Cadmore media player playing video VOLTAIRE-RA and VOLTAIRE-RA extension: Clinical equivalence studies of BI 695501 (Cyltezo®; adalimumab-adbm) and adalimumab reference product in rheumatoid arthritis
Video Player
Accessibility
Using forms mode, you can utilize keyboard shortcuts to make usability more efficient.
Space bar will play and pause the video. Pressing escape will close all displays and pressing it again will jump to the end of the player.
You can press A to open the Keyboard Shortcut Dialog which also provides an audio description of the player and all of its features.
Language
1x
Play Speed
Adjust Volume
Transcript
Search
Result Count
of
Click to jump to result
Search
Re-center
Segments
Result Count
of
Click to jump to result
Search
Name:
VOLTAIRE-RA and VOLTAIRE-RA extension: Clinical equivalence studies of BI 695501 (Cyltezo®; adalimumab-adbm) and adalimumab reference product in rheumatoid arthritis
Description:
VOLTAIRE-RA and VOLTAIRE-RA extension: Clinical equivalence studies of BI 695501 (Cyltezo®; adalimumab-adbm) and adalimumab reference product in rheumatoid arthritis
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/6ef81826-a930-4327-8129-7c702ed31d0f/videoscrubberimages/Scrubber_5.jpg
Duration:
T00H11M24S
Embed URL:
https://stream.cadmore.media/player/6ef81826-a930-4327-8129-7c702ed31d0f
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/6ef81826-a930-4327-8129-7c702ed31d0f/BI Biosimilars Animation_V3 (1).mp4?sv=2019-02-02&sr=c&sig=UkzH9uL%2BWBlvhiKhNRzVqjlUEqCZG9K5vnFi0dOlJ3c%3D&st=2024-11-23T04%3A04%3A21Z&se=2024-11-23T06%3A09%3A21Z&sp=r
Upload Date:
2023-09-12T00:00:00.0000000
Transcript:
Language: EN.
Segment:1 Introduction.
[MUSIC PLAYING]
DR. STANLEY COHEN: Hello, I'm Dr. Stanley Cohen from the Department of Internal Medicine at the University of Texas Southwestern Medical School and I'm medical director of Metroplex Clinical Research Center in Dallas, Texas. On behalf of the authors in this video, I'm going to discuss two papers that report the 48-week VOLTAIRE-RA study and the 48-week VOLTAIRE-RA open-label extension study, published in the Annals of Rheumatic Diseases and Expert Opinion On Biological Therapy. These studies compared head to head the biosimilar of adalimumab, BI 695501, with the reference product in a clinical population with rheumatoid arthritis.
Segment:2 What is a biosimilar?.
DR. STANLEY COHEN: Before discussing the two studies, we will briefly consider what a biosimilar is and the rigorous development process that led to these clinical trials. The FDA defines a biosimilar as a biological product that is highly similar to and has no clinically meaningful differences in safety and effectiveness to an existing FDA-approved reference product.
DR. STANLEY COHEN: A high degree of similarity includes molecular structure, purity and potency, which translate into similar safety and effectiveness for the patients. Biosimilars have the same mechanism of action and route of administration as their reference product. The main reason to develop and use biosimilars is to increase competition which should reduce the cost of biologic therapies and help to improve access to these therapies for patients.
Segment:3 BI 695501: Cyltezo® (adalimumab-adbm).
DR. STANLEY COHEN: Adalimumab is a biologic treatment for several immune-mediating inflammatory diseases, including rheumatoid arthritis. BI 695501 is adalimumab-biosimilar that was FDA approved in 2017 as biosimilar to its reference product. The bioequivalence of BI 695501 to the reference product was demonstrated in healthy volunteers and the VOLTAIRE-PK study. An additional study the, VOLTAIRE-X, enabled BI 695501 to be the first biosimilar of a TNF alpha inhibitor to achieve interchangeable designation to its reference product in the United States. These studies are part of the stepwise approach to biosimilar development.
Segment:4 Biosimilar development.
