A Randomized, Double-blind, Multicenter Study to Demonstrate Equivalent Efficacy and to Compare Safety and Immunogenicity of a Biosimilar Ustekinumab (AVT04) and Stelara® in Patients With Moderate to Severe Chronic Plaque-type Psoriasis

Safety and Efficacy study of AVT04 (Alvotech Biosimilar to Ustekinumab), in patients with moderate to severe plaque psoriasis

Start Date03 Jun 2021

Sponsor / Collaborator

Alvotech Swiss AG

NCT04744363

/ CompletedPhase 1

Phase 1, FIH, Randomized, Double-blind, Single-dose, Parallel-group, 3-arm Study Comparing the PK, Safety, Tolerability, and Immunogenicity Profiles of AVT04, EU-approved Stelara®, and US-licensed Stelara® in Healthy Adult Subjects

Protocol Title:
A Phase 1, first-in-human, randomized, double-blind, single-dose, parallel-group, 3-arm study comparing the pharmacokinetic, safety, tolerability, and immunogenicity profiles of AVT04, EU approved Stelara®, and US-licensed Stelara® in healthy adult subjects
Short Title:
A first-in-human randomized, double-blind study to compare AVT04 with EU-approved Stelara and US-licensed Stelara as a single-dose subcutaneous injection in healthy adult subjects
Rationale:
Alvotech (hereafter, the Sponsor) is developing AVT04 globally as a proposed biosimilar to the reference product Stelara (ustekinumab) for subcutaneous (SC) use. This is a first-in-human (FIH) clinical study with AVT04. The study aims to demonstrate pharmacokinetic (PK) similarity of the proposed biosimilar test product AVT04 and the reference products EU approved Stelara and US-licensed Stelara, in addition to evaluating the safety and tolerability of AVT04, when administered as a single 45 mg/0.5 mL SC dose.

Start Date25 May 2021

Sponsor / Collaborator

Alvotech Swiss AG

[+1]

100 Clinical Results associated with Ustekinumab biosimilar (Alvotech)

100 Translational Medicine associated with Ustekinumab biosimilar (Alvotech)

100 Patents (Medical) associated with Ustekinumab biosimilar (Alvotech)

Literatures (Medical) associated with Ustekinumab biosimilar (Alvotech)

01 Apr 2026·Dermatology and Therapy

AVT04, a Biosimilar to Reference Product Ustekinumab, for the Treatment of Plaque Psoriasis: Insights from a Real-World Experience up to 28 Weeks

Article

Author: Talamonti, Marina ; Tofani, Lorenzo ; Galluzzo, Marco ; Marrapodi, Domenico ; Gneo, Valerio ; Mortato, Edoardo ; Bianchi, Luca ; Marcelli, Lorenzo ; Savastano, Lorenzo ; Ingrosso, Maria Rosa

INTRODUCTION:

This study aims to evaluate the real-life efficacy and safety of a biosimilar to reference product (RP) ustekinumab for the treatment of plaque psoriasis in different patient scenarios. The cohort included ustekinumab-switched patients, who switched from the RP to the biosimilar, and ustekinumab-naïve patients, never treated with ustekinumab. Ustekinumab-naïve patients were subdivided into bio-naïve (no prior biologic therapy) and bio-experienced (previous non-ustekinumab biologic therapy).

METHODS:

Adult patients with chronic plaque psoriasis treated with AVT04 were followed up to 28 weeks. Efficacy of the biosimilar was assessed by improvement of the Psoriasis Area Severity Index (PASI) 75, 90, and 100 responses from baseline to weeks 16 and 28. A cost-minimisation analysis over a 1-year time horizon was performed to estimate costs and potential savings with AVT04 versus RP across the Italian National Health Service (NHS).

RESULTS:

Throughout the observation period, a sustained improvement in PASI was observed in the overall cohort of 183 patients, encompassing both the ustekinumab-switched and ustekinumab-naïve groups. Within the ustekinumab-naïve group, a trend toward more favourable PASI 75/90/100 responses was observed in bio-naïve patients compared to bio-experienced patients. By 28 weeks of treatment, a higher proportion of bio-naïve patients compared to the bio-experienced group achieved PASI 75 (72.7% vs. 56.2%), PASI 90 (72.7% vs. 50.0%), and PASI 100 (54.5% vs. 37.5%), respectively (p > 0.05). No adverse events were reported during the study. Furthermore, the cost-minimisation analysis suggested that compared to the RP, AVT04 has the potential to generate approximately €5200 in annual savings per patient for the Italian NHS, representing around €20 million in nationwide savings.

CONCLUSION:

AVT04 biosimilar shows consistent efficacy results in both ustekinumab-switching and ustekinumab-naïve patients, supporting its integration into real-world practice as an effective and cost-saving therapeutic option. Further studies are warranted to confirm and expand these preliminary findings across a broader bio-naïve cohort.

01 Jul 2024·Clinical Drug Investigation

AVT04: An Ustekinumab Biosimilar

Review

Author: Blair, Hannah A

AVT04 (Uzpruvo^®) is a biosimilar of the reference anti-interleukin (IL)-12 and IL-23 monoclonal antibody ustekinumab. It is approved in the EU for plaque psoriasis, paediatric plaque psoriasis, psoriatic arthritis and Crohn's disease as per the reference product. AVT04 has similar physicochemical characteristics to those of reference ustekinumab, and the pharmacokinetic similarity of the agents has been shown in healthy volunteers and patients with moderate to severe chronic plaque psoriasis. AVT04 demonstrated clinical efficacy similar to that of reference ustekinumab in patients with moderate to severe chronic plaque psoriasis, and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of AVT04 were similar to those of reference ustekinumab, and switching from reference ustekinumab to AVT04 had no impact on efficacy, safety or immunogenicity. The role of reference ustekinumab in the management of inflammatory diseases is well established and AVT04 provides an effective biosimilar alternative for patients requiring ustekinumab therapy.

03 Aug 2023·Expert opinion on biological therapy

Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis

Article

Author: Otto, Hendrik ; Berti, Fausto ; Stroissnig, Heimo ; Feldman, Steven R ; Haliduola, Halimu N ; Duijzings, Paul ; Leutz, Steffen ; Ruffieux, Ruth ; Reznichenko, Nataliya

BACKGROUND:

This study compared efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity between AVT04 and reference product (RP) ustekinumab (Stelara®) in patients with moderate-to-severe chronic plaque psoriasis (PsO).

PATIENTS AND METHODS:

This multicenter, double-blind, 52-week study randomized patients in 1:2 ratio to AVT04 or RP. At week 16, responsive patients (≥50% improvement in psoriasis area and severity index (PASI)) previously on AVT04 continued on AVT04, while those on RP were re-randomized 1:1 to switch to AVT04 or stay on RP. The primary endpoint was a percent improvement in PASI from baseline to week 12. Therapeutic equivalence was demonstrated if the confidence interval (CI) for the adjusted difference in means was contained within the equivalence margins; ±10% (90%CI).

RESULTS:

Of the 581 patients initially randomized (AVT04:RP, 194:387), 575 completed week 16 and 544 completed end of study visit. The percent PASI improvement for AVT04 vs RP was 87.3% vs 86.8% (CI: -2.14%, 3.01%); study met its primary endpoint. Efficacy, safety and PK profiles were comparable across treatment arms throughout the entire study duration, and the incidence of antibodies to ustekinumab had no clinically meaningful impact.

CONCLUSION:

This study demonstrates the therapeutic equivalence between AVT04 and RP in patients with moderate-to-severe chronic PsO, with similar safety and tolerability.

TRIAL REGISTRATION:

NCT04930042; EudraCT Number: 2020-004,493-22.

148

News (Medical) associated with Ustekinumab biosimilar (Alvotech)

10 Aug 2026

·www.biospace.com

Alvotech to Report Financial Results for H1 2026

REYKJAVIK, ICELAND (August 10, 2026) — Alvotech (NASDAQ: ALVO; ALVO-SDB) (the “Company”), a global biotechnology company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today announced that it will release its financial results for the first half of 2026 on Wednesday, August 19, 2026, after the U.S. market close. The Company will also host a webcast with a live Q&A on Thursday, August 20, 2026, at 08:00 ET (12:00 GMT, 13:00 BST, 14:00 CEST). To listen to the webcast, please register here: H1 2026 webcast To participate in the Q&A, please register here: Q&A registration Slides and other materials will be made available on alvotech.com/financials before the call. For further information, contact: ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Media Benedikt Stefansson Sarah MacLeod alvotech.media@alvotech.com Investors Dr. Balaji V Prasad (US) Benedikt Stefansson (IS) alvotech.ir@alvotech.com About Alvotech Alvotech is a biotechnology company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high-quality, cost-effective products and services, enabled by a fully integrated approach and broad in-house capabilities. Five biosimilars are already approved and marketed in multiple global markets, including biosimilars to Humira® (adalimumab), Stelara® (ustekinumab), Simponi® (golimumab), Eylea® (aflibercept) and Prolia®/Xgeva® (denosumab). The current development pipeline includes disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China and other Asian countries, and large parts of South America, Africa and the Middle East. For more information, please visit . For more information, please visit our website or follow us on social media on LinkedIn , Facebook , Instagram and YouTube . None of the information on the Alvotech website shall be deemed part of this press release.

