Cytel au service des maladies rares : exemple d un partenariat réussi

Transcription

1 Shaping the Future of Drug Development Cytel au service des maladies rares : exemple d un partenariat réussi RARE Novembre, 2015

2 Premier Provider of Clinical Research Services and Software Founded in 1987 by two pioneers of statistical methods Cyrus Mehta, PhD Founder and President Harvard School of Public Health faculty MIT Ph.D. Adaptive trial statistical methods pioneer Fellow of the American Statistical Association Nitin Patel, PhD Founder, Chairman and CTO MIT's Sloan School faculty MIT Ph.D. Leader of research on early stage adaptive trial methodologies Fellow of the American Statistical Association, Computer Society of India

3 Global Reach ~500 employees worldwide Low turnover rate (7% in 2011 & 2012) USA EU Asia 48% 47% 21% Biostatisticians Data Mgmt Statistical Programmers 38% 37% 3% Biostatisticians Data Mgmt Statistical Programmers 14% 16% 75% Biostatisticians Data Mgmt Statistical Programmers Offices Cambridge, New York, Philadelphia, San Francisco, Waltham Offices Geneva, London, Paris Offices Bangalore, Hyderabad, Navi Mumbai, Pune

4 Cytel US/EU Experience Median Experience in drug development Biostatisticians: 18 years Statistical Programmers: 15 years Data Managers: 12 years Medical Writers : 15 years Over 60% of programmers in US and Europe have Math or Statistics degree (others mainly in computer science) PhD: 45% of biostatisticians

5 Full Biometrics Service Consulting (adaptive and non adaptive designs) Biostatistics & Programming Randomization EDC & IWRS development (Rave/InForm/eCOS) Data Management DMC Support Services (inc expert contract management) CDISC migration (SDTM, ADaM) Medical Writing Submission Support (ISS/ISE, CSS/CSE)

6 Rare Metabolic Disease Case Study Improving the Lives of Patients With Severe, Rare Diseases Raptor Outsourcing Strategy A small company with limited resources Seeks effective partners with required expertise Originally reached out to Cytel for Phase 3 study due to adaptive design expertise

7 Rare Metabolic Disease Case Study Nephropathic Cystinosis, an ultra-orphan pediatric disease: 500 patients in the US, 800 patients in the EU Cysteamine bitartrate (immediate release) is the only FDA approved treatment Primary endpoint: white blood cell (WBC) cystine FDA wanted a demonstration of non-inferiority of RP103 (delayed release cysteamine bitrate) in very well controlled patients (WBC<1 nmol ½ cystine/mg protein) Cytel designed a suitable adaptive trial with unblinded Sample Size Re-estimation (SSR) Initial Sample Size of 20 patients Increase at interim to somewhere between 30 and 50 patients based on recalculated power

8 Rare Metabolic Disease Case Study Design and Operational Implementation Consulting Study Design and Simulation Protocol, DMC Charter & interim SAP (isap) Representation at FDA Special Protocol Assessment Meeting Blinded and unblinded Cytel teams Different physical locations with appropriate firewalls in place Independent Statistical Center (ISC) Interim Analysis based on isap Sample Size Reestimation ACES & DMC support Blinded Statistical Team Study SAP CDISC (SDTM & ADaM programming) Final statistical analysis

9 Rare Metabolic Disease Case Study: Submission Work and Outcome Abbreviated clinical and statistical report to submit for pre-nda meeting Representation at FDA pre-nda meeting Final CSR CDISC Migration of 6 studies (SDTM and ADaM, including Define files and Reviewer Guides for submission) ISS/ISE for NDA Outcome: The FDA and the EMA submissions were made in 2012 as scheduled. In 2013, Raptor s first product PROCYSBI was approved for American and European use. Raptor achieved orphan protected drug development success and will reap the benefits of an extended patent life. The success has fueled company growth and additional new product development.

10 Rare Metabolic Disease Case Study: Follow-up Studies Follow up studies awarded to Cytel for full biometrics services: Consulting EDC Development Data Management & Coding Statistics and Programming Medical Writing

11 Other Types of Adaptive Designs UCP% LCP% CP Adding/Dropping Doses Population Enrichment

12 Adaptive Trials: ACES Operational Structure Regulatory Agencies Sponsor Steering Committee Blinded Recommendations Project Management Regulatory Submissions Clinical & Medical Monitoring Study Sites Data Management & Blinded Statistics Central Lab (e.g. biology) Endpoint Adjudication Committee IP Supply Unblinded Stats (ISC) & Randomization (IRS) Data Monitoring Committee (DMC) Unblinded

13 What our customers think of us Cytel s innovative, yet practical adaptive design provided multiple favorable scenarios and allowed us to proceed with our pivotal study. Difficult to imagine our going forward with traditional methods alone. Steven B. Ketchum, Sr. VP, Research & Development Sunesis Pharmaceuticals, Inc. We want to acknowledge Cytel s pivotal role. Without Cytel we would not have got this far. You have been very service-oriented and responsive throughout. Scott Harris, Chief Medical Officer Napo Pharmaceuticals Cytel s work on the trial design, simulation and discussions with the FDA were instrumental in obtaining the regulatory acceptance for the proposed methodology in implementing a groundbreaking adaptive trial. Simona Skerjanec, Vice President, Medical Science The Medicines Company

14 Thank you for your time! Caroline Morgan Senior Director Tel: