Does the Direct-to-Employer Route for Biosimilars Make Sense?

Employers have strongly indicated that they would like to move away from the big 3 PBMs for cost transparency and the ability to capture as much of the savings as possible themselves. Going the direct-to-employer route, as Waltz Health and Fresenius Kabi are doing, would seem a natural option.

Waltz Health, a digital health company, has announced that it has agreed to team with Fresenius Kabi to help supply its three biosimilars in a direct-to-employer arrangement through its existing Waltz Connect platform.

First reported by Fierce Healthcare, the biosimilars that will be available direct-to-employer will be Fresenius Kabi’s Idacio (adalimumab), Tyenne (tocilizumab), and Otufli (ustekinumab). Waltz Health already has direct-to-employer arrangements with Eli Lilly and Novo Nordisk for their GLP-1 products.

By using Waltz Connect, corporate members can avoid traditional wholesaler and pharmacy benefit manager arrangements (and thus avoid rebate contracts). As the products are still delivered through specialty pharmacies, the typical provider and patient supports can still be provided.

The Direct-to-Employer Benefit for Biosimilars

This channel would appear to assure that patients directly benefit from discounts received by the corporate employer. In Fierce Healthcare, Fresenius Kabi’s President of Biopharma Sang-Jin Pak, MD, stated, “As we continue to expand our biosimilars portfolio, we remain focused on innovative partnerships that help employers and payers access high-quality treatment options.”

Employer benefit consultant F. Randy Vogenberg, PhD, told BR&R, “Making the costly drug purchase experience easier and engaging for the consumer as patient remains important. Leveraging biosimilar solutions could further the value to employers and their plan beneficiaries (patients) as other market forces change coverage affecting access to treatment options.” Dr. Vogenberg, Principal, FRV Health Strategy Advisory, Greenville, SC, said, “Addressing economic coverage gaps can be a win–win short-term solution for multiple stakeholders.”

Assuming that the employers signing onto Waltz Health have access to the same pricing for biosimilars as PBMs and others do, this seems a natural option. In surveys, employers have strongly indicated that they would like to move away from the big 3 PBMs for cost transparency and the ability to capture as much of the savings as possible themselves.

In Other Biosimilar News

Teva Pharmaceuticals received its second FDA approval for its denosumab biosimilar. After receiving its approval for Ponlimsi in March, referencing Prolia, to prevent osteoporosis, Degevma, referencing Xgeva, will be prescribed to prevent skeletal-related complications in patients with multiple myeloma or bone metastases. Teva plans to launch both products “in the coming months.” It joins a crowded field of 9 manufacturers with both denosumab indications.

Meitheal Pharmaceuticals announced September 28 that the FDA approved its high-concentration formulation of Yusimry, the company’s adalimumab biosimilar. The company will now be able to compete for prescriptions for this most-used adalimumab biosimilar formulation. “With this approval, we now have FDA approval for both low- and high-concentration formulations of Yusimry, marking an important step in expanding treatment options for patients with certain chronic autoimmune diseases,” said Tom Shea, Chief Executive Officer of Meitheal Pharmaceuticals. In July, the company had also received FDA approval for its insulin aspart biosimilar Garzulys, which is produced by Emerge Bioscience. Meitheal has marketing responsibility for this agent.

This article was written by our Director of Content, Stanton Mehr. Stan has been writing commentary and reporting news about the biosimilar industry since the submission of the first biosimilar 351(k) application to the FDA 13 years ago. Since that time, BR&R has been tracking the US biosimilar marketplace, with the industry’s original, comprehensive and updated database of biosimilar filings with the FDA.

Is the 505(b)2 Pathway Viable for Biosimilars?

With regulators focused on streamlining the 351(k) biosimilar development, it makes sense to wonder if the 505(b)2 pathway is valid for biosimilar approval.

Can discussions about streamlining biosimilar development reach into abbreviated approval pathways for small molecules? Based on a Stat News webinar I attended yesterday, they already have. What exactly are the differences between the 351(k) pathway for biosimilar candidates and the 505(b)2 pathway for small molecules?

Biosimilar-Type Products Already Approved Through the 505(b)2 Pathway

The 505(b)2 pathway was used for some products that are considered by most as biosimilars today. For example, Basaglar, the first copy of insulin glargine, was approved in 2015 through this pathway; it was before insulins transferred to the biosimilar pathway for approval in 2020. Admelog was the first insulin lispro copy, approved in 2017 through the 505(b)2 pathway as well. However, Granix, the first filgrastim molecule launched that was not Epogen or Procrit, utilized the 351(a) pathway, meant for innovator biologics; it predated the implementation of the 351(k) route to approval.

With streamlining of biosimilar development—a major focus of regulators today—it makes sense to wonder if the 505(b)2 pathway is a valid goal for biosimilar manufacturers.

Infographic comparing 505(b)(2) drug approval and 351(k) biosimilar pathways

The 505(b)2 application pathway was implemented through the Hatch–Waxman Amendments of 1984. It was not meant as an abbreviated pathway for generics, but rather a streamlined way to bring new forms of existing innovative medications to market. These are commonly referred to as “follow-on” products. The basis for its use is that the innovator product on which the follow-on molecule is based has a truckload of patient experience proving its safety and efficacy. The manufacturer would simply have to show that its product was very much like the innovator. Its application could range from new formulations, strengths, to other modifications that wouldn’t be expected to affect the structure or anticipated effectiveness.

According to Drug Patent Watch, development cost of a 505(b)2 product might be anywhere from $8 million to $20 million, and the timeline to reach the market (not counting patent litigation) could be as short as 3 years. The 505(b)2 pathway allows a manufacturer to utilize the innovator product’s preclinical and clinical data, requiring little more than comparability studies and bridging pharmacokinetic studies to reach the FDA application stage. The FDA may still require a phase 3 trial, which would change the costs dramatically, but it appears attractive in any case.

Of course, biosimilars require a bit more consideration, as they are far more complex than small molecules, for which the 505(b)2 pathway was intended. With the push to streamline biosimilar development, including waiving the phase 3 trial mandate, eliminate separate testing for interchangeability (and eliminate the designation itself), and drop the need for bridging studies, it is not difficult to visualize movement in this direction.

The Difference With Insulin as a Biosimilar

Yet, insulin is a relatively simple biologic molecule. It has decades of use and clinical experience supporting its safety and efficacy. When the 505(b)2 pathway was used to approve Basaglar and Admelog, few considered this a big risk (it may have helped that the first biosimilars were already approved and in clinical use).

Biosimilars are not follow-on products, unlike typical 505(b)2 agents. Rather, biosimilar manufacturers strive to make their candidates as close a copy as possible to the innovator (but realizing an exact match is impossible). Logically, it might seem that the biosimilar approval process should be at the same level of proof as the 505(b)2 pathway. No, that can never be the case—the structure of biosimilars will always be a little different than the innovator agent. And the structure will always change a bit over time (as will the innovator biologic).

It is better, instead, that the 351(k) pathway is modified to reflect the real-life experience of the biosimilars approved to date by the FDA and the EMA, and that does provide ample opportunity for lowering the bar, and costs, of development.

The Second Entyvio Biosimilar Is Under Review at FDA

On July 31, Fresenius Kabi and Polpharma Biologics announced that its 351(k) application was accepted by both the FDA and the EMA for PB016, a proposed vedolizumab biosimilar candidate to Entyvio

The second vedolizumab biosimilar candidate is now under review by the US FDA. On July 31, Fresenius Kabi announced that its 351(k) application was accepted by both the FDA and the EMA for PB016, a proposed vedolizumab biosimilar candidate to Entyvio lyophilized vial for intravenous administration.

PB016, in-licensed from Polpharma Biologics S.A., is a proposed biosimilar to IV vedolizumab, an integrin-receptor antagonist indicated for the treatment of adults with moderately to severely active ulcerative colitis and Crohn’s disease in adults.

“FDA and EMA acceptances for review of IV vedolizumab biosimilar marks important milestones in the development program and underscores our commitment to improving patient access to high-quality, affordable biologic medicines,” said Dr. Sang-Jin Pak, President Biopharma at Fresenius Kabi. “With IV vedolizumab, we are advancing our autoimmune biosimilars portfolio and taking another step toward providing additional treatment options for patients living with chronic inflammatory diseases.”

The first biosimilar biologic licensing application was submitted in June by Alvotech and Teva.

In Other Biosimilar News

Amneal closed on its purchase of Kashiv Biosciences, a deal which “combines Kashiv’s biologics research, development and manufacturing capabilities with Amneal’s commercial scale, establishing biosimilars as a major long-term growth pillar within the Company’s Affordable Medicines business.”

MFP Agreements Don’t Guarantee Better Patient Access

A study by IQVIA finds that first prescription rejection rates were unchanged for the first MFP negotiated drugs after implementation in January.

A notable study by IQVIA found that for the first drugs subject to Medicare maximum fair price (MFP) agreements, initial rejection rates were not significantly lower than before the new prices took effect in January 2026.

One of the main stipulations of the MFP agreements was that if the reference drug manufacturer signed an MFP agreement, Medicare Part D drug plans and Medicare Advantage plans would have to cover the drug on their formularies.

Enbrel and Stelara Rejection Rates

Enbrel and Stelara are the two Part D drugs of interest in this first round of Medicare MFP negotiations. Enbrel has no current biosimilar competition (though 2 approved products), and Stelara has plenty of it.

These two drugs comprise the immunology sector of the first 10 drugs subject to MFP. According to the IQVIA data, the initial rejection rates for those new to the brand were 59% for the first quarter of 2026. When looking forward 30 days, the average rejection rate on appeal was 22%. In the past 5 years, the initial rejection rates ranged from 61% to 73%. IQVIA did not break down the rejection rates for the two individual biologics.

In their post, IQVIA said, “Expectations for Medicare drug price negotiation to improve patient access have yet to come to fruition. Even more concerning, additional future IPAY-selected drugs are in the immunology and oncology therapeutic areas and other therapeutic areas with similar costs and treatment complexity, facing similarly high levels of payer control.”

The Result of Heavy Biosimilar Competition?

Granted, both etanercept and ustekinumab are unusual products, in that they are both subject to heavy competition from other agents within the same or similar drug categories. In fact, the MFP for Stelara is not competitive with several ustekinumab biosimilars on the market today. The existence of over 10 adalimumab biosimilars at deep discounts would be a highly attractive prior step before approval of either Enbrel or Stelara. Therefore, it is unlikely that payers will significantly change coverage policies to improve access to these two agents under current conditions.

As more Part B medications are subject to MFP negotiations, patient access may change somewhat for those particular drugs. However, one must remember that patient access improvement was not the primary goal of Medicare MFP negotiations under the Inflation Reduction Act. The real goal was cost reduction for the Centers for Medicare & Medicaid Services.

As we can see, cost reduction may not equal better patient access, even if deep price reductions on biologics are available on direct-to-consumer sites because of relatively high patient out-of-pocket costs. Therefore, this finding is not surprising. We saw the same lack of effect when the adalimumab biosimilars were first introduced in 2023: Much lower costs didn’t result in prescriptions to patients; only formulary policy changes did.

Instead, I tend to view IQVIA’s study as more supportive of a 360-degree view of the effectiveness of biosimilar competition for these two medications.

Are Biosimilar Patient Copay Assistance Programs Lacking?

Our survey found that 87% of biosimilar products were associated with patient copay assistance programs that cut out-of-pocket costs to $5 or less. Physician perceptions of important financial assistance differences between biosimilars and reference products seem generally unfounded.

The newly published edition of the Samsung Bioepis Biosimilar Market Report indicates that with few exceptions, biosimilar competition has driven average sales prices (ASPs) on the medical side by more than 60% for products available for at least three years. This ranges from epoetin alfa at -37% to rituximab at –81%. On the pharmacy benefit side, adalimumab wholesale acquisition costs are down more than 80% for most product offerings relative to the original cost of Humira.

Biosimilar Patient Copay Assistance Programs

Success in driving down costs also means less net revenue earned from individual products. This could influence the willingness of manufacturers and their commercialization partners to offer a suite of services to patients and physicians through financial assistance programs and hub programs for handling prior authorization and reimbursement coding questions.

Even at these great discounts, the monthly copay costs to patients would be hard to bear and may be unsustainable for some extended periods of time. I have reported on this problem with respect to direct-to-consumer access for specialty brands and biosimilars. It is the reason why patient copay assistance programs are so widespread across the pharmaceutical industry, particularly for expensive biologics.

Most in the biosimilar business had considered a robust patient copay assistance program and hub services program, matching that of the reference manufacturer, to be the cost of entering the market. The reference product generally had multiple service offerings to maximize prescriber comfort to optimize utilization of their products. If physicians, who sometimes rely on this suite of services, were given a choice of a lower-cost biosimilar with fewer services and the standard reference product offering, it would make them less willing to adopt the biosimilar.

In the last couple of years, I’ve been made aware of some rumblings in the provider community that manufacturers were in fact cutting back on their biosimilar patient copay assistance programs and hub services offerings. In a market research project I worked on for an upcoming publication, some dermatologists, rheumatologists, and neurologists brought up this perception, particularly for patient copay assistance programs. As a result, BR&R conducted a quick survey of manufacturers, based on their website resources, of their biosimilar copay assistance programs.

For standardization purposes, we assumed an adequate program to be one resulting in monthly copays of $5 or less for commercially insured patients, independent of the duration of access to the program. Of course, the overall impact does not consider copay maximizers or copay accumulators from health plans.

How Many Manufacturers Don’t Have Biosimilar Patient Copay Assistance Programs?

As of July 24, a total of 68 biosimilars were marketed; we counted denosumab biosimilars as a single molecule, despite having two brand names. We then removed insulin biosimilars from the survey: They each offer a form of copay assistance, with $35 monthly copay limits. Much of this was the result of government pressure. That brings the number of eligible surveyed biosimilars down to 63. Eight or 13% were without copay assistance programs. There were some interesting caveats for those lacking these packages.

Recent Biosimilar Launches

It takes many months to fully develop a launch plan for any pharmaceutical. Generally, a product launch would not occur if all the ancillary services were not in place and ready for immediate use. For Biocon Biologics, which launched its denosumab biosimilars (Bosaya/Aukelso) in April 2026, its website indicated that its patient copay assistance program would be “coming soon.” Gedeon Richter and Hikma’s denosumab biosimilars Enoby and Xtrenbo were launched in January this year, but do not any copay assistance program associated with them.

Bio-Thera Solutions’ bevacizumab biosimilar Avzivi likewise does not have a patient assistance program. Its commercialization partner, Sandoz, does not list it among its Sandoz One offerings.

Bio-Thera and its commercialization partner Hikma do not have a copay assistance program for its Starjemza ustekinumab biosimilar. It is the only ustekinumab program lacking copay assistance.

Low-Cost Products

Nypozi, a filgrastim biosimilar by Tanvex BioPharma and commercialized by Cipla for more than 6 months, has no such services listed. Pfizer does not list a patient assistance program for Retacrit, its epoetin biosimilar. These are the least costly drug categories (outside of insulin) overall. The ASP for epoetin products is approximately $7 per 1000 units. For filgrastim, prices for the three least expensive biosimilars are $107 to $133 per 480 mg.

