Rare Diseases: Together, We Can Advance Care
Rare diseases are one of the most scientifically complex health challenges of our time. The hurdles are well-documented and immense, but the successes achieved should be a constant reminder of the need to work together to advance care.
When we look at the rare disease landscape, it can often feel both dire and overwhelming when it comes to solving unmet needs. Worldwide, approximately 7,000 rare diseases have been identified thus far, and an estimated 250 new rare diseases are discovered annually. Although rare diseases affect small numbers of patients, when combined roughly 350 million people worldwide are living with a rare disease. Commonly presenting in early life, it can also present in adulthood with a chronic phase. Rare diseases are often progressive, disabling, and life-threatening. Worse so, approximately 30 percent of children suffering with a rare disease will die before they reach the age of 5.
Most rare diseases (95 percent) still do not have an FDA-approved treatment option, and people face an average of 5-7 years waiting for an accurate diagnosis. Approximately 80 percent of rare diseases are caused by abnormalities in a person’s genes. These genetic abnormalities may be passed down from parents’ genes or caused by mutations or changes to a person’s DNA during his or her lifetime. Because of the rarity of each disease, however, much remains unknown about the underlying causes and the clinical course of many of these diseases. Even within a rare disease category, there can be many variations or sub-types, resulting in different clinical manifestations and disease progressions. For those who are suffering, this presents an urgent need for continued research to map the genes responsible for rare diseases, identify genetic and other biologic anomalies that contribute to these conditions, and understand the natural history of rare diseases to inform the development of potential therapies.
Despite the many scientific hurdles in the development of medicines to treat rare diseases, researchers from government, academia, and the biopharmaceutical industry have leveraged new technologies combined with the growing scientific understanding of many of these diseases to develop some truly groundbreaking therapies over the last 10 years.
Healthcare marketers have an opportunity to play a significant part in advancing the care of rare diseases. Together, we can help develop partnerships between invested parties where every stakeholder has a role to play – government, academia, industry, advocacy, and communication agencies joined in the single purpose of driving research into actions.
Fueling the Engine of Innovation Through Collaboration
President Biden’s administration is working to form a new agency that has the potential to change the face of healthcare: the Advanced Research Projects Agency for Health (ARPAH). It’s anticipated this agency will pay academics and private companies to develop innovative health products and services, mimicking the process of the Defense Advanced Research Projects Agency (DARPA), whose work helped create the internet. The goal would be to create a government engine that could help advance innovation into real-world products for healthcare to solve persistent problems: high drug costs, lack of treatments for rare diseases, poor systems of care, and of course, pandemic preparedness.
HARPA – or ARPA-H, as President Biden calls it in his vision document – would do the same thing, but for common health issues. Similar to the U.S. Department of Health & Human Services’ BARDA (Biomedical Advanced Research and Development Authority), which is focused on health and biological threats such as COVID-19, HARPA would focus on the creation of new products that solve medical problems where there is often limited interest or incentive for investment from private companies.
The government has tried to drive healthcare innovation through a number of different means. The Orphan Drug Act of 1983 provides grants that are intended to defray costs associated with developing drugs for rare diseases. The Bayh-Dole Act, passed in 1980, allows for government-funded science to be patented. The National Center for Advancing Translational Sciences works with universities to fund innovative science that can be applied to the real world. But many of these projects never make it out of the lab. To bring any of them to scale, private companies still need to be involved.
One solution? Have research investments that build government-academia-industry partnerships successfully hand off and fund basic scientific research development all the way through to commercial products. These types of investments are in fact opportunities to make real-world differences in the lives of patients with rare diseases.
Advancing Care—The Genetic Revolution
Science has been the key driver of advancements, where our increasing knowledge of the human genome has helped to improve both the diagnosis and treatment of rare diseases, given that approximately 85% of these diseases are genetic. Progress in next-generation sequencing has shown that sequencing the whole genomes of large numbers of individuals in a standardized way can improve the diagnosis and treatment of patients with rare diseases. To date, scientists have identified the genes responsible for approximately 50% of the estimated 7,000 rare diseases. Genomic developments continue to be key in the advancement of therapeutic research.
The genetic revolution in rare diseases is here. After decades of promise tempered by many setbacks, gene therapies are now creating new treatment options for a wide variety of rare diseases. Gene therapy can safely correct many genetic diseases, where successes are the result of safety modifications and improvements in gene transfer efficiency and delivery, fueled by basic science research. Now, as clinical progress in the field rapidly grows, gene therapies are beginning to benefit those with inherited immunodeficiencies, blood disorders, blindness, neuromuscular disease, and more.
In the last 20 years, we’ve heard much about the promise of gene therapy, but with limited success. While the outlook for genetic cures is still in its infancy, it’s only in the last 5-8 years that we’ve seen an accelerating increase in finding effective, clinically beneficial gene therapy options for a variety of diseases.
Science has finally proven that gene therapy is not only a fascinating scientific idea, but also a viable therapeutic option. An integrated approach is needed between the various stakeholders (scientists from both academia and the pharma industry, regulatory authorities, patient representatives, etc.) to review the process as a whole, explore possibilities and find solutions to make these therapies available for as many patients as possible.
But it also remains unclear whether gene therapy with viral vectors will ultimately be the best cure for some of these diseases. These therapies all work based on gene insertion, while newer gene-editing techniques such as CRISPR-Cas9 may be able to directly correct genetic defects without the need for additional gene therapy. The CRISPR gene-editing technique has been revolutionizing scientific research by making it much easier to rewrite the genetic code. It’s also raising high hopes of curing many rare genetic diseases.
A New Era for Rare Genetic Diseases: Messenger RNA Therapy
Over the past decade, mRNA (messenger ribonucleic acid) has emerged as a promising next-generation technology for creating a new class of medications to potentially treat cystic fibrosis, heart disease, rare genetic conditions, and even some cancers.
Exogenous delivery of mRNA is a new class of medicine with broad applicability including the potential to treat rare monogenic disorders. Recent advances in mRNA technology have transformed the utility of mRNA as a potential therapy to restore or replace different types of therapeutic proteins. Preclinical proof-of-concept has been demonstrated for mRNA therapy for three different, rare metabolic disorders: methylmalonic acidemia, acute intermittent porphyria, and Fabry disease. For all three disorders, mRNA therapy restored functional protein to therapeutically relevant levels in target organs, led to sustained and reproducible pharmacology following each dose administration of mRNA, and was well tolerated as supported by liver function tests evaluated in animal models. These data provide compelling support for the continued clinical development of mRNA therapy as a potential treatment for a number of rare metabolic disorders.
Enhancing Patient-HCP Communication Is Needed Now, More Than Ever
The development of innovative therapeutics like gene therapy, gene editing, and mRNA therapies have the potential to significantly affect the lives of patients with rare diseases and alter the course of their disease, hinting at the possibility of being able to use language like “cure.” The rewards may be great, but these rewards are not without risk. This risk-reward benefit necessitates the need for stronger education and transparency among and between patients and HCPs.
Gene therapy trials are advancing across a range of diseases. But in the last year alone, several gene therapy trials in the United States were placed on clinical “hold” due to safety and manufacturing concerns, a reminder of the uncertainties still facing gene therapy. These “holds” also highlight the lingering worries about a one-time genetic treatment, and what this might mean for patients.
Bridging the gap between science and patients remains one of the biggest challenges facing genetic therapies. To ensure we don’t deliver false hope to patients and caregivers, we need to be transparent and thoughtful about the information we provide, finding the most effective ways to generate and share information so it reaches the patients who need it most. Most importantly, we need to deliver information that allows clinicians and patients to make the best treatment decisions possible.
Life-altering genetic therapies demand better education to help deliver enhanced HCP-patient communications and interactions to drive a fully-informed decision. Shared decision-making is the right approach for these times, as it’s a key component of patient-centered healthcare. Clinicians and patients are increasingly working together to make decisions and select tests, treatments, and care plans based on clinical evidence that balances risks and expected outcomes with patient preferences and values.
To benefit from possible gene therapies, patients need to have the knowledge and access to resources allowing them to connect with the right HCPs to make informed decisions. As we move gene therapies from the lab to the clinic, we need to make sure we’re providing patient-friendly information to the public so patients suffering from these diseases can learn about treatment options. Healthcare marketers need to be a strong voice for patients as these are often confusing and very complex diseases. Data visualization can help make the complex more understandable and relatable. Visualizing health data allows us to share key information via graphs, charts, and other visuals that show, as well as tell. Data visualization is a powerful way to share urgent health information, swiftly and effectively.
Educating clinicians is equally as important. Some primary care physicians may not encounter many patients with genetic diseases. As a result, these physicians may need more education about how gene therapy could affect a patient’s care. Additionally, the long-term effects of gene therapy remain understudied because the research is still so new. Patients volunteering for gene therapy clinical trials right now may be taking very different versions of the treatments than their contemporaries will who participate in trials for the same diseases five or more years down the road.
In summary, we need to provide patients, caregivers, and advocates with greater access to health information to improve their understanding of the illness they face and make them a more integral part of the decision-making process when assessing which course of treatment is best for them.
Elevating Advocacy Partnerships
Advocacy organizations are key stakeholders in advancing care in rare diseases, providing the much-needed link between research, industry, and education. Many of these organizations have created high-quality patient registries, where they collect information about individuals, usually with a focus around a specific diagnosis or condition. The goal is to enable rare disease patient organizations to better promote and support patient-focused research.
The gene therapy community heavily depends on the advocacy efforts of the rare disease community. Volunteers with rare diseases and their families can help scientists enhance their gene therapy platforms—the strength of this partnership will be integral in helping to deliver a more hopeful future. Gene therapy researchers need to convey to patients that they are working on these problems. Even though the process takes a long time, the patients need to know they are not being forgotten.
Despite these genetic advances, we know that much more work is needed to help patients with rare diseases advance their care. This is an opportunity for a stronger partnership to be fostered between all stakeholders, so they might work collaboratively to drive a spirit of “we’re in this together.”
The National Organization for Rare Diseases (NORD) says it best – “Alone we are rare. Together we are strong.”