An Expert Report on AVT-16: Clinical Development, Mechanism of Action, and Strategic Market Positioning of a Vedolizumab Biosimilar

Executive Summary

This report provides a comprehensive analysis of AVT-16, an investigational human monoclonal antibody developed by the global biotechnology company Alvotech. AVT-16 is a proposed biosimilar to Takeda's blockbuster reference product, Entyvio® (vedolizumab), a leading therapy for inflammatory bowel disease (IBD). The primary objective of the AVT-16 program is to establish biosimilarity, thereby offering a cost-effective alternative to Entyvio® and increasing patient access to this critical treatment modality.

The scientific foundation of AVT-16 lies in its mechanism of action as a gut-selective α4β7 integrin antagonist. By specifically binding to the α4β7 integrin on a subset of memory T-lymphocytes, AVT-16 blocks their interaction with the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) on endothelial cells within the gastrointestinal tract. This targeted inhibition prevents the migration of inflammatory leukocytes into the gut tissue, addressing the underlying pathophysiology of Ulcerative Colitis (UC) and Crohn's Disease (CD) while avoiding the broader systemic immunosuppression associated with older therapies. This gut-selectivity is a key differentiator, contributing to a favorable safety profile that has been instrumental in the commercial success of the reference product.

Alvotech is advancing AVT-16 through a standard and rigorous biosimilar clinical development pathway. The program has successfully completed a Phase 1 pilot study in healthy volunteers (NCT06400719; AVT16-GL-F01), which assessed the drug's safety, tolerability, and pharmacokinetic profile. Building on this foundation, Alvotech initiated a pivotal, global Phase 3 confirmatory study in September 2024 (NCT06570772; AVT16-GL-C01). This large-scale, randomized, double-blind trial is designed to demonstrate comparative efficacy, safety, and immunogenicity between AVT-16 and Entyvio® in approximately 748 patients with moderate to severe UC. The successful outcome of this trial is the most critical determinant for future regulatory submissions and commercialization.

The commercial opportunity for AVT-16 is substantial. The reference product, Entyvio®, generated global sales of approximately $5.4 billion in the twelve months preceding June 2024, with the market projected to exceed $7 billion by 2030. The competitive landscape for vedolizumab biosimilars is notably limited, with Alvotech and Polpharma Biologics (with its candidate PB016) emerging as the two primary front-runners in late-stage development. This contrasts sharply with the highly crowded markets for other biologic biosimilars, suggesting a potentially more favorable pricing and market share environment for the first entrants.

Alvotech's corporate strategy supports the AVT-16 program through a proven platform that has already brought biosimilars for Humira® and Stelara® to market. Furthermore, Alvotech has secured a key strategic partnership with Advanz Pharma for the commercialization of AVT-16 and other pipeline assets across Europe. This collaboration de-risks market entry and leverages Advanz Pharma's established commercial infrastructure, allowing Alvotech to focus on its core competencies in development and manufacturing. The success of AVT-16 hinges on flawless clinical trial execution, timely regulatory approvals, and a robust manufacturing and commercial launch strategy in partnership with Advanz Pharma.

Introduction: Profile of AVT-16, a Vedolizumab Biosimilar by Alvotech

Product Definition

AVT-16 is an investigational biological product being developed as a biosimilar to the reference drug Entyvio®, whose active ingredient is vedolizumab.[1] As a biosimilar, AVT-16 is a human monoclonal antibody engineered to be highly similar to the originator biologic in terms of its structural and functional characteristics, with the goal of demonstrating no clinically meaningful differences in safety, purity, and potency.[5] The development pathway for a biosimilar is distinct from that of a novel drug; it focuses on a comprehensive comparability exercise against the reference product rather than establishing efficacy and safety

de novo.[5] AVT-16 is specifically designed to replicate the therapeutic effects and safety profile of vedolizumab, targeting a significant share of its established market.[2]

