The and symptoms of active and progressive psoriatic arthritis in adults, when the response to previous disease-modifying antirheumatic therapy has been inadequate. Enbrel has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function. The signs and symptoms of active ankylosing spondylitis in adults. Golimumab: Simponi, alone or in combination with methotrexate, is indicated for: The treatment of active and progressive psoriatic arthritis in patients when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. Simponi has also been shown to inhibit the progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease, and improve physical function. Simponi is indicated for: The treatment of active ankylosing spondylitis in adult patients. Regulatory status The product received initial registration on the Australian Register of Therapeutic Goods (ARTG) on 20 January 2010. Certolizumab was considered by Advisory Committee on Prescription Medicines (ACPM) (previously ADEC) at the meeting (October 2009), leading to its approval in 2010 for rheumatoid arthritis. At the time the TGA considered this application, a similar application had been approved in the United States (US), Canada and had been submitted in the European Union (EU). Applications had not been submitted in Switzerland or New Zealand. Product Information The approved Product Information (PI) current at the time this AusPAR was prepared can be found as Attachment 1. For the most recent Product Information please refer to the TGA website at <>. II. Quality findings was no requirement for a quality evaluation in a submission of this type. III. Nonclinical findings There was no requirement for a nonclinical evaluation in a submission of this type. IV. Clinical findings A summary of the clinical findings is presented in this section. Further details of these clinical findings can be found in Attachment 2. trial trial trial
Drug specific antibody formation Injection site reactions Hypersensitivity reactions Change in morphology / severity of psoriasis The following should be added to the list of important missing information: Long term safety serious opportunistic infections”. UCB S.A. will assess all four bullet points mentioned in TGA proposals for the next version of the EU-RMP, once the next dataset for the PSUR is available (Mar 2014). The evaluator’s comments are noted in regards to: HIV or hepatitis C UCB S.A. advises that this will be evaluated at the next major update of the EU RMP for inclusion. It is clinically prudent that HIV and hepatitis C status are investigated prior to initiation of TNF antagonists. The evaluator’s comments are noted in regards to: Septic shock UCB S.A. considers septic shock a likely outcome of some serious infections (known and well characterized product risk). UCB S.A. respectfully advises that this will not be incorporated as an additional safety concern. Injection site reactions HIV or hepatitis C (important missing information) The Sponsor should add the above risks to the list of ongoing safety concerns. It is important to note that the ACSOM committee supported the inclusion of all the recommended additional safety concerns made by the evaluator. It is recommended that the sponsor justify the exclusion of the ongoing studies from the pharmacovigilance plan relating to PsA and AxSpA UCB has now updated Cimzia to version 9.3; studies are now included in the PV Plan (see page 194). This is acceptable. The sponsor should clarify the exact number of studies included within the pharmacovigilance plan, for example are studies included? Furthermore the milestones for the studies in the pharmacovigilance plan should be clarified. UCB has now updated Cimzia to version 9.3. The pharmacovigilance plan as summarised on p 193 contains: 4 registries (o Pregnancy data collections (ongoing studies, reports and ARTIS and RABBIT) o o Targeted follow-up with reporters with TB questionnaire This is acceptable. RMP RMP marketing
o Targeted malignancy questionnaire sent to HCP RA has now been completed and is now under table 5-2: Completed studies/activities from the Pharmacovigilance plan The Status (planned /started) and Date for submission of interim or final reports (planned or actual) for all ongoing and planned additional PhV studies / activities in the Pharmacovigilance Plan are provided in table 5-1 on page 193. Targeted follow-up questionnaires have not been submitted with the current application. It is recommended that the sponsor submit these for review by the TGA It is recommended to the sponsor that additional questionnaires regarding serious infection and hepatitis B reactivation be added Furthermore the method of supplying these questionnaires only after a spontaneous report has been made seems questionable. The sponsor should also consider including these questionnaires in the physician education material to prompt reporting and improve the quality of data collected. UCB has now updated Cimzia to version 9.3. The targeted follow-up questionnaires are now in Part VII Annex 7: Targeted follow-up with reporter with TB questionnaire Targeted malignancy questionnaire in paediatric, adolescent and young adult patients ( < 30 years of age) Targeted follow-up with pregnancy questionnaire UCB will evaluate the TGA request regarding questionnaires for serious infection and hepatitis B reactivation. UCB will evaluate the request to include questionnaires (TB, malignancy, pregnancy) in any physician education material that will be supplied. The Sponsor remains unclear regarding the inclusion of these additional questionnaires, the current distribution methods, data regarding RA and inclusion of these questionnaires in the educational material (please note that the Sponsor has also not yet clarified if an education programme will occur in Australia). The additional questionnaires suggested by the evaluator should be developed by the Sponsor and submitted to the TGA for review. RMP
