information should be assigned as appropriate, and as specified by the RMP evaluator. Efficacy and safety of Rixubis in these patients is not expected to differ from other patients. Therefore, Baxter proposes not to include safety and efficacy in patients who are HIV positive or immunocompromised as important missing information within the RMP. There is a high incidence of HIV in the target population. The sponsor states in the RMP that up to 10% of haemophilia patients are HIV positive. The RMP evaluator maintains the opinion that this patient population should be included as missing information in the of ongoing safety concerns of the RMP. Reporting of safety related events in this patient population should occur in every PSUR. It is recommended that the sponsor adds the unknown safety and efficacy for patients with liver disease as missing information. Risk minimisation and pharmacovigilance activities to address this missing information should be assigned as appropriate, and as specified by the RMP evaluator. Patients with hepatic disease were included in clinical studies with Rixubis. Patients with a medical history of hepatitis (excluding those with active disease) were included in clinical studies. Patients with a medical history of hepatitis or active hepatitis with ALT and/or AST not exceeding five times the upper limit of normal were included in clinical studies. In pivotal Study 250901, 63/73 subjects (86%) who received IP had a medical history of hepatitis (A and/or B and/or C). Of which, 38 had increased liver parameters (ALT and/or AST and/or ALP) at screening or at any time point during study participation. Patients with active hepatitis would need to be monitored more closely than other patients. The Australian PI reflects that patients with severe chronic liver disease (as evidenced by an INR > 1.4) were excluded from pivotal Study 250901. In addition, patients with hepatic disease are discussed within the context of It is noted that a statement is included in the Clinical Trials section of the PI stating that this patient population has been excluded from participation in clinical trials. It is understood that Baxter does not believe that there is a safety concern with this patient population using the product. However, the RMP evaluator maintains the opinion that this patient population should be included as missing information in the table of ongoing safety concerns of the RMP. Reporting of safety related events in this patient population should occur in every PSUR.
thromboembolic events in the Australian PI. Therefore, Baxter proposes not to include safety and efficacy in patients with hepatic disease as important missing information within the RMP. It is recommended that the sponsor adds the unknown safety and efficacy for patients with renal disease as missing information. Risk minimisation and pharmacovigilance activities to address this missing information should be assigned as appropriate, and as specified by the RMP evaluator. Patients with renal disease were excluded from clinical populations for Rixubis and are routinely excluded from clinical trial populations. Baxter does not believe this constitutes Important Missing Information for inclusion in the RMP. As the haemophilia B population ages, there may be an increased incidence of renal disease. However, it is not currently considered a leading co-morbidity in this population. Therefore, Baxter proposes not to include the safety and efficacy in patients with renal disease as important missing information within the RMP. It is that a statement is included in the Clinical Trials section of the PI stating that this patient population has been excluded from participation in clinical trials. It is understood that Baxter does not believe that there is a safety concern with this patient population using the product. However, the RMP evaluator maintains the opinion that this patient population should be included as missing information in the table of ongoing safety concerns of the RMP. Reporting of safety related events in this patient population should occur in every PSUR. It is recommended that the sponsor submits final or interim study reports, resulting from the ongoing clinical trials, to the TGA at the same time as reports are submitted to other regulatory agencies. Baxter will endeavour to submit final or interim study reports (resulting from the ongoing clinical trials) to the TGA. However, as there is no existing process in TGA that allows sponsors to submit study reports independently of a major variation, the timing of these submissions may not be in sync with that of other regulatory agencies. The sponsor should note that relevant study results from studies, referenced in the RMP, can be submitted to the RMP coordinator. Such a submission should include a cover letter summarising the study results and any impact the results may have on the RMP. Please submit to the RMP coordinator e-mail address: VI. Overall conclusion and risk/benefit assessment The submission was summarised in the following Delegate’s overview and recommendations: