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.

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.

First Opdivo Biosimilar FDA Application Submitted by Amgen

Amgen became the first manufacturer to submit an application to the FDA for a nivolumab (Opdivo) biosimilar. It also was the first to be sued for patent infringement.

Last week, Amgen became the first manufacturer to disclose that they submitted an application to the FDA for a nivolumab (Opdivo) biosimilar. In doing so, Amgen also became the first manufacturer to be sued by the reference manufacturer Bristol-Myers Squibb for patent infringement.

The company disclosed the 351(k) application during a business presentation on September 10. Amgen’s product, ABP 206, is one of several publicly disclosed nivolumab biosimilar candidates. The company reported, “...for ABP 206, our biosimilar candidate to OPDIVO, our Biologics License Application with the FDA has been submitted and accepted for review. We expect an FDA action on that BLA by end of the year.”

Net 2025 US revenues for Bristol-Myers Squibb’s PD-L1 inhibitor were $5.9 billion. The intravenously administered drug was first approved in 2014 (and market exclusivity ends this year), and its main patent expiration is expected to expire in 2028. Bristol-Myers Squibb also introduced a subcutaneously administered version of Opdivo in 2024, which is approved only for specific cancers. Among other manufacturers who have publicly disclosed potential nivolumab biosimilars Sandoz, Xbrane, Henlius, and mAbxience, are in various stages of development.

Patent Infringement Suit Filed Against Amgen’s Opdivo Biosimilar

Within days of the announcement of Amgen’s FDA biosimilar application for ABP 206, Bristol-Myers Squibb initiated a lawsuit claiming infringement on at least 7 patents on their product. We estimate the earliest expected launch date for intravenously administered nivolumab biosimilars to be in 2029 based on a main patent expiration in late 2028. Based on past experience, the likelihood of a settlement between the two parties may be lower than for other prospective biosimilar manufacturers, as Amgen has been willing to go at-risk for launch in the past (specifically for its aflibercept biosimilar Pavblu, a product with a similar market size as nivolimumab).

Of further interest, Opdivo is often prescribed in combination with Yervoy (ipilimumab), which is also the focus of considerable biosimilar research (also involving Amgen). Amgen also disclosed during its business presentation that it intends to file its biosimilar application for ABP 234, its biosimilar candidate to compete with Keytruda, before the end of the year.

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.

Biosimilar Bytes: Biocon’s Yesafili Launches and Dr. Reddy’s Rituximab Biosimilar Is Approved

Biocon announced the launch of its Yesafili biosimilar, in competition now with Pavblu, for the aflibercept market. Dr. Reddy’s and its marketing partner Fresenius Kabi have received FDA approval for its rituximab biosimilar.

Biocon Begins Marketing Its Aflibercept Biosimilar Yesafili

Shreehas Tambe, Chief Executive Officer and Managing Director of Biocon Limited, said, “The commercial launch of Yesafili in the United States is an important milestone in our efforts to improve access to high-quality biosimilar medicines. It strengthens our presence in ophthalmology and reflects our commitment to making advanced treatments more accessible and affordable for patients around the world.”

The second aflibercept biosimilar has reached the US market, as Biocon Biologics announced the launch of Yesafili. Initially approved in May 2024, along with a slew of other aflibercept biosimilars, launches were delayed by settlement agreements with the manufacturer of the reference product, Eylea.

Pricing information was not reported for Yesafili. Significant sales volume of the first marketed aflibercept biosimilar, Pavblu, was achieved with a relatively small wholesale acquisition cost discount (–16%). Amgen, in its second-quarter 2026 earnings, reported $280 million in US sales, putting it on pace to be the first billion-dollar biosimilar. It has largely driven Amgen’s overall biosimilar revenues, which are up 29% from the same quarter in 2025.

Dr. Reddy’s Readying Rituximab Biosimilar for Launch with Fresenius Kabi After FDA Approval

On August 1, 2026, Dr. Reddy’s Laboratories received FDA approval for its rituximab biosimilar. The brand name and nonproprietary name suffix were not announced at the time of posting.

