9 November 2017 EMA/747932/2017 Veterinary Medicines Division Committee for Medicinal Products for Veterinary Use CVMP assessment report for GALLIPRANT (EMEA/V/C/004222/0000) International non-proprietary name: grapiprant Assessment report as adopted by the CVMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Introduction ........................................................................................................................... 4 Scientific advice ........................................................................................................................ 4 MUMS/limited market status ...................................................................................................... 4 Part 1 - Administrative particulars ......................................................................................... 5 Detailed description of the pharmacovigilance system ................................................................... 5 Manufacturing authorisations and inspection status ....................................................................... 5 Overall conclusions on administrative particulars .......................................................................... 5 Part 2 - Quality ...................................................................................................................... 5 Composition ............................................................................................................................. 5 Containers ............................................................................................................................... 5 Development pharmaceutics ...................................................................................................... 6 Method of manufacture .............................................................................................................. 6 Control of starting materials ....................................................................................................... 6 Active substance ....................................................................................................................... 6 Excipients ................................................................................................................................ 7 Specific measures concerning the prevention of the transmission of animal spongiform encephalopathies ...................................................................................................................... 7 Control tests on the finished product ........................................................................................... 7 Stability ................................................................................................................................... 7 Overall conclusions on quality ..................................................................................................... 7 Part 3 – Safety ....................................................................................................................... 8 Pharmacodynamics ................................................................................................................... 8 Pharmacokinetics ...................................................................................................................... 8 Toxicological studies .................................................................................................................. 8 Single dose toxicity ................................................................................................................... 9 Repeat dose toxicity .................................................................................................................. 9 Tolerance in the target species of animal ..................................................................................... 9 Reproductive toxicity ................................................................................................................. 9 Genotoxicity ........................................................................................................................... 10 Carcinogenicity ....................................................................................................................... 10 Studies of other effects ............................................................................................................ 10 Excipients .............................................................................................................................. 10 User safety ............................................................................................................................ 11 Environmental risk assessment ................................................................................................. 11 Overall conclusions on the safety documentation ........................................................................ 11 Part 4 – Efficacy ................................................................................................................... 12 Pharmacodynamics ................................................................................................................. 12 Pharmacokinetics .................................................................................................................... 13 Dose justification .................................................................................................................... 14 Dose determination/confirmation studies ................................................................................... 14 Target animal tolerance ........................................................................................................... 15 Clinical field trials .................................................................................................................... 16 Dose determination/confirmation study ..................................................................................... 16 Pivotal field study ................................................................................................................... 17 EMA/747931/2017 Page 2/22 Overall conclusion on efficacy ................................................................................................... 19 Part 5 – Benefit-risk assessment ......................................................................................... 21 Introduction ........................................................................................................................... 21 Benefit assessment ................................................................................................................. 21 Direct therapeutic benefit ......................................................................................................... 21 Additional benefits ............................................................................................................... 21 Risk assessment ..................................................................................................................... 21 Risk management or mitigation measures .................................................................................. 22 Evaluation of the benefit-risk balance ........................................................................................ 22 Conclusion ............................................................................................................................. 22 EMA/747931/2017 Page 3/22 Introduction The applicant Aratana Therapeutics NV submitted on 26 January 2016 an application for a marketing authorisation to the European Medicines Agency (The Agency) for GALLIPRANT, through the centralised procedure under Article 3(2)(a) of Regulation (EC) No 726/2004 (optional scope). The eligibility to the centralised procedure was agreed upon by the CVMP on 7 May 2015 as GALLIPRANT contains a new active substance (grapiprant) which was not authorised as a veterinary medicinal product in the Union on the date of entry into force of Regulation (EC) No 726/2004. The applicant applied for the following indication: For the treatment of pain and inflammation associated with osteoarthritis in dogs. The active substance in GALLIPRANT is grapiprant, a non-steroidal, non-cyclooxygenase inhibiting anti- inflammatory drug in the piprant class. Grapiprant is a selective antagonist of the prostaglandin E2 EP4 receptor, resulting in a reduction of pain and inflammation. The target species is dog. GALLIPRANT is presented in tablets of 20, 60 or 100 mg of grapiprant in a bottle containing 7 or 30 tablets. The applicant (Aratana Therapeutics NV) is registered as an SME pursuant to the definition set out in Commission Recommendation 2003/361/EC; however, the applicant out-licensed their application for GALLIPRANT to Elanco on 22 April 2016. The rapporteur appointed is Keith Baptiste and the co-rapporteur is Bruno Urbain. The dossier has been submitted in line with the requirements for submissions under Article 12(3) of Directive 2001/82/EC – full application. On 9 November 2017, the CVMP adopted an opinion and CVMP assessment report.