Recommendation in Sponsor’s response (or RMP evaluator’s comment RMP evaluation report summary of the response) TGA recommendation 1: All of the questions have The sponsor’s response is Safety considerations may been answered separately in acceptable and no modification to the RMP is be raised by the nonclinical the sponsor’s response to required at this point in and clinical evaluators the clinical questions. The time. This may change through the consolidated following is a brief when the final CSR for section 31 request and/or summary, and the actions Study SB4-G31-RA which the Nonclinical and Clinical required regarding the RMP includes the 100 week data Evaluation Reports are discussed. is provided. respectively. The issues Section 1) No significant identified by the sponsor as difference in the incidence relevant to the RMP were: of TEAEs was observed Section 1) Any association between opioid users / non- between opioid use / Body and across categories Mass Index (BMI) and the of BMI values. There are no incidence of TEAEs (Q8) pre-existing safety concerns proposed in the RMP for Section 2) Any explanation SB4 related to this question. for the lower incidence of As no safety concerns were injection site reactions raised in this section, the Section 3) Any comment for Applicant believes that there the incidence of is no need for further antibodies discussion to address these issues in the RMP. Section 4) Data from the open extension study Section 2) Injection site and discussion for any reactions (ISRs) are safety concerns, including designated as an important results post-switching. identified risk in the RMP for SB4. However, as a decreased risk compared with the originator Enbrel was reported, the sponsor does not consider this finding a safety concern. Besides this, the study is already described in the RMP section SVII.3.1.5 Injection site reactions. Therefore the Applicant concludes there is no need for further discussion. Section 3) Similar to question 2, the sponsor does not consider lower immunogenicity to be a safety concern. Also, immunogenicity is not listed as a safety concern in the RMP for SB4. As described
Recommendation in RMP evaluation report Sponsor’s response (or summary of the response) RMP evaluator’s comment TGA recommendation 1: Safety considerations may be raised by the nonclinical and clinical evaluators through the consolidated section 31 request and/or the Nonclinical and Clinical Evaluation Reports respectively. The issues identified by the sponsor as relevant to the RMP were: Section 1) Any association between opioid use / Body Mass Index (BMI) and the incidence of TEAEs (Q8) Section 2) Any explanation for the lower incidence of injection site reactions Section 3) Any comment for the incidence of antibodies Section 4) Data from the open extension study and discussion for any safety concerns, including results post-switching. All of the questions have been answered separately in the sponsor’s response to the clinical questions. The following is a brief summary, and the actions required regarding the RMP are discussed. Section 1) No significant difference in the incidence of TEAEs was observed between opioid users / and across categories of BMI values. There are no pre-existing safety concerns proposed in the RMP for SB4 related to this question. As no safety concerns were raised in this section, the Applicant believes that there is no need for further discussion to address these issues in the RMP. Section 2) Injection site reactions (ISRs) are designated as an important identified risk in the RMP for SB4. However, as a decreased risk compared with the originator Enbrel was reported, the sponsor does not consider this finding a safety concern. Besides this, the study is already described in the RMP section SVII.3.1.5 Injection site reactions. Therefore the Applicant concludes there is no need for further discussion. Section 3) Similar to question 2, the sponsor does not consider lower immunogenicity to be a safety concern. Also, immunogenicity is not listed as a safety concern in the RMP for SB4. As described The sponsor’s response is acceptable and no modification to the RMP is required at this point in time. This may change when the final CSR for Study SB4-G31-RA which includes the 100 week data is provided. non-
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