Date: 2017-09-22
Type of information: Refusal of a Market Autorisation in the US
Product name: Plivensia™
Compound: sirukumab
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Action mechanism:
- monoclonal antibody. Sirukumab is a fully human anti-interleukin-6 (IL-6) immunoglobulin G1-kappa with a high affinity and specificity for binding to the human IL-6 molecule. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6.
- In December 2011, Janssen and GSK entered into a licensing and co-development agreement with respect to sirukumab. Janssen has exclusive rights to commercialise sirukumab in Asia Pacific, Europe, the Middle East and Africa, while GSK
retains commercialisation rights in North, Central and South America, with global profit shared equally between the two companies. Prior to the agreement, Janssen had been
developing sirukumab for rheumatoid arthritis. As part of the collaboration, a Phase 3 program began in August 2012 to investigate sirukumab for the treatment of moderately to severely active rheumatoid arthritis. Janssen is responsible for the MHLW regulatory file in Japan. The agreement gives both companies the option to investigate sirukumab for other indications beyond rheumatoid arthritis.
Company: Janssen-Cilag International, a J&J company (USA - NJ) GSK (UK)
Disease: moderately to severely active rheumatoid arthritis
Latest news:
- • On September 22, 2017, Janssen Biotech announced that it has received a complete response letter from the FDA for the Biologics License Application (BLA) seeking approval of sirukumab for the treatment of moderately to severely active rheumatoid arthritis. The complete response letter indicates additional clinical data are needed to further evaluate the safety of sirukumab in the treatment of moderately to severely active rheumatoid arthritis.
- • On August 2, 2017, Janssen Biotech announced that the Arthritis Advisory Committee of the FDA did not recommend approval of sirukumab (proposed trade name Plivensia™) for the treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs. The Arthritis Advisory Committee voted unanimously in support of the efficacy data. There was uncertainty regarding the safety profile and the committee did not support approval for the proposed indication.
- The committee reviewed sirukumab efficacy and safety data from a global Phase 3 clinical development program inclusive of five studies and more than 3,000 patients living with rheumatoid arthritis, including those who continue to have active disease despite previous disease modifying anti-rheumatic drugs and biologic treatments. Sirukumab, studied at 50 mg and 100 mg doses every four and two weeks, respectively, demonstrated significant efficacy in the treatment of rheumatoid arthritis, improving signs and symptoms, inhibiting the progression of structural damage and demonstrating improvement in patient-reported outcome measures including fatigue, pain, quality of life and physical function.
- The most common adverse events reported in the sirukumab clinical development program included laboratory abnormalities, colds, upper respiratory tract infections, and redness, pain or swelling at the injection site. Serious adverse events reported included serious infections such as pneumonia and cellulitis, abscess, sepsis, osteomyelitis, hypersensitivity reactions, low platelets, lipid elevations and gastrointestinal perforations. Cardiovascular adverse events, malignancies and mortality were observed in sirukumab clinical studies.
- Sirukumab is currently being evaluated by health authorities in the U.S., Europe and Japan as a subcutaneous therapy for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
- • On October 20, 2016, Janssen Pharmaceutical K.K. submitted a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare (MHLW), seeking approval of sirukumab for the treatment of adult patients with moderately to severely active rheumatoid arthritis in Japan. The application is based on five pivotal Phase 3 studies from the SIRROUND clinical development program, including SIRROUND-D, which was presented at the 2016 European League Against Rheumatism annual meeting and showed sirukumab significantly inhibited radiographic progression or joint destruction, from baseline to week 52, and improved signs and symptoms of rheumatoid arthritis at week 16 compared with placebo, the study's co-primary endpoints.
- Patient-reported outcomes from SIRROUND-D show the efficacy of sirukumab in improving health-related physical and emotional well-being, including fatigue, morning stiffness and work productivity/interference associated with moderately to severely active rheumatoid arthritis.
- SIRROUND-M, which was presented at the 2015 American College of Rheumatology (ACR) annual meeting, also demonstrated the safety and efficacy of sirukumab in Japanese patients who had an inadequate response to methotrexate (MTX) or sulfasalazine.
- • On September 23, 2016, Janssen Biotech announced the submission of a Biologics License Application (BLA) to the FDA seeking approval of sirukumab for the treatment of adult patients with moderately to severely active rheumatoid arthritis.Data from the Phase 3 SIRROUND clinical development program, which includes five studies (SIRROUND-D, SIRROUND-T, SIRROUND-H, SIRROUND-M and SIRROUND-LTE) served as the basis for submission.
- • On September 12, 2016, Janssen-Cilag International announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking approval of sirukumab for the treatment of adult patients with moderately to severely active rheumatoid arthritis. Data from the Phase 3 SIRROUND clinical development program, which includes five studies (SIRROUND-D, SIRROUND-T, SIRROUND-H, SIRROUND-M and SIRROUND-LTE), is incorporated into the submission. Results from the SIRROUND-D study were recently presented at the Annual European Congress of Rheumatology (EULAR 2016), and results from the SIRROUND-T and SIRROUND-H studies are planned to be presented later in 2016.
The SIRROUND Clinical Program is a phase 3 clinical program in patients with active rheumatoid arthritis includes five studies investigating subcutaneously administered sirukumab 50 mg every four weeks and sirukumab 100 mg every two weeks in combination with conventional disease-modifying antirheumatic drugs (DMARDs) or as monotherapy. The comprehensive development program involves more than 3,000 patients, comprising the following five studies:
- - SIRROUND-D study: patients who had an inadequate response to DMARDs. This study is estimated to complete in 2017.
- - SIRROUND-T study: patients who had an inadequate response or were intolerant to anti-TNF alpha agents. This study has completed.
- - SIRROUND-H study: patients with an inadequate response or who were intolerant to methotrexate (MTX) or for whom MTX was inappropriate. This study has completed.
- - SIRROUND-M study: Japanese patients who had an inadequate response to MTX or sulfasalazine. This study has completed.
- - SIRROUND-LTE study: a long-term extension study for patients completing SIRROUND-D and SIRROUND-T. This study is estimated to complete in 2020.
Patents:
Submission of marketing authorization application USA : 2016-09-23
Submission of marketing authorization application UE: 2016-09-12
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
