Etanercept biosimilar proves effective, tolerated in phase III trial

LONDON – Biosimilar etanercept (CHS-0214) is as effective and well tolerated as etanercept (Enbrel) for the treatment of rheumatoid arthritis according to the results of a randomized, double-blind, phase III trial conducted in 13 countries.

The primary endpoint of an American College of Rheumatology (ACR) 20 at 24 weeks was achieved by 91% of patients given CHS-0214 and 90.6% of those given etanercept, giving a treatment difference of just 0.4%. The percentages of patients achieving ACR 50 (67.6% and 63.7%) and ACR 70 (38.3% and 37.9%) were also comparable.

These are the first clinical data to be presented on this biosimilar, which is a fusion protein comprising the soluble human p75 tumor necrosis factor (TNF) receptor and the Fc region of human immunoglobulin G1.

“Like all biosimilars CHD-0214 has undergone extensive analytical characterization, which had demonstrated highly similar structure and function to etanercept,” study investigator James O’Dell, MD, of the University of Nebraska Medical Center, Omaha, said at the European Congress of Rheumatology. “Studies have demonstrated that CHS-0214 is similar to etanercept with regard to in vitro pharmacology, in vivo pharmacokinetics, and toxicology,” he observed.

A total of 644 patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were enrolled in the phase III trial and randomized to receive CHS-0214 or etanercept at a subcutaneous dose of 50 mg once a week for 24 weeks. After the double-blind period had ended, patients could continue on open-label CHS-0214 for another 24 weeks. Assessment of efficacy was performed on 512 patients as an issue with the production of the biosimilar resulted in a dosing interruption for 132 patients.

Remission, defined as a DAS28-CRP (Disease Activity Score 28–C-reactive protein) score of less than 2.6, was achieved in a similar percentage of subjects in the CHS-0214 and etanercept groups, at 40.6% and 42.4%, respectively.

There was a similar percentage of any adverse event (60.8% vs. 65%) occurring among patients receiving the biosimilar and those getting etanercept. Treatment-related adverse events (16.4% vs. 21.9%), and treatment-related serious adverse events (0.9% vs. 0.3%) were also comparable. Drug-drug antibodies occurred in numerically fewer patients treated with the biosimilar than with etanercept (1.3% vs. 4.7%).

Asked after his presentation about why he thought the ACR responses seen in the study were so high, Dr. O’Dell said: “We were surprised by that.” There are a number of potential explanations, he suggested. “We had a remarkable completion rate in the trial, 95%, so we lost very few patients, and we are in the process of analyzing other trials to see if that is a major factor.” In addition, patients were on relatively lower doses of methotrexate than in some other trials “because a quarter of them came from Japan,” he said. Patients were also all biologic naive and many were recruited from countries where they don’t have the opportunity to be exposed to a lot of therapies.

“The studies on all biosimilars so far suggest that they are indeed biosimilar,” Dr. O’Dell said in an interview. So how might clinicians begin to choose between the various biosimilars? “Well, there is very, very little data to compare any biologic to another biologic,” he answered.

“You haven’t seen studies comparing one TNF inhibitor to another TNF inhibitor. So it’s not surprising that we don’t have data that compare this biosimilar to that biosimilar,” he added. Such studies are probably also unlikely to ever be conducted so the choice of biosimilar, like anti-TNF therapy is probably going to be dictated by national and local guidelines, and medical insurance policies.

“Today, the biosimilars look biosimilar, so I have no problems if somebody tells me I have to start a biosimilar as opposed to the innovator product. I do have a problem if they tell me I have to switch, because that’s interchangeability and that’s a whole different story,” he noted.

Dr. O’Dell observed, however, that data from the DANBIO registry presented during the same session had shown that an enforced national switch from infliximab (Remicade) to biosimilar infliximab had shown that this did not appear to pose a problem in routine care in Denmark. Indeed 3 months’ clinical outcomes in patients with RA, psoriatic arthritis, or axial spondyloarthritis who were switched appeared to be comparable. Whether this is true across all the biosimilars needs to be established.

Coherus Biosciences funded the study. Dr. O’Dell has been a study investigator for, received research grants from, or acted as a speaker or consultant to Coherus Biosciences, Medac, Eli Lilly, Bristol-Myers Squibb, GlaxoSmithKline, Antares, and Crescendo.

LONDON – Biosimilar etanercept (CHS-0214) is as effective and well tolerated as etanercept (Enbrel) for the treatment of rheumatoid arthritis according to the results of a randomized, double-blind, phase III trial conducted in 13 countries.

The primary endpoint of an American College of Rheumatology (ACR) 20 at 24 weeks was achieved by 91% of patients given CHS-0214 and 90.6% of those given etanercept, giving a treatment difference of just 0.4%. The percentages of patients achieving ACR 50 (67.6% and 63.7%) and ACR 70 (38.3% and 37.9%) were also comparable.

These are the first clinical data to be presented on this biosimilar, which is a fusion protein comprising the soluble human p75 tumor necrosis factor (TNF) receptor and the Fc region of human immunoglobulin G1.

“Like all biosimilars CHD-0214 has undergone extensive analytical characterization, which had demonstrated highly similar structure and function to etanercept,” study investigator James O’Dell, MD, of the University of Nebraska Medical Center, Omaha, said at the European Congress of Rheumatology. “Studies have demonstrated that CHS-0214 is similar to etanercept with regard to in vitro pharmacology, in vivo pharmacokinetics, and toxicology,” he observed.

A total of 644 patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were enrolled in the phase III trial and randomized to receive CHS-0214 or etanercept at a subcutaneous dose of 50 mg once a week for 24 weeks. After the double-blind period had ended, patients could continue on open-label CHS-0214 for another 24 weeks. Assessment of efficacy was performed on 512 patients as an issue with the production of the biosimilar resulted in a dosing interruption for 132 patients.

Remission, defined as a DAS28-CRP (Disease Activity Score 28–C-reactive protein) score of less than 2.6, was achieved in a similar percentage of subjects in the CHS-0214 and etanercept groups, at 40.6% and 42.4%, respectively.

There was a similar percentage of any adverse event (60.8% vs. 65%) occurring among patients receiving the biosimilar and those getting etanercept. Treatment-related adverse events (16.4% vs. 21.9%), and treatment-related serious adverse events (0.9% vs. 0.3%) were also comparable. Drug-drug antibodies occurred in numerically fewer patients treated with the biosimilar than with etanercept (1.3% vs. 4.7%).

Asked after his presentation about why he thought the ACR responses seen in the study were so high, Dr. O’Dell said: “We were surprised by that.” There are a number of potential explanations, he suggested. “We had a remarkable completion rate in the trial, 95%, so we lost very few patients, and we are in the process of analyzing other trials to see if that is a major factor.” In addition, patients were on relatively lower doses of methotrexate than in some other trials “because a quarter of them came from Japan,” he said. Patients were also all biologic naive and many were recruited from countries where they don’t have the opportunity to be exposed to a lot of therapies.

“The studies on all biosimilars so far suggest that they are indeed biosimilar,” Dr. O’Dell said in an interview. So how might clinicians begin to choose between the various biosimilars? “Well, there is very, very little data to compare any biologic to another biologic,” he answered.

“You haven’t seen studies comparing one TNF inhibitor to another TNF inhibitor. So it’s not surprising that we don’t have data that compare this biosimilar to that biosimilar,” he added. Such studies are probably also unlikely to ever be conducted so the choice of biosimilar, like anti-TNF therapy is probably going to be dictated by national and local guidelines, and medical insurance policies.

“Today, the biosimilars look biosimilar, so I have no problems if somebody tells me I have to start a biosimilar as opposed to the innovator product. I do have a problem if they tell me I have to switch, because that’s interchangeability and that’s a whole different story,” he noted.

Dr. O’Dell observed, however, that data from the DANBIO registry presented during the same session had shown that an enforced national switch from infliximab (Remicade) to biosimilar infliximab had shown that this did not appear to pose a problem in routine care in Denmark. Indeed 3 months’ clinical outcomes in patients with RA, psoriatic arthritis, or axial spondyloarthritis who were switched appeared to be comparable. Whether this is true across all the biosimilars needs to be established.

Coherus Biosciences funded the study. Dr. O’Dell has been a study investigator for, received research grants from, or acted as a speaker or consultant to Coherus Biosciences, Medac, Eli Lilly, Bristol-Myers Squibb, GlaxoSmithKline, Antares, and Crescendo.