Developer Profile: Alvotech

The developer of AVT-16 is Alvotech, a global biotechnology company headquartered in Reykjavik, Iceland, with a specialized focus on the development and manufacture of biosimilar medicines.[2] Founded by Robert Wessman, Alvotech operates with a fully integrated, end-to-end business model, encompassing comprehensive in-house capabilities from cell line development and process engineering to clinical manufacturing and regulatory affairs.[2] The company's stated mission is to improve global health by increasing patient access to high-quality, cost-effective biologic therapies.[2]

Alvotech's pipeline is robust, with eight disclosed biosimilar candidates targeting a range of high-value therapeutic areas, including autoimmune disorders, eye diseases, osteoporosis, respiratory conditions, and cancer.[2] The company has a proven track record of execution, having successfully developed and commercialized biosimilars to two of the world's best-selling biologics: AVT02, a biosimilar to Humira® (adalimumab), and AVT04, a biosimilar to Stelara® (ustekinumab).[2] This history of successful development and regulatory approval lends significant credibility to its ongoing programs, including AVT-16.

Therapeutic Indication

AVT-16 is being developed to treat the same conditions for which its reference product, Entyvio®, is approved: moderately to severely active Inflammatory Bowel Disease (IBD), which primarily includes Ulcerative Colitis (UC) and Crohn's Disease (CD).[2] These chronic, debilitating inflammatory conditions affect millions of patients worldwide and represent a significant unmet medical need, particularly for patients who have had an inadequate response to or are intolerant of conventional therapies or other biologics like tumor necrosis factor (TNF) inhibitors.[2]

Formulation and Administration

AVT-16 is a peptide/protein-based modality formulated as a solution for intravenous (IV) infusion.[1] This route of administration and formulation matches the established IV induction and maintenance therapy regimen of the reference product, Entyvio®, which is a critical aspect of establishing biosimilarity and ensuring seamless adoption by healthcare providers and infusion centers.

Table 1: AVT-16 Drug Profile Summary

Attribute	Description	Source(s)
Product Name	AVT-16	1
Alternative Names	AVT 16, AVT16	1
Developer	Alvotech	1
Modality	Monoclonal Antibody (Human) / Peptide/Protein	1
Classification	Biosimilar	1
Reference Product	Entyvio® (vedolizumab)	2
Mechanism of Action (MoA)	α4β7 Integrin Antagonist	1
Route of Administration	Intravenous (IV)	1
Primary Therapeutic Area	Immunology (Inflammatory Bowel Disease)	2
Target Indications	Ulcerative Colitis, Crohn's Disease	2

Scientific and Clinical Foundation: The Role of α4β7 Integrin Antagonism in IBD

Pathophysiology of Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease, encompassing both Ulcerative Colitis and Crohn's Disease, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract.[17] The pathogenesis of IBD is complex and multifactorial, involving a dysregulated immune response to intestinal flora in genetically susceptible individuals.[17] A central feature of this pathological process is the massive and sustained infiltration of circulating leukocytes—particularly memory T-lymphocytes—from the bloodstream into the intestinal mucosa.[18] This process of leukocyte trafficking is mediated by a series of interactions between adhesion molecules on the surface of leukocytes and their corresponding ligands on endothelial cells lining the gut vasculature.[17] Once these inflammatory cells migrate into the gut tissue, they release a cascade of pro-inflammatory cytokines and other mediators, perpetuating the inflammatory cycle, causing direct tissue damage, and leading to the clinical manifestations of IBD, such as diarrhea, abdominal pain, and rectal bleeding.[17]

Detailed Mechanism of Action of Vedolizumab (and by extension, AVT-16)

The therapeutic strategy of AVT-16 is to replicate the highly specific, gut-selective mechanism of action of its reference product, vedolizumab.[16] AVT-16 is a humanized immunoglobulin G1 (IgG1) monoclonal antibody designed to function as a potent and selective antagonist of the α4β7 integrin.[14]

The mechanism can be broken down into the following key steps:

1. Target Identification: The α4β7 integrin is a heterodimeric protein expressed preferentially on the surface of a specific subset of circulating memory T-helper lymphocytes. These particular lymphocytes are known to be "gut-homing," meaning they are predisposed to migrate to the gastrointestinal tract.[2]
2. Specific Binding: AVT-16 is engineered to bind with high affinity and specificity to the α4β7 integrin on these gut-homing T-lymphocytes.[2]
3. Blocking Adhesion: The ligand for the α4β7 integrin is the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1). MAdCAM-1 is almost exclusively expressed on the endothelial cells of post-capillary venules within the gastrointestinal tract and its associated lymphoid tissues.[17] The binding of AVT-16 to the α4β7 integrin physically blocks the interaction between the lymphocyte and MAdCAM-1 on the gut wall.[20]
4. Inhibition of Leukocyte Trafficking: This blockade of the α4β7-MAdCAM-1 adhesion pathway is the critical step. It prevents the firm attachment and subsequent migration (a process known as diapedesis) of these inflammatory T-lymphocytes from the bloodstream into the intestinal parenchymal tissue.[17]
5. Reduction of Gut Inflammation: By interrupting the continuous recruitment of inflammatory cells to the site of disease, AVT-16 aims to dampen the local inflammatory cascade, leading to a reduction in mucosal inflammation, improvement in endoscopic appearance, and remission of clinical symptoms.[20]

Gut-Selectivity and Differentiated Safety Profile

A paramount feature of the α4β7 integrin antagonist mechanism, and a central pillar of the value proposition for vedolizumab and its biosimilars, is its gut-selectivity.[17] This specificity is derived from the restricted expression of its target ligand, MAdCAM-1, to the gastrointestinal vasculature.

This contrasts with earlier, less specific integrin antagonists like natalizumab, which targets the α4 subunit of both α4β7 and α4β1 integrins.[19] The α4β1 integrin interacts with the Vascular Cell Adhesion Molecule-1 (VCAM-1), which is widely expressed, including on the endothelium of the blood-brain barrier. By blocking the α4β1-VCAM-1 interaction, natalizumab interferes with normal immune surveillance of the central nervous system (CNS), which has been linked to an increased risk of a rare but often fatal brain infection known as progressive multifocal leukoencephalopathy (PML).[19]

Vedolizumab, and by extension AVT-16, was specifically designed to avoid this liability. It does not bind to or inhibit the function of the α4β1 or αEβ7 integrins.[17] Its activity is confined to the α4β7-MAdCAM-1 pathway, thereby selectively inhibiting lymphocyte trafficking to the gut without affecting immune cell migration to the CNS or other tissues.[17] This gut-selective mechanism underpins its more favorable safety profile compared to less specific agents and is a key reason for its widespread adoption in clinical practice.[11] The ability of AVT-16 to precisely replicate this targeted mechanism is fundamental to its potential success as a biosimilar, as it promises to deliver not only equivalent efficacy but also the same reassuring safety profile that has made Entyvio® a preferred choice for many clinicians and patients.

Comprehensive Review of the AVT-16 Clinical Development Program

Overview of Clinical Strategy

Alvotech's clinical development strategy for AVT-16 adheres to the well-established and rigorous pathway mandated by global regulatory agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for biosimilar approval. This pathway is designed to demonstrate a high degree of similarity to the reference product, focusing on comparative analytical, non-clinical, and clinical data. The progression from a Phase 1 study in healthy volunteers to a large-scale Phase 3 confirmatory trial in a sensitive patient population is a standard and necessary approach to generate the evidence required for regulatory submission. The successful initiation of the pivotal Phase 3 study indicates that the preceding Phase 1 trial likely yielded positive results regarding safety and pharmacokinetic similarity, providing Alvotech with the confidence to commit the substantial resources necessary for late-stage development. This progression represents a significant de-risking milestone for the AVT-16 program.

