A Randomised, Double-blind, Parallel-group, Phase 3 Study to Compare the Efficacy, Safety, and Immunogenicity of the Proposed Biosimilar Ustekinumab FYB202 to Stelara® in Patients With Moderate-to-Severe Plaque Psoriasis

This is a randomized, double-blind, multicenter study to evaluate the efficacy, safety, and immunogenicity of FYB202 compared to Stelara® in patients with Moderate-to-Severe Plaque Psoriasis.

Start Date09 Nov 2020

Sponsor / Collaborator

bioeq GmbH

100 Clinical Results associated with Ustekinumab-Aauz

100 Translational Medicine associated with Ustekinumab-Aauz

100 Patents (Medical) associated with Ustekinumab-Aauz

Literatures (Medical) associated with Ustekinumab-Aauz

01 Dec 2024·Clinical Pharmacology in Drug Development

New Ustekinumab Biosimilar Candidate FYB202: Pharmacokinetic Equivalence Demonstrated in a Randomized, Double‐Blind, Parallel‐Group, Single‐Dose Trial in Healthy Subjects

Article

Author: Wedemeyer, Ralph‐Steven ; Anschütz, Maria ; Nopora, Katrin ; Balser, Sigrid ; Schug, Barbara ; Körner, Juliane

Abstract:

In the RUSTIC trial, pharmacokinetic (PK) similarity between the proposed ustekinumab biosimilar FYB202 and EU‐approved (EU‐Ref) and US‐licensed ustekinumab (US‐Ref) as well as between both reference drugs was assessed after a single 45‐mg subcutaneous injection. Safety analyses comprised immunogenicity (antidrug antibodies, neutralizing antibodies), adverse events, and local tolerability. Overall, 491 healthy adults were randomized 1:1:1 and observed for up to 112 days; 486 completed the trial, and 478 were included in the PK analysis. All 3 comparisons showed PK similarity, since the 90% confidence intervals of the respective geometric mean ratios for area under the concentration‐time curve from time 0 to infinity and maximum serum concentration were contained within the acceptance interval of 80%‐125%. No clinically meaningful differences regarding overall safety, immunogenicity, and local tolerability were observed. Notably, after FYB202 administration, in fewer subjects at least 1 positive antidrug antibody result was observed compared to the reference groups (FYB202, 20%; EU‐Ref, 42%; US‐Ref, 51%). In conclusion, the RUSTIC trial demonstrated equivalent PK characteristics for FYB202 when compared to both EU‐Ref and US‐Ref ustekinumab and between both reference drugs. It provides the basis for the marketing authorization of FYB202, together with an extensive analytical characterization and the results of a confirmatory efficacy and safety trial in patients with moderate to severe plaque psoriasis.

ADVANCES IN THERAPY

A Randomised, Double-Blind Trial to Compare the Efficacy, Safety, and Immunogenicity of the Biosimilar Ustekinumab FYB202 with Reference Ustekinumab in Patients with Moderate-to-Severe Plaque Psoriasis

Article

Author: Freudensprung, Brigitte ; Nopora, Katrin ; Balser, Sigrid ; Trieb, Michael ; Papp, Kim ; Rewerski, Piotr

INTRODUCTION:

Biosimilars allow more patients access to affordable treatment options and help reduce the financial burden on healthcare systems. This multicentre trial compared the efficacy, safety, and immunogenicity of the approved biosimilar ustekinumab FYB202 with reference ustekinumab.

METHODS:

Eligible patients were ≥ 18 years old with stable moderate-to-severe plaque psoriasis for ≥ 6 months and inadequate treatment response to or intolerance of ≥ 1 previous systemic treatment. Patients were randomised (1:1) to double-blind treatment with FYB202 or reference ustekinumab; patients in the reference group who achieved Psoriasis Area and Severity Index (PASI) 75 percent improvement at week 28 were re-randomised to FYB202 or reference product. The primary efficacy endpoint was percent improvement in PASI score from baseline to week 12. Therapeutic equivalence was demonstrated if, depending on the regulatory requirement with respect to the significance level, the two-sided 95% and 90% confidence intervals (CIs) were within the pre-defined equivalence intervals of ± 11% and ± 10%, respectively.

RESULTS:

A total of 392 patients were randomised to FYB202 (n = 197) or reference ustekinumab (n = 195). Baseline characteristics were well balanced between groups. Mean percent improvement in PASI score at week 12 was equivalent between FYB202 and reference ustekinumab with an estimated least-squares mean treatment difference of 3.27% and the two-sided 95% (- 0.90%, 7.44%) and 90% (- 0.22%, 6.77%) CIs fully contained within the pre-defined equivalence margins. Safety and immunogenicity profiles were comparable between groups. Switching from reference product to FYB202 had no clinically relevant effect on efficacy, safety, or immunogenicity.

CONCLUSION:

FYB202 demonstrated therapeutic equivalence to reference ustekinumab in patients with moderate-to-severe plaque psoriasis.

TRIAL REGISTRATION:

NCT04595409; EudraCT 2019-004364-21.

News (Medical) associated with Ustekinumab-Aauz

03 Mar 2025

·pipelinereview.com

Fresenius Continues Growth of Biosimilars Portfolio with the U.S. Availability of Otulfi® (ustekinumab-aauz)

LAKE ZURICH, IL, USA I March 03, 2025 I Fresenius Kabi, an operating company of Fresenius, and Formycon AG, a leading, independent developer of high-quality biosimilars, announced today that the ustekinumab biosimilar Otulfi ® (ustekinumab-aauz) developed by Formycon AG, is now available in the United States. Otulfi ® is an ustekinumab biosimilar for the reference product Stelara ® (ustekinumab). Otulfi ® is indicated for the treatment of moderately to severely active Crohn’s disease and ulcerative colitis in adult patients, moderate to severely plaque psoriasis for adult patients and pediatric patients six years or older, who are candidates for phototherapy or systemic therapy, and active psoriatic arthritis in adults and pediatric patients six years or older. The development and commercialization of the ustekinumab biosimilar is the first biosimilar product launched in the U.S. from the partnership between Fresenius and Formycon AG . In February 2023, Fresenius and Formycon entered a global commercialization partnership for the ustekinumab biosimilar covering key global markets. The drug received FDA approval in September 2024. “The U.S. availability of Otulfi demonstrates our commitment to serving patients and clinicians. Through the expansion of our biopharma portfolio, we are able to do this globally and, in the U.S.,” said Dr. Sang-Jin Pak, President Biopharma and member of the Fresenius Kabi Management Board. “In addition to approving Otulfi last year for all indications matching the reference product Stelara, the FDA has also granted a provisional determination of interchangeability for Otulfi.” Otulfi will be available in the U.S. in the following presentations: a 45 mg/0.5 mL and 90 mg/mL single-dose prefilled syringe for injection and a 130 mg/26 mL (5 mg/mL) single dose vial for IV infusion. Otulfi in a 45 mg/0.5 mL single-dose vial for subcutaneous injection is expected to receive FDA approval in the first half of 2025. About Otulfi Otulfi (ustekinumab-aauz) is a human monoclonal antibody that targets the cytokines interleukin-12 and interleukin-23 which play an important role in inflammatory and immune responses. The FDA approval of Otulfi (ustekinumab-aauz) was based on a thorough evaluation of a comprehensive data package including analytical, pre-clinical, clinical and manufacturing data. Otulfi demonstrated comparable efficacy, safety, pharmacokinetics and immunogenicity to the reference drug Stelara® in patients with moderate to severe plaque psoriasis. Otulfi was approved for both subcutaneous and intravenous formulations which will offer a comprehensive, alternative treatment solution for health care professionals and patients treated with ustekinumab in the U.S. Otulfi (ustekinumab-aauz) is the fourth Fresenius biosimilar commercialized in the U.S., following the approvals and launches of Idacio ® (adalimumab-aacf), Tyenne ® (tocilizumab-aazg) and Stimufend ® (pegfilgrastim-fpgk). Fresenius’s growing pipeline of autoimmune and oncology biosimilars has several molecules in early and late-stage development. Indications OTULFI (ustekinumab-aauz) is an IL-12/23 antagonist indicated for treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy; active psoriatic arthritis; moderately to severely active Crohn’s disease; moderately to severely active ulcerative colitis. Otulfi is also indicated for pediatric patients ≥6 years of age with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis. Please click to see full Prescribing Information and Medication Guide for Otulfi ® (ustekinumab-aauz) here . About Fresenius Kabi As a global health care