Financial StatementBiosimilar

29 Jul 2026

·www.globenewswire.com

Alvotech announces successful closure of FDA inspection of manufacturing facility

REYKJAVIK, ICELAND (July 29, 2026) — Alvotech (NASDAQ: ALVO; ALVO-SDB) (the “Company”), a global biotechnology company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today announced that the U.S Food and Drug Administration (FDA) has closed its inspection of the company’s manufacturing facility in Reykjavik, Iceland, conducted in May 2026. The FDA has confirmed the inspection classification of the manufacturing site is Voluntary Action Indicated (VAI). “This is an important milestone for Alvotech and reflects the significant work our teams have undertaken to further strengthen our quality systems and manufacturing operations,” said Lisa Graver, CEO of Alvotech. “With the conclusion of the FDA’s recent inspection, we are confident that the actions we have taken have effectively addressed the observations identified. We continue to work with the FDA to advance our recent Biologics Licence Applications towards approval.” Alvotech continues to advance its pipeline of biosimilar candidates. The company recently announced the resubmission of Biologics License Applications (BLAs) for AVT05, Alvotech’s biosimilar to Simponi® (golimumab), and AVT06, Alvotech’s biosimilar to Eylea® (aflibercept), and the acceptance by the FDA of the submission of a BLA for AVT16, Alvotech’s proposed biosimilar to Entyvio® (vedolizumab) to the FDA in June 2026. Alvotech continues to work closely with health authorities worldwide to bring high-quality, affordable biologic medicines to patients. For further information, contact: MediaBenedikt StefanssonSarah MacLeodalvotech.media@alvotech.com InvestorsDr. Balaji V Prasad (US)Benedikt Stefansson (IS)alvotech.ir@alvotech.com About AlvotechAlvotech is a biotechnology company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high-quality, cost-effective products and services, enabled by a fully integrated approach and broad in-house capabilities. Five biosimilars are already approved and marketed in multiple global markets, including biosimilars to Humira® (adalimumab), Stelara® (ustekinumab), Simponi® (golimumab), Eylea® (aflibercept) and Prolia®/Xgeva® (denosumab). The current development pipeline includes 13 disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China and other Asian countries, and large parts of South America, Africa and the Middle East. For more information, please visit https://www.alvotech.com. For more information, please visit our investor portal, and our website or follow us on social media on LinkedIn, Facebook, Instagram and YouTube. None of the information on the Alvotech website shall be deemed part of this press release. Use of trademarks Simponi® and Simponi Aria® are trademarks of Johnson & Johnson. Eylea® is a trademark of Regeneron Pharmaceuticals Inc. Entyvio® is a registered trademark of Millennium Pharmaceuticals, Inc.

BiosimilarDrug Approval

29 Jul 2026

·www.globenewswire.com

Alvotech announces successful closure of FDA inspection of manufacturing facility

