3^rd Annual Congress on Rare Diseases and Orphan Drugs October 30-31, 2017
(10 Plenary Forums - 1 Event)
San Antonio, Texas, USA

Biography:

Sara G Tylosky has over 20 years of experience in strategic management and global marketing in the pharmaceutical and biotech industries. Working with large pharmas to start- up biotechs, her enrollment and training consultancy in Phase 2-4 trials through the boutique CRO Farmacon has allowed companies to reach enrollment early and reduce study costs. By bringing real-time feedback and uncovering issues, her team helps insure targets stay on track. She holds a Master’s in Business from Florida Atlantic University and an undergraduate degree from Whitman College.

Abstract:

Statement of the Problem: The paucity and scattered rare disease patient population across the globe and with more than 50% of rare diseases affecting the pediatric population are the major factors that impede successful and faster enrollment into pediatric rare disease trials, therefore slowing down innovative treatment options. Particularly in Latin America, many rare disease patients have not been in a clinical trial before and many go misdiagnosed or not diagnosed at all. In 2016, there were only 25 ongoing pediatric rare disease clinical trials in Latin America in 7 countries, and yet Latin America as a whole represents 626.7 million people, or about twice the population of the United States and 8.63% of the entire world. With a growing middle class in Latin America and the US Latino population representing 17% of that population, pediatric rare disease trials in Latin America are worth their weight to be studied.

Methodology: This case study explores the unique study enrollment challenges in Latin America and shares three solutions within a global Phase 3 pediatric rare disease trial for a major pharmaceutical company.

Findings: Even with the most seasoned CROs and strong site feasibility reports, more than 80%; 7 of all clinical trials do not meet critical milestones and more than 50% of sites do not enroll a single subject, increasing costs of the study and delaying data capture. This project demanded innovative thinking and creative problem solving from not only Sponsors, Investigators, CROs, but also from the referring physicians, families and most critically, patient advocacy groups.

Conclusion & Significance: By applying detective skills, relationship building, data based motivation tools and having a deep understanding of the cultural landscape, communication and innovative management practices were integrated for successful enrollment, which can be duplicated in future trials.

Biography:

Sujatha Kannan MD is an Associate Professor in Anesthesiology and Critical Care Medicine and Co-Director of the Pediatric Neurocritical Care Program at the Charlotte Bloomberg Children’s Center at Johns Hopkins University, Baltimore, MD. She is also the CMO of Orpheris Inc. Orpheris is focused on the treatment of neuroinflammatory orphan diseases that result in death or severe disabilities, ccALD, neonatal brain injury, Huntington's disease, Rett syndrome and autism spectrum disorders. Orpheris' patented hydroxyl dendrimer technology selectively targets inflammation in injured glial cells implicated in a number of brain diseases. Controlling inflammation through targeting injured glia with OP-101 is a potent weapon against CNS disorders. OP-101 is the company's first potential drug candidate utilizing hydroxyl dendrimer technology to deliver therapeutic doses of an anti-inflammatory drug across the blood brain barrier to reduce inflammation in glial cells.

Abstract:

