Sarilumab shown safe, effective for RA in phase III trial

PARIS – Rheumatoid arthritis patients who received the interleukin-6–blocking drug sarilumab plus methotrexate had significantly better short-term and 1-year outcomes than did patients on methotrexate alone in a phase III trial with 1,197 patients.

Sarilumab treatment also was relatively safe, with no new safety concerns arising from the study, Dr. Mark Genovese said at the annual European Congress of Rheumatology.

"Both sarilumab-dose groups showed a statistically significant improvement, compared to the placebo group, thereby demonstrating that, in this study, sarilumab plus methotrexate improved the signs and symptoms of rheumatoid arthritis [RA], improved physical function, and inhibited progression of joint damage in adult patients with active RA and inadequate response to methotrexate. Importantly, in this first phase III study with this agent, we did not see any unique safety issues," Dr. Genovese said in an interview.

The SARIL-RA-MOBILITY trial is the first study to finish from a panel of four phase III studies of sarilumab in patients with RA. The three other phase III trials currently in progress have enrolled a total of about 1,400 patients. A submission to the Food and Drug Administration for marketing approval of sarilumab for patients with RA will await completion of these three additional studies, said Dr. Genovese, professor of medicine and cochief of the division of immunology and rheumatology at Stanford (Calif.) University.

The trial enrolled patients with RA and an inadequate response to methotrexate alone at more than 200 centers in more than 30 countries, including the United States. The study randomized patients to treatment with methotrexate plus 150 mg sarilumab administered as a subcutaneous injection every 2 weeks, 200 mg injected every 2 weeks, or placebo.

The study had three primary efficacy endpoints:

• The percentage of patients achieving an American College of Rheumatology 20 response after 24 weeks of treatment, which was achieved by 58% of 400 patients who received 150 mg sarilumab, 66% of 399 patients who received the 200-mg dose, and 33% of the 398 patients who received placebo injections.

• The average change from baseline in the Health Assessment Questionnaire disability index after 16 weeks of treatment, which fell by 0.53 in patients who received the 150-mg dose of sarilumab, by 0.55 in those who received 200-mg sarilumab injections, and by 0.29 in those who received placebo.

• The average change from baseline in the van der Heijde–modified total Sharp score after 52 weeks of treatment, which increased by 0.90 among patients on the lower sarilumab dose, increased by 0.25 in patients on the higher dose, and increased by 2.78 among patients who received placebo.

For all three endpoints, the differences between each of the sarilumab groups and the placebo controls were statistically significant as well as clinically meaningful. "We are encouraged by the potential of sarilumab to offer a new alternative in the treatment armamentarium for patients suffering from RA," Dr. Genovese said. When the two companies developing sarilumab submit their approval application, they will likely initially seek indications for treating adult patients with moderately to severely active RA who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor–alpha inhibitors, he predicted.

Serious adverse events during 52 weeks of follow-up occurred in 23 placebo patients, 38 patients on the lower sarilumab dose, and 46 on the higher dose. The most common serious adverse event was infection, which occurred in 10 patients on placebo, 11 patients on low-dose sarilumab, and 17 on the higher dose. No serious infections occurred in patients whose neutrophil level fell below 1,000/mcL.

"The number of serious adverse events thus far remains low, and it will be important to see the integrated safety data across the phase III program before making any judgments regarding the ideal dose and the benefit-to-safety risk ratio of any single dose," Dr. Genovese said.

"Among patients treated with sarilumab, a dose-dependent decrease in mean neutrophil counts was observed. Serious infections were not associated with grades 3 and 4 neutropenia in this study. Increases in mean LDL cholesterol level and transaminases were observed. These safety findings were consistent with those observed in prior investigational studies with sarilumab. The choice of doses will ultimately depend on the integrated safety data across the program and the performance of each dose across a broad range of patient populations," he said.

Sarilumab is the first agent tested from the class of interleukin (IL)-6 blockers. "IL-6 is a key proinflammatory cytokine that impacts inflammation, bone, and metabolism," Dr. Genovese noted.

"Blockade of IL-6 should provide significant improvements in all these areas. This study has demonstrated that inhibition of IL-6 can reduce the signs and symptoms of RA and help to stop the destruction of joints in patients with RA. Additional phase III studies of sarilumab are underway and should provide additional evidence that anti–IL-6 receptor therapy with sarilumab may be a future option for RA patients. It is possibly too early to say if there are any special advantages or opportunities from the strategy of IL-6 blockage, compared with any other class of biologic DMARD," he said.