DR. STANLEY COHEN: Before a biosimilar can be evaluated in clinical trials, it undergoes rigorous testing that is set out by the FDA. A manufacturer must establish that the minor differences between the biosimilar and the reference product have no impact on the function of the molecule and do not result in clinically-meaningful differences. When evaluating a biosimilar, the FDA considers the totality of evidence and in order to obtain FDA approval as an adalimumab biosimilar, BI 695501 had to follow this regulatory process.
DR. STANLEY COHEN: A large amount of pre-clinical research is done to demonstrate a highly similar structure between the biosimilar and the reference product. As part of the approval process, at least one clinical trial must be completed with the biosimilar for one or more of the indications for which the product is licensed. This trial must demonstrate biosimilarity, including pharmacokinetics, pharmacodynamics, and immunogenicity.
Segment:5 What were the objectives?.
DR. STANLEY COHEN: As previously discussed, the VOLTAIRE-PK study and the VOLTAIRE-X study were part of the stepwise development process for BI 695501. In the rest of the video, we will be discussing the results of the VOLTAIRE-RA and the VOLTAIRE-RA extension studies which are pivotal phase III trials that were required for the biosimilar approval process set out by the FDA.
DR. STANLEY COHEN: The aim of the VOLTAIRE-RA study was to demonstrate clinical equivalence of the biosimilar adalimumab with the reference product by comparing efficacy, safety, and immunogenicity. The extension study evaluated the long-term safety, efficacy, pharmacokinetics, and immunogenicity of the biosimilar adalimumab in patients who had completed the VOLTAIRE-RA study.
Segment:6 VOLTAIRE-RA: Study design.
DR. STANLEY COHEN: The VOLTAIRE-RA study was a multinational, multicenter, randomized, parallel arm, double blind study. Participants had moderate to severe active rheumatoid arthritis and were on stable treatment with methotrexate. Participants were excluded if they had had previous treatment for rheumatoid arthritis with adalimumab or more than one other biologic. Other exclusion criteria included active infection, hypersensitivity reactions, or adverse events in relation to the use of agents similar to the study drugs.
DR. STANLEY COHEN: Patients were randomized to receive either the biosimilar or the reference product, both at a dose of 40 milligram. Treatment was administered subcutaneously via prefilled syringe every other week by blinded trial personnel, either on-site or at the patient's home. At week 24, patients on the reference product were re-randomized to either continue on the same treatment or switch to the biosimilar until week 41. Patients on the biosimilar were dummy re-randomized, and all continued on the same treatment.
Segment:7 VOLTAIRE-RA: Endpoints.
DR. STANLEY COHEN: The main endpoints in the VOLTAIRE-RA and extension study evaluated efficacy and safety. The first composite efficacy measure was the ACR20. The second measure of efficacy was the 28 joint Disease Activity Score, or DAS28, at week 12 and 24 versus baseline. As part of the scores, we have used the ESR as an inflammatory marker. For the safety evaluation, all patients were assessed by the investigators for the development of treatment-emergent adverse events.
DR. STANLEY COHEN: The co-primary endpoints were the proportion of patients achieving ACR20 in weeks 12 and 24. Equivalence between the two agents was demonstrated at the confidence intervals for the differences in ACR20 response rates were within the predefined margins. The changes from baseline in DAS28 ESR at weeks 12 and 24 was also evaluated as secondary endpoints and was assessed using an analysis of covariance model.
Segment:8 VOLTAIRE-RA: Patient disposition.
DR. STANLEY COHEN: Following a screening of 940 patients, a total of 645 participants entered the VOLTAIRE-RA study. The patients were randomized to receive biosimilar adalimumab or the reference product. At week 24, 593 patients were re-randomized to continue on the biosimilar, or to continue with the reference product, or to switch to the biosimilar. 13.3% of the randomized patients left the trial early before 48 weeks. There were no differences in rates of treatment or trial discontinuations between the treatment groups.
Segment:9 VOLTAIRE-RA extension: Study Design.
