Anaphylactic reactions including anaphylactic shock have been observed with Grazax during post-marketing surveillance. The risk of systemic allergic reactions with Grazax is small and most likely to occur at the first does and may be manageable with appropriate supervision of the initial doing. Local allergic reactions of varying severity are common particularly oral pruritus, throat irritation, mouth oedema and ear pruritus. Acute asthma may occur. Use in children below 5 years of age and in elderly above 65 years of age as well as use in pregnant and lactating women was excluded from the trials and so is unknown. Use in children < 5 is not requested and is unlikely but efficacy and safety in the elderly is unknown. First round assessment of benefit-risk balance The benefit-risk balance of Grazax, given the proposed usage, is favourable. First Round Recommendation Regarding Authorisation Based on the clinical data submitted it is recommended that Grazax be approved for the following indication: Grazax is indicated for treatment of Timothy grass (Phleum pratense) pollen allergic rhinitis with our without conjunctivitis in adults, adolescents and children (above the age of 5) with clinically relevant symptoms, confirmed by a positive cutaneous test and/or a positive titre of the specific IgE to Phleum pratense. VI. Pharmacovigilance findings Risk management plan Seqirus Pty Ltd has submitted EU-RMP version 8 (10 2015; DLP 24 June 2013) and Australian Specific Annex (ASA) version 1 (10 November 2015) in support of this application. The sponsor submitted ASA version 2 (23 August 2016) with the response to issues raised in the first round evaluation. Safety Concerns and Risk Minimisation The proposed summary of safety concerns and their associated risk monitoring and mitigation strategies are summarised in Table 10. Table 10: Summary of safety concerns and risk minimisation activities Summary of safety concerns Pharmacovigilance Risk Minimisation Routine Additional Routine Additional Important identified risks Anaphylactic reaction including anaphylactic shock – – Progression of oral reaction into the throat – – Acute asthma – –
Important potential risks None identified Missing Use in children 5 years of age – – Use in elderly 65 years of age – – Use in pregnant and lactating women – – Inflammatory condition in the oral cavity# – – Forced expiratory volume in 1 second (FEV1) < 70% of predicted value (adults)# – – Severe asthma (children)# – – Malignancy or systemic diseases affecting the immune system (for example autoimmune diseases, immune complex diseases or immune deficiency diseases)# – – Children with symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infectious process at randomisation have been excluded from clinical trials as inter-current infections are a concern at initiation of treatment before the patient has developed tolerance.# – – Simultaneous immunotherapy with other allergens# – – # indicates safety concerns that were recommended for inclusion by the RMP evaluator, and which the sponsor has committed to including at the next revision of the EU-RMP and ASA. Adequate risk minimisation statements are included in the current version of the PI. New and outstanding recommendations - Round 2 The sponsor has adequately addressed the recommendations made in the round RMP evaluation. The sponsor has committed to update the Summary of Safety Concerns in accordance with the recommendations of the RMP evaluator. Specifically, it is noted that the sponsor has committed to add the following safety concerns as missing information: trial