Meeting NewsPerspective

NOR-SWITCH: Switching to Remicade biosimilar safe, noninferior

Switching to biosimilar Remicade was safe and noninferior to continued treatment with the originator product across multiple indications, including inflammatory bowel disease, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis and chronic plaque psoriasis, according to data from the NOR-SWITCH study presented at UEG Week 2016.

CT-P13 (Celltrion), the biosimilar to Remicade (infliximab, Janssen) was the first biosimilar monoclonal antibody ever approved, according to a press release from the manufacturer. It was first approved by the European Medicines Agency in September 2013 (Remsima), and the FDA’s approval followed in April 2016 (Inflectra). It is now approved in more than 75 countries, and just last week, Pfizer announced it will become available in the U.S. in November.

Jøorgen Jahnsen, MD, PhD

Jørgen Jahnsen

“We conducted this study to assess how switching to biosimilar infliximab affects patients who are stable on the originator biologic,” Jørgen Jahnsen, MD, PhD, professor of gastroenterology at the University of Oslo, Norway, said in a press release from Celltrion. “The data shows that safety and efficacy are maintained post-switch and should give confidence to physicians looking to move their patients onto biosimilar infliximab for non-medical reasons such as cost. I am hopeful that switching will lead to financial savings that can in turn enable more patients to receive this life-changing medicine.”

The Norwegian government-sponsored phase 3 randomized, double blind, noninferiority trial involved 481 patients recruited from 40 sites who were on stable treatment with Remicade for at least 6 months. Between October 2014 and July 2016, Jahnsen and colleagues randomly assigned about half of participants to either continue Remicade therapy or switch to the biosimilar, and followed them for 52 weeks.

Worsening of disease served as the primary endpoint, and this occurred in 26.2% of those who remained on the originator and in 29.6% of those who switched to the biosimilar. This fell within the pre-specified noninferiority margin of 15%. Disease worsening was also comparable among specific diagnoses, and adverse event rates including infusion reactions, development of anti-drug antibodies and trough drug levels were also comparable.

Real- world safety and efficacy

Several real-world studies supporting the safety and efficacy of CT-P13 in patients with inflammatory bowel disease were also presented at UEG Week.

For example, a prospective Hungarian nationwide observational cohort study of 291 IBD patients (184 with Crohn’s disease, 107 with UC) found that 47% of Crohn’s patients and 53% of UC patients reached clinical remission by 54 weeks, and 58% and 64%, respectively, experienced clinical response by the same time point. They concluded that CT-P13 was safe and effective for induction and maintenance of remission in both Crohn’s and UC, but also found that prior anti-TNF exposure was associated with lower response and remission rates.

Similarly, researchers from a tertiary center in Prague performed a cohort study of 119 patients with inflammatory bowel disease (90 with Crohn’s disease, 29 with UC) who were naive to anti-TNF therapy and began treatment with CT-P13 beginning in January 2015.

By week 38, 84.1% of the Crohn’s patients and 65.2% of the UC patients were complete or partial responders, while 7.8% and 20.7% discontinued therapy, respectively. Safety and efficacy appeared comparable to that observed with originator infliximab, the researchers concluded.

Real-world cost savings

Several cost-utility studies of CT-P13 were also presented at UEG Week, which demonstrated real-world cost savings and the potential to increase patient access.

One such study compared the cost-effectiveness of the biosimilar infliximab to the originator and other anti-TNFs in patients with luminal Crohn’s disease across nine European countries, including Belgium, France, Germany, Hungary, Italy, the Netherlands, Spain, Sweden and the U.K. The Markov model developed to analyze cost-effectiveness used third-party payer perspective over 5 years.

“In all countries, biosimilar infliximab was dominant relative to originator infliximab-standard care strategy [and] the biosimilar infliximab-adalimumab-vedolizumab sequence dominated the originator infliximab-adalimumab-vedolizumab sequence,” the researchers wrote, concluding that CT-P13 is a cost-effective alternative and may increase the affordability of biologic therapies throughout Europe.

Andrew Greenspan, MD

Andrew Greenspan

Other data presented at UEG Week showed total cost savings in 2015 ranged from 1.35 million euros in Germany to 5.97 million euros in Spain, with the latter suggesting CT-P13 could provide access to an additional 1,085 patients per year, per the press release from Celltrion. There were no cost-savings in France, the press release noted.

“The NOR-SWITCH study builds on a wealth of data that support appropriate switching of patients to biosimilar infliximab, with new studies being presented all the time,” Man Hoon Kim, Celltrion Healthcare’s president and CEO, said in the press release. “We are proud that our biosimilar may enable more people with chronic inflammatory conditions to benefit from infliximab.”

According to Andrew Greenspan, MD, vice president of medical affairs at Janssen Biotech, the manufacturer of the originator Remicade, these study results "highlight the need for additional clinical research on biosimilars."

In an email statement, Greenspan told Healio Gastroenterology: "These findings are consistent with Janssen’s concern about switching patients who are stable on therapy.  The study pooled the results in patients with inflammatory arthritis, psoriasis, and inflammatory bowel disease which are very different diseases. In patients with Crohn’s disease, the largest sub-group in the study, there was a higher rate of disease worsening in patients who switched from Remicade to the biosimilar: 36.5% had disease worsening versus 21.2% who continued on Remicade. 

Despite the findings in the subgroups favoring either Remicade or the biosimilar,  overall study results showed patients who switched from Remicade to the infliximab biosimilar didn’t do any worse than those who continued on Remicade." – by Adam Leitenberger

References:

Jørgensen K, et al. Abstract LB15. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Gecse K, et al. Abstract OP145. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Bortlik M, et al. Abstract P0872. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Rencz F, et al. Abstract OP146. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Disclosures: Jahnsen reports he has served as a speaker, a consultant or an advisory board member for MSD, Tillot, Ferring, AbbVie, Celltrion, Hospira, Orion Pharma, Takeda, Napp Pharm, Meda, AstroPharma, Hikma, Janssen, Shire, Sandoz, MundiPharma and Pfizer. Greenspan is employed by Janssen Biotech.

Editor's Note: This article was updated on October 25 with relevant financial disclosures and a statement from Greenspan.

Switching to biosimilar Remicade was safe and noninferior to continued treatment with the originator product across multiple indications, including inflammatory bowel disease, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis and chronic plaque psoriasis, according to data from the NOR-SWITCH study presented at UEG Week 2016.

CT-P13 (Celltrion), the biosimilar to Remicade (infliximab, Janssen) was the first biosimilar monoclonal antibody ever approved, according to a press release from the manufacturer. It was first approved by the European Medicines Agency in September 2013 (Remsima), and the FDA’s approval followed in April 2016 (Inflectra). It is now approved in more than 75 countries, and just last week, Pfizer announced it will become available in the U.S. in November.

Jøorgen Jahnsen, MD, PhD

Jørgen Jahnsen

“We conducted this study to assess how switching to biosimilar infliximab affects patients who are stable on the originator biologic,” Jørgen Jahnsen, MD, PhD, professor of gastroenterology at the University of Oslo, Norway, said in a press release from Celltrion. “The data shows that safety and efficacy are maintained post-switch and should give confidence to physicians looking to move their patients onto biosimilar infliximab for non-medical reasons such as cost. I am hopeful that switching will lead to financial savings that can in turn enable more patients to receive this life-changing medicine.”

The Norwegian government-sponsored phase 3 randomized, double blind, noninferiority trial involved 481 patients recruited from 40 sites who were on stable treatment with Remicade for at least 6 months. Between October 2014 and July 2016, Jahnsen and colleagues randomly assigned about half of participants to either continue Remicade therapy or switch to the biosimilar, and followed them for 52 weeks.

Worsening of disease served as the primary endpoint, and this occurred in 26.2% of those who remained on the originator and in 29.6% of those who switched to the biosimilar. This fell within the pre-specified noninferiority margin of 15%. Disease worsening was also comparable among specific diagnoses, and adverse event rates including infusion reactions, development of anti-drug antibodies and trough drug levels were also comparable.

Real- world safety and efficacy

Several real-world studies supporting the safety and efficacy of CT-P13 in patients with inflammatory bowel disease were also presented at UEG Week.

For example, a prospective Hungarian nationwide observational cohort study of 291 IBD patients (184 with Crohn’s disease, 107 with UC) found that 47% of Crohn’s patients and 53% of UC patients reached clinical remission by 54 weeks, and 58% and 64%, respectively, experienced clinical response by the same time point. They concluded that CT-P13 was safe and effective for induction and maintenance of remission in both Crohn’s and UC, but also found that prior anti-TNF exposure was associated with lower response and remission rates.

Similarly, researchers from a tertiary center in Prague performed a cohort study of 119 patients with inflammatory bowel disease (90 with Crohn’s disease, 29 with UC) who were naive to anti-TNF therapy and began treatment with CT-P13 beginning in January 2015.

By week 38, 84.1% of the Crohn’s patients and 65.2% of the UC patients were complete or partial responders, while 7.8% and 20.7% discontinued therapy, respectively. Safety and efficacy appeared comparable to that observed with originator infliximab, the researchers concluded.

Real-world cost savings

Several cost-utility studies of CT-P13 were also presented at UEG Week, which demonstrated real-world cost savings and the potential to increase patient access.

One such study compared the cost-effectiveness of the biosimilar infliximab to the originator and other anti-TNFs in patients with luminal Crohn’s disease across nine European countries, including Belgium, France, Germany, Hungary, Italy, the Netherlands, Spain, Sweden and the U.K. The Markov model developed to analyze cost-effectiveness used third-party payer perspective over 5 years.

“In all countries, biosimilar infliximab was dominant relative to originator infliximab-standard care strategy [and] the biosimilar infliximab-adalimumab-vedolizumab sequence dominated the originator infliximab-adalimumab-vedolizumab sequence,” the researchers wrote, concluding that CT-P13 is a cost-effective alternative and may increase the affordability of biologic therapies throughout Europe.

Andrew Greenspan, MD

Andrew Greenspan

Other data presented at UEG Week showed total cost savings in 2015 ranged from 1.35 million euros in Germany to 5.97 million euros in Spain, with the latter suggesting CT-P13 could provide access to an additional 1,085 patients per year, per the press release from Celltrion. There were no cost-savings in France, the press release noted.

“The NOR-SWITCH study builds on a wealth of data that support appropriate switching of patients to biosimilar infliximab, with new studies being presented all the time,” Man Hoon Kim, Celltrion Healthcare’s president and CEO, said in the press release. “We are proud that our biosimilar may enable more people with chronic inflammatory conditions to benefit from infliximab.”

According to Andrew Greenspan, MD, vice president of medical affairs at Janssen Biotech, the manufacturer of the originator Remicade, these study results "highlight the need for additional clinical research on biosimilars."

In an email statement, Greenspan told Healio Gastroenterology: "These findings are consistent with Janssen’s concern about switching patients who are stable on therapy.  The study pooled the results in patients with inflammatory arthritis, psoriasis, and inflammatory bowel disease which are very different diseases. In patients with Crohn’s disease, the largest sub-group in the study, there was a higher rate of disease worsening in patients who switched from Remicade to the biosimilar: 36.5% had disease worsening versus 21.2% who continued on Remicade. 

Despite the findings in the subgroups favoring either Remicade or the biosimilar,  overall study results showed patients who switched from Remicade to the infliximab biosimilar didn’t do any worse than those who continued on Remicade." – by Adam Leitenberger

References:

Jørgensen K, et al. Abstract LB15. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Gecse K, et al. Abstract OP145. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Bortlik M, et al. Abstract P0872. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Rencz F, et al. Abstract OP146. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Disclosures: Jahnsen reports he has served as a speaker, a consultant or an advisory board member for MSD, Tillot, Ferring, AbbVie, Celltrion, Hospira, Orion Pharma, Takeda, Napp Pharm, Meda, AstroPharma, Hikma, Janssen, Shire, Sandoz, MundiPharma and Pfizer. Greenspan is employed by Janssen Biotech.

Editor's Note: This article was updated on October 25 with relevant financial disclosures and a statement from Greenspan.

    Perspective
    David T. Rubin, MD

    David T. Rubin

    It was recently announced that the biosimilar for infliximab called Inflectra will be available in the U.S. in November. Based on the existing data that have been presented in Europe and Asia, where this agent has been available for a while, it is expected that there will be payers making switches to this biosimilar agent, or requiring that the biosimilar be used first when a biologic agent is recommended. The data so far have shown that the agent is safe in that setting.

    At the same time as the ACG meeting in Las Vegas was occurring, researchers at UEG Week in Vienna presented the results of the first and largest prospective double blind randomized study of patients in multiple indications undergoing switches from Remicade to the biosimilar or continuing Remicade. This is called the NOR-SWITCH study, sponsored by the Norwegian government, and included all indications for Remicade in that country, including Crohn’s and UC.

    The study results showed that the patients who continued Remicade compared with those who were switched to the biosimilar agent of infliximab did not have any difference in worsening disease at 1 year, which was the primary outcome. There were some subtle differences in the way that they looked at Crohn’s and UC that are worth talking about at a later date, but the bottom line is biosimilars are here in the U.S.

    The biosimilar infliximab is around the corner and is going to be available, and doctors need to understand what these agents are, how they are going to be used, and be prepared to think carefully about whether they are going to be able to ask for the brand originator drug, whether they will not even have an option, and when switching to one of these agents may not be the right thing for their patients. So, it’s a very exciting time and there’s a lot for us to learn.

    • David T. Rubin, MD
    • Professor of Medicine
      University of Chicago Medicine

    Disclosures: Rubin reports serving on the CCFA Board of Directors and the advisory board for Cornerstones Health Inc., reports consulting for AbbVie Pharmaceuticals, Amgen, Emmi, Janssen, Pfizer, Prometheus Laboratories, Takeda Pharmaceuticals and UCB Pharma, reports receiving research grants from AbbVie, Given Imaging, Janssen, Pfizer, Prometheus Laboratories and UCB, and receives royalties from Slack Publications.

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