company, Fresenius Kabi is Committed to Life. The company’s products, technologies, and services are used for the therapy and care of patients with critical and chronic conditions. With more than 43,000 employees and present in more than 100 countries, Fresenius Kabi’s expansive product portfolio focuses on providing access to high-quality and lifesaving medicines and technologies. In Biopharma, Fresenius Kabi offers cutting-edge biosimilars for autoimmune diseases and oncology. With leading market positions in Clinical Nutrition, a broad portfolio of enteral and parenteral products makes a distinct difference in patients’ nutritional status – notably as the only corporation offering both product groups. In MedTech, the company provides vital infusion pumps, cell and gene therapy devices, disposables, and more. Fresenius Kabi is a global leader in supplying blood collection bags and devices, supporting blood banks and health care facilities worldwide. The company’s I.V. Generics and Fluids for infusion therapy help save millions of lives every year, in emergency medicine, surgery, oncology, and intensive care. Fresenius Kabi takes a holistic approach to health care and uniquely combines experience, expertise, innovation, and dedication – making a difference in the lives of almost 450 million patients annually. With Vision 2026, as part of the #FutureFresenius strategy, the company is developing, producing, and selling new products and technologies and aspires to expand its position as a leading global provider of therapies, improve patient care, generate sustainable value for stakeholders – shaping the future of health care. Fresenius Kabi is an operating company of the Fresenius Group, founded in 1912, along with Helios and Quirónsalud. As ONE team, the companies in the Fresenius Group are committed to providing lifesaving and life-changing health care solutions on a global scale. For more information, please visit www.fresenius-kabi.com and www.fresenius-kabi.com/us in the United States. About Formycon Formycon AG (FSE: FYB) is a leading, independent developer of high-quality biosimilars, follow-on products of biopharmaceutical medicines. The company focuses on therapies in ophthalmology, immunology, immuno-oncology and other key disease areas, covering almost the entire value chain from technical development through clinical trials to approval by the regulatory authorities. For commercialization of its biosimilars, Formycon relies on strong, well-trusted and long-term partnerships worldwide. With FYB201/ranibizumab, Formycon already has a biosimilar on the market in Europe and the USA. Two further biosimilars, FYB202/ustekinumab and FYB203/aflibercept, have been approved by the FDA, EMA, and MHRA; FYB202 is also approved in Canada. Another four biosimilar candidates are currently in development. With its biosimilars, Formycon is making an important contribution to providing as many patients as possible with access to highly effective and affordable medicines. Formycon AG is headquartered in Munich, listed in the Prime Standard of the Frankfurt Stock Exchange: FYB / ISIN: DE000A1EWVY8 / WKN: A1EWVY and is part of the SDAX and TecDAX selection indices. Further information can be found at: https://www.formycon.com . This release contains forward-looking statements that are subject to various risks and uncertainties. Future results could differ materially from those described in these forward-looking statements due to certain factors, e.g., changes in business, economic and competitive conditions, regulatory reforms, results of clinical trials, foreign exchange rate fluctuations, uncertainties in litigation or investigative proceedings, and the availability of financing. Fresenius Kabi does not undertake any responsibility to update the forward-looking statements in this release. Management Board: Pierluigi Antonelli (Chairman), Marc Crouton, Andreas Duenkel, Dr. Christian Hauer, Dr. Marc-Alexander Mahl, Dr. Sang-Jin Pak Chairman of the Supervisory Board: Michael Sen Registered Office: Bad Homburg, Germany Commercial Register: Amtsgericht Bad Homburg – HRB 11654 Otulfi ® (ustekinumab-aauz) is a trademark of Fresenius Kabi Deutschland GmbH in selected countries. Stelara ® is a registered trademark of Johnson & Johnson. Idacio ® (adalimumab-aacf) is a registered trademark of Fresenius Kabi Deutschland GmbH in selected countries. Tyenne ® (tocilizumab-aazg) is a registered trademark of Fresenius Kabi Deutschland GmbH in selected countries. Stimufend ® (pegfilgrastim-fpgk) is a registered trademark of Fresenius Kabi Deutschland GmbH in selected countries. SOURCE: Fresenius Kabi

Drug ApprovalBiosimilar

03 Mar 2025

·www.fresenius.com

Continuing Biopharma Growth with U.S. and EU Launch of Ustekinumab Biosimilar

Fresenius announced today that its Operating Company Fresenius Kabi’s ustekinumab biosimilar Otulfi® (ustekinumab-aauz), developed by Formycon AG, is now available in the United States and European Union. Otulfi® is an ustekinumab biosimilar for the reference product Stelara® (ustekinumab). In February 2023, Fresenius Kabi and Formycon entered a global commercialization partnership for the ustekinumab biosimilar covering key global markets. In September 2024, U.S. FDA and EC approval for both subcutaneous and intravenous formulations was received. Otulfi® is indicated for the treatment of Crohn’s disease, ulcerative colitis, moderate to severe plaque psoriasis and active psoriatic arthritis in the U.S. Being Fresenius’ fourth biosimilar on the market, the company continues the growth path of its BioPharma platform in line with #FutureFresenius.

Drug ApprovalBiosimilarPatent Expiration

17 Feb 2025

·pipelinereview.com

Formycon announces decision on Phase III trial with FYB206 and provides update on potential need to adjust the valuation of FYB202 and FYB201

PLANEGG-MARTINSRIED I Germany I February 17, 2025 I The Executive Board of Formycon AG (FSE: FYB, Prime Standard) (“Company”) has decided today to prematurely terminate the Phase III trial (“Lotus”) for its biosimilar candidate FYB206. Based on an intensive scientific dialogue with the U.S. Food and Drug Administration (FDA), the Executive Board, after careful consideration, has concluded that the continuation of the study is no longer necessary for the development and approval of FYB206 in the U.S. The therapeutic comparability of FYB206 with the reference drug Keytruda ®3 can be sufficiently demonstrated using data from the ongoing parallel study in the melanoma indication (“Dahlia”), combined with a comprehensive analytical program. According to preliminary estimates, discontinuing the Phase III trial could lead to investment savings in the high double-digit million range over the next few years, positively impacting the Company’s cash flow statement and liquidity. In coordination with commercialization partner Fresenius Kabi AG, as part of the imminent market launch of FYB202/Otulfi ™4 in the U.S., Formycon anticipates that the valuation model and balance sheet measurement for FYB202 will need to be reviewed and adjusted due to an emerging, significantly higher-than-expected price discount for biosimilars. Based on preliminary calculations, Formycon currently expects a non-cash impairment requirement in the high double-digit to low triple-digit million range. Due to the increasing price discounts among ranibizumab providers in the U.S., Bioeq AG, the exclusive license holder of FYB201/CIMERLI ® , is currently in discussions with its commercialization partner Sandoz AG regarding the future commercialization strategy for FYB201/CIMERLI ® in the U.S. Based on the status of these discussions, Formycon currently expects that the commercialization of FYB201/CIMERLI ® will likely be temporarily paused. This would result in an extraordinary adjustment to the valuation model and the balance sheet measurement for FYB201, as well as the stake in Bioeq AG, amounting to a high single-digit to low double-digit non-cash million figure for the 2024 financial year. In this context, Bioeq AG is exploring alternative commercialization strategies for