LONDON – Biosimilar etanercept (CHS-0214) is as effective and well tolerated as etanercept (Enbrel) for the treatment of rheumatoid arthritis according to the results of a randomized, double-blind, phase III trial conducted in 13 countries.

The primary endpoint of an American College of Rheumatology (ACR) 20 at 24 weeks was achieved by 91% of patients given CHS-0214 and 90.6% of those given etanercept, giving a treatment difference of just 0.4%. The percentages of patients achieving ACR 50 (67.6% and 63.7%) and ACR 70 (38.3% and 37.9%) were also comparable.

These are the first clinical data to be presented on this biosimilar, which is a fusion protein comprising the soluble human p75 tumor necrosis factor (TNF) receptor and the Fc region of human immunoglobulin G1.

“Like all biosimilars CHD-0214 has undergone extensive analytical characterization, which had demonstrated highly similar structure and function to etanercept,” study investigator James O’Dell, MD, of the University of Nebraska Medical Center, Omaha, said at the European Congress of Rheumatology. “Studies have demonstrated that CHS-0214 is similar to etanercept with regard to in vitro pharmacology, in vivo pharmacokinetics, and toxicology,” he observed.

A total of 644 patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were enrolled in the phase III trial and randomized to receive CHS-0214 or etanercept at a subcutaneous dose of 50 mg once a week for 24 weeks. After the double-blind period had ended, patients could continue on open-label CHS-0214 for another 24 weeks. Assessment of efficacy was performed on 512 patients as an issue with the production of the biosimilar resulted in a dosing interruption for 132 patients.

Remission, defined as a DAS28-CRP (Disease Activity Score 28–C-reactive protein) score of less than 2.6, was achieved in a similar percentage of subjects in the CHS-0214 and etanercept groups, at 40.6% and 42.4%, respectively.

There was a similar percentage of any adverse event (60.8% vs. 65%) occurring among patients receiving the biosimilar and those getting etanercept. Treatment-related adverse events (16.4% vs. 21.9%), and treatment-related serious adverse events (0.9% vs. 0.3%) were also comparable. Drug-drug antibodies occurred in numerically fewer patients treated with the biosimilar than with etanercept (1.3% vs. 4.7%).

Asked after his presentation about why he thought the ACR responses seen in the study were so high, Dr. O’Dell said: “We were surprised by that.” There are a number of potential explanations, he suggested. “We had a remarkable completion rate in the trial, 95%, so we lost very few patients, and we are in the process of analyzing other trials to see if that is a major factor.” In addition, patients were on relatively lower doses of methotrexate than in some other trials “because a quarter of them came from Japan,” he said. Patients were also all biologic naive and many were recruited from countries where they don’t have the opportunity to be exposed to a lot of therapies.

“The studies on all biosimilars so far suggest that they are indeed biosimilar,” Dr. O’Dell said in an interview. So how might clinicians begin to choose between the various biosimilars? “Well, there is very, very little data to compare any biologic to another biologic,” he answered.

“You haven’t seen studies comparing one TNF inhibitor to another TNF inhibitor. So it’s not surprising that we don’t have data that compare this biosimilar to that biosimilar,” he added. Such studies are probably also unlikely to ever be conducted so the choice of biosimilar, like anti-TNF therapy is probably going to be dictated by national and local guidelines, and medical insurance policies.

“Today, the biosimilars look biosimilar, so I have no problems if somebody tells me I have to start a biosimilar as opposed to the innovator product. I do have a problem if they tell me I have to switch, because that’s interchangeability and that’s a whole different story,” he noted.

Dr. O’Dell observed, however, that data from the DANBIO registry presented during the same session had shown that an enforced national switch from infliximab (Remicade) to biosimilar infliximab had shown that this did not appear to pose a problem in routine care in Denmark. Indeed 3 months’ clinical outcomes in patients with RA, psoriatic arthritis, or axial spondyloarthritis who were switched appeared to be comparable. Whether this is true across all the biosimilars needs to be established.

Coherus Biosciences funded the study. Dr. O’Dell has been a study investigator for, received research grants from, or acted as a speaker or consultant to Coherus Biosciences, Medac, Eli Lilly, Bristol-Myers Squibb, GlaxoSmithKline, Antares, and Crescendo.