar market,” contends Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth. “The availability of biosimilars across multiple therapeutic areas provides opportunities for physicians, patients and payers to have additional clinical and cost-saving treatment choices.”
In a span of just more than two months in the second half of the year, the FDA approved Tysabri biosimilar Tyruko (natalizumab-sztn) from Sandoz and Polypharma Biologics, Actemra biosimilar Tofidence (tocilizumab-bavi) from Bio-Thera and Biogen and Stelara biosimilar Wezlana (ustekinumab-auub) from Amgen Inc.
Szczotka points to a recently published study that “found no differences in terms of major safety parameters such as death, significant adverse effect and discontinuation when patients were switched to or from a biosimilar and its reference product or not switched. It was interesting to note that this was found across multiple therapeutic areas and was independent of the reference product class, the direction of the switch or following one or multiple switches.” Such data should help ease any concerns around the drugs’ use and help boost uptake.
“As more biosimilars enter the U.S. market, we are seeing more uptake of biosimilar use,” observes Renee Rayburg, R.Ph., vice president of specialty clinical consulting at Pharmaceutical Strategies Group (PSG), an EPIC company. Citing data from Artemetrx, PSG’s proprietary integrated data platform, she says that “biosimilar optimization increased from 20.5% to 26.3% in 2021 and 2022, respectively,” with the biggest uptake occurring with biosimilars of Genentech and Biogen’s Rituxan (rituximab) and Genentech’s Herceptin (trastuzumab). “Overall, the highest utilization of biosimilars is for Herceptin at 85.8%, and the lowest is for Remicade at 12.6%,” she states, citing the most recent Artemetrx Specialty Spend & Trend Report, which was published this summer.
In addition, she tells AIS Health, a division of MMIT, the competition posed by biosimilars is driving down the average sales price (ASP) for some of the reference drugs, as seen with the Janssen Pharmaceutical Companies of Johnson & Johnson’s Remicade (infliximab) and Amgen’s Neulasta (pegfilgrastim).
Multiple manufacturers, particularly with the adalimumab biosimilars, are offering both low wholesale acquisition cost/low rebate and high WAC/high rebate products. However, says Rayburg, evidence does not yet exist that payers are selecting the low WAC/low rebate offerings. “There seems to be interest from the payer perspective in more transparency,” she says. “Consequently, there may be interest in upfront savings and avoiding the complexities of rebates in the future. This strategy can also benefit their members enrolled in high deductible plans where their cost share will be lower based on a lower list price.”
She notes that these companies also are under pressure to provide, “at a minimum, the same level of service as the brand manufacturers, including patient support services and even copay assistance programs on top of the lower pricing. This can be appealing to a payer to add to their savings. Which seems to be most effective? Manufacturers who can match sufficient supply to keep up with the demand, patient support services equivalent to that of the brand manufacturers and optimal pricing to deliver savings will have a much better chance.”
What Considerations Are Most Important?
A variety of factors may differentiate biosimilars both from each other as well as the reference drug. For example, most of Humira’s use is for a high-concentration formulation, but not all of its biosimilars are approved for it, with most of them having only a low-concentration version. In addition, only two of the nine available adalimumabs have interchangeable status. With the exception of the seven Humira biosimilars that launched in the beginning of July, most of the available biosimilars have come onto the market at different times, sometimes years apart. Other factors include type of administration device and rebates. So what is most important to payers?
Rayburg points out that PBMs are the main decision maker due to their role in rebating and contracting. “While payers in this situation can ask questions and pressure the PBM, they have little say in the final decisions.”
While many factors play a role, she says, “the contracting/negotiating and decisions come down to the lowest net cost product, which is reliant on competition, more products entering the market and competing. That’s where those other elements could make some difference. The expectation, however, is that if members are expected to transition to a biosimilar, they will receive an equivalent product in efficacy, supply, ease of use (device), patient support services, etc. I am not sure the market entry timing impacted Amgen and Amjevita as the first to enter the [Humira] market.” With small molecule drugs, the first generic to launch usually has the most share, but “in this case, the biosimilars are also competing against the brand, and Humira brand’s continued coverage has widely limited the uptake of any Humira biosimilars. Amjevita has seen little to no advantage for being first in the market.”
Szczotka agrees that cost — both gross cost and net after rebates — is a main consideration. “Biosimilars, while offering a safe and clinically effective product, traditionally have offered a list cost that is a discount to the reference product but may or may not be the lowest net cost option for that product or class and/or provide enough incentive for all the costs and impacts involved with a product switch. Payers will continually need to align that products available are not only safe and clinically effective, but also provide a cost-effective option. As market dynamics change, payers will reevaluate coverage decisions to ensure alignment.”
What’s Ahead for Humira Biosimilars?
While nine Humira biosimilars have launched in the U.S. so far, industry experts did not expect the agents to have an immediate impact on payer coverage. Looking ahead to 2024, Szczotka points out that additional adalimumabs are expected and “will provide additional options for the higher concentration product, along with potential interchangeable designations. Payers will continue to evaluate their options amongst the adalimumab products to align their coverage strategy to ensure choices of product selection and cost. The anticipated arrival of multiple FDA-approved interchangeable products will be welcomed by payers, as long as they continue to provide a cost-competitive option. In 2024, payers will likely continue coverage of both reference and biosimilar product(s) to ensure therapy continuation and options for physicians and patients.”
Rayburg says that it may be difficult to anticipate what will happen, but “I think many will be watching the new CVS arrangement with its new subsidiary Cordavis and the white labeling of Sandoz’s Humira biosimilar. Will this be the beginning of transitioning patients to secure savings? How will AbbVie compete in that scenario? CVS has promised savings for clients in 2024, so there is expectation around how they will make that happen.”
Perhaps other PBMs may require a step through a biosimilar before Humira, says Rayburg. That said, PSG does “not have any information to confirm that will happen, and as long as AbbVie keeps pricing competitive, this may not happen to a great extent. There is tremendous competition in pricing” among the adalimumabs, with some priced at a discount around 85% off Humira. “It may take more than just Mark Cuban’s Cost Plus company to move the needle and figure out the best ways to optimize the savings that the presence of these biosimilars is creating.”
Biosimilar Pipeline Boasts Variety of Agents
Over the last few years, PSG’s State of Specialty Spend and Trend reports have found drugs for inflammatory conditions to be the No. 1 category of specialty spend for most payers, so biosimilars of any of these agents would be significant, including Tofidence and biosimilars of Stelara, says Rayburg. This year’s report had Stelara at No. 2 behind Humira in the list of the top 10 specialty drugs by spend. She also points to biosimilars for Simponi Aria (golimumab) from the Janssen Pharmaceutical Companies of Johnson & Johnson and UCB, Inc.’s Cimzia (certolizumab pegol), with anticipated approvals “in the next year or so.”
Szczotka agrees on the significance of Tofidence and the ustekinumab biosimilars. “Stelara has been Johnson & Johnson’s (J&J) top-selling drug since 2019, with global sales reaching $9.7 billion in 2022,” says Szczotka.
The FDA approved the first Stelara biosimilar shortly before AIS Health press time: On Oct. 31, the agency approved Amgen’s Wezlana (ustekinumab-auub) as biosimilar to and interchangeable with Stelara. In May, following the settlement of patent lawsuits with Johnson & Johnson, Amgen said that it would be allowed to launch the agent “no later than January 1st, 2025.”
According to the Sept. 1 edition of the U.S. Biosimilars Report from Cencora (formerly known as AmerisourceBergen), there are seven additional ustekinumab biosimilars in various stages of development. In addition, Celltrion and Rani Therapeutics said earlier this year that they are developing an oral formulation of ustekinumab for psoriasis, Crohn’s and ulcerative colitis known as RT-111 that utilizes the latter’s robotic RaniPill capsule.
Two other companies developing a ustekinumab biosimilar also have settled patent lawsuits. In June, Alvotech and Teva said that their AVT04 has a license entry date “no later than February 21, 2025.” Most recently, Fresenius Kabi and Formycon revealed that they can launch FYB202 “no later than April 15, 2025.”
“While J&J seems to be managing a staggered release of the biosimilars into the marketplace in 2025, the number of manufacturers available in a relatively short time frame has the potential to create a variety of pricing strategies similar to the scenarios created when numerous adalimumab products launched in July,” observes Szczotka. “This should ultimately increase competition and provide physicians and patients with additional ustekinumab treatment options.” He notes that information about delivery devices and product formulation components for the ustekinumab biosimilars are not yet known at this point, and those have the potential to impact how significant those launches are.
Tofidence was approved Sept. 29 in an intravenous formulation for three of the seven indications of Actemra, which is approved in both IV and subcutaneous formulations. Biogen is “evaluating the potential launch timeline” for the agent; as of AIS Health deadline, the biosimilar had yet to launch. During Roche’s Oct. 19 call to discuss third-quarter results, CEO Thomas Schinecker said the company expected U.S. biosimilar competition for Actemra next year.
The launch delay may be due to a patent infringement lawsuit (No. 1:23-cv-11573) that Roche, Genentech and Chugai Pharmaceutical filed against Biogen and Bio-Thera on July 13. Just over three months later, on Oct. 23, the companies settled the case but did not provide details of the settlement. “The outcome of this litigation will likely be a significant factor on the launch of Tofidence,” maintains Szczotka.
“In 2022, Actemra sales declined as compared to 2021, but still represented over $1.2 billion in sales,” he says. “The biosimilar will provide another infusible product option in the anti-inflammatory category when it finally becomes market available.”
Szczotka also points to Udenyca Onbody (pegfilgrastim-cbqv), an on-body injector from Coherus BioSciences, Inc. Udenyca is one of five available biosimilars of Neulasta. But because of the Neulasta Onpro on-body injector, the reference drug has “maintain[ed] significant market share,” states Szczotka. Pegfilgrastim is given the day after a person receives chemotherapy to decrease the incidence of infection, and Neulasta Onpro automatically delivers a dose 27 hours after it is applied to a patient’s skin.
“There are certain types of cancer patients — those who live far away, have an active lifestyle or who are supporting the needs of a busy family — for whom the Neulasta Onpro eliminates the need to return to the clinic the day after completing a chemotherapy cycle for a dose of pegfilgrastim,” Szczotka says. If Udenyca Onbody is approved, it “would offer providers the same highly desired alternative delivery system to Neulasta’s Onpro at a presumably lower price.”
“Biosimilar adoption continues to grow and expand across all available therapeutic areas, and this will continue to be seen as more biosimilars gain FDA approval and become market available in new products and therapeutic categories,” predicts Szczotka. “Cost savings achieved with biosimilars can be used to help stretch the health care dollar. While the future impact may not rival the adalimumab biosimilar opportunity, biosimilars will continue to bring cost-saving opportunities to payers and patients.”
This article was reprinted from AIS Health’s monthly publication Radar on Specialty Pharmacy.