A Phase III Randomised, Double-masked, Parallel Group, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity between SB15 (proposed aflibercept biosimilar) and Eylea® in Subjects with Neovascular Age-related Macular Degeneration

Start Date07 May 2020

Sponsor / Collaborator

Samsung Bioepis Co., Ltd.

100 Clinical Results associated with AFLIBERCEPT-YSZY

100 Translational Medicine associated with AFLIBERCEPT-YSZY

100 Patents (Medical) associated with AFLIBERCEPT-YSZY

Literatures (Medical) associated with AFLIBERCEPT-YSZY

01 Aug 2024·Ophthalmology and Therapy

Analytical Characterization for Similarity Assessment Between an Aflibercept Biosimilar SB15 and Reference Product (Eylea®)

Article

Author: Lee, Jaeil ; Kim, Beom Chan ; Song, Jinsu ; Lee, Hangyeore ; Lee, Soye ; Kim, Dayoung ; Huh, Jongcheol ; Lee, Jungmin

INTRODUCTION:

SB15 is a proposed biosimilar product of reference aflibercept (Eylea^®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties.

METHODS:

A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted.

RESULTS:

Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept.

CONCLUSIONS:

Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.

01 Dec 2023·BMJ open ophthalmology

Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial

Article

Author: Studnička, Jan ; Oh, Inkyung ; Csutak, Adrienne ; Yun, Cheolmin ; Ernest, Jan ; Vajas, Attila ; Jang, Hyerin ; Sadda, SriniVas R ; Choi, Wooree ; Tóth-Molnár, Edit ; Enyedi, Lajos ; Patel, Sunil ; Wylegala, Edward ; Veith, Miroslav ; Woo, Se Joon ; Astakhov, Sergei ; Sagong, Min ; Orski, Michal ; Bradvica, Mario

Background/aims:

To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD).

Design:

Prospective, double-masked, randomised, phase 3 trial.

Methods:

Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch’s membrane). Additional endpoints included safety, PK and immunogenicity.

Results:

Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (−2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were −119.2 µm and −132.4 µm for SB15/SB15 and −126.6 µm and −136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (−6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (−18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (−2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups.

Conclusions:

Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

01 Jul 2023·JAMA ophthalmology

Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.

Article

Author: Oh, Inkyung ; Kim, Taehyung ; Csutak, Adrienne ; Yun, Cheolmin ; Ernest, Jan ; Vajas, Attila ; Jang, Hyerin ; Enyedi, Lajos ; Tóth-Molnár, Edit ; Patel, Sunil ; Wylegala, Edward ; Sadda, SriniVas R ; Veith, Miroslav ; Woo, Se Joon ; Astakhov, Sergei ; Studnicka, Jan ; Sagong, Min ; Orski, Michal ; Bradvica, Mario

Importance:

Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy.

Objective:

To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD).

Design, Setting, and Participants:

This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up.

Intervention:

Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56.

Main Outcomes and Measures:

The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity.

Results:

The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable.

Conclusions and Relevance:

In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD.

Trial Registration:

ClinicalTrials.gov Identifier: NCT04450329.

News (Medical) associated with AFLIBERCEPT-YSZY

18 Nov 2024

·pipelinereview.com

Samsung Bioepis and Biogen Receive European Commission (EC) Approval for Aflibercept Biosimilar, OPUVIZ