Dr. Reddy’s entered into a commercialization agreement with Fresenius Kabi to market the monoclonal antibody biosimilar in the United States.

The agent was known as DRL_RI in clinical trials, is already commercialized in the European Union in the United Kingdom. It is sold under the brand name Ituxredi in those markets. A launch date has not been announced for this fourth rituximab biosimilar approved by the FDA.

Currently, two biosimilars (Truxima and Ruxience) lead the rituximab category, each with 35% market share by volume, based on IQVIA data.

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.

Are Two Pegfilgrastims for Accord BioPharma Better Than One?

The FDA has approved the eighth pegfilgrastim biosimilar; now Accord BioPharma owns two of them: newly approved Ennumo and Udenyca

Accord BioPharma and its parent company Intas Pharmaceuticals announced that had it received approval on July 9th for a new pegfilgrastim biosimilar, which it has dubbed Ennumo (pegfilgrastim-pccg). The new biosimilar has been approved for all of the indications of the reference product Neulasta.

Why Two Pegfilgrastims?

What makes this approval interesting is that Accord and Intas already have a pegfilgrastim biosimilar, the product Udenyca, which is the number 2 pegfilgrastim product as of the end of 2025 (according to IQVIA). Udenyca was approved in 2018 by the FDA, and Accord acquired Udenyca once the original manufacturer, Coherus, decided to exit the biosimilar market. In the press release announcing the newest approval, Accord stated that it now has three separate granulocyte colony-stimulating factor, and “two distinct pegfilgrastim biosimilars” in its portfolio.

BR&R contacted Accord regarding how they intend to differentiate the two pegfilgrastim biosimilars. At present, Udenyca is available as both an injectable and in on-body injector forms. The new biosimilar Ennumo is available in the injectable form only. Otherwise, there is no difference in terms of dosing or indication. While Accord did not respond in time for publication, it may be possible that Accord intends to stop marketing Udenyca as an injectable, allowing Ennumo to take its place, or potentially selling only one brand or the other to certain segments of the US audience.

“Every FDA approval marks a step forward in our mission to expand patient access to high-quality, affordable biologic therapies,” said Chrys Kokino, President, Accord North America. “With Ennumo, we now offer healthcare providers the largest G-CSF portfolio in the world from a single biosimilar company.”

However, it is not yet clear how the additional pegfilgrastim biosimilar improves access. Overall, eight pegfilgrastim biosimilars are marketed today, in addition to the reference product.

Why State Employee Health Plans Should Push Hard for Biosimilar Use

A focus on biosimilars will save individual state employee health plans a conservative average of over $17 million, based on net costs.

A new survey from the Pacific Research Institute found that a greater focus on biosimilar utilization will save individual state employee health plans on average over $17 million each year, based on net costs.

In 2024, the year on which savings calculations were based, adalimumab biosimilars had begun to significantly cut into Humira’s market share, and savings were already being registered in a number of biologic categories, especially the oncology-related therapies.

State employee health plan savings with biosimilars

The study used data from CMS, IQVIA estimates, and a third party’s estimate of nonretail prescription drug expenditures. Based on these three sources, state private health insurance plans spent $20 billion on biologics in 2024. The author, Wayne Winegarden, PhD, Senior Fellow at Pacific Research Institute, confirmed to BR&R that these estimates are based on net prices, not gross costs. He estimates that roughly one-quarter of those expenditures were spent on biosimilars in categories of biologics with biosimilar competition, or a total of 7% of overall biologic expenditures.

State Employee Health Plans Save Big With Biosimilars

The research assumed two different scenarios: (1) biosimilars attain 52% of the biologic volume in categories with biosimilar competition (or 15% of overall biologic expenditures) and (2) 81% within those categories, or 24% of the overall biologic spend.

The author found that across the US, savings ranges from $871 million to $1.8 billion each year. From the analysis of individual states’ public employee health plans, biosimilars will save annually in the range in the from $0.9 million in Wyoming to $88.4 million in California (conservative scenario). In the more aggressive scenario, the biosimilars savings range was $1.8 million in Wyoming and $178.9 million in California.

Dr. Winegarden concludes, “Due to the savings potential, prioritizing biosimilars in state employee health plans will enhance the fiscal soundness of the state budget while ensuring state employees have access to efficacious treatments. This is an easy win-win outcome that will benefit both taxpayers and state employees.”

In Other Biosimilar News

According to a report in the Korea Biomedical Review, Celltrion was given the FDA interchangeability designation for its rituximab biosimilar product Truxima. This is perplexing for all of the reasons I’ve stated in the past: (1) the drug is not covered under the pharmacy benefit so it is not subject to the sole automatic substitution purpose of the designation and (2) the interchangeability designation does not in any way infer that the product is better than another biosimilar, yet the report noted that “Truxima remains the only rituximab biosimilar officially recognized by the FDA as interchangeable with the reference product, which it believes will provide a competitive advantage through greater physician confidence and market differentiation.” Any suggestion that an interchangeable is better than a conventional biosimilar is false. Rituximab biosimilars were first approved in 2018. How much additional confidence do prescribers need?

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.

Sunshine Lake Pharma and Lanexa Biologics Get Their First FDA Biosimilar Approval

The Guangdong, China–based generics manufacturer and its commercialization partner Lanexa Biologics received FDA approval for their insulin glargine biosimilar Langlara. In addition to its insulin glargine product, which is approved in China, other biosimilars may follow based on Sunshine Lake’s other existing insulin formulations.

Another insulin glargine biosimilar has joined the ranks of Semglee and Rezvolglar. A new, lesser-known manufacturer from China has received its first FDA approval, joining the ranks of insulin glargine competitors in the US. The product, Langlara (insulin glargine-aldy) was approved by the FDA in late April. Langlara is manufactured by Guandong, China–based Sunshine Lake Pharma Co, Ltd (we think–see below).

The drug will be commercialized in the US by a Lannett subsidiary called Lanexa Biologics. Lannett had an insulin glargine biosimilar in the pipeline, and was expected to file for FDA approval several years ago. Instead, it filed for Chapter 11 bankruptcy. Lannett emerged from bankruptcy in June 2023. In July 2025, Aurobindo Pharma began the process of acquiring Lannett. According to Lannett, upon completion of the acquisition, Lanexa Biologics will become a free-standing company, and will focus exclusively on biosimilar commercialization in the US.

Tim Crew, CEO of Lannett, stated, “Often, the greatest barrier to care for patients living with diabetes is the cost or the availability of the medicine itself. Upon the launch of Langlara, supported by the tremendous manufacturing scale of our partner, patients will have expanded access to a safe, affordable and available treatment option.”

It is unknown at present whether (or how) this biosimilar approval is related to the earlier Lannett drug candidate. However, Lannett’s press release also refers to a collaboration with Sunshine Lake Pharma on the latter’s short-acting insulin aspart biosimilar candidate, which is also approved in China. Sunshine Lake Pharma also has an R human insulin and 70/30 mix insulin among its product portfolio.

The Chinese-end of this partnership is possibly even more complex. Clicking on the website for Sunshine Lake Pharma leads to HECpharm.com, which also operates under the name Guangdong Dongguangyang Pharmaceutical. The HECpharm.com website explains that Dongguangyang Pharmaceutical was founded in 2003, the same date as listed for Sunshine Lake Pharma. A merger occurred between Sunshine Lake and a Dongguangyang Changjiang Pharmaceutical, in 2025, and yet another name is mentioned on the website—Dongguangyang Lake. In the US, a subsidiary named HEC Pharm USA Inc is based in Plainsboro, New Jersey, but that website’s link was inoperative when checked for this article. Yet, the FDA’s approval letter for Langlara was directed to “Sunshine Lake Pharma Co, Ltd, c/o HEC Pharm USA Inc,” indicating that HEC Pharm USA was operating as the liaison with the FDA during the approval process. Perhaps HEC Pharm is a parent company in this maze of entities. In any case, there is a new insulin glargine biosimilar approved in the US on behalf of a confusing organization in China!

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.