Phase 1 Pilot Study in Healthy Volunteers (AVT16-GL-F01 / NCT06400719)

• Study Design and Purpose: The initial clinical evaluation of AVT-16 was conducted in the trial identified as AVT16-GL-F01 (NCT06400719).[12] This was a pilot study designed primarily to assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of AVT-16 following a single intravenous administration.[12] The study followed a single-group assignment design, where all participants received the active investigational drug.[12] The intervention consisted of a single 300 mg IV dose of AVT-16.[12] Such studies are fundamental for biosimilar development, as they provide the initial human data comparing the PK profile of the biosimilar candidate to the known profile of the reference product.
• Population: The study enrolled 18 healthy adult subjects, including both males and females, between the ages of 18 and 55.[12] Key exclusion criteria included a history of hypersensitivity to vedolizumab or its constituents, as well as any clinically significant medical conditions that could interfere with the study evaluations or pose a risk to subject safety.[12]
• Status and Timeline: The trial was conducted at a site in New Zealand and has been completed, with a primary completion date listed as November 6, 2024.[1]
• Significance: The successful completion of this Phase 1 study is a critical prerequisite for advancing to late-stage clinical development. It provides the foundational safety and PK data package that regulators require before approving a large-scale efficacy trial in a patient population. The subsequent initiation of the Phase 3 trial strongly suggests that the data from AVT16-GL-F01 were acceptable and demonstrated a PK profile consistent with that of Entyvio®.

Phase 3 Confirmatory Efficacy and Safety Study (AVT16-GL-C01 / NCT06570772)

• Title and Objective: The pivotal trial for the AVT-16 program is identified as AVT16-GL-C01 (NCT06570772), titled "A Study to Investigate Comparative Efficacy, Safety and Immunogenicity Between AVT16 and Entyvio".[13] The primary objective is to demonstrate that AVT-16 has no clinically meaningful differences from its reference product, Entyvio®, in terms of efficacy, safety, and immunogenicity when used to treat patients with moderate to severe active Ulcerative Colitis.[2]
• Study Design: The trial employs a randomized, double-blind, two-arm, parallel-group, multicenter design.[2] This is the gold-standard design for a biosimilar confirmatory study, as it minimizes bias and allows for a direct, robust comparison between the biosimilar candidate and the originator biologic. Participants are randomized to one of two treatment arms and followed for approximately 46-52 weeks.[13]
• Arms and Interventions: The study consists of two arms:
• Experimental Arm: Participants receive AVT16 at a dose of 300 mg administered intravenously.[13]
• Active Comparator Arm: Participants receive the reference product, Entyvio® (vedolizumab), at a dose of 300 mg administered intravenously.[13]
• Population: The study aims to enroll approximately 748 adult male and female participants, aged 18 to 80 years, with a confirmed diagnosis of moderate to severe active Ulcerative Colitis.[2] The selection of UC as the indication for the confirmatory trial is strategic, as it is considered a sensitive population in which potential differences between the biosimilar and the reference product would likely be detected. Key exclusion criteria are designed to ensure a homogenous patient population and include a diagnosis of Crohn's colitis, a history of extensive colonic resection, and the presence of active or latent tuberculosis.[13]
• Endpoints: The primary endpoints are focused on demonstrating comparative efficacy. Efficacy will be assessed using standardized measures of UC disease activity, such as the Mayo Score.[2] Key efficacy outcomes include the proportion of patients achieving clinical response and clinical remission at predefined time points (e.g., Week 6 and Week 52).[22] Secondary endpoints will include assessments of mucosal healing (endoscopic improvement), safety (incidence of adverse events), and immunogenicity (development of anti-drug antibodies).[22]
• Status and Timeline: The study was initiated in September 2024 and is currently listed as recruiting participants.[1] The estimated primary completion date is March 31, 2026.[1] The multicenter, global nature of the trial is evidenced by its registration in numerous countries, including Georgia, Ukraine, Poland, Sri Lanka, and India.[13] This geographic distribution is a common strategy to accelerate patient recruitment, manage operational costs, and generate a dataset representative of a global population suitable for worldwide regulatory submissions.

