The sponsor has not provided study protocols or protocol synopses for all studies referenced in the pharmacovigilance plan. The sponsor should provide the missing study protocols or protocol synopses as soon as they become available. With regard to references made to additional pharmacovigilance activities in the submitted EU-RMP, the sponsor has not provided consistent study name labelling or protocol number labelling throughout the document; for example the nonclinical placental and lactation study/studies is/are referred to by different names and it remains unclear whether the same study is meant. The sponsor should update the RMP document and refer to the same studies by the same name throughout. Risk minimisation activities The sponsor proposes routine and additional risk minimisation activities. Reconciliation of issues outlined in the RMP report Table 12 summarises the OPR’s first round evaluation of the RMP, the sponsor’s responses to issues raised by the OPR and the OPR’s evaluation of the sponsor’s responses. Table 12: Reconciliation of issues outlined in the First Round RMP Evaluation Report Recommendation in RMP evaluation report Sponsor’s response/summary of the response OPR evaluator’s comment 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. It is important to ensure that the information provided in response to includes a consideration of the relevance for the Risk Management Plan, and any specific information needed to address this issue in the RMP. For any safety considerations so raised, please provide information that is relevant and necessary to address the issue in the RMP. ‘The Sponsor confirms that the Nonclinical and Clinical Evaluation Reports have been reviewed to ensure that any responses provided to issues raised have been considered for relevance to the Risk Management Plan.’ The sponsor’s response has been noted. 2. The sponsor should clarify the above and in particular should provide a compelling justification for the following: ‘Cerdelga is formulated as a hard capsule for oral administration containing 84 mg eliglustat which is equivalent to 100 mg eliglustat tartrate. Information on the dose conversion for the salt was included as part of the cover letter for the The sponsor’s response has been noted. The sponsor has not specified which documents support an immediate dose of 100
risk management approach in Australia.’ in accordance with best practice. 8. The sponsor should make available the prescriber education materials to all health care professionals involved in the treatment of a patient taking eliglustat. ‘The Sponsor confirms educational materials will be made available to all health care professionals involved in the treatment of a patient taking eliglustat. They will be distributed using a variety of methods which may include electronic or hard copy formats to ensure accessibility to all key stakeholders involved in the management of Gaucher patients. The prescriber education materials for Prescriber) are intended for the physicians/specialists who initiate/supervise treatment with eliglustat only. The physicians have the responsibility to discuss/remind the patient the importance of using the Patient Alert Card. The Patient Alert Card is a liaison tool to provide educational materials to all the other healthcare professionals who are involved in the treatment of Gaucher disease. It focuses particularly on the potential drug-drug interactions prior prescription or delivery of any additional medicinal products (including herbal products). All healthcare professionals are encouraged to to the Product Information or contact Sanofi Medical Information for additional information required. The sponsor’s response has been noted. However, that a multidisciplinary team is likely to provide care for patients with Gaucher disease, the recommendation remains. The sponsor should make available the prescriber education materials not only to prescribers, but to all health care professionals involved in the treatment of a patient taking eliglustat. 9. Given that the sponsor has not proposed a titration schedule for eliglustat but proposes that patients take the 84 mg/100 mg dose from the start, the sponsor should outline what additional monitoring should occur, in this initial period of administration. ‘The rationale for the single dose regimen is explained in detail in the clinical documentation included with the application and subject of clinical evaluation. As demonstrated during clinical development the safety profile of eliglustat in GD1 patients does not warrant any additional monitoring as part of the initial period of administration.’ The sponsor’s response has been noted. ACSOM made the following comments: ‘In noting the relatively population group affected by GD (and that most patients live in or around Sydney), the committee made the additional suggestion that it would also be useful to consider implementing ongoing therapeutic monitoring protocols (given the variability of results shown in the clinical trial data) and to also have a set of guidelines to ensure