The protocols for the ongoing registry studies have not been reviewed as part of this evaluation. Should this application be approved it is recommended that the sponsor consider completing an Australian Specific Registry study including patients diagnosed with RA, PsA and AxSpA. An Australian Specific Registry study for patients diagnosed with RA, PsA and AxSpA is already established in Australia. The registry is known as the Australian Rheumatology Association Database (ARAD). ARAD is a national Australian database, which is supported by the Australian Rheumatology Association, and which collects important health information from individuals with inflammatory arthritis including rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The aim of ARAD is to determine the short and long term effectiveness and safety of new biological drugs, including certolizumab pegol, used to treat inflammatory arthritis conditions. The registry captures information on patient’s anti-rheumatic medications, including reasons for stopping or switching, current symptoms, and suspected adverse effects. Information about intercurrent infections, new comorbidities including malignancy, joint surgery, and hospitalizations, are also collected. Patients and rheumatologists across Australia contribute to ARAD. In addition, registries exist in the EU with a much larger cohort of patients. Examples of these specific registries include DANBIO. It is recommended that the Sponsor report on both the ARAD and DANBIO studies within the PSUR. It is also important to note that the Sponsor makes the following statement regarding the DANBIO registry within the EU-RMP page 22: “DANBIO is not a safety registry and does not look for specific adverse events. All adverse events are received as spontaneous adverse events”. The sponsor should justify why the important missing information of “Potential for medication errors” will not be further elucidated via additional pharmacovigilance. Medication Potential medication errors are listed as missing information for Cimzia in the UCB Risk Management Plan (RMP). Medication error refers to any unintentional error in the prescribing, dispensing, or administration of a medicinal product while in the control of the This is acceptable. It is important to note that the Sponsor discusses the risk of medication error within the EU-RMP and makes the following statement regarding the importance of additional risk
healthcare professional, patient, or consumer. [information has been redacted] minimisation for this risk: “The product packaging, labelling, and supporting CZP educational program are designed to minimize the potential for medication errors in the administration of the product.” Therefore, the Sponsor should also apply additional risk minimisation activities in Australia. The sponsor should clarify the status of the auto-injector and update the RMP accordingly. The sponsor should also comment on the number and types of medication errors that have occurred during post-market experience. [information redacted] [information redacted] Therefore, the Sponsor should apply additional risk minimisation activities in Australia. It is recommended that the sponsor summarise all reports of overdose from post-market experience with RA. The sponsor does not discuss the risk of overdose in the PsA EU-RMP or the EU-RMP and simply refers to the comments within the RA-RMP UCB directs the evaluator to page 95 of the Cimzia RMP Version 9.3, additionally: [information redacted]. This concern is considered addressed as part of the overall enhancement in product as previously discussed. The potential for harm from overdose has not been adequately addressed in the Version 9.3 Part II Section 1. This section should be updated to include the cumulative data regarding overdose that the Sponsor has provided in the adjacent comment. The sponsor should clarify from experience the number of Off-label use of Cimzia is listed as missing information for Cimzia in the UCB Risk Management Plan (RMP). Off-label use is the use of pharmaceutical drugs for an The potential for use has not been adequately addressed in the Version 9.3 label RMP RMP