the U.S. Formycon will provide updates on further developments in due course. Further details regarding the aforementioned matters and their specific financial implications for the company, including the forecast for the 2025 financial year, are currently being reviewed by the company and are expected to be communicated no later than with the publication of the final financial results for the 2024 financial year on March 27, 2025. Formycon currently assumes that the key financial forecast figures for the 2024 financial year will not be affected by these adjustments. The company’s net result, however, is expected to be negatively impacted by the impairment related to FYB202 and FYB201. 1) Stelara ® is a registered trademark of Johnson & Johnson 2) CIMERLI ® is a registered trademark of Coherus BioSciences, Inc 3) Keytruda ® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ/USA 4) Otulfi TM is a trademark of Fresenius Kabi Deutschland GmbH in selected countries. Important Notice : This announcement and the information contained herein are for informational purposes only and do not constitute a prospectus or an offer to sell or a solicitation of an offer to buy any securities of the Company in the United States of America (including its territories and possessions, the states of the United States of America and the District of Columbia) (“United States”) or any other jurisdiction. This publication may not be distributed, published or circulated in the United States, Australia, Canada, Japan and other countries where such distribution or publication may be unlawful. The Company’s securities have not been and will not be registered under the U.S. Securities Act of 1933, as amended (“Securities Act”), and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act, or in a transaction not subject to the registration requirements of the Securities Act. or the applicable securities laws of Australia, Canada or Japan. There will be no public offering of shares of the Company. The distribution of this announcement may be restricted by law in certain jurisdictions and persons in possession this announcement or the information referred to herein should inform themselves about and observe any such restrictions. Failure to comply with such restrictions may constitute a violation of the securities laws of such jurisdictions. About Formycon: Formycon is a leading, independent developer of high-quality biopharmaceutical medicines, especially biosimilars. Formycon AG is listed in the Open Market (“Scale”) of the Frankfurt Stock Exchange (ISIN: DE000A1EWVY8 / WKN: A1EWVY). About Biosimilars: Since their introduction in the 1980s, biopharmaceuticals have revolutionized the treatment of serious diseases such as cancer, diabetes, rheumatoid arthritis, multiple sclerosis and eye diseases. In the coming years, many of these biotech drugs will lose their patent protection – and by 2025, medications with revenues of approximately USD 100 billion will be off patent. Biosimilars are follow-on versions of biopharmaceuticals, for which exclusivity has expired. They are approved via stringent regulatory pathways in highly regulated markets (such as EU, US, Japan, Canada, Australia) based on proven similarity of the biosimilar with the originator biopharmaceutical reference product. Currently, global sales of biosimilars are estimated at more than USD 15 billion. By 2030, analysts estimate that this figure could rise to over USD 74 billion. SOURCE: Formycon