Discontinued Programs

In only two cases did a program exist but be discontinued. For Boehringer Ingelheim’s Cyltezo, the program ended July 15, 2026. Quallent, which sells a private-label version of this adalimumab biosimilar, claims to have a copay assistance program, but the website listed only terms and conditions, without an opportunity to enroll. Perhaps, this is in the process of rolling out in the transition. Until then, it is the only adalimumab biosimilar without a copay assistance program.

Byooviz is Samsung Bioepis’ ranibizumab biosimilar, originally in partnership with Biogen. Biogen included Byooviz in its patient assistance offerings, until the partnership ended. Harrow took over US commercialization for the biosimilar but has not unveiled a patient copay assistance program for it.

What About the Private-Label Biosimilars?

The private-label distributors add an interesting aspect to the mix, as we do not count their products as separate from the biosimilar parent. Yet, there is some interesting nuance in this area.

For example, OptumRx’s specialty distributor Nuvaila has a separate site for adalimumab-atto’s copay assistance, but it links back to Amgen’s own patient assistance site. Patients needing copay assistance for another adalimumab, Sandoz’s Hyrimoz, can access it through the Sandoz One Source, but the private-label version through Cordavis also has its own website. Finally, Cordavis, which also distributes a private-label version of Samsung Bioepis’ Hadlima, offers patient copay assistance, as does Samsung’s marketing partner for Hadlima, Organon. As mentioned above, Quallent also claims to offer such a program for its Simlandi private label (Teva provides one for the Simlandi brand), but this seems to be a terms sheet without access to online enrollment.

The Take Aways

Generally, the marketed biosimilars have patient copay assistance programs but the greatest variability seems to be associated with companies recently entering the US market or where product costs are the lowest.

Only 13% of marketed biosimilars are currently without qualified patient assistance packages. In terms of these financial assistance programs, physicians who believe that biosimilars manufacturers are lacking these offerings seem to be off base. We do not know if they are similarly incorrect about other services, like eligibility verification, prior authorization assistance, and handling returns. We may investigate the availability of these hub services in the future.

A slew of new biosimilars are expected to be launched in the next 12 months, including those in the aflibercept, denosumab, golimumab, omalizumab, and pertuzumab categories. We’ll have to watch closely.

Tracking Two Bills to Remove the Clinical Efficacy Study Requirement for Biosimilar Development

Proposals in the House and Senate, both titled the Expedited Access to Biosimilars Act, may officially remove the FDA’s requirement for clinical efficacy studies for biosimilar candidates.

On July 15^th, a new bipartisan bill was introduced into the House of Representatives that would expand access to biosimilars by modernizing the FDA’s biosimilar approval process. This could be paired with a similar proposal just reaching Senate Committee discussion. Both of these proposals seek to reduce the cost of biosimilar development through squeezing out the need for comparative efficacy studies.

As reported earlier, the FDA in October 2025 announced a draft guidance that would achieve the same end, to remove the mandate for late-stage clinical efficacy trials for biosimilar manufacturers. However, a final guidance has not yet been released.

Introduced by Representatives Nick Langworthy (R-NY) and Kim Schrier, MD (D-WA), the Expedited Access to Biosimilars Act (HR 9661) could codify long-awaited regulatory changes to comparative trial expectations in the 351(k) biosimilar pathway.

According to a press release from Congressman Langworthy’s office, the act would eliminate unnecessary regulatory hurdles while preserving the FDA’s authority to require additional studies whenever scientifically warranted. This supports the October 2025 announcement of a draft guidance for removal of a mandate for phase 3 clinical efficacy studies for biosimilars. A key stipulation of the proposal would be a requirement for FDA to notify manufacturers early in the review process if additional late-stage comparative efficacy studies will be required. The aim would be to provide greater certainty around the clinical trial resources required for a successful biosimilar application process as well as avoiding unnecessary delays in the application process.

A number of associations have express support for the legislation including the Association for Accessible Medicines, the American Society of Health-System Pharmacists, and America’s Health Insurance Plans, among others.

