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 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.

04 May 2023·Expert opinion on investigational drugs

A randomized, double-blind, 3-arm, parallel study assessing the pharmacokinetics, safety, tolerability and immunogenicity of AVT04, an ustekinumab candidate biosimilar, in healthy adults

Article

Author: Otto, Hendrik ; Hamilton, Paul ; Haliduola, Halimu N ; Wynne, Christopher ; Duijzings, Paul ; McLendon, Kristi ; Smith, Matthew ; Stroissnig, Heimo ; Berti, Fausto ; Sattar, Abid ; Ruffieux, Ruth ; Leutz, Steffen

BACKGROUND:

This study assessed pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT04, a candidate biosimilar, compared with reference product (RP) ustekinumab (EU-approved and US-licensed Stelara®).

METHODS:

Healthy subjects (N = 298) were randomized 1:1:1 to receive one 45 mg dose of AVT04, EU-RP, or US-RP. The primary PK parameters were Cmax and AUC0-inf. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means were all contained within the prespecified margins of 80% and 125%. Additional PK parameters, including AUC0-t, were also assessed. Safety and immunogenicity were also assessed until Day 92.

RESULTS:

After pre-specified protein content normalization, the 90% CI for the ratio of geometric means for primary PK parameters were all contained within the pre-specified bioequivalence margins of 80% and 125%, supporting demonstration of PK similarity between AVT04 and both EU- and US-RP. Secondary PK parameters supported the analysis. Safety and immunogenicity profiles were comparable across all three treatment arms, although the study was not powered to detect small differences in these parameters.

CONCLUSION:

Results supported a demonstration of PK similarity between candidate biosimilar AVT04, US-RP and EU-RP. Similar safety and immunogenicity were also shown.Clinical trial registration: www.clinicaltrials.gov identifier is NCT04744363.

News (Medical) associated with Ustekinumab biosimilar (Alvotech)

05 Nov 2024

·pipelinereview.com

European Medicines Agency Confirms Acceptance of Marketing Authorization Application for AVT05, a Proposed Biosimilar to Simponi® (golimumab)

November 04, 2024 I Alvotech (NASDAQ: ALVO), a global biotech company specializing in the development and manufacture of biosimilar medicines for patients worldwide and Advanz Pharma, a UK headquartered global pharmaceutical company with a strategic focus on specialty, hospital, and rare disease medicines in Europe, today announced that the European Medicines Agency (EMA) has accepted a Marketing Authorization Application for AVT05, Alvotech’s proposed biosimilar to Simponi® (golimumab), a biologic used to treat several chronic inflammatory diseases. This is believed to be the first marketing authorization application filing announced globally for a biosimilar candidate to Simponi. The approvals process is anticipated to be completed in the fourth quarter of 2025. “This is a welcome milestone for us, our partners, patients and caregivers, as we take one step closer to being able to offer access to biosimilar Simponi®,” said Joseph McClellan, Chief Scientific Officer of Alvotech. “We believe having the capability and know-how inhouse to utilize a host cell line and process also used to manufacture the reference biologic, has given us an important head start in developing a biosimilar candidate to Simponi®.” “The EMA’s acceptance of the application for AVT05 represents a significant step forward in expanding treatment options for patients with chronic inflammatory diseases across Europe,” said Nick Warwick, Chief Medical Officer of Advanz Pharma. “We are committed to improving patient access to high-quality biologic medicines.” Alvotech and Advanz Pharma first announced in February 2023 that the companies had entered into a commercialization agreement, for AVT23, a proposed biosimilar to Xolair® (omalizumab). In May this year, the partners announced an expansion of the strategic partnership, to include five additional biosimilar candidates being developed by Alvotech, AVT05, AVT16 a proposed biosimilar to Entyvio® (vedolizumab) and three additional early-stage biosimilar candidates which remain undisclosed. In April 2024 Alvotech announced positive top-line results from a confirmatory clinical study comparing efficacy, safety, and immunogenicity between AVT05 and Simponi® in patients with moderate to severe rheumatoid arthritis. In November 2023, Alvotech announced positive topline results from a pharmacokinetic study which assessed the pharmacokinetics, safety, and tolerability of AVT05 compared to Simponi® in healthy adult participants. About AVT05 AVT05 is a biosimilar candidate for Simponi® and Simponi Aria® (golimumab). Golimumab is a monoclonal antibody that inhibits tumor necrosis factor alpha (TNF alpha). Elevated TNF alpha levels have been implicated in several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis [1]. AVT05 is an investigational product and has not received regulatory approval in any country. Biosimilarity has not been established by regulatory authorities and is not claimed. About AVT16 AVT16 is a human monoclonal antibody and a biosimilar candidate to Entyvio® (vedolizumab). AVT16 is an investigational product and has not received regulatory approval in any country. Biosimiliarity has not been established by regulatory authorities and is not claimed. About AVT23 AVT23 is a monoclonal antibody and proposed biosimilar to Xolair® (omalizumab). AVT23 is an investigational compound and has not received regulatory approval in any country. Biosimilarity has not been established by regulatory authorities and is not claimed. Sources [1] EMA, Simponi product information Use of trademarks Simponi® is a registered trademark of Johnson & Johnson. Entyvio® is a trademark of Millennium Pharmaceuticals, Inc. Xolair® is a registered trademark of Novartis AG. About Alvotech Alvotech is a biotech 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. Two biosimilars to Humira® (adalimumab) and Stelara® (ustekinumab) are already approved and marketed in multiple global markets. The current development pipeline includes nine 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. Alvotech’s commercial partners include Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd. (US), STADA Arzneimittel AG (EU), Fuji Pharma Co., Ltd (Japan), Advanz Pharma (EEA, UK, Switzerland, Canada, Australia and New Zealand), Dr. Reddy’s (EEA, UK and US), Biogaran (FR), Cipla/Cipla Gulf/Cipla Med Pro (Australia, New Zealand, South Africa/Africa), JAMP Pharma Corporation (Canada), Yangtze River Pharmaceutical (Group) Co., Ltd. (China), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS Holding LLC (Middle East and North Africa), Abdi Ibrahim (Turkey), Kamada Ltd. (Israel), Mega Labs, Stein, Libbs, Tuteur and Saval (Latin America) and Lotus Pharmaceuticals Co., Ltd. (Thailand, Vietnam, Philippines, and South Korea). Each commercial partnership covers a unique set of product(s) and territories. Except as specifically set forth therein, Alvotech disclaims responsibility for the content of periodic filings, disclosures and other reports made available by its partners. For more information, please visit https://www.alvotech.com. None of the information on the Alvotech website shall be deemed part of this press release. Please visit our investor portal , and our website or follow us on social media on LinkedIn , Facebook , Instagram , X and YouTube . About Advanz Pharma Partner of choice in specialty, hospital, and rare disease medicines, ADVANZ PHARMA is a global pharmaceutical company with the purpose to improve patients’ lives by providing and enhancing the specialty, hospital, and rare disease medicines they depend on. Our headquarters are in London, UK. We have commercial sales in more than 90 countries globally and have a direct commercial presence in more than 20 countries, including key countries in Europe, the US, Canada, and Australia, a Centre of Excellence in Mumbai, India, as well as an established global distribution and commercialization partner network. Advanz Pharma’s product portfolio and pipeline comprises innovative medicines, specialty generics & biosimilars, and originator brands. Our products cover a broad range of therapeutic areas, including hepatology, gastroenterology, anti-infectives, critical care, endocrinology, oncology, CNS, and, more broadly, rare disease medicines. Our ambition is to be a partner of choice for the commercialization of specialty, hospital, and rare disease medicines in Europe, Canada, and Australia. In line with our ambition, we are partnering with biopharma and development companies to bring medicines to patients. We can only achieve this due to our dedicated and highly qualified employees, acting in line with our company values of entrepreneurship, speed, and integrity. SOURCE: Advanz Pharma

Drug ApprovalLicense out/inBiosimilar

05 Nov 2024

·www.pharmaceutical-technology.com

EMA accepts Alvotech and Advanz Pharma’s AVT05 MAA

This application marks the first global MAA filing for a biosimilar candidate to Simponi for treating chronic inflammatory conditions. Credit: BlurryMe/Shutterstock. The European Medicines Agency (EMA) has accepted a marketing authorisation application (MAA) for Alvotech and Advanz Pharma’s AVT05, a proposed biosimilar to Johnson & Johnson ’s (J&J) Simponi (golimumab). The application marks the first global MAA filing for a biosimilar candidate to Simponi, a biologic for treating chronic inflammatory conditions. AVT05 is being developed as a biosimilar to both Simponi and Simponi Aria (golimumab). The approval process for AVT05 is expected to conclude by the fourth quarter (Q4) of 2025. This development follows Alvotech and Advanz Pharma’s initial commercialisation agreement in February 2023 for AVT23, a Novartis ’ Xolair (omalizumab) biosimilar. Alvotech and Advanz Pharma expanded their strategic partnership in May 2024 to include five additional biosimilar candidates, along with AVT05, AVT16 and three early-stage biosimilar candidates which have not been disclosed. In June 2024, both companies entered a commercialisation agreement for two biosimilar candidates to Eylea, AVT06 and AVT29, targeting different dosage presentations. Alvotech chief scientific officer Joseph McClellan stated: “This is a welcome milestone for us, our partners, patients and caregivers, as we take one step closer to being able to offer access to biosimilar Simponi. “We believe having the capability and know-how inhouse to utilise a host cell line and process also used to manufacture the reference biologic, has given us an important head start in developing a biosimilar candidate to Simponi.” Alvotech announced positive top-line results from a confirmatory trial in April 2024, demonstrating comparable safety, efficacy and immunogenicity between AVT05 and Simponi in treating moderate to severe rheumatoid arthritis. In November 2023, Alvotech released positive topline results from a pharmacokinetic study comparing AVT05 to Simponi in healthy adults. Golimumab, the active ingredient in Simponi, is a monoclonal antibody that targets tumour necrosis factor-alpha (TNF alpha), a substance involved in systemic inflammation. The US Food and Drug Administration recently approved a presentation for SELARSDI (ustekinumab-aekn) , a collaborative product of Alvotech and Teva Pharmaceuticals, for treating adults with ulcerative colitis and Crohn’s disease.

Drug ApprovalLicense out/inBiosimilar

23 Oct 2024

·www.pharmaceutical-technology.com

Ocuphire and Opus Genetics merge to develop IRD gene therapy

The merger is set to create a company dedicated to gene therapy development for inherited retinal diseases. Credit: elenavolf/Shutterstock. Ocuphire Pharma has announced the acquisition of Opus Genetics to create a biotech company dedicated to gene therapy development for inherited retinal diseases (IRDs). The combined entity will be named Opus Genetics. Ocuphire has issued 5.2m common stock shares and 14,100 shares of its convertible preferred stock to Opus Genetics’ stockholders. The preferred shares will be convertible into common stock, pending approval at the annual meeting in April 2025. Post-merger, Ocuphire’s pre-acquisition stockholders will hold 58% of the fully diluted capitalisation of the combined company, while Opus Genetics’ stockholders will own almost 42%. See Also: FDA approves Alvotech and Teva’s SELARSDI for new indications AAO 2024: NMA reveals Vabysmo’s superior CST improvement over Eylea HD Newly combined company president Ben Yerxa stated: “With the Ocuphire team’s late-stage ophthalmic drug development and regulatory approval experience and resources, we believe we are well-positioned to accelerate our pipeline of potentially transformative gene therapies for inherited retinal diseases. “We see this transaction as a win for patients with IRDs around the world, and we look forward to efficiently progressing our combined pipeline.” The expanded pipeline of the new company includes adeno-associated virus (AAV)-based gene therapy assets for IRDs and Ocuphire’s late-stage product candidate RYZUMVI (phentolamine ophthalmic solution 0.75%), which is being assessed for presbyopia and dim light vision disturbances following keratorefractive surgery. RYZUMVI is designed to reduce pupil size by blocking alpha-1 receptors on the radial iris dilator muscles. The combined company’s expected cash runway is extended into 2026, anticipating clinical data readouts for several trials. Leerink Partners is the exclusive financial advisor to Ocuphire. Sidley Austin and Smith Anderson are serving as legal counsels to Ocuphire and Opus Genetics, respectively. In 2022, Opus Genetics signed an agreement with National Resilience for developing and manufacturing AAV vector-based gene therapies for IRD. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