the case, the card should be updated for the Australian population, for example changing referenced to the SMPC. will be adapted to the local requirements in Australia. proposed for Australia. Due to the potential for serious adverse events with certolizumab treatment, in addition to the ongoing safety concerns associated with the product, additional risk minimisation activities, as applied in the EU, are required in Australia. It is recommended that the sponsor amend the following: This document should be updated for the Australia population, for example changing references to the SmPC. The steps describing the injection preparation and administrated should be numbered. Each administration picture should be placed with the corresponding administration step. The three pages regarding “clinical efficacy of Cimzia” should be removed and a reference made to the prescriber guide, or placed at the back of the UCB Australia currently have a how to prescribe brochure, which includes dosing instructions, a copy of which is attached. This can be expanded upon to address the comments above. UCB confirm that, if UCB decide to roll-out additional educational material in Australia, the material will be adapted to the local requirements. This response appears inconsistent with those provided below and with the content of the ASA. The Sponsor remains unclear regarding their risk minimisation plan proposed for Australia. The ASA states that no additional risk minimisation activities will be applied in Australia, however the Sponsor implies in this response that an additional risk minimisation activity (in the form of a brochure) will be applied. The “how to prescribe brochure” was not attached to the S31 responses. Furthermore, there is no mention of this document within the ASA. Due to the potential for serious adverse
document to ensure that the most relevant information is at the front of the document. A statement regarding appropriate dosing and/or a dosing table should be added to enhance safe use of medicine. A should be added showing the very common, common and rare side effects of certolizumab, similar to that shown in the SmPC. • A statement should be regarding the potential of certolizumab to influence the ability to drive and use machines. This statement should be to the effect of “Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including vertigo, vision disorder and fatigue) may occur following administration of Cimzia” events with certolizumab treatment, in addition to the ongoing safety concerns associated with the product, additional risk minimisation activities, as applied in the EU, are required in Australia. PsA and axSpA Patient Medication Guide It is recommended that the sponsor amend the following: UCB Australia currently produces a for patients, which will be extended to patients with PsA and axSpA. This guide includes an overview of adverse events and incorporates risks, such as hepatitis infection and infections, but can be updated to include ability to drive and use machines. This response appears inconsistent with those provided below and the content of the ASA. The Sponsor remains unclear regarding their risk trial
This document should be updated for the Australian population, for example changing references to the SmPC. A statement should be added regarding hepatitis B infection under the heading “information you should know about Cimzia”. A statement should be added regarding the potential of certolizumab to influence the ability to drive and use machines. This statement should be to the effect of “Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including vertigo, vision disorder and fatigue) may occur following administration of Cimzia)”. A section should be added regarding when to seek medical advice, such as signs of infection or an injection site reaction. A statement should be added regarding the use of the patient alert card, its purpose and the importance of carrying it with the patient at all times. A copy of the patient guide is attached. minimisation plan proposed for Australia. The “guide for patients” was not attached to the S31 responses. Furthermore, there is no mention of this document within the ASA. Due to the potential for serious adverse events with certolizumab treatment, in addition to the ongoing safety concerns associated with the product, additional risk minimisation activities, as applied in the EU, are required in Australia.
General Comments on the Education program It is recommended that the sponsor provide the updated versions of following RA materials to the TGA for review prior to approval [information redacted] [information redacted] This response appears inconsistent with those provided below and the content of the ASA. The Sponsor remains unclear regarding the risk minimisation plan proposed for Australia. [Information redacted] The evaluation of the educational materials is discussed in the RA EU-RMP Section 4.2.4 and Annex 8. It is recommended that the Sponsor consider evaluating the effectiveness of these educational materials for Australian physicians and patients. The sponsor should give details of the “third party provider” in Australia as mentioned in the PsA and AS [information redacted] This response appears inconsistent with those provided above. The Sponsor remains unclear regarding the risk minimisation plan proposed for Australia. [information redacted] The Sponsor should confirm the risk minimisation plan proposed for Australia. Due to the potential for serious adverse events with certolizumab treatment, in addition to the ongoing safety concerns associated with the product, additional risk minimisation activities, as applied in the EU, are required in Australia. The sponsor states that “Training on the updated materials and the associated need for UCB confirms that this training as it occurred in the European Union will also take place Australia prior to the distribution of the new educational material if UCB The Sponsor remains unclear regarding their risk minimisation plan