- CiPA Update December 2018 December 11, 2018
Dear CiPA Community,
Welcome to the CiPA Quarterly Update!
We are happy to share news from the recent ICH face-to-face meeting held in November 2018. The ICH S7B/E14 Q&A concept paper and work plan have been approved! The ICH Assembly endorsed the establishment of an Implementation Working Group (IWG) to begin the process of developing a Q&A document. This IWG will build on work done by the former E14/S7B Discussion Group (DG) including work on the CiPA initiative.
The purpose of the IWG will be to provide guidance around the proposed nonclinical assays (in vitro, in silico, and in vivo). The current plan calls for a two-staged Q&A approach starting with S7B and then E14 guidance with the goal to have this be a more efficient process. Read more online including the concept paper and work plan:
- Vicente J, Zusterzeel R, Johannesen L, Ochoa-Jimenez R, Mason JW, Sanabria C, Kemp S, Sager PT, Patel V, Matta MK, Liu J, Florian J, Garnett C, Stockbridge N, Strauss DG. (2018.) Assessment of Multi-Ion Channel Block in a Phase-1 Randomized Study Design: Results of the CiPA Phase 1 ECG Biomarker Validation Study. Clin Pharmacol Ther. 2018 Nov 17. doi: 10.1002/cpt.1303.
- Li Z., Ridder B. J., Han X., Wu W. W., Sheng J., Tran P. N., Wu M., Randolph A., Johnstone R. H., Mirams G. R., Kuryshev Y., Kramer J., Wu C., Crumb W. J., Strauss,
D. G. (2018). Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative. Clinical Pharmacology and Therapuetics. Available online August 27, 2018. doi:10.1002/cpt.1184
- Blinova K., Dang Q., Millard D., Smith G., Pierson J., Liang G., Brock M., Lu H.R., Kraushaar U., Zeng H., Shi H., Zhang X., Sawada K., Osada T., Kanda Y., Sekino Y., Pang L., Feaster T.K., Kettenhofen R., Stockbridge N., Strauss D.G., Gintant G. (2018). (2018). International Multisite Study of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment. Cell Reports. Available online September 25, 2018. https://doi.org/10.1016/j.celrep.2018.08.079.
If you’re interested in finding past Quarterly Updates, they are available online.
Jennifer Pierson, MPH
Senior Scientific Program Manager
Health and Environmental Sciences Institute (HESI)
CiPA and Cardiac Safety
The Comprehensive In Vitro Proarrhythmia Assay (CiPA) effort will substantially evolve the preclinical and clinical proarrhythmia assessment of new chemical entities. At its simplest levels, more comprehensive channel-screening efforts could be implemented early in drug discovery using automated patch-clamp techniques, with the resulting data used to assess proarrhythmic risk using in silico APD reconstructions. Such data could be used for candidate selection as well as to guide further testing.
It is encouraging that elements of the CiPA are already being used in early drug discovery (for example, increasing the number of ionic currents being interrogated and using stem cell cardiomyocytes) as well as guiding early medicinal chemistry efforts, refining early hazard identification, and potentially impacting clinical development. Such efforts should reduce the automatic exclusion of IKr-blocking drugs from early drug discovery. It is anticipated that the commercial costs for such services would be substantially reduced as these efforts are implemented.
Academicians, clinicians and regulators who are familiar with clinical QT studies, mechanisms of proarrhythmia, drug safety assessments, and regulatory submissions are working together under the auspices of the CiPA Steering Committee, Cardiac Safety Research Consortium, HESI, FDA, SPS, EMA, Health Canada, Japan NIHS, and PMDA on this effort. For more information and updates, please contact us at firstname.lastname@example.org.
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- CiPA Update September 2018 September 19, 2018 Dear CiPA Community, On behalf of the CiPA Steering Team, I would like to share some exciting updates. We are pleased to share materials from the recent May CiPA Update meeting, “The ...