DR. STANLEY COHEN: VOLTAIRE-RA extension was a 48-week, open-label, multicenter extension study that included patients with moderate to severely active rheumatoid arthritis, who completed the VOLTAIRE-RA study, who wished to continue treatment with the biosimilar adalimumab. Patients were included following assessment by the investigator. Participants were excluded from the extension study if they had experienced any drug-related serious adverse events, other acquired disorders, infections, or hypersensitivity events during the VOLTAIRE-RA study. Patients were also excluded if they had sniffing and/or uncontrolled disease other than rheumatoid arthritis or were taking any other treatment.
Segment:10 VOLTAIRE-RA extension: Endpoints.
DR. STANLEY COHEN: With the extension study, the primary endpoint was the proportion of patients with drug-related adverse events as assessed by the investigator. The second area of the endpoints evaluated efficacy in the same way as the original study. The extension study also evaluated ACR and EULAR remission rates and the ACR 20/50/70 response at week 48.
Segment:11 VOLTAIRE-RA extension: Patient disposition.
DR. STANLEY COHEN: Following screening of 479 patients that completed the VOLTAIRE-RA study, 430 continue the extension study. Overall, 90.2% of patients completed the trial and 93.7% completed the safety follow-up.
Segment:12 Results: Baseline demographics and clinical characteristics.
DR. STANLEY COHEN: Baseline characteristics were similar among the treatment groups in both studies.
Segment:13 Results: Efficacy.
DR. STANLEY COHEN: The VOLTAIRE-RA study showed similar efficacy for biosimilar adalimumab and the reference product after 48 weeks. These results were confirmed by sensitivity analysis, secondary endpoints, and exploratory inputs. Patients who responded in the initial study continued to respond in the extension study, indicating that the initial efficacy is maintained over time.
Segment:14 Results: Safety.
DR. STANLEY COHEN: In the VOLTAIRE-RA study, for safety, there were no major differences in safety between the biosimilar or the reference product. In the extension study, a similar proportion of patients with investigator-assessed, drug-related treatment, emergent-adverse events were reported across the three treatment groups. Importantly, the type and frequency of adverse events observed were consistent with the known safety profiles of biosimilar adalimumab in the reference product. One death was reported, although this was not deemed to be related to the study group. The majority of the adverse events reported were non-serious and of mild or moderate intensity. Serious adverse events were reported infrequently, 6% in the extension study. This was similar to the rate reported for VOLTAIRE-RA, with a rate of 7%.
Segment:15 Results: Immunogenicity.
DR. STANLEY COHEN: Another important aspect of evaluating a biosimilar agent is to look at immunogenicity. In view of this, a highly sensitive and drug-tolerant, anti-drug antibody assay was developed. Our findings show similar immunogenicity between the biosimilar and the reference product in both studies. Furthermore, blinded switching from the reference product to the biosimilar did not lead to increased immunogenicity or more hypersensitivity reactions, compared with patients who continue on the reference plan.
Segment:16 Results: Pharmokinetics.
DR. STANLEY COHEN: In the pharmacokinetic assessment, plasma concentrations of both drugs were shown to have reached steady state by the end of the VOLTAIRE-RA study. The extension study showed that plasma concentrations of both agents were maintained until week 98. As expected, these levels declined after the last administration of week 108, which was 10 weeks after the last administration of biosimilar adalimumab. Mean drug plasma concentrations were comparable across VOLTAIRE-RA and the extension study, indicating that switching treatment does not affect drug plasma concentration.
Segment:17 Conclusions.
DR. STANLEY COHEN: The VOLTAIRE-RA and extension studies demonstrated the clinical equivalence of the biosimilar adalimumab and the reference product in participants with moderate to severely active rheumatoid arthritis. During this treatment period, the efficacy of treatment was maintained. Importantly, safety and tolerability profiles were similar between groups, and no new side effects were identified with biosimilar adalimumab.
DR. STANLEY COHEN: [MUSIC PLAYING]
Segment:18 Disclosures & Outro.
DR. STANLEY COHEN:
Segment:1 Introduction.