Phase 3

100 Deals associated with Ustekinumab-Aauz

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KEGG	Wiki	ATC	Drug Bank
-	-	L04AC05	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Psoriasis	Canada	Fresenius Kabi Canada Ltd.	01 Dec 2024
Arthritis, Psoriatic	European Union	Formycon AG	25 Sep 2024
Arthritis, Psoriatic	European Union	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Arthritis, Psoriatic	Iceland	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Arthritis, Psoriatic	Iceland	Formycon AG	25 Sep 2024
Arthritis, Psoriatic	Liechtenstein	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Arthritis, Psoriatic	Liechtenstein	Formycon AG	25 Sep 2024
Arthritis, Psoriatic	Norway	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Arthritis, Psoriatic	Norway	Formycon AG	25 Sep 2024
Crohn's disease, active moderate	European Union	Formycon AG	25 Sep 2024
Crohn's disease, active moderate	European Union	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Crohn's disease, active moderate	Iceland	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Crohn's disease, active moderate	Iceland	Formycon AG	25 Sep 2024
Crohn's disease, active moderate	Liechtenstein	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Crohn's disease, active moderate	Liechtenstein	Formycon AG	25 Sep 2024
Crohn's disease, active moderate	Norway	Formycon AG	25 Sep 2024
Crohn's disease, active moderate	Norway	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Crohn's disease, active severe	European Union	Fresenius Kabi Deutschland GmbH	25 Sep 2024
Crohn's disease, active severe	European Union	Formycon AG	25 Sep 2024
Crohn's disease, active severe	Iceland	Formycon AG	25 Sep 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Immune System Diseases	Phase 1	-	Aristo Pharma GmbH	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed Manual	Not Applicable	-	491	FYB202	obcwdxjzpl(llmsnwnooo) = All 3 comparisons showed PK similarity, since the 90% confidence intervals of the respective geometric mean ratios for area under the concentration-time curve from time 0 to infinity and maximum serum concentration were contained within the acceptance interval of 80%-125%. lremvxzynj (bzqkrfrgtn ) View more	Similar	19 Oct 2024
				EU-Ref
FDA_CDER Manual	Not Applicable	Crohn Disease	388	Placebo (CD-3)	cnntoomjvl(rycnlzodgj) = thxplhwzxn dhgxkyovpl (qitkooydio ) View more	Positive	27 Sep 2024
				Ustekinumab (CD-3)	cnntoomjvl(rycnlzodgj) = pcoyoruzyq dhgxkyovpl (qitkooydio ) View more
FDA_CDER Manual	Not Applicable	Plaque psoriasis	73	Placebo	jhxkaejtfq(yextqvtdxh) = eqyzdykjea omrlwjvqvx (lhwnjhkfmn ) View more	Positive	27 Sep 2024
				Ustekinumab	jhxkaejtfq(yextqvtdxh) = crjnjqeeze omrlwjvqvx (lhwnjhkfmn ) View more
FDA_CDER Manual	Not Applicable	Colitis, Ulcerative	961	Placebo (Prior biologic failure)	ieeybdtdqm(dpueyobmpz) = lvuyzqopqj hsivcarwzo (xeawjedjrq ) View more	Positive	27 Sep 2024
				Ustekinumab	ieeybdtdqm(dpueyobmpz) = jlhplsltzg hsivcarwzo (xeawjedjrq ) View more
FDA_CDER Manual	Not Applicable	Plaque psoriasis	1,996	Placebo (Ps STUDY 1)	ryhibsirza(nedfrhbggv) = irurbsmlsg nkuvpjwfca (sfvgmhjdjb ) View more	Positive	27 Sep 2024
				Ustekinumab 45 mg (Ps STUDY 1)	ryhibsirza(nedfrhbggv) = qzrqvasvtv nkuvpjwfca (sfvgmhjdjb ) View more
FDA_CDER Manual	Not Applicable	Crohn Disease	1,368	Placebo (CD-1)	jzunboeqmy(ztpohevhid) = gpzfszkdgf tctsihxevp (qlihlcoizb ) View more	Positive	27 Sep 2024
				Ustekinumab (CD-1)	jzunboeqmy(ztpohevhid) = wgykzuaspb tctsihxevp (qlihlcoizb ) View more
FDA_CDER Manual	Not Applicable	Arthritis, Psoriatic	927	Placebo (PsA STUDY 1)	bakntlzoup(rlxghmgarb) = vpdwnqmlme fiobzqqmsc (adyjubvidf ) View more	Positive	27 Sep 2024
				Ustekinumab 45 mg (PsA STUDY 1)	bakntlzoup(rlxghmgarb) = kghsjofqol fiobzqqmsc (adyjubvidf ) View more

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