The Senate’s 2025 Proposal

A Senate proposal by the same name (S.1414), introduced in April 2025 by Senator Rand Paul (R-KY), seeks largely the same goals. It has languished in the Committee on Health, Education, Labor, and Pensions, without additional cosponsors, until now. A committee meeting is scheduled for July 22 to finally consider this legislative proposal. It has one co-sponsor (Sen. Mike Lee, R-UT).

We’ll be monitoring whether the Expedited Access to Biosimilars Act can break through for an eventual debate and vote on either the House or Senate floor.

Biosimilar Bytes: Golimumab Patent Litigation, Positive Keytruda Biosimilar Trial Results

Janssen files BPCIA patent suit against an impending Alvotech golimumab biosimilar, and Samsung Bioepis releases positive phase 3 trial results

Golimumab Patent Battle for Alvotech and Bio-Thera Biosimilars

Alleging patent infringement, Janssen Biotech filed BPCIA litigation in US District Court for the Eastern District of Virginia against Alvotech involving AVT05, its golimumab biosimilar candidates. According to Janssen, 14 patents each are at issue on its reference products Simponi and Simponi Aria.

Janssen BIotech v Alvotech patent litigation

Alvotech and its commercialization partner Teva resubmitted its 351(k) application for approval of ATV05 on June 4. It is not known why Janssen did not file the BPCIA patent suit once Alvotech first sent its biologic licensing application to the FDA in January 2025.

Bio-Thera Solutions and its marketing partner Accord BioPharm received the first FDA approval for golimumab biosimilars on May 15, 2026. Of course, they are also in the midst of patent litigation with Janssen to prevent a delay in marketing of this biosimilar as well. Janssen first filed its complaint in March 2026, involving 17 patents. In response, Bio-Thera filed for Inter Partes Review on 4 patents involving methods of treatment, while claiming the others were either obvious or publicly available. According to Big Molecule Watch, a District Court hearing is scheduled for September 1. The principal patents on Simponi have already expired. Accord BioPharm had previously announced an expected launch later this year.

Samsung Bioepis’ SB27 Phase 3 Results

Despite several other prospective pembrolizumab biosimilar makers foregoing or discontinuing phase 3 trials, Samsung Bioepis has plowed forward, announcing preliminary positive results for its investigational product SB27.

Although the phase 1 and phase 3 trials are not yet completed, the initial results announced indicated equivalent pharmacokinetic data for SB27 compared with the reference product Keytruda, as well as clinically similar outcomes (i.e., objective response rates) in the double-blind, parallel-group, phase 3 investigation at week 24.

The FDA announced last October that late-stage clinical trials will no longer be routinely required for biosimilar development and approval. Most manufacturers pulled the plug on ongoing or planned trials for pembrolizumab biosimilars, as we reported in November.

Samsung reported that it expects to complete both the phase 1 and phase 3 trials by the end of 2026.

When is a Biosimilar a Biosimilar?

In 2026, is the definition of a biosimilar the same for countries’ drug regulatory systems around the globe? A recently published scoping survey attempted to answer the question.

Although there has been a decade of interest in moving towards global biosimilar regulatory standards, we first must answer a more foundational question: Is the definition of a biosimilar the same worldwide?

You may suspect that the answer is obvious, but then again, why are we asking it? Is it a trick question? Years ago, the answer was not so simple. Those of us covering the biosimilar field in the 2010s will recall that some Indian companies, for example, were producing what might be considered “follow-on” medicines by the FDA’s regulatory standards, but were promoting them as biosimilars.

No Guidances by FDA on Follow-on vs. Biosimilar Products

The FDA’s own regulatory definition was not set in stone: Basaglar, the second insulin glargine product to receive FDA approval, is a biosimilar but technically not a biosimilar. Even today, there may be some confusion as to whether Basaglar is considered a biosimilar or a follow-on product. It was indeed approved by the FDA under a 505(b)2 application, principally because insulins were not considered eligible for the 351(k) approval pathway until 2020. The FDA would probably support that it is clinically equivalent to Lantus in any way that matters. Yet, from a regulatory perspective, it was not evaluated as part of the biosimilar pathway, so it cannot be designated a biosimilar.

The same can be said for Granix, the second filgrastim product approved by the FDA, which underwent its approval process before the 351(k) was implemented (and under which Zarxio was licensed). It is important to note that the FDA itself has not tried to improve clarity by announcing retrospectively that these agents can be considered either biosimilar or an equivalent.

A Survey of Biosimilar Definitions

So, is a biosimilar a biosimilar throughout the world? An article published in JAMA Health Forum described a survey of 19 countries’ biosimilar regulatory guidelines. These included 12 with emerging and developing economies and 7 with advanced economies, according to the World Health Organization classification. The authors, from the University of San Francisco and GlaxoSmithKline, found that most countries define “biosimilarity as the absence of differences in the medicine’s quality, safety, and efficacy compared with the RP. Sixteen countries explicitly required comparability exercises to demonstrate biosimilarity, and 13 countries specified that the same RP must be used in these studies.

“Of the 19 countries in the study sample, 17 (89%) have adopted the WHO’s biosimilar terminology; the exceptions were Indonesia, which uses the term follow-on biological in addition to biosimilar,and Tanzania, which uses the term similar biotherapeutic product. A total of 17 countries (89%; except India and South Korea) define biosimilarity according to the absence of differences in quality, safety, and efficacy between the biosimilar and the reference product, although in some countries (Egypt, Turkey, UK, and US), this is heavily implied rather than explicitly stated. Most countries (n = 16 [84%]) require comparability exercises (by definition), but 3 (Mexico, Indonesia, and China) do not explicitly include this requirement.”

The authors also stated that all advanced economies waived the need for clinical efficacy and immunogenicity testing when justifiable, but guidelines from emerging and developing economies differed on clinical study waivers.”

Interestingly, one of the areas of least consensus is that of biosimilar naming and labeling guidance provided. Countries such as France, Germany, Japan, and South Korea do not specify any requirements, whereas the UK, US, and Canada do, among the WHO advanced economic sector. Among countries in the emerging and developing economic region, China and Mexico do have naming and labeling guidelines, whereas Brazil, India, and Indonesia do not. The area of greatest agreement seemed to be in acceptance of extrapolation, with all but Saudi Arabia among the surveyed countries with published extrapolation guidelines.

Scoping surveys such as this are necessary steps in a march towards global regulatory standards for biosimilars. They show not only how far we’ve come in reaching basic agreements, but also how far we need to go. Perhaps, most importantly, they show us areas where a push for global standards would have the least likelihood of success.

Alvotech Submits First Entyvio Biosimilar Application to FDA

The first 351(k) application for a vedolizumab (Entyvio) biosimilar has been submitted by Alvotech. If approved, the biosimilar would be marketed by Teva. Alvotech also resubmitted biosimilar applications for golimumab and aflibercept.

On June 8, Alvotech announced that the FDA has accepted its biologic licensing application for AVT16, a biosimilar candidate for the reference drug Entyvio. This marks the first FDA 351(k) drug application for a vedolizumab biosimilar.

In its press release, Joseph McClellan, Chief Operating Officer of Alvotech, stated, “FDA acceptance of the BLA for AVT16 is another important step in advancing our mission to increase access to biologic medicines for patients worldwide. Our proposed interchangeable biosimilar to Entyvio builds on our experience in immunology and reflects the strength of our fully integrated development and manufacturing platform.”

Vedolizumab, an integrin-receptor antagonist, is currently approved to treat adults with moderate-to-severe ulcerative colitis and Crohn’s disease. The reference product is available in both intravenous infusion and subcutaneous injections.

Takeda’s US Entyvio net revenues were over $4 billion in 2024, but the biologic has been targeted for Medicare maximum fair price negotiation. The negotiated price will be implemented on January 1, 2028, unless biosimilar launch is imminent. The original drug patent is set to expire in 2026.