[MUSIC PLAYING]
DR. STANLEY COHEN: Hello, I'm Dr. Stanley Cohen from the Department of Internal Medicine at the University of Texas Southwestern Medical School and I'm medical director of Metroplex Clinical Research Center in Dallas, Texas. On behalf of the authors in this video, I'm going to discuss two papers that report the 48-week VOLTAIRE-RA study and the 48-week VOLTAIRE-RA open-label extension study, published in the Annals of Rheumatic Diseases and Expert Opinion On Biological Therapy. These studies compared head to head the biosimilar of adalimumab, BI 695501, with the reference product in a clinical population with rheumatoid arthritis.
Segment:2 What is a biosimilar?.
DR. STANLEY COHEN: Before discussing the two studies, we will briefly consider what a biosimilar is and the rigorous development process that led to these clinical trials. The FDA defines a biosimilar as a biological product that is highly similar to and has no clinically meaningful differences in safety and effectiveness to an existing FDA-approved reference product.
DR. STANLEY COHEN: A high degree of similarity includes molecular structure, purity and potency, which translate into similar safety and effectiveness for the patients. Biosimilars have the same mechanism of action and route of administration as their reference product. The main reason to develop and use biosimilars is to increase competition which should reduce the cost of biologic therapies and help to improve access to these therapies for patients.
Segment:3 BI 695501: Cyltezo® (adalimumab-adbm).
DR. STANLEY COHEN: Adalimumab is a biologic treatment for several immune-mediating inflammatory diseases, including rheumatoid arthritis. BI 695501 is adalimumab-biosimilar that was FDA approved in 2017 as biosimilar to its reference product. The bioequivalence of BI 695501 to the reference product was demonstrated in healthy volunteers and the VOLTAIRE-PK study. An additional study the, VOLTAIRE-X, enabled BI 695501 to be the first biosimilar of a TNF alpha inhibitor to achieve interchangeable designation to its reference product in the United States. These studies are part of the stepwise approach to biosimilar development.
Segment:4 Biosimilar development.
DR. STANLEY COHEN: Before a biosimilar can be evaluated in clinical trials, it undergoes rigorous testing that is set out by the FDA. A manufacturer must establish that the minor differences between the biosimilar and the reference product have no impact on the function of the molecule and do not result in clinically-meaningful differences. When evaluating a biosimilar, the FDA considers the totality of evidence and in order to obtain FDA approval as an adalimumab biosimilar, BI 695501 had to follow this regulatory process.
DR. STANLEY COHEN: A large amount of pre-clinical research is done to demonstrate a highly similar structure between the biosimilar and the reference product. As part of the approval process, at least one clinical trial must be completed with the biosimilar for one or more of the indications for which the product is licensed. This trial must demonstrate biosimilarity, including pharmacokinetics, pharmacodynamics, and immunogenicity.
Segment:5 What were the objectives?.
DR. STANLEY COHEN: As previously discussed, the VOLTAIRE-PK study and the VOLTAIRE-X study were part of the stepwise development process for BI 695501. In the rest of the video, we will be discussing the results of the VOLTAIRE-RA and the VOLTAIRE-RA extension studies which are pivotal phase III trials that were required for the biosimilar approval process set out by the FDA.
DR. STANLEY COHEN: The aim of the VOLTAIRE-RA study was to demonstrate clinical equivalence of the biosimilar adalimumab with the reference product by comparing efficacy, safety, and immunogenicity. The extension study evaluated the long-term safety, efficacy, pharmacokinetics, and immunogenicity of the biosimilar adalimumab in patients who had completed the VOLTAIRE-RA study.
Segment:6 VOLTAIRE-RA: Study design.
DR. STANLEY COHEN: The VOLTAIRE-RA study was a multinational, multicenter, randomized, parallel arm, double blind study. Participants had moderate to severe active rheumatoid arthritis and were on stable treatment with methotrexate. Participants were excluded if they had had previous treatment for rheumatoid arthritis with adalimumab or more than one other biologic. Other exclusion criteria included active infection, hypersensitivity reactions, or adverse events in relation to the use of agents similar to the study drugs.
DR. STANLEY COHEN: Patients were randomized to receive either the biosimilar or the reference product, both at a dose of 40 milligram. Treatment was administered subcutaneously via prefilled syringe every other week by blinded trial personnel, either on-site or at the patient's home. At week 24, patients on the reference product were re-randomized to either continue on the same treatment or switch to the biosimilar until week 41. Patients on the biosimilar were dummy re-randomized, and all continued on the same treatment.
Segment:7 VOLTAIRE-RA: Endpoints.
DR. STANLEY COHEN: The main endpoints in the VOLTAIRE-RA and extension study evaluated efficacy and safety. The first composite efficacy measure was the ACR20. The second measure of efficacy was the 28 joint Disease Activity Score, or DAS28, at week 12 and 24 versus baseline. As part of the scores, we have used the ESR as an inflammatory marker. For the safety evaluation, all patients were assessed by the investigators for the development of treatment-emergent adverse events.
DR. STANLEY COHEN: The co-primary endpoints were the proportion of patients achieving ACR20 in weeks 12 and 24. Equivalence between the two agents was demonstrated at the confidence intervals for the differences in ACR20 response rates were within the predefined margins. The changes from baseline in DAS28 ESR at weeks 12 and 24 was also evaluated as secondary endpoints and was assessed using an analysis of covariance model.
Segment:8 VOLTAIRE-RA: Patient disposition.
DR. STANLEY COHEN: Following a screening of 940 patients, a total of 645 participants entered the VOLTAIRE-RA study. The patients were randomized to receive biosimilar adalimumab or the reference product. At week 24, 593 patients were re-randomized to continue on the biosimilar, or to continue with the reference product, or to switch to the biosimilar. 13.3% of the randomized patients left the trial early before 48 weeks. There were no differences in rates of treatment or trial discontinuations between the treatment groups.
Segment:9 VOLTAIRE-RA extension: Study Design.
DR. STANLEY COHEN: VOLTAIRE-RA extension was a 48-week, open-label, multicenter extension study that included patients with moderate to severely active rheumatoid arthritis, who completed the VOLTAIRE-RA study, who wished to continue treatment with the biosimilar adalimumab. Patients were included following assessment by the investigator. Participants were excluded from the extension study if they had experienced any drug-related serious adverse events, other acquired disorders, infections, or hypersensitivity events during the VOLTAIRE-RA study. Patients were also excluded if they had sniffing and/or uncontrolled disease other than rheumatoid arthritis or were taking any other treatment.
Segment:10 VOLTAIRE-RA extension: Endpoints.
DR. STANLEY COHEN: With the extension study, the primary endpoint was the proportion of patients with drug-related adverse events as assessed by the investigator. The second area of the endpoints evaluated efficacy in the same way as the original study. The extension study also evaluated ACR and EULAR remission rates and the ACR 20/50/70 response at week 48.
Segment:11 VOLTAIRE-RA extension: Patient disposition.
DR. STANLEY COHEN: Following screening of 479 patients that completed the VOLTAIRE-RA study, 430 continue the extension study. Overall, 90.2% of patients completed the trial and 93.7% completed the safety follow-up.
Segment:12 Results: Baseline demographics and clinical characteristics.
DR. STANLEY COHEN: Baseline characteristics were similar among the treatment groups in both studies.
Segment:13 Results: Efficacy.
DR. STANLEY COHEN: The VOLTAIRE-RA study showed similar efficacy for biosimilar adalimumab and the reference product after 48 weeks. These results were confirmed by sensitivity analysis, secondary endpoints, and exploratory inputs. Patients who responded in the initial study continued to respond in the extension study, indicating that the initial efficacy is maintained over time.
Segment:14 Results: Safety.
DR. STANLEY COHEN: In the VOLTAIRE-RA study, for safety, there were no major differences in safety between the biosimilar or the reference product. In the extension study, a similar proportion of patients with investigator-assessed, drug-related treatment, emergent-adverse events were reported across the three treatment groups. Importantly, the type and frequency of adverse events observed were consistent with the known safety profiles of biosimilar adalimumab in the reference product. One death was reported, although this was not deemed to be related to the study group. The majority of the adverse events reported were non-serious and of mild or moderate intensity. Serious adverse events were reported infrequently, 6% in the extension study. This was similar to the rate reported for VOLTAIRE-RA, with a rate of 7%.
