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The Voice of the Patient Report: CDKL5 Deficiency Disorder (CDD)

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The Voice of the Patient Report: CDKL5 Deficiency Disorder (CDD) The Voice of the Patient Report: CDKL5 Deficiency Disorder (CDD) A report on the Externally Led Patient---Focused Drug Development Meeting corresponding to FDA’s Patient-Focused Drug Development Initiative Externally Led Public Meeting: November 1, 2019 Report Date: June 17, 2020 Hosted by: Loulou Foundation International Foundation for CDKL5 Research Submitted to: Center for Drug Evaluation and Research (CDER) & Center for Biologic Evaluation and Research (CBER) U.S. Food and Drug Administration (FDA) The Voice of the Patient: CDKL5 Deficiency Disorder This document represents a comprehensive summary report composed by patient advocacy organizations as a result of an externally led patient-focused drug development meeting; a parallel effort to FDA’s Patient- Focused Drug Development Initiative. This report reflects the organization’s account of the perspectives of patients and caregivers who participated in the public meeting. Submitted to: Center for Drug Evaluation and Research (CDER) & Center for Biologic Evaluation and Research (CBER) U.S. Food and Drug Administration (FDA) Authors and collaborators: Ana Mingorance, PhD, Amanda Jaksha, Theo Smart, technical writer, Lance Sherriff, transcript reviewer, and James Valentine, JD, MHS. Mingorance, Jaksha, Smart, and Sherriff have no disclosures. Valentine is employed by Hyman, Phelps & McNamara, P.C., a law firm that represents sponsors who are developing drugs for rare diseases as well as rare disease patient advocacy organizations, including BSF. Technical services: Provided by John Dudley & Eric Quigley of Dudley Digital Works. Funding received: Funding for patient travel received from Marinus Pharmaceuticals, Zogenix and Ovid Therapeutics. The CDKL5 Deficiency Disorder Externally Led Patient-Focused Drug Development Meeting was designed and implemented by the Loulou Foundation and the International Foundation for CDKL5 Research. The resulting “The Voice of the Patient Report: CDKL5 Deficiency Disorder (CDD)” was also prepared by the Loulou Foundation and the International Foundation for CDKL5 Research. Travel sponsoring companies had no control over the meeting content or related activities. Statement of use: The Loulou Foundation and the International Foundation for CDKL5 Research have the necessary permissions to submit “The Voice of the Patient Report: CDKL5 Deficiency Disorder (CDD)” to U.S. FDA. Linking to the report from the FDA website will not violate the proprietary rights of others. Version Date: June 17, 2020 Revision statement: This document has not been revised and/or modified after the version date listed above. The submitters have received all necessary permissions to submit this external resource to FDA. Linking to this resource from the FDA website does not violate the proprietary rights of others. Permission to link from the FDA website is granted by the Loulou Foundation and the International Foundation for CDKL5 Research. Point of Contact: Ana Mingorance, PhD, Chief Development Officer of the Loulou Foundation: [email protected]. ii Table of Contents Introduction ................................................................................................................................. 1 Overview of CDKL5 deficiency disorder .................................................................................................. 1 CDD pathogenesis ....................................................................................................................................................... 2 The clinical manifestations of CDD .............................................................................................................................. 2 Treatment overview .................................................................................................................................................... 3 Meeting overview .................................................................................................................................. 5 Report overview and key themes ........................................................................................................... 6 Topic 1: Key messages on the burden of disease in CDD ............................................................................................ 7 Topic 2: Key messages regarding perspectives on the treatment options in CDD ...................................................... 8 Feedback on benefit-risk in post-meeting questionnaire ........................................................................................... 8 Benefit-Risk Framework ......................................................................................................................... 9 Appendices ............................................................................................................................................ 9 Topic 1: Most significant symptoms and their impact on daily life .............................................. 10 Panel testimony ................................................................................................................................... 10 Perspectives on symptoms that matter most to patients and their caregivers ...................................... 13 A. Global developmental delay ............................................................................................................................. 14 B. Epilepsy/seizures .............................................................................................................................................. 15 C. Gastrointestinal and feeding problems ............................................................................................................ 16 D. Limited or absent speech ................................................................................................................................. 17 E. Visual impairment ............................................................................................................................................ 18 F. Behavioral disturbances (e.g. hypersensitivity, agitation, irritability, stereotypies, bruxism, and self-injury) 19 G. Limited hand control ........................................................................................................................................ 19 H. Difficulty walking .............................................................................................................................................. 19 I. Respiratory problems (e.g., aspiration, irregular breathing, etc.) .................................................................... 20 J. Sleep problems ................................................................................................................................................. 20 K. Scoliosis (curvature of the spine) ..................................................................................................................... 21 Impact on activities of daily life that child cannot do or do as fully due to CDD .................................... 22 A. Verbal communication (using words and sentences) ...................................................................................... 22 B. Independence for most activities of daily living ............................................................................................... 22 C. Non-verbal communication (e.g., using gestures and facial expressions to communicate with others) ......... 23 D. Using their hands to manipulate objects ......................................................................................................... 23 E. Social interaction and participation ................................................................................................................. 24 F. Feeding oneself ................................................................................................................................................ 25 G. Walking ............................................................................................................................................................. 25 H. Sitting unaided ................................................................................................................................................. 25 I. Have regular sleep patterns ............................................................................................................................. 25 J. Other issues mentioned related to the burden of CDD ................................................................................... 26 Topic 2: Caregiver perspectives on treatment/management of the condition ............................. 27 Panel testimony ................................................................................................................................... 27 The effectiveness of treatment and care of existing therapy for CDD ................................................... 29 Experiences with prescription treatments and supplements ................................................................ 29 A. Anti-epilepsy drugs [AEDs] ............................................................................................................................... 30 B. Supplements ..................................................................................................................................................... 32 iii C. Sleep medication .............................................................................................................................................
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