CONDITIONAL MARKETING AUTHORISATION guideline HOURIA CHIKHI Master AREIPS 14/11/2016

CMA.. A European MA ( Centralised Procedure) A regulatory tool for early access for medicines that are likely to have a significant benefit for patients, before all of the formal studies on its efficacy and safety have been completed In March 2006: European Commission adopted the Regulation on the CMA

Legislation Regulation (EC) No 507/2006 of 29 March 2006: 13 articles Guideline on the scientific application and the practical arrangements necessary to implement Commission Regulation (EC) No 507/2006 on the CMA for medicinal products for human use falling in the scope of regulation (EC) No 726/2004 [2007] Updated Guideline: 2016

Guideline Guideline , CHMP (5 december 2006): Forms the basis for requesting or renewing a CMA The Legal basis of this guideline is article 11 of commission regulation (EC) No 507/2006 The Purpose of this guideline is to provide advice on the Scientific application and the practical arrangements necessary to implement the legal provisions on the CMA ( art 11) Should be followed and will be regularly updated to include more specific guidance and examples based on the CHMP experience with CMA EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

Granting of a CMA The possibility of obtaining a CMA only applies to new MA applications Applicant’s request for a CMA: A CMA may be requested by the applicant or proposed by the CHMP (art 3 No 507/2006) The applicant is invited to notify the EMA about its intention to request a CMA as part of the « letter of intent » to be sent to the EMA in advance of the MA application submission CHMP scientific advice or protocole assistance EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

Granting of a CMA Justification that the medicinal product falls within the scope of the CMA: The categories of MP that fall within the scope of the CMA regulation are defined in art 2 CR 507/2006 These products belong to at least one of the following categories Seriously debilitating diseases or life-threatening diseases MP to be used in emergency situation Orphan medicinal products EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

Granting of a CMA Fulfilment of the requirements for CMA (art 4) The risk-benefit balance of the product is positive It is likely that the applicant will be able to provide comprehensive data Fulfilment of unmet medical need The benefits to public health of the immediate avaibility outweigh the risk inherent in the fact that additional data are still required EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

GRANTING OF A CMA CHMP assessment of a request for CMA: Summary of the assessment and claims Upon granting of a CMA, the specific obligations and the timeframe for their completion will be clearly specified and will be made publicly available by the Agency as part of the EPAR EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

GRANTING OF A CMA Information included in the summary of product characteristics and package leaflet (art 5) Mention that certain specific obligations are reviewed annually Periodic Safety Update Report Art 9 of CR No 507/2006 states that the PSUR shall be submitted to the Agency and member states immediately upon request or at least 6 months following the granting or renewal of a CMA EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

Renewal of a CMA Based on art 6 (1) of CR 507/2006, the CMA may be renewed annually : at least 6 months before its expiry and MAH shall provide the Agency with an interim report on the fulfilment of the specific obligations to which it is subject Timetable : The CHMP will assess the renewal application on the basis of the R-B balance and formulate an opinion within 90 days after receipt of a valid renewal application EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

Updated Guideline (2016) On the 25 February 2016 The updated guideline is expected to optimize the use of this tool by medicine developers and consequently allow more medicines that address unmet medical needs to reach patients earlier EMA (2016) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

Updated Guideline (2016) Overview of proposed key changes Emphasis on importance of planning CMA prospectively to ensure swift assessment procedure (part “Agency Advice prior to submission of a request for CMA”) Emphasis on advantages of engaging in early dialogue with EMA on the development programme Clarification of how a positive B-R balance should be substantiated (where there are less complete data ) Example and further guidance on the level of evidence and post-authorisation data (co-medication, sub-population, efficacy results ) Guidance on when a condition could be considered life threatening or seriously debilitating if these effects are in the long-term EMA (2016) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

TAGRISSO EPAR Summary for the public Explains how the Agency assessed the medicine to recommend its authorization in the EU and its conditions of use Tagrisso : a cancer medicine ,adults with a type of lung cancer NSCLC. Tagrisso is used in patients whose cancer is advanced or has spread and who have the T790M mutation, a particular change in the gene for a protein called epidermal growth factor receptor (EGFR). osimertinib 2 February 2016 EMA (2015). Tagrisso. EPAR summary for the public

TAGRISSO- EPAR Summary for the public Tagrisso has been investigated in two main studies involving 411 patients who had the T790M Mutation and in whom the disease progressed despite previous treatment with EGFR TK inhibitors. In both studies, which were still ongoing at the time of Tagrisso's inital evaluation, the medicine was not compared with any other treatment EMA (2015). Tagrisso. EPAR summary for the public

TAGRISSO Assessment Report (CHMP) The applicant requested consideration of its application for a Conditional Marketing Authorization in accordance with Article 14(7) of the above mentioned Regulation based on the following claim(s): Medicinal product which aims at the treatment of a life-threatening disease in accordance with Article 2(1) of Commission Regulation No. 507/2006 The application was received by the EMA on 5 June 2015 During the meeting on 14-17 December 2015, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, issued a positive opinion for granting a CMA for Tagrisso EMA. (2015) Assessment report .Tagrisso

TAGRISSO Assessment Report (CHMP) Tagrisso is included in the additional monitoring list, Statement mentioned in the SMP characteristics, preceded by an inverted equilateral black triangle Benefice-Risk balance «  Data available are not considered sufficiently comprehensive to grant a full MA however they are of sufficient relevance in the context of a life- threatening disease where an unmet medical need exists, Therefore, a conditional approval is supported subject to presentation submission of comprehensive data within reasonable timelines EMA. (2015) Assessment report .Tagrisso

TAGRISSO Assessment Report Specific obligation to complete post-authorisation measures for the CMA, the MAH shall complete, within the stated timeframe, the following measures : EMA. (2015) Assessment report .Tagrisso

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Commission Regulation (EC) No 507/2006 of 29 March 2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004 of the European Parliament and of the Council EMA. (2015) Assessment report .Tagrisso ema.europa.eu (2015) guideline/2015/07/WC500190556 EMA (2006) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004 EMA (2015). Tagrisso. EPAR summary for the public EMA (2016) Guideline on the scientific application and the practical arrangements necessary to implement commission regulation (EC) No 507/2006 on the CMA products for human use falling within the scope of regulation (EC) No 726/2004

TAGRISSO European Public Assessment Report Why is Tagrisso approved ? The CHMP decided that Tagrisso's benefits are greater than its risks Patients with the T790M mutation currently have a poor prognosis and very limited treatment options ; therefore there is a high unmet medical need The evidence available so far showed promising results in terms of Tagrisso's ability to reduce tumor size The european Commission granted a MA on 2 February 2016