INCHEON, South Korea and CAMBRIDGE, MA, USA I November 18, 2024 I Samsung Bioepis Co., Ltd. and Biogen Inc. (Nasdaq: BIIB) today announced that the European Commission (EC) has approved OPUVIZ™ 40 mg/mL solution for injection in a vial, a biosimilar referencing Eylea 1,2 (aflibercept), developed and registered by Samsung Bioepis. OPUVIZ, also known as SB15, is approved in adult patients for the treatment of neovascular (wet) age related macular degeneration (AMD), visual impairment due to macular oedema secondary to retinal vein occlusion (RVO; branch or central RVO), visual impairment due to diabetic macular oedema (DME), and visual impairment due to myopic choroidal neovascularisation (myopic CNV). “Retinal disorders are affecting millions of people’s lives in Europe, yet many patients face barriers to treatment due to high costs,” said Byoungin Jung, Vice President, Regulatory Affairs at Samsung Bioepis. “The EC approval for OPUVIZ represents a major step toward our goal of expanding access to vital biologic therapies for those in need. We will continue working to expand access to our quality-assured, safe and effective biosimilars to improve patient’s quality of life and support sustainability of healthcare systems.” “This approval is an exciting milestone for both patients and healthcare systems in Europe. OPUVIZ has the potential to create a new treatment option for eligible patients, while also easing the burden of costs associated with these retinal conditions,” said Wolfram Schmidt, Head of Europe at Biogen. “We are delighted to continue our partnership with Samsung Bioepis, with the approval of our fifth biosimilar treatment option in Europe.” The EC approval was based on a totality of evidence including analytical, non-clinical data, and clinical data. A randomized, double-masked, parallel group, multicenter Phase 3 study demonstrated equivalent efficacy and comparable safety, immunogenicity, and pharmacokinetics (PK) profiles between SB15 and reference aflibercept (AFL). The primary endpoint was met in terms of change from baseline in best corrected visual acuity (BCVA) at week 8, and the 32-week interim analysis and 56-week analysis demonstrated comparability in other secondary efficacy, safety, immunogenicity, and PK endpoints between SB15 and AFL. 3, 4 OPUVIZ is the second ophthalmology biosimilar approved in Europe and fifth biosimilar in the portfolio developed by Samsung Bioepis with commercialization rights held by Biogen, which includes BYOOVIZ™ (ranibizumab), BENEPALI™ (etanercept), IMRALDI™ (adalimumab) and FLIXABI™ (infliximab). In November 2019, Samsung Bioepis and Biogen announced that they had entered into a commercialization agreement for two ophthalmology biosimilar candidates, BYOOVIZ (SB11, ranibizumab) and OPUVIZ (SB15, aflibercept), in the U.S., Canada, Europe and certain other markets. About the SB15 Phase 3 study 3,4 The study is a randomized, double-masked, parallel group phase 3 study conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were randomized 1:1 to receive either SB15 (n = 224) or AFL (n = 225). At Week 32, patients were re-randomized to either continue SB15 or AFL, or switch from AFL to SB15 resulting in three treatment groups; continuing SB15 (SB15/SB15, n=219), continuing AFL (AFL/AFL, n=108), switching from AFL to SB15 (AFL/SB15, n=111). In total, 425 patients completed up to Week 56. Key efficacy endpoints of the study were 1) change from baseline in best corrected visual acuity (BCVA), 2) change from baseline in central subfield thickness (CST), and 3) proportion of patients with intra or sub-retinal fluid. About Samsung Bioepis Co., Ltd. Established in 2012, Samsung Bioepis is a biopharmaceutical company committed to realizing healthcare that is accessible to everyone. Through innovations in product development and a firm commitment to quality, Samsung Bioepis aims to become the world’s leading biopharmaceutical company. Samsung Bioepis continues to advance a broad pipeline of biosimilar candidates that cover a spectrum of therapeutic areas, including immunology, oncology, ophthalmology, hematology, nephrology, and endocrinology. For more information, please visit: www.samsungbioepis.com and follow us on social media – X , LinkedIn . About Biogen Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at www.biogen.com . Follow us on social media – Facebook , LinkedIn , X , YouTube . References: SOURCE: Samsung Bioepis

Phase 3Clinical ResultDrug ApprovalLicense out/in

23 Oct 2024

·www.biospace.com

Roche Beats Q3 Sales Estimates as CEO Voices Opposition to Novo Holdings-Catalent Merger

