Duchenne Newborn Screening in the U.S.

Transcription

1 Duchenne Newborn Screening in the U.S. NEXT Michele A. Lloyd-Puryear, M.D., Ph.D. 1, Annie Kennedy 1, R. Rodney Howell, M.D. 2 and Jerry R. Mendell, M.D. 3 1 Parent Project Muscular Dystrophy 2 University of Miami School of Medicine; Muscular Dystrophy Association 3 Nationwide Children s Hospital, Paul D. Wellstone Muscular Dystrophy Cooperative Research Center

2 About Duchenne muscular dystrophy

3 Consequences of Absent Dystrophin -The process continues with scar tissue replacing lost muscle fibers causing muscular dystrophy

4 Duchenne is not just a muscle disease

5 Duchenne Treatment: Major Approaches Glucocorticoids Exon Skipping Mutation Suppression Early Intervention 1 new product review result pending in U.S. Deflazacort review underway (EAP for U.S. families). PTC Ataluren review in discussion with FDA

6 Stop-codon Readthrough Exon-Skipping Gene Therapy Functional replacement with other proteins Anti-fibrotics Inflammation & Fibrosis Dystrophin Restoration/ Replacement Poloxymer Steroid Replacements Treating Duchenne Cardiac Serca 2A Ryanodine Receptor Calcium Regulators Muscle Mass Blood Flow Traditional cardiac drugs GsMTx4 Muscle growth pathways Stem Cells PDE5

7 Duchenne Newborn Screening in the U.S. With life-altering treatments on the near horizon, the Duchennecommunity recognizes the need to identify boys with Duchennewho will derive optimal benefit from these emerging therapies as early as possible before irreversible fibrosis and muscle deterioration occurs. Are treatments available that make a difference in intermediate outcomes when the condition is caught early or detected by screening? Are treatments available that make a difference in long-term health outcomes when the condition is caught early or detected by screening?

8 Key Questions and Issues 1. Usual Care and Course 2. Screening and Short-Term Follow-Up 3. Diagnosis 4. Benefits & Harms - Screening & Diagnosis (unrelated to treatment) 5. Treatment and Long-Term Follow-up 6. Intermediate Outcome Measures 7. Primary Health Outcomes (Patient) 8. Secondary Outcomes (Patient, Caregivers) 9. Benefits & Harms - Treatment & Long-Term Follow-up 10. Health Care System Needs

9 Duchenne Newborn Screening Efforts Underway Duchenne NBS Steering Committee 6 Working Groups Expanded Duchenne Newborn Screening Pilot Planning: what infrastructure is needed? Development of Educational Materials: for Clinical Professionals for Patient Community CK Validation Effort with PerkinElmer & California State Health Dept. National DBMD Carrier study underway led by PPMD Health economic data collection Evidence review and Generation of evidence to support nomination of Duchenne to RUSP

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11 Outreach & Education HCP & Patient Community Activities: reviewing Patient Community Outreach Materials from previous pilots refining Baby s First Test Flow Chart Interviewing other patient communities with experience in NBS to assess best practices Developing materials for provider outreach (state labs, birthing centers, PCPs, etc) Workgroup Members: Micki Gartzke*, Legacy of Angels/ Save Babies Through Screening Natasha Bonhomme*, Baby s First Test Mardee DeSantis, Duchenne community Michelle Morgan, MDA Ann Lucas, PPMD/Duchenne Connect Joan Scott, HRSA Annie Kennedy, PPMD SamiahAl-Zaidy, Nationwide Children s Yaacov Anziska, SUNY-Downstate

12 Clinical Care Considerations & Follow Up for Pre- Symptomatically Identified Infants with DMD Activities: Publication accepted (Muscle & Nerve) Phase II underway to include additional organizations (AAP, ACMG) ACT sheet update in process Workgroup Members: Anne Connolly*, Washington University Julie Bolen*, CDC Valerie Cwik, MDA Samiah Al-Zaidy, Nationwide Children s Kathi Kinnett, PPMD Jennifer Kwon, U Rochester Hoda Abdel-Hamid, U Pitt Jerry Mendell, Nationwide Children s John Day, Stanford Annie Kennedy, PPMD