Intravenous Infusion vs. Subcutaneous Injection

AVT16 would be available only as an intravenous infusion. Alvotech’s biologic licensing application does not cover the subcutaneous injectable. A separate investigational product, AVT80, promises a biosimilar version of the prefilled syringe and autoinjector administration. Alvotech noted that the European Medicines Agency has received a marketing application for both AVT16 and AVT80. It is not clear whether Alvotech and its marketing partner Teva, intends to market these products under separate brand names if approved. The patent on the subcutaneous formulation may not expire until the 2030s, according to some sources, which may play into Alvotech’s decision to separate the FDA applications.

In Other Alvotech Biosimilar News

In November 2025, Alvotech received complete response letters from the FDA on two products—its biosimilar versions of golimumab and aflibercept. On June 4, 2026, the biosimilar manufacturer revealed that it had resubmitted its 351(k) applications to the FDA for both products (AVT05 for golimumab and AVT06 for aflibercept). Alvotech noted that it expects an FDA decision within 6 months. The complete response letters cited production facility issues, and not data or clinical quality questions. The latest FDA surveillance inspection of the Reykjavik production facility was completed by May 11, according to the company.

How Comfortable Are Neurologists With Biosimilar Prescribing?

With the October 2025 launch of Tyruko (natalizumab), neurologists have now been exposed to three different biosimilar categories, and one has been around since before the COVID-19 pandemic.

It’s logical to assume that when a specialty is exposed to biosimilar competition for the first time, acceptance and uptake of the biosimilar might be slow. The effort to educate specialists around the safety and efficacy of the biosimilar(s) may take time. In the past, manufacturers of the reference products countered competition with misleading marketing efforts to preserve their revenues. To cite just two examples, this occurred with gastroenterologists with the introduction of infliximab and with ophthalmologists with the launch of the first ranibizumab biosimilar. And then of course, there was the slow acceptance of adalimumab, based on different formulations.

Last October, the natalizumab biosimilar Tyruko was launched by Sandoz, primarily for the treatment of multiple sclerosis. Will neurologists’ biosimilar prescribing follow this stunted path? Only if you think natalizumab marks the first foray of biosimilars into the field of neurology medicine. In reality, this is not the case.

Eculizumab and Rituximab Biosimilars in the Neurology Toolbox

One reason that neurologists’ biosimilar prescribing will be quicker is that natalizumab is actually the third biosimilar used by these specialists. Eculizumab is usesd to treat patients with the neurological condition generalized myasthenia gravis. That drug has been available as a biosimilar since March 2025.

Although many neurologists have moved from the eculizumab reference drug Soliris to the follow-on brand Ultomiris, the appearance of biosimilars has likely exposed them to more prior authorization and/or step therapy, encouraging the use of lower-cost eculizumab biosimilars. Additionally, their experience with buy-and-bill eculizumab biosimilars gave them a brief preview of buy-and-bill reimbursement for the natalizumab biosimilar.

Another factor impacting neurologists’ biosimilar prescribing is not so obvious: A significant portion have been prescribing rituximab and its biosimilars off label to treat some neurologic disorders, including myasthenia gravis, multiple sclerosis, and neuromyelitis optica spectrum disorder. And rituximab biosimilars were approved since 2018.

Neurologists May Be More Comfortable With Biosimilars Than You Think

In working on a survey of 40 practicing neurologists for a biosimilar manufacturer and marketer, it became apparent that the respondents were far more familiar with biosimilars than we may have assumed.

In the case of the present survey, which was conducted just before the launch of Tyruko, 41% of the neurology sample had indicated they had experience with rituximab biosimilar prescribing s within the previous 12 months. This may have contributed to the view by 40% of the sample that the use of either eculizumab or natalizumab biosimilars would not have any effect on their practice. An additional 22% believed the biosimilars might actually result in greater profits. This should certainly make it easier for makers of biosimilar forms of market-leading Ocrevus, when they are launched in 2028.

Watch for further insights from this survey project in the next month, once the full results are published.