Segment:15 Results: Immunogenicity.
DR. STANLEY COHEN: Another important aspect of evaluating a biosimilar agent is to look at immunogenicity. In view of this, a highly sensitive and drug-tolerant, anti-drug antibody assay was developed. Our findings show similar immunogenicity between the biosimilar and the reference product in both studies. Furthermore, blinded switching from the reference product to the biosimilar did not lead to increased immunogenicity or more hypersensitivity reactions, compared with patients who continue on the reference plan.
Segment:16 Results: Pharmokinetics.
DR. STANLEY COHEN: In the pharmacokinetic assessment, plasma concentrations of both drugs were shown to have reached steady state by the end of the VOLTAIRE-RA study. The extension study showed that plasma concentrations of both agents were maintained until week 98. As expected, these levels declined after the last administration of week 108, which was 10 weeks after the last administration of biosimilar adalimumab. Mean drug plasma concentrations were comparable across VOLTAIRE-RA and the extension study, indicating that switching treatment does not affect drug plasma concentration.
Segment:17 Conclusions.
DR. STANLEY COHEN: The VOLTAIRE-RA and extension studies demonstrated the clinical equivalence of the biosimilar adalimumab and the reference product in participants with moderate to severely active rheumatoid arthritis. During this treatment period, the efficacy of treatment was maintained. Importantly, safety and tolerability profiles were similar between groups, and no new side effects were identified with biosimilar adalimumab.
DR. STANLEY COHEN: [MUSIC PLAYING]
Segment:18 Disclosures & Outro.
DR. STANLEY COHEN:
Form Title Download
Transcript
Form Title Bookmark
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Form Title Share
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Form Title Accessibility and Keyboard Shortcuts
The cadmore media player is a professional video and audio player experience designed to deliver media as well as relevant transcript, segmentation, and metadata. On the screen is a traditional html video player with buttons such as play, pause, forward, captioning, language and play speed selection and more. Adjacent to the video player are generally tabs, one of which shows a scrolling transcript of the video and the other shows any segmentation of the media, sometimes referred to as chapters. At the top of the video is a menu bar containing an Explore button and Tools button. The Explore button allows you to dig deeper into the video by opening up an explore dialog which contains tabs for a visual navigation of the video using thumbnails, an about tab which contains rich metadata about the media, a segments tab which contains further information about the video, and a related tab which contains links to other media related to this media. The tools button opens a menu with options for sharing the media on social media, creating bookmarking links, creating embed codes for your website, generating citations, and more.
Keyboard Shortcuts
Keyboard shortcuts only work while you are in forms mode. By entering forms mode, you will be able to quickly access portions of the media player with single key commands.
Spacebar: Play/Pause Toggle
I: Info Menu,
O: Tools Menu
T: Transcript Tab,
S: Segments Tab
F: Forward 15,
R: Rewind 15
L: Languages,
P: Playspeed
M: Mute Toggle,
V: Volume Bar
N: Video Only Toggle,
B: Full Screen Toggle
C: Captions Toggle
Escape: Closes dialogs and menus / Exits Player
Z: Next Transcript Chapter
X: Previous Transcript Chapter
Q: Next Transcript Paragraph
W: Previous Transcript Paragraph
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Embed Size
-
You Size - Responsive
-
We Size - Responsive
-
Picture Overlay Popup
-
400 x 225
-
512 x 288
-
400 x 700
-
768 x 1024
-
1024 x 512
-
1280 x 608
Form Title Cite
No citation provided.
Info
Segments
Related
Thumbnails
Exit Clip Mode
You have requested to see a portion of the video outside of the clip.
Click OK to switch to the full video or click if you would like to stay inside the clip. You can always go back to the clip with Tools and Clip Mode