iStock, Robert Way Jefferies analyst Peter Welford noted that Roche’s pharma group came just slightly ahead of consensus expectations, driven by strong performance of its multiple sclerosis therapy Ocrevus and eye injection Vabysmo. Roche on Wednesday released its third-quarter earnings report , posting nearly $17.5 billion in sales, representing 9% year-on-year growth and exceeding Wall Street expectations. According to Jefferies analyst Peter Welford, Roche’s Q3 sales were 1% ahead of the consensus estimate. The company’s pharmaceuticals division, which remains its strongest unit with $13.4 billion in the quarter, beat analysts’ expectations by 2%. Roche’s top-performing asset in the quarter was the multiple sclerosis drug Ocrevus, which grew 11% to bring in almost $2 billion. Despite mounting biosimilar competition in the eye diseases space, Roche’s intravitreal injection Vabysmo continues its strong market momentum. The age-related macular degeneration (AMD) treatment surged 59% year-over-year, bringing in nearly $1.2 billion in Q3. Vabysmo, a dual inhibitor of VEGF and angiopoietin-2, is also indicated for diabetic macular edema (DME). In May 2024, the FDA greenlit two biosimilars to Regeneron’s blockbuster therapy Eylea—Samsung Bioepis and Biogen’s Opuviz and Biocon Biologics’ Yesafili—which are expected to compete with Vabysmo in the AMD and DME markets. On the negative side of the Q3 ledger, Roche’s PD-L1 antibody Tecentriq was “weak” in the quarter, according to Jefferies’ Welford, noting that its sales of just over $1 billion fell short of consensus estimates. Looking forward to the rest of the year, Roche reiterated its business outlook with growth of around mid-single-digit in group sales and in the high-single-digit range for core earnings-per-share. Opposition to Novo-Catalent Deal On the M&A front, Roche is urging regulatory authorities to block Novo Holdings’ proposed $16.5 billion acquisition of CDMO giant Catalent, arguing that the deal would have wide-ranging negative effects on the industry. “Limiting the competition in this space is not a good idea,” Roche CEO Thomas Schinecker said in a media call Wednesday morning, however insisting that the company itself would not be affected by the merger, according to Reuters . The acquisition would further restrict the contract manufacturing ecosystem, Schinecker said, which “could be a problem for other smaller players.” “From an industry perspective, it would be a wrong decision by authorities” if they let the transaction proceed, according to Schinecker. Pressure on the deal has been mounting. Last week, more than 10 unions, consumer organizations and public interest groups wrote to the Federal Trade Commission , urging the antitrust watchdog to “challenge” the proposed acquisition and to ensure that “competition is protected.” Sen. Elizabeth Warren (D-Mass.) earlier this month also flagged potential anti-competitive concerns with the transaction. In a letter to the FTC, Warren warned that the acquisition of contract manufacturer Catalent could increase Novo Nordisk’s dominance over the hot GLP-1 market, reducing competition and increasing prices. Referring to rival Eli Lilly, Warren said the deal could give Novo Nordisk “unprecedented visibility into and control over its competitor’s production capacity, costs, and business practices,” as well as “the ability to preference its own products and obstruct its competitors’ use of Catalent to produce GLP-1 drugs.” Lilly CEO David Ricks said in a Q2 earnings call in August that the company remains concerned about the Novo-Catalent deal. “We do rely on one of the Catalent sites for GLP-1 and other diabetes production,” Ricks told analysts. “We’ve aired those concerns publicly and privately since the proposed transaction was announced, and we’re waiting to see what happens.”

Acquisition

24 Sep 2024

·www.fiercepharma.com

Regeneron's stock drops as it loses bid to block Amgen's Eylea biosimilar

Regeneron suffered a setback in its defense of blockbuster eye drug Eylea, startling investors. Three months after a federal judge in West Virginia sided with Regeneron, blocking the market entry of two biosimilars for blockbuster eye disease drug Eylea, the same judge has rejected the company’s attempt to block Amgen’s Eylea biosimilar.In an order issued under seal—which would explain his decision—Judge Thomas Kleeh of the U.S. District Court for Northern District of West Virginia denied Regeneron’s request for a preliminary injunction which would prevent Amgen’s Pavblu from entering the market.The knockoff, which replicates the original 2 mg version of Bayer and Regeneron’s Eylea, was approved by the FDA last month. In its complaint against Amgen, which was filed in January of this year, Regeneron listed 32 patents it claimed were infringed. Upon the decision, the company immediately filed an appeal."We are disappointed in the court decision that was specific to Amgen only. Importantly, this decision has no effect on previous decisions against other biosimilars manufacturers of Eylea," Regeneron said in an emailed statement. "We continue to believe that Amgen is infringing our patent rights, and this decision denying our request for a preliminary injunction is not the final word in this litigation. We have appealed this decision, and we also look forward to presenting our case at trial."The New York-based company’s regulatory exclusivity for Eylea—which was originally approved in 2011 to treat wet age-related macular degeneration (AMD)—expired in May, according to the complaint.As Regeneron's case plays out, Amgen could now pursue an "at-risk" biosimilar launch. Under such an approach, the biosimilar maker would be liable for damages should Regeneron ultimately prevail in establishing patent infringement.In the wake of the injunction decision, Regeneron’s shares dropped roughly 9% between Monday and Tuesday, an indicator of the company’s reliance on Eylea.With U.S. sales of $5.9 billion in 2023, the vascular endothelial growth factor (VEGF) inhibitor accounted for 44% of Regeneron revenue of $13.1 billion.An Amgen spokesperson said that the company will "announce our launch timing in due course," Eylea’s market share has been dented by Roche’s longer-acting Vabysmo, which requires dosing as little as every four months as opposed to every other month for Eylea. Regeneron has since countered with a high-dose (8 mg) version of Eylea. In the second quarter, Eylea HD accounted for $304 million of the $1.53 billion generated overall by the Eylea franchise. The Amgen ruling runs counter to Kleeh’s decisions three days apart in June when he granted Regeneron’s requests for preliminary injunctions, blocking the sale of Biogen and Samsung Bioepis’ Eylea biosimilar Opuviz and Biocon’s Eylea copycat Yesafili until 2027. The court ruled that both knockoffs infringed Regeneron patents.Opuviz and Yesafili were approved by the FDA in May as interchangeable biosimilars, meaning that a pharmacist can freely switch them out for the reference product. Regeneron’s defense of Eylea is a high-priority endeavor for the drugmaker. Four weeks ago, the company filed a lawsuit in New Jersey against Sandoz and its Eylea biosimilar. The company also is jousting with South Korea-based Celltrion and Germany-based Formycon over their Eylea biosimilars.Eylea works by inhibiting the growth of abnormal blood vessels in the retina and reducing fluid leakage. This mechanism helps in managing and treating conditions that lead to vision loss. In addition to its AMD nod, Eylea has been endorsed by the FDA to treat diabetic macular edema (DME), retinal vein occlusion (RVO), diabetic retinopathy (DR) and retinopathy of prematurity (ROP).

Drug ApprovalPatent InfringementBiosimilar

100 Deals associated with AFLIBERCEPT-YSZY

R&D Status

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Indication	Country/Location	Organization	Date
Diabetic Retinopathy	US	Samsung Bioepis Co., Ltd.	20 May 2024
Diabetic macular oedema	KR	Samsung Bioepis Co., Ltd.	23 Feb 2024
Myopic choroidal neovascularization	KR	Samsung Bioepis Co., Ltd.	23 Feb 2024
Retinal vein occlusion-related macular edema	KR	Samsung Bioepis Co., Ltd.	23 Feb 2024
Wet age-related macular degeneration	KR	Samsung Bioepis Co., Ltd.	23 Feb 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04450329 (CTgov)	Phase 3	Wet age-related macular degeneration	449	SB15 (Proposed aflibercept biosimilar) (SB15 (Proposed Aflibercept Biosimilar))	kvvtmpmnjn(gfhjydaqdt) = tqzndegtkd fhvejsptun (uxoqjdeehu, hywpsbvfdr - ckmarndhzs) View more	-	05 Feb 2024
				SB15 (Proposed aflibercept biosimilar) (Eylea (Aflibercept))	kvvtmpmnjn(gfhjydaqdt) = onidlpkixc fhvejsptun (uxoqjdeehu, ssxhnblten - gzhpyhkgmp) View more
EURETINA2023 Manual	Phase 3	Wet age-related macular degeneration	438	SB15	qdstzcanwm(cmszdcfwcd) = xpianidoun icibevytph (lpngmbyjgp ) View more	Positive	05 Oct 2023
				Aflibercept	qdstzcanwm(cmszdcfwcd) = octrthprgn icibevytph (lpngmbyjgp ) View more
EURETINA2023 Manual	Phase 3	Age Related Macular Degeneration	449	SB15	morypizjsk(lhihzaiufh) = ecinrctbgb psqscuocsj (ulnqcuazdm )	Similar	05 Oct 2023
				Aflibercept	morypizjsk(lhihzaiufh) = bijwtbgswe psqscuocsj (ulnqcuazdm )
NCT04450329 (Pubmed)	Phase 3	Wet age-related macular degeneration	449	SB15	nklevzhqmc(bnetlgudoh) = tyyxlsieza rqnznizvfv (ejglhrqplx ) View more	-	08 Jun 2023
				AFL	nklevzhqmc(bnetlgudoh) = eqhypeoynx rqnznizvfv (ejglhrqplx ) View more
Phase III Randomized Clinical Trial Comparing SB15 with Reference Aflibercept in Neovascular Age-Related Macular Degeneration (ARVO2023)	Phase 3	Wet age-related macular degeneration	449	SB15 2 mg	ucmrcgvgfo(bwufatueow) = wqirxuvhds mytjtheamw (pecwesvnmj )	Positive	01 Jun 2023
				Aflibercept	ucmrcgvgfo(bwufatueow) = ndhtfliuyg mytjtheamw (pecwesvnmj )
AAO2022	Phase 3	Wet age-related macular degeneration	-	SB15	nstdnhdlao(guwfajdwvw) = pzutuohidl ftrqdlcemw (lmimqwrajh )	Positive	29 Sep 2022
				Aflibercept	nstdnhdlao(guwfajdwvw) = vbobfccokx ftrqdlcemw (lmimqwrajh )

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