AcquisitionGene Therapy

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	US	Alvotech USA, Inc.	18 Oct 2024
Ulcerative colitis, active severe	US	Alvotech USA, Inc.	18 Oct 2024
Psoriasis	EU	Alvotech	10 Jan 2024
Psoriasis	IS	Alvotech	10 Jan 2024
Psoriasis	LI	Alvotech	10 Jan 2024
Psoriasis	NO	Alvotech	10 Jan 2024
Crohn's disease, active moderate	EU	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active moderate	IS	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active moderate	LI	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active moderate	NO	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	EU	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	IS	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	LI	STADA Arzneimittel AG	05 Jan 2024
Crohn's disease, active severe	NO	STADA Arzneimittel AG	05 Jan 2024
Crohn Disease	CA	JAMP Pharma Corp.	01 Nov 2023
Arthritis, Psoriatic	JP	Fuji Pharma Co., Ltd.	25 Sep 2023
Plaque psoriasis	JP	Fuji Pharma Co., Ltd.	25 Sep 2023

Clinical Result

Indication

Phase

Evaluation

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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)	cqdjlfnktw(kvhnrslpjb) = lhexmzrndi ckzovrmivj (bxkyvaalpv ) View more	Positive	16 Apr 2024
				Ustekinumab 45 mg (Ps STUDY 1 + Adult)	cqdjlfnktw(kvhnrslpjb) = vpvzidgodu ckzovrmivj (bxkyvaalpv ) View more
NCT04930042 (AVT04-GL-301, FDA_CDER) Manual	Phase 3	Arthritis, Psoriatic	927	Ustekinumab 45 mg (PsA STUDY 1)	nzqaqqmbqx(puvxpjpdvv) = zcsdaorzev hzhllmxwob (nbfjcgnxdu ) View more	Positive	16 Apr 2024
				Ustekinumab90 mg (PsA STUDY 1)	nzqaqqmbqx(puvxpjpdvv) = mhddtssisp hzhllmxwob (nbfjcgnxdu ) View more
EADV2023	Not Applicable	Plaque psoriasis	581	AVT04	yoazzubnqw(abzrxqwhyh) = aepjwvjadt zelrpjzocn (omdbbfnmei )	Positive	11 Oct 2023
				Reference Product Ustekinumab	yoazzubnqw(abzrxqwhyh) = jhcazphgle zelrpjzocn (omdbbfnmei )
NCT04930042 (Pubmed)	Phase 3	Plaque psoriasis	581	AVT04	qbzsnnclaj(pczixiwfqc) = arfcailcwc pqozkfkmac (zosbrrpzjw )	Positive	12 Jul 2023
				Reference product ustekinumab (Stelara®)	qbzsnnclaj(pczixiwfqc) = cbpadyshlj pqozkfkmac (zosbrrpzjw )
NCT04930042 (AAD2023)	Phase 3	Psoriasis	581	AVT04	vjjvttglbr(concesawor) = soahsiwmbe tdrovqxfqq (fjcwbjacfh ) View more	-	17 Mar 2023
				Reference Ustekinumab	vjjvttglbr(concesawor) = crpzzikpwi tdrovqxfqq (fjcwbjacfh ) View more

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