Sarilumab, Given Subcutaneously Every Other Week, Met All Three Co-Primary Endpoints
Sarilumab is the First Fully-Human Monoclonal Antibody Directed Against the Interleukin-6 Receptor (IL-6R)
PARIS, France and TARRYTOWN, NY, USA I November 22, 2013 I Sanofi (EURONEXT: SAN and NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that in the SARIL-RA-MOBILITY Phase 3 clinical trial in adult patients with active rheumatoid arthritis (RA) who were inadequate responders to methotrexate (MTX) therapy, sarilumab (the first fully-human anti-IL-6R monoclonal antibody) treatment in combination with MTX improved disease signs and symptoms as well as physical function, and inhibited progression of joint damage.
“IL-6 blockade is emerging as an important therapeutic approach for rheumatoid arthritis,” said Neil Graham, M.B.B.S., M.D., M.P.H., Vice President, Program Direction, Immunology and Inflammation, Regeneron Pharmaceuticals. “We are encouraged with these Phase 3 results, which demonstrated efficacy at both doses of sarilumab, each administered every other week.”
The 52 week SARIL-RA-MOBILITY Phase 3 trial enrolled approximately 1,200 patients with active, moderate-to-severe rheumatoid arthritis, and who were inadequate responders to MTX therapy. Patients were randomized to one of three subcutaneous treatment groups, all in combination with MTX and dosed every other week: sarilumab 200 milligrams (mg), sarilumab 150 mg, or placebo.
Both sarilumab groups showed clinically relevant and statistically significant improvements compared to the placebo group in all three co-primary endpoints (p<0.0001).
(1) Improvement in signs and symptoms of RA at 24 weeks, as measured by the American College of Rheumatology score of 20 percent improvement (ACR20).
- 66 percent, 58 percent, and 33 percent in the sarilumab 200 mg, sarilumab 150 mg, and placebo groups respectively, all in combination with MTX.
(2) Improvement in physical function, as measured by change from baseline in the Health Assessment Question-Disability (HAQ-DI) at week 16.
(3) Inhibition of progression of structural damage at Week 52, as measured by the change in the modified Van der Heijde total Sharp score (mTSS).
- 0.25, 0.90, and 2.78 in the sarilumab 200 mg, sarilumab 150 mg, and placebo groups respectively, all in combination with MTX.
- The group receiving the 200 mg dose of sarilumab + MTX had a reduction of approximately 90 percent in the radiographic progression assessed by the mTSS compared to the radiographic progression with placebo + MTX at week 52.
ACR Results at week 24
|
Treatment Group
|
ACR20^
(%)
|
ACR50
(%)
|
ACR70
(%)
|
|
200 mg sarilumab + MTX
|
66*
|
46*
|
25*
|
|
150 mg sarilumab + MTX
|
58*
|
37*
|
20*
|
|
Placebo + MTX
|
33
|
17
|
7
|
^Primary Endpoint
*p<0.0001 compared to placebo group
In the SARIL-RA-MOBILITY trial, there was a higher incidence of treatment emergent adverse events leading to withdrawal in the sarilumab treatment groups compared to placebo (13.9 percent in 200 mg, 12.5 percent in 150 mg and 4.7 percent in placebo).
Infections were the most frequently reported adverse events and were reported with a higher incidence in the sarilumab groups compared to placebo, all in combination with MTX (39.6 percent for 200 mg, 40.1 percent for the 150 mg group and 31.1 percent for placebo). The incidence of serious infections was 4.0 percent in the 200 mg + MTX group, 2.6 percent in the 150 mg + MTX group, and 2.3 percent in the placebo + MTX group. 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, and transaminases were observed. These safety findings were consistent with those observed in prior investigational studies with sarilumab.
“Irreversible joint damage can be a consequence for patients suffering from rheumatoid arthritis, and this is accompanied by reduced physical function in these patients,” said Tanya M. Momtahen, M.S., Sarilumab Global Project Head, Sanofi. “This remains a major concern for rheumatoid arthritis patients. We are encouraged by these Phase 3 results and the impact sarilumab demonstrated on inhibition of progression of structural damage assessed radiographically in this study.”
Additional analyses of efficacy and safety data from the SARIL-RA-MOBILITY study will be presented at a future medical conference.
About Sarilumab
Sarilumab (REGN88/SAR153191) is the first fully-human monoclonal antibody directed against the IL-6 receptor (IL-6R). Sarilumab is a subcutaneously delivered inhibitor of IL-6 signaling, which binds with high affinity to the IL-6 receptor. It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling. Sarilumab was developed using Regeneron’s VelocImmune® antibody technology.
The investigational agent described above is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.
About Sanofi
Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (SAN) and in New York (SNY).
About Regeneron Pharmaceuticals
Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including hypercholesterolemia, oncology, rheumatoid arthritis, asthma, and atopic dermatitis. For additional information about the company, please visit www.regeneron.com.
SOURCE: Sanofi
Post Views: 121
Sarilumab, Given Subcutaneously Every Other Week, Met All Three Co-Primary Endpoints
Sarilumab is the First Fully-Human Monoclonal Antibody Directed Against the Interleukin-6 Receptor (IL-6R)
PARIS, France and TARRYTOWN, NY, USA I November 22, 2013 I Sanofi (EURONEXT: SAN and NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that in the SARIL-RA-MOBILITY Phase 3 clinical trial in adult patients with active rheumatoid arthritis (RA) who were inadequate responders to methotrexate (MTX) therapy, sarilumab (the first fully-human anti-IL-6R monoclonal antibody) treatment in combination with MTX improved disease signs and symptoms as well as physical function, and inhibited progression of joint damage.
“IL-6 blockade is emerging as an important therapeutic approach for rheumatoid arthritis,” said Neil Graham, M.B.B.S., M.D., M.P.H., Vice President, Program Direction, Immunology and Inflammation, Regeneron Pharmaceuticals. “We are encouraged with these Phase 3 results, which demonstrated efficacy at both doses of sarilumab, each administered every other week.”
The 52 week SARIL-RA-MOBILITY Phase 3 trial enrolled approximately 1,200 patients with active, moderate-to-severe rheumatoid arthritis, and who were inadequate responders to MTX therapy. Patients were randomized to one of three subcutaneous treatment groups, all in combination with MTX and dosed every other week: sarilumab 200 milligrams (mg), sarilumab 150 mg, or placebo.
Both sarilumab groups showed clinically relevant and statistically significant improvements compared to the placebo group in all three co-primary endpoints (p<0.0001).
(1) Improvement in signs and symptoms of RA at 24 weeks, as measured by the American College of Rheumatology score of 20 percent improvement (ACR20).
- 66 percent, 58 percent, and 33 percent in the sarilumab 200 mg, sarilumab 150 mg, and placebo groups respectively, all in combination with MTX.
(2) Improvement in physical function, as measured by change from baseline in the Health Assessment Question-Disability (HAQ-DI) at week 16.
(3) Inhibition of progression of structural damage at Week 52, as measured by the change in the modified Van der Heijde total Sharp score (mTSS).
- 0.25, 0.90, and 2.78 in the sarilumab 200 mg, sarilumab 150 mg, and placebo groups respectively, all in combination with MTX.
- The group receiving the 200 mg dose of sarilumab + MTX had a reduction of approximately 90 percent in the radiographic progression assessed by the mTSS compared to the radiographic progression with placebo + MTX at week 52.
ACR Results at week 24
|
Treatment Group
|
ACR20^
(%)
|
ACR50
(%)
|
ACR70
(%)
|
|
200 mg sarilumab + MTX
|
66*
|
46*
|
25*
|
|
150 mg sarilumab + MTX
|
58*
|
37*
|
20*
|
|
Placebo + MTX
|
33
|
17
|
7
|
^Primary Endpoint
*p<0.0001 compared to placebo group
In the SARIL-RA-MOBILITY trial, there was a higher incidence of treatment emergent adverse events leading to withdrawal in the sarilumab treatment groups compared to placebo (13.9 percent in 200 mg, 12.5 percent in 150 mg and 4.7 percent in placebo).
Infections were the most frequently reported adverse events and were reported with a higher incidence in the sarilumab groups compared to placebo, all in combination with MTX (39.6 percent for 200 mg, 40.1 percent for the 150 mg group and 31.1 percent for placebo). The incidence of serious infections was 4.0 percent in the 200 mg + MTX group, 2.6 percent in the 150 mg + MTX group, and 2.3 percent in the placebo + MTX group. 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, and transaminases were observed. These safety findings were consistent with those observed in prior investigational studies with sarilumab.
“Irreversible joint damage can be a consequence for patients suffering from rheumatoid arthritis, and this is accompanied by reduced physical function in these patients,” said Tanya M. Momtahen, M.S., Sarilumab Global Project Head, Sanofi. “This remains a major concern for rheumatoid arthritis patients. We are encouraged by these Phase 3 results and the impact sarilumab demonstrated on inhibition of progression of structural damage assessed radiographically in this study.”
Additional analyses of efficacy and safety data from the SARIL-RA-MOBILITY study will be presented at a future medical conference.
About Sarilumab
Sarilumab (REGN88/SAR153191) is the first fully-human monoclonal antibody directed against the IL-6 receptor (IL-6R). Sarilumab is a subcutaneously delivered inhibitor of IL-6 signaling, which binds with high affinity to the IL-6 receptor. It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling. Sarilumab was developed using Regeneron’s VelocImmune® antibody technology.
The investigational agent described above is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.
About Sanofi
Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (SAN) and in New York (SNY).
About Regeneron Pharmaceuticals
Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including hypercholesterolemia, oncology, rheumatoid arthritis, asthma, and atopic dermatitis. For additional information about the company, please visit www.regeneron.com.
SOURCE: Sanofi
Post Views: 121