13 Activities: Laboratory Performance Recommended a project to test the traditional method of screening for CK vs use of an immunoassay PKI project to start in California in September/October 2016 Workgroup Members: Harry Hannon*, CDC Foundation Medhuri Hegde, Emory Fred Lorey, Retired CA Public Health Dept Bob Currier, CA Public Health Department Michele Caggana, NY Public Health Department Petra Furu, PerkinElmer Stuart Moat, Wales Victor DeJesus, CDC Brad Therrell, NNSGRC Michele Puryear, PPMD

14 Clinical Integration Group and Longitudinal Pediatric Data Resource Development Activities: Creating Common Data Elements Creating an LPDR from the PPMD and MDA data sets Workgroup Members Amy Brower*, NBSTRN Ann Martin, PPMD Lauren Webb, MDA Richard Finkel, Nemours Children s, FL Michele Puryear, PPMD

15 Bioethical & Legal Considerations Activities: Series of ELSI issues identified Papers in progress ELSI considerations for NBS for DMD Working with NBSTRN ELSI group Workgroup Members: Aaron Goldenberg* Case Western Tom Crawford* Johns Hopkins Ed Goldman, WI/NBSTRN Aaron Goldenberg Angus Clarke UK Michele Puryear, PPMD Annie Kennedy, PPMD Rodney Howell, Univof Miami & MDA Kristin Stephenson, MDA Jeff Brosco*, Univof Miami, NBSTRN & Don Bailey, Fragile X Foundation served as WG members until recently when service on SACHDNC presented conflict

16 Evidence Review Workgroup Activities: Compiled evidence for DMD NBS utilizing the ACHDNC nomination form Workgroup Members Melissa McPheeters*, Vanderbilt Craig McDonald, UC Davis Natalie Street, CDC MD STARnet Ann Martin, PPMD DuchenneConnect Michele Puryear, PPMD Larry Charnas, Novartis Holly Peay, RTI

17 Proposed Distribution of Results: Screening Algorithm for DMD CK Testing Normal CK NBS State Lab Abnormal CK Results to Family via MH * Emory DNA Lab * Follow up Plan for Test Results: CK performed at NBS State Health Lab DMD Normal results sent to Family via Pediatric Clinic care provider. Abnormal CK to Emory DNA Laboratory If DMD/BMD mutation found results to Family via MH and referred to DMD Clinic. If female, parents see genetic counselor at DMD Clinic. If other muscular dystrophy mutation found, family informed and sent to DMD Clinic. If CK Elevated and no mutation found, the family is informed and patient advised to follow up in DMD Clinic for retesting of CK.

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19 Pilot Will need to determine: males only vs universal screening If males only, a deviation that needs to be explained If both, substantial educational/training needs Educational needs for parents/hc providers to understand limitations of screen False negative vs false positive carriers Adequacy of genetic service infrastructure PH infrastructure for proper gender assignment

20 Items Needed for Pilot Short Term Follow-up Need engagement of Muscular Dystrophy [MD] clinical infrastructure LPDR with CDEs for newborns and infants underdevelopment Long term Follow-up Need to establish guidelines for newborns-2 years of age Determine clinical outcome measures Monitoring females Monitoring other muscular dystrophies? Clinical trial arm testing therapies in newborns

21 Items Needed for Pilot Education/Training Informed consent process development Development of education and training materials for parents; for providers; for laboratory; for NBS program Quality Assurance Have analytic specificity parameters from Emory Working with CDC to set up QA/QC Refinement of CK screen: CA/PKI study Begin working with R4S: Need analytic parameters from CA study

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