Table 2: Overview of AVT-16 Clinical Trials

Trial Identifier	Title	Phase	Status	Condition	Population	# of Participants	Design	Primary Purpose
NCT06400719 / AVT16-GL-F01	Pilot Study of AVT16 in Healthy Adult Subjects	1	Completed	Healthy Volunteers	18	Single-arm	Safety, Tolerability, PK, Immunogenicity
NCT06570772 / AVT16-GL-C01	Study to Investigate Comparative Efficacy, Safety and Immunogenicity Between AVT16 and Entyvio	3	Recruiting	Moderate to Severe Ulcerative Colitis	~748	Randomized, Double-Blind, Active-Comparator	Efficacy, Safety, Immunogenicity

Strategic and Commercial Landscape Analysis

Market Opportunity Assessment

The commercial potential for a successful vedolizumab biosimilar is exceptionally large. The reference product, Takeda's Entyvio®, has established itself as a blockbuster therapy in the IBD market, driven by its strong efficacy and differentiated gut-selective safety profile.[17] Global sales of Entyvio® reached approximately US

5.4billioninthe12−monthperiodendingJune30,2024,withforecastsprojectingthemarketforthissingleproducttogrowtooverUS7 billion by 2030.[2] This substantial market size creates a significant revenue opportunity for the first biosimilar entrants.

The primary driver for the adoption of biosimilars is the potential for significant cost savings for healthcare systems and increased patient access.[2] High-cost biologics like Entyvio® place a considerable financial burden on payers and patients, and the introduction of lower-priced, therapeutically equivalent biosimilars is a key strategy for managing healthcare expenditures while maintaining quality of care.[25]

Competitive Intelligence

The competitive landscape for vedolizumab biosimilars is uniquely favorable compared to other major biologic markets. While the broader IBD therapeutic area is crowded with multiple mechanisms of action, the race to develop a direct biosimilar to Entyvio® is currently limited to a small number of players.

Direct Vedolizumab Biosimilar Competitors

Analysis of the development landscape indicates that the competition to bring a vedolizumab biosimilar to market is effectively a two-horse race between Alvotech and Polpharma Biologics.[2]

• Alvotech (AVT-16): As detailed, Alvotech has initiated its global, pivotal Phase 3 confirmatory study (AVT16-GL-C01), positioning it as a clear front-runner in the development race.[2]
• Polpharma Biologics (PB016): The other leading competitor is Polpharma Biologics, a European biotech company, with its candidate PB016.[16] In February 2024, Polpharma announced positive topline results from its own single-dose PK/PD comparability study in 120 healthy volunteers, which demonstrated that PB016 was comparable to Entyvio® across all investigated parameters.[23] Following these results, Polpharma is also conducting a global clinical safety and efficacy study in patients with UC to support its regulatory submissions.[23]

This limited field of direct competitors is a stark contrast to the biosimilar market for adalimumab (Humira®), which saw numerous companies launch products simultaneously, leading to intense price competition.[30] The less crowded vedolizumab biosimilar space suggests that the first one or two entrants, including AVT-16, could capture a more significant market share and potentially maintain more favorable pricing and margins.

Table 3: Competitive Landscape of Vedolizumab Biosimilars

Company	Product Candidate	Development Status	Key Recent Milestone
Alvotech	AVT-16	Phase 3 (Recruiting)	Initiated confirmatory patient study (NCT06570772) in Sep 2024 2
Polpharma Biologics	PB016	Phase 3 (Ongoing)	Announced positive PK/PD data from healthy volunteer study in Feb 2024; global efficacy study ongoing 23

Indirect Competitors (The Broader IBD Market)

While direct competition is limited, AVT-16 will enter a dynamic and competitive IBD market. It will compete not only with the originator, Entyvio®, but also with other classes of advanced therapies.[31] These include:

• TNF Inhibitors: Adalimumab (Humira®) and infliximab (Remicade®) are established therapies, but their market is now heavily influenced by the availability of multiple biosimilars.[30]
• IL-12/23 and IL-23 Inhibitors: This class includes ustekinumab (Stelara®), which already faces biosimilar competition from Alvotech's own AVT04 (SELARSDI), as well as newer agents like risankizumab (Skyrizi) and mirikizumab (Omvoh).[7]
• JAK Inhibitors: Oral small molecules like tofacitinib (Xeljanz) offer a different modality of treatment.[31]

Within this broader landscape, the primary competitive advantage for the vedolizumab class, which AVT-16 will inherit, remains its gut-selective mechanism and the associated safety benefits.[20]

Corporate Strategy and Partnerships

Alvotech's strategy for AVT-16 is consistent with its overall corporate approach, which focuses on leveraging its development and manufacturing expertise while forming strategic partnerships for commercialization.

• Alvotech's Pipeline and Track Record: AVT-16 is a key asset in a deep pipeline of biosimilar candidates.[2] The company's prior success in gaining approval for AVT02 (adalimumab biosimilar) and AVT04 (ustekinumab biosimilar) validates its scientific and regulatory capabilities.[2] This history provides confidence to partners and investors regarding Alvotech's ability to execute on the AVT-16 program.
• The Advanz Pharma Partnership: A cornerstone of the commercial strategy for AVT-16 in Europe is the strategic partnership with Advanz Pharma.[9] This agreement, initially signed in May 2023 and subsequently expanded, grants Advanz Pharma exclusive rights to commercialize AVT-16 in the European Economic Area (EEA), the United Kingdom, and Switzerland.[35] Under the terms of the deal, Alvotech is responsible for the development and commercial supply of the product, while Advanz Pharma will handle registration and all commercial activities in the partnered territories.[35] This model is capital-efficient for Alvotech, as it obviates the need to build a costly European commercial infrastructure from the ground up.
• Financial Structure of the Partnership: The partnership with Advanz is structured to provide Alvotech with both near-term and long-term value. The initial agreement for five products included upfront payments totaling €56 million, with the potential for up to €264 million in additional development and commercial milestone payments.[4] A key financial milestone for the AVT-16 program was the recognition of $16.8 million in revenue upon the submission of the Clinical Trial Application (CTA).[7] In addition to these milestones, Alvotech will receive a substantial share of the product's revenue through a royalty of approximately 40% of the estimated net selling price, ensuring a significant long-term revenue stream upon commercialization.[4]

This partnership strategy validates the AVT-16 asset, provides non-dilutive funding for its continued development, and establishes a clear path to market in a key global region.

Synthesis, Outlook, and Strategic Recommendations

Integrated Analysis: SWOT Framework

A strategic assessment of AVT-16 reveals a promising profile characterized by significant market opportunity and a strong competitive position, balanced by the inherent risks of biosimilar development.

• Strengths:
• Large Market Opportunity: Targeting a blockbuster reference product, Entyvio®, with over $5.4 billion in annual sales provides a massive commercial runway.[2]
• Favorable Competitive Landscape: The vedolizumab biosimilar market is essentially a two-horse race between Alvotech and Polpharma, a stark contrast to more saturated biosimilar markets, which may allow for more stable pricing and market share.[2]
• Differentiated Mechanism: The gut-selective α4β7 integrin antagonist mechanism offers a compelling safety and efficacy profile that has driven the success of the originator product.[17]
• Proven Developer Platform: Alvotech has a demonstrated track record of successfully developing and gaining regulatory approval for complex biosimilars, including those for Humira® and Stelara®, which de-risks the execution of the AVT-16 program.[2]
• Secured Commercial Partner: The strategic partnership with Advanz Pharma provides a clear and funded path to market in the key European territories.[9]
• Weaknesses:
• Lack of Clinical Innovation: As a biosimilar, AVT-16 offers no novel clinical benefit over the reference product; its value proposition is based entirely on cost-effectiveness and access.
• Single Point of Failure: The success of the entire program hinges on the positive outcome of the single, pivotal Phase 3 trial (NCT06570772). Any unexpected negative results in efficacy, safety, or immunogenicity would be catastrophic for the asset.
• Development Timelines: The program is still in Phase 3, with an estimated primary completion in 2026, meaning market entry is still several years away.[1]
• Opportunities:
• Significant Cost Savings: AVT-16 has the potential to generate substantial savings for healthcare systems, driving rapid formulary adoption and payer support.
• Increased Patient Access: A lower-cost alternative can broaden access to vedolizumab therapy for patients who may have previously been unable to afford it.
• Interchangeability Designation: In the U.S. market, securing an "interchangeable" designation from the FDA would be a significant commercial advantage, as it allows for substitution at the pharmacy level without prescriber intervention, potentially accelerating uptake.[39]
• Threats:
• Direct Competition: Polpharma's PB016 is a direct and credible competitor. A race to market is underway, and being the second entrant could be a commercial disadvantage.
• Originator Defense Strategies: The reference product manufacturer, Takeda, may employ defensive strategies to protect Entyvio's market share, such as launching new formulations (e.g., a subcutaneous version has been approved), engaging in aggressive contracting with payers, or initiating litigation.[27]
• Evolving IBD Market: The broader IBD treatment landscape is continually evolving with new mechanisms of action. Over the long term, the market share of the entire vedolizumab class could be eroded by newer, potentially more effective or convenient therapies.[31]

Future Outlook

The market entry of AVT-16 and its direct competitor, PB016, is poised to mark the first wave of biosimilar competition for vedolizumab. This will inevitably lead to price erosion for the molecule, benefiting payers and patients. The key battles for market share will be fought on three fronts: timing of market entry, securing favorable formulary access through contracts with payers and pharmacy benefit managers, and, in the U.S., the pursuit of an interchangeability designation. Given Alvotech's success in achieving interchangeability for its other products, this will likely be a key strategic goal for AVT-16 in the U.S. market. The limited number of direct competitors suggests that the initial biosimilar market for vedolizumab could be a duopoly, offering a more rational and profitable environment than has been seen for biologics with many biosimilar challengers.

Key Success Factors

The ultimate success of the AVT-16 program will depend on Alvotech's ability to execute across several critical domains:

1. Clinical and Regulatory Excellence: The foremost priority is the flawless execution and timely completion of the pivotal AVT16-GL-C01 Phase 3 study. Generating a robust data package that unequivocally demonstrates biosimilarity to Entyvio® is non-negotiable for securing approvals from the FDA, EMA, and other global regulatory bodies.
2. Manufacturing and Supply Chain Reliability: As a vertically integrated company, Alvotech must ensure its manufacturing processes are robust, scalable, and cost-effective to meet projected global demand and fulfill its supply commitments to commercial partners like Advanz Pharma.
3. Strategic Commercial Launch: In collaboration with its partners, Alvotech must develop and execute a sophisticated commercial launch strategy. This includes effective communication of the biosimilar value proposition, strategic pricing to capture market share while maintaining profitability, and securing advantageous formulary placement with key payers.

Appendices

Appendix A: Detailed Company Profile of Alvotech

Alvotech is a global biopharmaceutical company founded in 2013 by Robert Wessman, with headquarters in Reykjavik, Iceland.[3] The company is publicly traded on the NASDAQ stock exchange under the ticker ALVO.[3] Alvotech's business model is exclusively focused on the development and manufacture of high-quality biosimilar medicines with the aim of improving affordability and access for patients worldwide.[2] The company operates a fully integrated platform, with in-house capabilities spanning from cell line development and upstream/downstream processing to clinical development, fill-finish manufacturing, and regulatory affairs.[2]

The company reported record financial results for the full year 2024, with total revenues reaching $492 million, a 427% increase over the prior year, and product revenues reaching $273 million, a 462% increase.[7] This growth reflects the successful commercialization of its initial products.

Alvotech's disclosed pipeline includes eight biosimilar candidates targeting major therapeutic areas [9]:

• AVT02 (adalimumab): A biosimilar to Humira®, approved in over 50 countries and marketed as SIMLANDI in the U.S. and HUKYNDRA in Europe.[2]
• AVT04 (ustekinumab): A biosimilar to Stelara®, launched as JAMTEKI in Canada, UZPRUVO in the EEA, and approved as SELARSDI in the U.S..[2]
• AVT05 (golimumab): A proposed biosimilar to Simponi®/Simponi Aria®, for which a Marketing Authorization Application has been accepted by the EMA.[41]
• AVT03 (denosumab): A proposed biosimilar to Prolia®/Xgeva®, for which a Marketing Authorization Application has been accepted by the EMA.[41]
• AVT06 (aflibercept): A proposed biosimilar to Eylea®.[42]
• AVT16 (vedolizumab): A proposed biosimilar to Entyvio®, currently in Phase 3 development.[2]
• AVT23 (omalizumab): A proposed biosimilar to Xolair®.[7]
• AVT33 (pembrolizumab): A proposed biosimilar to Keytruda®.[4]

Alvotech pursues a partnership-driven commercialization model, entering into strategic agreements with established pharmaceutical companies to market its products in various regions. Key partners include Teva Pharmaceuticals for the U.S. market and Advanz Pharma for Europe.[9]

Appendix B: Detailed Company Profile of Advanz Pharma

ADVANZ PHARMA is a global pharmaceutical company with headquarters in London, UK.[35] The company has a strategic focus on specialty, hospital, and rare disease medicines.[35] Its business model involves acquiring, developing, and commercializing a portfolio of both originator and generic medicines to serve patients in Europe, Canada, and Australia.[38]

Advanz Pharma has positioned itself as a key partner for biosimilar developers looking to enter the European market. In May 2023, Alvotech and Advanz Pharma announced a strategic partnership for the commercialization of five biosimilar candidates in Europe, including AVT16 (vedolizumab).[35] This partnership was later expanded in May 2025 to cover more than ten proposed biosimilars, including candidates for Ilaris® (canakinumab) and Kesimpta® (ofatumumab).[9]

Under the terms of these agreements, Advanz Pharma is responsible for the registration and commercialization of Alvotech's biosimilars in the European Economic Area, the UK, and Switzerland.[35] This partnership allows Alvotech to leverage Advanz Pharma's established commercial infrastructure and market access expertise, creating a synergistic relationship that facilitates the entry of new, cost-effective biologics into the European healthcare system.[9]

Appendix C: Full Eligibility Criteria for Clinical Trial NCT06570772

The following are the key inclusion and exclusion criteria for the pivotal Phase 3 study of AVT-16 (AVT16-GL-C01; NCT06570772) [13]:

Inclusion Criteria:

• Participants must be male or female, aged 18 to 80 years, inclusive.
• Must be capable of providing signed and dated informed consent prior to any study-related procedures.
• Must have a confirmed diagnosis of Ulcerative Colitis.
• Women of childbearing potential must not be pregnant or breastfeeding and must agree to use a reliable method of contraception during the study and for 18 weeks after the final dose of the investigational product. Women not of childbearing potential are eligible if they are surgically sterile or postmenopausal for at least 12 months.

Exclusion Criteria:

• A diagnosis of Crohn's Disease, Crohn's colitis, or indeterminate colitis.
• History of extensive colonic resection.
• Presence of active or latent tuberculosis that has not been adequately treated.
• Other conditions or medical histories that, in the judgment of the investigator, would pose a risk to the participant's safety or interfere with the study evaluations.

Works cited

1. AVT-16 Drug Profile - Ozmosi, accessed June 18, 2025, https://pryzm.ozmosi.com/product/avt-16
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