Post Marketing Translarna Registry

Proprietary and Confidential1

9th TGDOC Curator MeetingLeuven, Belgium

Lauren Morgenroth, MS, CGCCOO TRiNDS

Tuesday September 20th, 2016

Disclosures• Employee of TRiNDS, LLC (new specialized neuromuscular contract

research organization (CRO)) which serves the academic clinical trial network, Cooperative International Neuromuscular Research Group (CINRG), as its Coordinating Center

• The CINRG network and its clinical sites are the recipient of grants from NIH, DOD, PPMD, FED, MDA, FSH Society, and FSHD Global

• CINRG and TRiNDS have business relationships with several pharmaceutical companies for data summaries, study design, study planning, study operations, data management, and statistical analysis

• 2015 Funding from FED for post marketing research and training• Consulting agreement with Marathon

Key Points and Conclusions• De-risk infrastructure with pragmatic partnership with academic

researchers and patient registries• Conservation of patient, family, and physician resources by

leverage of existing tools and networks: TREAT-NMD, CINRG/TRiNDS, Regulatory Expert CRO (Quintiles, etc.)

• Build platform that can reinvigorate research and share information with the public and community at large

• Maintain successful post marketing study and allow expansion to additional studies

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Traditional Challenges: Orphan Drug Development

• Academic medicine has domain expertise in rare disease• Private industry develops drugs for rare disease:

• Focus on ‘value’ of drug development program• Typically little rare disease domain expertise

• Pragmatic partnership of academic medicine and industry seems to make sense however there are some barriers:

• Need of industry to control aspects of drug development• Need of academic researchers to be better versed in regulatory

requirements• Industry default to use contract research organizations (CROs) that have

expertise in drug development, but not in neuromuscular disease

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Review of Post Marketing Efforts

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• Meeting of KOLs• Existing

resources

Information Gathering

• Consulting firm assessment

• Meetings with key Pharma

Market Research • Webinars

• Presentations at curator meeting

Education

• Joining of resources: TREAT-NMD and CINRG

Platform Development • PTC: PASS

• Continued education and updates

Maintenance

2014 2015 2016

Post Marketing Resources • TREAT-NMD: http://www.treat-nmd.eu/resources/post-marketing-

surveillance/introduction/• EMA:

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000037.jsp

• FDA: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/

• Pharma: http://www.pfizer.com/research/pmc/what_pmc, Shire, Amgen, Janssen, Novartis, etc.

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EMA Guidance – Updated in 2016

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FDA Guidance

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FDA Post Marketing Database

Proprietary and Confidential9

http://www.accessdata.fda.gov/scripts/cder/pmc/

Example from FDA Database • NDA Approval Date: 01/31/2012• Postmarketing requirement: Conduct an open-label, single-arm trial to

evaluate the long-term safety of Kalydeco…the trial will enroll pediatric patients < 18 years of age and who are registered in the US Cystic Fibrosis Foundation (CFF) Patient Registry. Patients will be followed for at least 3 years and long-term efficacy will also be assessed. The trial assessments will comprise the data collected as part of the CFF registry…results of this trial will be presented in the context of observational data on the same outcomes for all patients in the CFF registry…who are treated with Kalydeco (ivacaftor).

• Projected Completion Date: 12/31/2020

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TRiNDS – Official Coordinating Center of CINRG

• Cooperative International Neuromuscular Research Group (CINRG)

• Academic based clinical trial network launched in 2000• Multi-disciplinary and cross-institutional network of clinicians and

scientists• Study the cause(s), pathogenesis and clinical outcomes of

neuromuscular disorders through controlled clinical studies

• Access to over 25 specialized neuromuscular clinical sites around the world

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TRiNDS – CINRG Organization

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Patient Support Organizations

CINRG Clinical Study Sites

CINRG Executive Committee (EC)

CINRG Publication Subcommittee

(CPS)

CINRG Outcomes Subcommittee

(COS)

CINRG Data and Safety Monitoring

Board (DSMB)

TRiNDS – New Contract Research Organization (CRO)

• TRiNDS: Therapeutic Research in Neuromuscular Disorders Solutions

• Specialized neuromuscular CRO providing four main solutions to pharmaceutical and biotechnology industries as well as academic investigators and clinical centers for their clinical study needs:1. Clinical Operations 2. Data Management 3. Biostatistics4. Study Measurements

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Neuromuscular Domain Expertise

• TRiNDS team completed 12 neuromuscular clinical studies• Diseases: Duchenne, Becker, limb girdle, and facioscapulohumeral• Type: Observational, pilot, phase II, phase III, and post marketing

• Network of certified physical therapists • Clinical study protocol templates, manuals, and common case

report forms• Domain specific site monitoring, centralized data processing and

collection of site documents across over 25 clinical centers

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Data Management • Specialized neuromuscular and rare disease expert data

managers that provide a full range of data services• TRiNDS uses OpenClinica for electronic data capture (EDC)

• 21 CFR Part 11 and GCP Compliant• Online data entry• Fully integrated system including a randomization and online participant

survey modules• Network of trained study team members for data entry and queries

• CINRG Quantitative Measurement System (CQMS) connectivity

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Data Management

Study Measurements• Specialized neuromuscular expertise to select the most

appropriate study measurements across the entire disease spectrum: Biomarkers Strength and function Pulmonary Cardiac Patient reported outcomes Quality of life

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Study Measurements

Natural History: Foundation and Validation

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EndpointDevelopment

StudyDesign Clinical Trials Post

Marketing

Natural History Pathophysiology Effects of intervention

PTC: Translarna™ Post Marketing Commitments

• Purpose: Post-approval safety study (PASS) per pharmacovigilance risk assessment committee (PRAC) of EMA to gather data on Translarna (ataluren) safety, effectiveness, and prescription patterns in routine clinical practice

• Type: Observational [Patient Registry]• Design: Prospective• Duration: 5 years• Estimated Enrollment: 200 • Estimated Study Start – End: April 2015 – April 2022• Information from: https://clinicaltrials.gov/ct2/show/NCT02369731

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Key Outcome Measures• Primary: Incidence of adverse events • Secondary:

• Change in laboratory parameters • Change in blood pressure • Prescriber and patient compliance per approved labelling

• Other: Patient health management measures

• Important note: No protocol-mandated procedures, it is expected that physicians and other caregivers follow published treatment guidelines and standards of care

• Information from: https://clinicaltrials.gov/ct2/show/NCT02369731

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OpenClinica Database

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OpenClinica Database (2)

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Integrated Monitoring to Database

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Registry of Translarna™ PASS Status• Key partnerships: PTC, TREAT-NMD, CINRG/TRiNDS, and

Quintiles• Status as of September 2016

• 10 active sites across 3 different countries• France: 4 sites (1 patient)• Germany: 5 sites (17 patients)• Austria: 1 site (3 patients)

• 21 enrolled participants • Other countries under activation, in total 60 sites will participate

across 16 different countries in Europe and outside Europe• Questions: Abdallah Delage adelage@ptcbio.com

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