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There are approximately 7 000 Rare Diseases, which from a regulatory perspective are defined as those diseases where there are less than 200 000 patients in the US or that affect no more than five in 10 000 of the general population in the EU. S uch diseases usually have a genetic basis, often affecting patients early in childhood, and are frequently progressive, disabling and life threatening in nature. These characteristics can have a devastating psychological impact on families of children suffering from these diseases. Better known examples of Rare Disease include Duchenne Muscular Dystrophy, Cystic Fibrosis, Mucopolysaccharidoses and Rare Cancers. While each rare disease alone affects a small number of patients, it has been estimated that the combined number of people suffering from Rare Diseases in the US and EU exceeds 55 million, highlighting the huge societal impact of these diseases. A number of unique clinical, regulatory and commercial challenges are associated with the development of Therapies for Treatment of Rare Diseases. In recognition of these challenges, there has been legislation in the US, EU and elsewhere in the world which provides regulatory and financial incentives aimed at stimulating investment in Orphan Drugs to treat Rare Diseases. In addition, FDA has created an Office of Orphan Products Development to focus on challenges of developing therapeutics for Treatment of Rare Disease and to help companies navigate the regulatory review process. In addition, in 2010, FDA created the Rare Disease Program within the Office of New Drugs with the specific focus on developing policies and procedures for review of New Drug applications for Orphan Drug Products and to ensure appropriate training for FDA reviewers. In both the US and the EU, Orphan Drug Designation can BE applied at any stage of the development process. Orphan Drug legislation has generally been considered to be extremely successful. Prior to these legislative acts there were essentially no drugs specifically developed to treat Rare Diseases, whereas since passage of the Orphan Drug Act in the US in 1983, 2 755 agents have received Orphan Drug Designation in the US, with 424 Orphan Drug approvals. Analysis of compounds progressing from clinical Development To Approval in the US between 2006 and 2010 shows that 28% of all New Drug applications were for Rare Diseases, and that approval rates for Rare and common Disease applications have been similar. Recent success in development of Orphan Drugs coupled with productivity challenges in classic pharma R & D Model for indications with higher prevalence, has resulted in a number of major pharmaceutical companies recently establishing business units focus on Rare Diseases. In turn, this has resulted in increased investment of venture capital companies and early - stage biotechs in Rare Disease programmes. In part, increased interest in Rare Diseases may also be attributed to advances in knowledge of disease biology and genomics, which has made it clear that a number of more prevalent diseases may be categorise into several distinct subsets of disease with unique characteristics.
Although individually uncommon, Rare Diseases collectively affect as many as one in 17 people. In European Union alone, that is around 30 million people! Around half of them are children. Rare Diseases span all areas of Medicine and have a substantial impact on public health, society and national economies. Their rarity and diversity pose specific challenges for research, healthcare provision and for development and marketing of treatments. Many patients with Rare Diseases lack timely and accurate diagnosis and even fewer receive tailored treatments. 80% of rare diseases have a genetic component, and the genomics revolution has brought hope of gene - base treatments for many rare diseases step closer. The first sequencing of Human Genome completed in 2003 required work of hundreds of scientists for more than 10 years at a cost of over 3 billion. The same task is now feasible on a single sequencing instrument within days at a cost of less than 10000, and this cost is continuously decreasing. Genomics and other newly emerging omics techniques hold the key to new diagnoses and therapies for Rare Diseases. These new technologies, which allow researchers to look into way diseases affect the entirety of DNA, proteins, lipids and metabolites in the human body, are generating data on a huge scale unprecedented in biomedical research. Despite advances in computing technology, processing and analysis of data, or even its transfer from one location to another, is difficult and far from routine. To date, thousands of complete Human genomes and hundreds of thousands of exomes have been sequence. Exome sequencing is a technique that captures part of the genome that holds coding instructions to make body proteins. This has led to an explosion of data that reveals ways in which one individual's DNA differs from another and this rapid growth is expected to continue. The limiting factor is now our ability to share and analyse these vast quantities of data, rather than capacity to generate them. The highest costs are associated with bioinformatics processing of these large datasets. Consequently, new and innovative bioinformatics solutions are require. However, sequencing is only the first part of the story and does replace clinical expertise - in fact, combining genetic and clinical data is more important than ever. The genome sequence of each individual has several hundred thousand private variants that are not found in the general population. The majority of these changes are not directly disease causing, but may still be relevant for gene regulation and symptom severity. Our current understanding of underlying biology is often too limited to make appropriate predictions for individual Patient. Combining and integrating different types of omics: genomics, transcriptomics, proteomics, metabolomics, lipidomics and detailed phenotype data across research centres and across diseases is essential to advance knowledge. While competition between different research groups is the driving force to advance science, harmonisation and sharing of data is ultimately required to compare, combine and make best use of results.
Patients affected by rare diseases often find there are no treatments for their condition. Of 7 000 known diseases in this category, 95 percentreferred to as Orphan diseasesdo not have a single FDA - approved drug treatment. Rare diseases by definition affect small number of patients, and they historically have not attracted significant pharmaceutical investment. 1 1. Evaluatepharma Orphan Drug Report, 2014. Recently, though, large pharmaceutical companies have begun to pay more attention to rare diseases, drawn by government incentives and a greater likelihood that treatments for what are often life - threatening or severely debilitating diseases will be successful for both pharmacos and for patients. Sidebar Government incentives describes some of the measures governments and regulators have introduced to encourage innovation in diseases with low prevalence 2 2. Define as occurring in fewer than five people in every 10 000 in the European Union, and in fewer than seven people in every 10 000or 200 000 of the total population United States. And high unmet need.S effect has been that, in 2015, 45 novel rare disease Therapies were approved by the FDA Center for Drug Evaluation and Research, significantly more than the average of 28 approved during each of the previous nine years. 3 3. 2015: Another Strong Year for Patients in Need of New Drug Therapies, FDA Voice, January 4 2016. With sales of Orphan drugs forecast to achieve compound annual growth of 10. 5 percent Year 4 4. Almost twice the rate of the overall prescription market, excluding generics. To account for 19 percent of worldwide prescription sales at a value of $176 billion by 2020, and with typically low commercialization costs, rare disease therapies are becoming increasingly attractive and are expected to further bring transformational patient benefits. How pharmaceutical companies with new rare disease drugs launch their products will be crucial to their success, however. For while all drug launches are complex, launches of rare disease treatments are particularly so. Usually, when a large company introduces such treatment, it is entering the relevant therapeutic area for the first time. It is therefore likely to lack both expertise in disease and in - depth understanding of the health ecosystem and of Patients experience of disease. Because conditions are rare, launch team will have few, if any, analogs from which to draw lessons. And because the company is likely to have buy drug from a small biotech company at a late stage of development, it might allow too little time to prepare for its launch. To be successful, launch of rare disease treatment needs a different approach from the standard launch framework. This paper explains why, and describes the hallmarks of success.
This guest blog was written by Rosie Rosati, Health advocate for Mesothelioma + Asbestos Awareness Center. In recent years, healthcare industry has begun embracing the benefits of telehealth and acknowledging obstacles this digital advancement can overcome. Patient - centered technology provides easy access to quality care for patients residing in remote areas or living in locations with limited access to specialists. Through video, digital images, and web - base applications, this technology allows physicians to remotely manage and monitor patients ' symptoms, consequently saving them significant amounts of energy, time, and money. Telehealth is being deployed across industry, yet it has been particularly helpful for those living with rare diagnoses who often have limited information about their condition and the best route for treatment. This method of care not only makes it easier for patients to receive necessary monitoring and treatment they need, but connects researchers, physicians, and specialists from around the world, allowing them to collaborate and determine the best way to manage and treat each individual. Rare Diseases were once called Orphan Diseases because researchers and pharmaceutical companies expressed little interest in studying these difficult and uncommon cases. Fortunately, Orphan Drug Act was passed in 1983, which advocated for Rare Disease patients and their fight for substantial treatment and care. This movement encourages pharmaceutical companies to invest in research and treatment for those suffering from uncommon illnesses, which has resulted in 7 000 rare conditions recognized today. Although only 5% of Rare Diseases have access to FDA - approved treatments, ODA has proven to be promising as the pipeline for Rare Diseases continues to grow. This progress can be seen in 566 medicines in review for patients suffering from rare conditions, with 40% of these treatments targeting patients with rare forms of cancer. However, while pharmaceutical companies are investing more money into researching and developing Orphan drugs, patients are still often left feeling frustrated and alone as they realize how little is known about their disease and personal experience. Early detection is a pressing challenge, so patients whose symptoms baffle health professionals may be forced to visit a handful of doctors over a span of several years before receiving an accurate diagnosis. This overwhelming process sometimes requires patients to endure extensive travel which can be physically and financially draining, especially if their condition has regress. These challenges shed light on the advantages of telehealth, which can provide remote consultations through video, phone, or email, and has potential to improve patients ' outcome. Technology has immense potential for One in eight adults aged 20 or older is diagnosed with a rare form of cancer, which can be extremely difficult to diagnose because symptoms are usually nonspecific and confused with more common diagnoses. Receiving valid and early diagnosis has become an undeniable obstacle for Rare Disease patients and clinicians, making the idea of tele - oncology appealing to those struggling to determine the root of their condition.
Some authors have suggested use of certain advanced methods to tackle confounding in studies of Rare Disease health outcomes, such as propensity scores. 28 29 When comparing patients being treated for particular Rare Disease to patients with the same disease but who are not being treat, confounding will occur if determinants of one patient's receipt of treatment over another are also risk factors for outcome of interest. Often, many such confounders can be present. The Propensity score reduces the dimensionality of confounding in observational studies by summarizing all potential confounders into single scalar score. 30 This tool is particularly useful in studies in which there are few outcome events relative to the number of confounders, which is a defining characteristic of Rare Diseases. 31 in a study of dose - response effect of enzyme replacement therapy in patients with Gaucher Disease type 1, Grabowski and colleagues created propensity scores to summarize multiple confounders and then use scores to match patients who received different doses of enzyme therapy. 32 Though propensity scores can facilitate adjustment for many potential confounders by modeling exposure rather than outcome, neither propensity score nor traditional outcome regression modeling can overcome confounding due to unmeasured variables.
In general, six focus countries in Southeast Asia have made healthy progress towards Rare Disease management. However, progress differs widely across themes and region.S For example, Singapore has a mature Health System and several disease awareness initiatives but limited Rare Disease legislation or funding. On the other hand, Philippines falls short relative to its peers in terms of health capacity and health expenditure, but IT is the first country in the region to introduce a national strategy specifically for Rare Disease management. In following, we observe results for each theme, highlighting countries ' progress and shortcomings.
There are major barriers toward effective Rare Disease Management worldwide. The challenging nature of rare diseases, most notably their low incidence rate, renders management difficult as average annual cost per person work inverse to prevalence. Moreover, increasing number of Orphan drugs and budget impact continue to concern decision makers. As such, governments worldwide face problem in prioritising funding for orphan drugs. In particular to Southeast Asia, over 45 million people in the region are estimated to suffer from rare diseases. However, Southeast Asia also shoulders other health challenges that are more common, and therefore more publicised. With fewer resources than those in many other areas of the world, region has historically focused its health policy on ensuring primary and preventive care, acute care, and management of disease with high epidemiologic burden. Concentration on broadening access in such areas understandably leaves little room for funding, let alone discussions, on rare diseases. Despite limited prioritisation, horizontal and vertical equity arguments from various stakeholders, including patient advocacy groups, have elevated the need to tackle rare diseases across the region. We can accordingly observe that Southeast Asian countries consider rare diseases initiatives as in scope and salient, although current efforts are fragment and disperse across the region.
Rare or Orphan Diseases are defined in the United States as Diseases and Conditions that have an incidence of < 200 000 patients, or elsewhere in the world as having a prevalence ranging from < 1: 2000 - < 1: 50 000. Approximately 80% of thousands of defined Rare Diseases have an underlying genetic basis and approximately three - fourths affect children. Many of these Rare Diseases lack treatments or cures and are fatal, making new treatments potentially transformative for the lives of patients. However, there are several unique challenges surrounding development of Orphan Diseases treatments. Low patient numbers, incomplete understanding of disease pathology, phenotypic heterogeneity, and lack of established endpoints are barriers to efficient and effective clinical trials, which can make meeting Regulatory Requirements for Drug approval challenging. The interactive, 1 - day BioNJ meeting, Developing Rare Disease Regulatory Strategy Under Current Global Statutes: Stakeholder Discussion, was held at Amicus Therapeutics, Inc. On March 28, 2018 to discuss challenges in developing Rare - Disease Regulatory strategies Under Current Global Regulatory Statutes. The meeting includes representatives from the Food and Drug Administration, biopharmaceutical industry, and not - for - profit agencies, and focus on Orphan Diseases in pediatric and adult patients. It was attended by more than 90 leaders in various therapeutic areas, Regulatory policy, pharmacology, biostatistics, and Research ethics. This summary of proceedings identifies potential strategies to overcome regulatory hurdles through Open collaboration.
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