X-linked adrenoleukodystrophy (ALD) is an ultra-rare disorder (incidence of 1:17,000 males) caused by mutation of the ABCD1 gene, resulting in high levels of circulating very long chain fatty acids (VLCFA). The childhood cerebral form (ccALD) occurs in ~35% of X-ALD boys between the ages of 2-10 years, and is characterized by oxidative stress, neuroinflammation and microglial activation leading to a rapidly progressive cerebral demyelination fatal within 2-3 years. Hematopoietic stem cell transplant (HSCT), the only currently approved therapy, is effective in arresting neuroinflammation and demyelination only if provided early. There is a crucial need for therapies for patients who are diagnosed late or are not eligible for HSCT (~50% patients), and for arresting disease progression during HSCT. Rapid progression of neuroinflammation as characterized by MRI imaging correlates with loss of neurological function. Gadolinium enhancement on MRI indicating an impairment of the blood brain barrier (BBB) is a characteristic feature in rapidly progressing ccALD. Therefore, reducing or inhibiting neuroinflammation caused by activated microglia can lead to disease stabilization in ccALD patients not eligible for HSCT. OP-101 is a new chemical entity consisting of N-acetyl cysteine (NAC) covalently coupled to a metabolically- stable inactive dendrimer. Studies in several small and large pre-clinical models have demonstrated the selective endocytosis uptake of OP-101 by activated microglia/ and astrocytes upon intravenous administration, localizing only in brain regions where there is with neuroinflammation-induced BBB impairment of the blood brain barrier. OP-101 releases NAC intracellularly in activated microglia and astrocytes, which then acts to reduce the attenuating oxidative stress and inflammation, in these cells and leads producing to significant improvements in neurobehavioral outcomes in the preclinical models, unlike the free drug. Macrophages isolated from ccALD patients and stimulated with VLCFA have significantly reduced cytokine expression and glutamate secretion with increased glutathione levels, when treated ex vivo with OP-101. Pilot toxicity studies in juvenile rats show that no toxicity of OP-101 is safe at doses as high as even at 1000 mg/kg IV QOD. A phase 1/2/3 placebo controlled trial for patients with ccALD who are not eligible for HSCT is planned to start in 2018.

Biography:

Romina Ortiz completed her Bachelor’s and Master’s degrees at Johns Hopkins University in Neuroscience and Molecular Microbiology and Immunology, respectively. Her thesis focused on the interplay between the microbiome and hormones in autoimmune disease. She is a Co-founder of Rare Genomics Institute (RG), COO and VP of Patient Advocacy at RG. In 2016, she was awarded the Patient Advocacy Leadership award by Sanofi Genzyme. She trains volunteers on the topics of Genetics and Sequencing, directs a Patient Advocacy Program in next generation sequencing and research services to undiagnosed and rare disease patients and currently directs a philanthropic program with Illumina called iHope, offering free whole genome sequencing to children in need of a diagnosis. Her goal is to integrate phenotypic medical information with genomic data to identify the genetic cause to disease and accelerate the path to treatment and a cure.

Abstract:

From the Orphan Drug Act of 1983, a rare disease is a condition that affects fewer than 200,000 people in the United States. In the European Union, the condition must only affect fewer than 1 in 2,000 people. While the numbers seem small, there is an estimated 350 million people that suffer from rare diseases, with 25-30 million belonging to the US alone and so far there have been over 7,000 different rare diseases identified. To put this in perspective, there are more Americans affected by rare disease than for HIV, Heart Disease or Stroke combined. It is important to understand that by nature rare diseases are difficult to diagnose, and consequently are not tracked. Thus, it is hard to accurately determine the number of rare diseases and their impact on a population. The average length of tume from onset of symptoms to an accurate rare disease diagnosis is nearly 5 years, and patients see an average of over 7 different physicians before a diagnosis is made. This delay in diagnosis results in chronic physical, emotional and socioeconomic burden to both the patient and their family. A European Cost of Illness Study interrogating published literature on the cost of 10 selected rare diseases found that overall, the availability of data on economic burden for rare diseases was correlated with the availability of therapies, not the severity of the disease. Also, most rare diseases reviewed were found to have significant economic burden and indirect costs (many associated with loss of productivity) exceeded the level of direct costs. Rare Genomics has served over 500 undiagnosed patients since 2011, helping them access next generation sequencing to accelerate their pathway to a cure. We have seen the same patterns reported for rare diseases in our own patients including heterogeneous disease marked by a range of severity across a variety of biological systems. The most common systems affected are neurologic, respiratory, gastrointestinal, muscular and cardiovascular. The average RG patient has also seen a range of physicians, the top three specialties consulted are: neurologist, clinical geneticist, opthamologist and gastroenterologist. Lastly, undiagnosed/rare disease patients typically have already undergone a gamete of testing, the most common tests are: MRI, DNA microarray and single/panel sequencing. Because 80% of rare disease are genetic in origin, we hope that by providing support and access to next generation sequencing, we can help reduce the time and burden these families must undergo before identifying appropriate treatment for their disease.