Day 1 :
George Mason University, USA
Keynote: Rare diseases and orphan drugs: Passion and compassion or growing market with career opportunities for scientists and technologists?
Time : 10:30-11:15
Harsha K Rajasimha is internationally recognized in the field of life sciences consulting, systems biology, healthcare IT systems integration, BigData analytics, genomics of rare diseases and precision medicine. He is currently the Global Head of life sciences R&D at Dell Healthcare and Life Sciences (acquired by NTT DATA Inc.), Founder President of Jeeva Informatics and Founder Board Member of the non-profit organization for rare diseases India, Affiliate Faculty and Co-Director of the Center for Metabolic and Rare Diseases at George Mason University. He was the global Vice President at Strand Life Sciences, a precision medicine company that develops genomics-based clinical lab-developed tests for cancer and inherited diseases. In collaboration with Rare Genomics Institute, he has received the Sanofi Genzyme’s rare diseases Patient Advocacy Leadership award in 2016. He has authored over 15 peer-reviewed articles and is often invited speaker at conferences. He has earned Baccalaureate degree in Computer Science from Bangalore University, Master’s in Computer Science and Doctorate in Genetics, Bioinformatics and Computational Biology from Virginia Tech.
The words rare and orphan often generate a compassionate response from those affected but rarely generates any excitement among scientists or technologists or entrepreneurs. The progress in diagnosing or treating a disease has been largely driven by patient advocacy groups fighting against specific diseases. While this continues to be a driver, numerous recent trends indicate a thriving orphan drugs market with over 4000 orphan designations and ~600 orphan drugs approved by FDA since 1983. Until recently, only a handful of countries had a formal national policy on rare diseases or umbrella organizations advocating patients’ interests, clinical research involving rare diseases and patients registries to engage the biopharmaceutical industry. A number of new national and international organizations are spurring innovation and creating opportunities for collaboration and progress never before possible. The international consortium for rare diseases research, international collaboration of rare diseases, rare diseases international are examples of international organizations. The organization for rare diseases India (ORDI) and Chinese organization for rare diseases are examples of the umbrella organization representing the collective voices of all stakeholders of rare diseases in the most populous countries. Technology trends in clinical-speed, low-cost genome sequencing is enabling diagnosis of thousands of genetic diseases in a single test, BigData integration and analysis technologies are enabling unprecedented global patients access, wearable devices and real-world data extracted from EMRs are empowering patients with a 360o view of their health data and mobile apps are enabling them to participate in drug discovery and clinical development process. Collectively, these trends point towards a very promising area of research and development for young scientists and engineers to pursue as career options with much hope for patients globally. I will present how ORDI is tapping into these opportunities for India.
Keynote: Speeding up access to medicines for patients with unmet medical need: Integrating evidence and regulatory pathways
Time : 11:35-12:20
Stella Blackburn has spent over 30 years in Pharmacovigilance and Pharmacoepidemiology in both regulatory and industry environments. She was trained in Medicine at Cambridge and London Universities and has an MSc in Epidemiology from the London School of Hygiene and Tropical Medicine. At the European Medicines Agency, she was responsible for developing risk management for Europe and was the lead author of the guidelines. She is passionate about optimizing the benefit risk balance of medicines and to helping bring medicines to patients with unmet medical needs; particularly those with rare diseases. She is a Visiting Scientist at the Center for Biomedical Innovation, Massachusetts Institute of Technology where she continues to work on innovative methods for bringing medicines to market. She is a Fellow of the Royal College of Physicians of Edinburgh and a Fellow and Past President of the International Society of Pharmacoepidemiology.
Patients with life-limiting diseases and few or no treatment options want early access to medicines which show potential benefits. At the same time, regulators want reassurance that the potential benefits outweigh the potential risks; that the risks can be managed effectively and that comprehensive evidence will be provided. Getting a balance between these two stakeholders needs can be difficult. This can be compounded by the needs of payers who want evidence of cost-effectiveness. In the context of a rare disease, developing comprehensive evidence for all stakeholders is even more difficult when patients may be relatively scarce. In Europe, the European Medicines Agency (EMA) developed Adaptive Pathways as a means whereby a medicine could receive an initial authorization in a niche indication with a condition that development work would continue and that real world evidence would be gathered by close monitoring of patients receiving the marketed medicine. Regulators, HTA bodies, patients and healthcare practitioners are involved in the development discussions. Access to patients beyond those with most need would be gradually expanded as more evidence became available with the expectation that a “normal” marketing authorization would be achieved. This concept of using a combination of real world evidence along with clinical trials to optimize drug development is being further developed by the Center for Biomedical Innovation, part of the Massachusetts Institute of Technology. The purpose of this presentation is to explain the Adaptive Pathways concept and the multinational discussions which led to it and how early use of real world evidence can help drug development; particularly in the rare disease field. In particular, it will explore the use of disease registries as a means of speeding up trials, providing invaluable information on the natural history of the disease and monitoring patients in the post-approval setting.
University of Alabama at Birmingham, USA
Time : 12:20-13:05
Ashwani K Singal is working as Associate Professor of Medicine in the division of Hepatology and Director of Porphyria Center at the UAB, Birmingham AL. His clinical research interests include alcohol and non-alcohol fatty liver disease, porphyria, and renal dysfunction in liver cirrhosis. He has over 110 publications, on editorial board of reputed journals, and research award committees of the AGA and AASLD. His research is funded by the Transplant Institute of the UAB, ACG, NIAAA, and NIDDK from the NIH, and pharmaceutical industry.
Porphyria is a group of metabolic disorders due to altered enzyme activities within the heme biosynthetic pathway. It is a systemic disease with multiple potential contributions to mitochondrial dysfunction and oxidative stress. Recently, it has become possible to measure mitochondrial function from cells isolated from peripheral blood (cellular bioenergetics) using the XF96 analyzer (Seahorse Bioscience). Using various inhibitors and activators of mitochondrial respiration, this technique measures various components of O2 consumption rate (OCR) in peripheral cells such as basal, ATP linked, proton leak, maximal, reserve capacity, non-mitochondrial, and oxidative burst, all measured as pmol/min./100,000 monocytes. We performed cellular bioenergetics on 18 porphyria (9 PCT, 6 acute, and 3 protoporphyria) patients and 39 age/gender matched healthy controls. Of porphyria cases, 5 were active (1 PCT and 4 acute) and 13 in biochemical remission. Monocyte bioenergetics was significantly decreased in active porphyria vs. porphyria in remission and vs. healthy controls. Among 6 acute porphyria, a negative correlation (-0.8 to -0.93) was observed between urinary porphobilinogen and various components of monocyte OCR. In two pseudporphyria patients, monocyte OCR was similar to healthy controls and higher than active porphyria. These novel and interesting preliminary findings suggest existence of mitochondrial dysfunction in porphyria and potential non-invasive biomarker for disease activity. Studies are suggested to examine mechanisms of these findings as basis for deriving mitochondrial based therapies in management of porphyria.