REYKJAVIK, Iceland, July 29, 2026 (GLOBE NEWSWIRE) -- Alvotech (NASDAQ: ALVO; ALVO-SDB) (the “Company”), a global biotechnology company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today announced that the U.S. Food and Drug Administration (FDA) has closed its inspection of the company’s manufacturing facility in Reykjavik, Iceland, conducted in May 2026. The FDA has confirmed the inspection classification of the manufacturing site is Voluntary Action Indicated (VAI). “This is an important milestone for Alvotech and reflects the significant work our teams have undertaken to further strengthen our quality systems and manufacturing operations,” said Lisa Graver, CEO of Alvotech. “With the conclusion of the FDA’s recent inspection, we are confident that the actions we have taken have effectively addressed the observations identified. We continue to work with the FDA to advance our recent Biologics Licence Applications towards approval.” Alvotech continues to advance its pipeline of biosimilar candidates. The company recently announced the resubmission of Biologics License Applications (BLAs) for AVT05, Alvotech’s biosimilar to Simponi® (golimumab), and AVT06, Alvotech’s biosimilar to Eylea® (aflibercept), and the acceptance by the FDA of the submission of a BLA for AVT16, Alvotech’s proposed biosimilar to Entyvio® (vedolizumab) to the FDA in June 2026. Alvotech continues to work closely with health authorities worldwide to bring high-quality, affordable biologic medicines to patients. For further information, contact: MediaBenedikt StefanssonSarah MacLeodalvotech.media@alvotech.com InvestorsDr. Balaji V Prasad (US)Benedikt Stefansson (IS)alvotech.ir@alvotech.com About AlvotechAlvotech is a biotechnology company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high-quality, cost-effective products and services, enabled by a fully integrated approach and broad in-house capabilities. Five biosimilars are already approved and marketed in multiple global markets, including biosimilars to Humira® (adalimumab), Stelara® (ustekinumab), Simponi® (golimumab), Eylea® (aflibercept) and Prolia®/Xgeva® (denosumab). The current development pipeline includes 13 disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China and other Asian countries, and large parts of South America, Africa and the Middle East. For more information, please visit https://www.alvotech.com. For more information, please visit our investor portal, and our website or follow us on social media on LinkedIn, Facebook, Instagram and YouTube. None of the information on the Alvotech website shall be deemed part of this press release. Use of trademarks Simponi® and Simponi Aria® are trademarks of Johnson & Johnson. Eylea® is a trademark of Regeneron Pharmaceuticals Inc. Entyvio® is a registered trademark of Millennium Pharmaceuticals, Inc.

BiosimilarDrug Approval

100 Deals associated with Ustekinumab biosimilar (Alvotech)

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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Ulcerative colitis, active moderate	United States	Alvotech USA, Inc.	18 Oct 2024
Ulcerative colitis, active severe	United States	Alvotech USA, Inc.	18 Oct 2024
Psoriasis	European Union	Alvotech	10 Jan 2024
Psoriasis	Iceland	Alvotech	10 Jan 2024
Psoriasis	Liechtenstein	Alvotech	10 Jan 2024
Psoriasis	Norway	Alvotech	10 Jan 2024
Crohn's disease, active moderate	European Union	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active moderate	Iceland	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active moderate	Liechtenstein	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active moderate	Norway	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	European Union	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	Iceland	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	Liechtenstein	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	Norway	STADA Arzneimittel AG	05 Jan 2024
Crohn Disease	Canada	JAMP Pharma Corp.	01 Nov 2023
Arthritis, Psoriatic	Japan	Fuji Pharma Co., Ltd.	25 Sep 2023
Plaque psoriasis	Japan	Fuji Pharma Co., Ltd.	25 Sep 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04930042 (AVT04-GL-301, FDA_CDER) Manual	Phase 3	Plaque psoriasis	2,069	Placebo (Ps STUDY 1 + Adult)	rtsthlaxvf(pjedhrmbuz) = unpulxmvxo vegaotfhvz (pwurdwerqa ) View more	Positive	16 Apr 2024
				Ustekinumab 45 mg (Ps STUDY 1 + Adult)	rtsthlaxvf(pjedhrmbuz) = cypaaszziy vegaotfhvz (pwurdwerqa ) View more
NCT04930042 (AVT04-GL-301, FDA_CDER) Manual	Phase 3	Arthritis, Psoriatic	927	UstekinumabUstekinumab 45 mg (PsA STUDY 1)	gdrbmpxfgf(jemoryrzpg) = jxfwgssdim gakkfgmbwl (pwlfxzccmx ) View more	Positive	16 Apr 2024
				Ustekinumab 90 mgUstekinumab90 mg (PsA STUDY 1)	gdrbmpxfgf(jemoryrzpg) = tiaxyyluxb gakkfgmbwl (pwlfxzccmx ) View more
NCT04930042 (Pubmed \| Expert Opin Biol Ther)	Phase 3	Plaque psoriasis	581	AVT04	pyvtfweymj(aebqsdbert) = mikgslvdhe kxoszzmcon (fmafeervrv )	Positive	12 Jul 2023
				Reference product ustekinumab (Stelara®)	pyvtfweymj(aebqsdbert) = dwvlcaieql kxoszzmcon (fmafeervrv )
NCT04930042 (AAD2023)	Phase 3	Psoriasis	581	AVT04	coojvducuq(qwuzorpyfg) = psxaqqvxdm ghemtdemnb (zslmuvcgjx ) View more	-	17 Mar 2023
				Reference Ustekinumab	coojvducuq(qwuzorpyfg) = zkaxdzqbuy ghemtdemnb (zslmuvcgjx ) View more

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