The trial was sponsored by Sanofi and Regeneron, the companies developing the drug. Dr. Genovese said that he has been a consultant to and received research support from Sanofi. Several coauthors are employees of Sanofi or Regeneron.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Rheumatoid arthritis patients who received the interleukin-6–blocking drug sarilumab plus methotrexate had significantly better short-term and 1-year outcomes than did patients on methotrexate alone in a phase III trial with 1,197 patients.

Sarilumab treatment also was relatively safe, with no new safety concerns arising from the study, Dr. Mark Genovese said at the annual European Congress of Rheumatology.

"Both sarilumab-dose groups showed a statistically significant improvement, compared to the placebo group, thereby demonstrating that, in this study, sarilumab plus methotrexate improved the signs and symptoms of rheumatoid arthritis [RA], improved physical function, and inhibited progression of joint damage in adult patients with active RA and inadequate response to methotrexate. Importantly, in this first phase III study with this agent, we did not see any unique safety issues," Dr. Genovese said in an interview.

The SARIL-RA-MOBILITY trial is the first study to finish from a panel of four phase III studies of sarilumab in patients with RA. The three other phase III trials currently in progress have enrolled a total of about 1,400 patients. A submission to the Food and Drug Administration for marketing approval of sarilumab for patients with RA will await completion of these three additional studies, said Dr. Genovese, professor of medicine and cochief of the division of immunology and rheumatology at Stanford (Calif.) University.

The trial enrolled patients with RA and an inadequate response to methotrexate alone at more than 200 centers in more than 30 countries, including the United States. The study randomized patients to treatment with methotrexate plus 150 mg sarilumab administered as a subcutaneous injection every 2 weeks, 200 mg injected every 2 weeks, or placebo.

The study had three primary efficacy endpoints:

• The percentage of patients achieving an American College of Rheumatology 20 response after 24 weeks of treatment, which was achieved by 58% of 400 patients who received 150 mg sarilumab, 66% of 399 patients who received the 200-mg dose, and 33% of the 398 patients who received placebo injections.

• The average change from baseline in the Health Assessment Questionnaire disability index after 16 weeks of treatment, which fell by 0.53 in patients who received the 150-mg dose of sarilumab, by 0.55 in those who received 200-mg sarilumab injections, and by 0.29 in those who received placebo.

• The average change from baseline in the van der Heijde–modified total Sharp score after 52 weeks of treatment, which increased by 0.90 among patients on the lower sarilumab dose, increased by 0.25 in patients on the higher dose, and increased by 2.78 among patients who received placebo.

For all three endpoints, the differences between each of the sarilumab groups and the placebo controls were statistically significant as well as clinically meaningful. "We are encouraged by the potential of sarilumab to offer a new alternative in the treatment armamentarium for patients suffering from RA," Dr. Genovese said. When the two companies developing sarilumab submit their approval application, they will likely initially seek indications for treating adult patients with moderately to severely active RA who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor–alpha inhibitors, he predicted.

Serious adverse events during 52 weeks of follow-up occurred in 23 placebo patients, 38 patients on the lower sarilumab dose, and 46 on the higher dose. The most common serious adverse event was infection, which occurred in 10 patients on placebo, 11 patients on low-dose sarilumab, and 17 on the higher dose. No serious infections occurred in patients whose neutrophil level fell below 1,000/mcL.

"The number of serious adverse events thus far remains low, and it will be important to see the integrated safety data across the phase III program before making any judgments regarding the ideal dose and the benefit-to-safety risk ratio of any single dose," Dr. Genovese said.

"Among patients treated with sarilumab, a dose-dependent decrease in mean neutrophil counts was observed. Serious infections were not associated with grades 3 and 4 neutropenia in this study. Increases in mean LDL cholesterol level and transaminases were observed. These safety findings were consistent with those observed in prior investigational studies with sarilumab. The choice of doses will ultimately depend on the integrated safety data across the program and the performance of each dose across a broad range of patient populations," he said.

Sarilumab is the first agent tested from the class of interleukin (IL)-6 blockers. "IL-6 is a key proinflammatory cytokine that impacts inflammation, bone, and metabolism," Dr. Genovese noted.

"Blockade of IL-6 should provide significant improvements in all these areas. This study has demonstrated that inhibition of IL-6 can reduce the signs and symptoms of RA and help to stop the destruction of joints in patients with RA. Additional phase III studies of sarilumab are underway and should provide additional evidence that anti–IL-6 receptor therapy with sarilumab may be a future option for RA patients. It is possibly too early to say if there are any special advantages or opportunities from the strategy of IL-6 blockage, compared with any other class of biologic DMARD," he said.

The trial was sponsored by Sanofi and Regeneron, the companies developing the drug. Dr. Genovese said that he has been a consultant to and received research support from Sanofi. Several coauthors are employees of Sanofi or Regeneron.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Rheumatoid arthritis patients who received the interleukin-6–blocking drug sarilumab plus methotrexate had significantly better short-term and 1-year outcomes than did patients on methotrexate alone in a phase III trial with 1,197 patients.

Sarilumab treatment also was relatively safe, with no new safety concerns arising from the study, Dr. Mark Genovese said at the annual European Congress of Rheumatology.

"Both sarilumab-dose groups showed a statistically significant improvement, compared to the placebo group, thereby demonstrating that, in this study, sarilumab plus methotrexate improved the signs and symptoms of rheumatoid arthritis [RA], improved physical function, and inhibited progression of joint damage in adult patients with active RA and inadequate response to methotrexate. Importantly, in this first phase III study with this agent, we did not see any unique safety issues," Dr. Genovese said in an interview.

The SARIL-RA-MOBILITY trial is the first study to finish from a panel of four phase III studies of sarilumab in patients with RA. The three other phase III trials currently in progress have enrolled a total of about 1,400 patients. A submission to the Food and Drug Administration for marketing approval of sarilumab for patients with RA will await completion of these three additional studies, said Dr. Genovese, professor of medicine and cochief of the division of immunology and rheumatology at Stanford (Calif.) University.

The trial enrolled patients with RA and an inadequate response to methotrexate alone at more than 200 centers in more than 30 countries, including the United States. The study randomized patients to treatment with methotrexate plus 150 mg sarilumab administered as a subcutaneous injection every 2 weeks, 200 mg injected every 2 weeks, or placebo.

The study had three primary efficacy endpoints:

• The percentage of patients achieving an American College of Rheumatology 20 response after 24 weeks of treatment, which was achieved by 58% of 400 patients who received 150 mg sarilumab, 66% of 399 patients who received the 200-mg dose, and 33% of the 398 patients who received placebo injections.

• The average change from baseline in the Health Assessment Questionnaire disability index after 16 weeks of treatment, which fell by 0.53 in patients who received the 150-mg dose of sarilumab, by 0.55 in those who received 200-mg sarilumab injections, and by 0.29 in those who received placebo.

• The average change from baseline in the van der Heijde–modified total Sharp score after 52 weeks of treatment, which increased by 0.90 among patients on the lower sarilumab dose, increased by 0.25 in patients on the higher dose, and increased by 2.78 among patients who received placebo.

For all three endpoints, the differences between each of the sarilumab groups and the placebo controls were statistically significant as well as clinically meaningful. "We are encouraged by the potential of sarilumab to offer a new alternative in the treatment armamentarium for patients suffering from RA," Dr. Genovese said. When the two companies developing sarilumab submit their approval application, they will likely initially seek indications for treating adult patients with moderately to severely active RA who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor–alpha inhibitors, he predicted.

Serious adverse events during 52 weeks of follow-up occurred in 23 placebo patients, 38 patients on the lower sarilumab dose, and 46 on the higher dose. The most common serious adverse event was infection, which occurred in 10 patients on placebo, 11 patients on low-dose sarilumab, and 17 on the higher dose. No serious infections occurred in patients whose neutrophil level fell below 1,000/mcL.

"The number of serious adverse events thus far remains low, and it will be important to see the integrated safety data across the phase III program before making any judgments regarding the ideal dose and the benefit-to-safety risk ratio of any single dose," Dr. Genovese said.

"Among patients treated with sarilumab, a dose-dependent decrease in mean neutrophil counts was observed. Serious infections were not associated with grades 3 and 4 neutropenia in this study. Increases in mean LDL cholesterol level and transaminases were observed. These safety findings were consistent with those observed in prior investigational studies with sarilumab. The choice of doses will ultimately depend on the integrated safety data across the program and the performance of each dose across a broad range of patient populations," he said.

Sarilumab is the first agent tested from the class of interleukin (IL)-6 blockers. "IL-6 is a key proinflammatory cytokine that impacts inflammation, bone, and metabolism," Dr. Genovese noted.

"Blockade of IL-6 should provide significant improvements in all these areas. This study has demonstrated that inhibition of IL-6 can reduce the signs and symptoms of RA and help to stop the destruction of joints in patients with RA. Additional phase III studies of sarilumab are underway and should provide additional evidence that anti–IL-6 receptor therapy with sarilumab may be a future option for RA patients. It is possibly too early to say if there are any special advantages or opportunities from the strategy of IL-6 blockage, compared with any other class of biologic DMARD," he said.

The trial was sponsored by Sanofi and Regeneron, the companies developing the drug. Dr. Genovese said that he has been a consultant to and received research support from Sanofi. Several coauthors are employees of Sanofi or Regeneron.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler