About 30 million Americans are affected by a rare disease, and globally the figure is at a staggering 400 million. Children make up approximately half of the population affected by rare disease, and roughly one third of these children will not live to see their 5th birthday. Most rare diseases (~ 80%) have an identified genetic origin and the majority of these diseases (~65%) are associated with a reduced lifespan. There is an urgent need for more therapies, as about 95% of these diseases do not have a single FDA-approved treatment. Adding to these challenges, Americans of color are largely underrepresented in clinical trials which leads to a lack of understanding about how effective current therapies are for diverse and traditionally underrepresented populations. Compounding this issue further is the fact that some rare diseases such as sarcoidosis, sickle cell anemia, thalassemia, and some forms of lupus are known to disproportionately affect people of color. Understanding the nuances of the rare disease space is critical to increasing diversity and equity for underserved and underrepresented minorities.
The evolution of clinical trials to better serve minority populations
Scott Schliebner, Senior Vice President, Scientific Affairs at PRA Health Sciences, has over 25 years of experience in clinical drug development and is particularly experienced in developing innovative solutions for carrying out clinical research in challenging patient populations. "From a purely scientific standpoint, the goal is to test new treatments to make sure that they're safe and efficacious in representative populations," says Mr. Schliebner. Diversity of the population being studied for a new therapy ensures that the researcher understands how the investigational therapy works specifically for certain subsets of patients. Clinical trials in a lot of ways, mirror healthcare explained Mr. Schliebner. "When we think about clinical research as a care option (CRAACO), we need to consider how healthcare is evolving and make sure that clinical research evolves in parallel." The COVID-19 pandemic was a potent catalyst for speeding up the adoption of decentralized mechanisms to allow clinical trials to continue to proceed during these difficult times. "A paradigm shift is moving us from the traditional site-based, brick and mortar clinical trials, to decentralized trials (DCTs), that meet patients where they are. DCTs provide the potential for greater access in a new way," emphasized Schliebner. More far reaching access is possible with a DCT model and therefore the potential to reach diverse populations is increased.
Challenges for sponsor companies developing rare disease therapies
Pharma and biotech companies that are developing treatments for rare diseases face numerous challenges from being able to enroll enough subjects in their clinical trials to evaluating the correct clinical endpoints to show efficacy. "Patients with rare diseases face a diagnostic odyssey, a journey of going from physician to physician, in a frustrating attempt to secure an accurate diagnosis," explains Mr. Schliebner. This translates into sponsor companies searching for needles in a haystack due to frequent misdiagnoses. Then even when they are able to find enough trial subjects, these patients will be more than likely scattered over a large geographic area. "Logistically it makes it very hard to connect these disparate patients with investigators participating in a clinical trial," says Mr. Schliebner. Another challenge arises from the inherent nature of rare diseases themselves, the fact that there are so few people with the disease and not much is known about the selection of clinical endpoints. "We may not even know what the natural history of a particular rare disease is, making it difficult to know if we are improving things above and beyond some threshold, when we don't often know what the underlying baseline is," pointed out Mr. Schliebner. "Often, sponsors end up using endpoints that aren't really relevant to patients, which makes it difficult to enroll subjects in a study that they do not consider important or relevant to their disease," explained Schliebner, who went on to say that "engaging with patients upfront enables sponsors to learn what's critical to them and this provides insight to direct their development programs."
Positive trends and incentives
Mr. Schliebner believes that sponsors are getting better at identifying patients with rare diseases. "Tools for diagnosing patients are improving our understanding of some of these nuanced disease states," he explains. Biopharma as a whole, whether it be small biotechs, or large pharma, are getting involved in the rare disease space and are adding rare disease divisions and business units as an area of focus, explained Schliebner. "It is no longer limited to a one-off endeavor or a specialty company as there is so much opportunity and unmet medical need in the rare disease space." The challenges may be greater, but perhaps they are not insurmountable. "I think that while it's more challenging in a lot of ways, at the same time some clinical trials might be fairly small in size and fairly short in duration. The overall cost of a clinical development program may be less than if you were to try to pursue an approval for a drug in diabetes or heart failure or some more prevalent indication" emphasized Schliebner.
There are several incentives provided by the FDA that come with orphan drug status such as tax credits, a provision for 7-year exclusive marketing rights post approval, waiver of prescription drug user fees, assistance from the FDA with clinical research study design, and several accelerated development pathways. The European counterpart to the FDA, the European Medicines Agency (EMA) has passed several legislations in recent years to also incentivize the development of orphan drug therapies. "In the last several years, you've seen regulatory agencies go much further in terms of being flexible with study designs that they think are acceptable for rare disease studies where we know the diseases are particularly challenging," says Mr. Schliebner. "Legislators understand that there is a need to put out incentives for drug developers to go into the rare disease space that may not be as profitable, or certainly isn't going to result in a blockbuster drug." Mr. Schliebner explained that the proverbial bar is set somewhat lower for sponsors to show a positive safety to efficacy ratio for rare fatal genetic diseases for which there are currently no available treatment options.
Reaching the goal of diversity, inclusivity and equity
Recently, the Centers for Disease Control and Prevention (CDC) Officially Declared Racism a 'Serious Public Health Threat'. The director of the CDC, Rochelle Walensky, M.D., M.P.H., stated explicitly that the pandemic illuminated inequities that have existed for generations and labeled racism as an unaddressed epidemic impacting public health. "The pandemic has shone a spotlight on inequities in various parts of society and especially around access to healthcare," says Mr. Schliebner, who concurred with Walensky's statement.
Considerable efforts are needed to create diversity, inclusivity and equity in healthcare and clinical research. "Sponsors should authentically engage with patients and communities in a manner that reflects their long-term commitment to a particular disease. Those patient communities become their ultimate stakeholders, customers, participants and their critical partners as well," states Mr. Schliebner. The biopharma industry needs to focus on achieving diversity with regards to age, gender, race, and even, sexual orientation as well for subjects participating in clinical research, explains Schliebner. Policies need to be put in place that mandate certain enrollment targets for some ethnic minority groups that have typically been underrepresented in clinical research and there are several organizations making significant strides towards leveling the playing field, explained Schliebner. Women of Color and Pharma (WOCIP), Black Health Matters, Proud Science Alliance for the LGBTQ+ populations and the Rare Disease Diversity Coalition (RDDC) are some of the prominent organizations that are working towards increasing equity and diversity.
Learn more about how PRA is using DCTs to make research more accessible to the patient—regardless of their race, gender, socioeconomic status, or ethnicity at prahs.com/dct.
- Global Genes "RARE Facts" Global Genes. Assessed: 7 June 2021. https://globalgenes.org/rare-facts/
- Taylor, Karen "Why Improving Inclusion and Diversity in Clinical Trials Should Be a Research Priority" Deloitte United States, 4 Sept 2019. https://www2.deloitte.com/us/en/blog/health-care-blog/2019/why-improving-inclusion-and-diversity-in-clinical-trials-should-be-a-research-priority.
- Pfizer "Health Disparities Among African-Americans" Your Health, Pfizer. Assessed: 7 June 2021, http://www.pfizer.com/news/hot-topics/health_disparities_among_african_americans
- Black Health Matters "Rare Diseases and African Americans" BlackHealthMatters com. Assessed: 7 June, 2021. blackhealthmatters com/health-conditions-hub/hattr- amyloidosis/rare-diseases-and-african-americans/
- Black Health Matters The CDC Officially Declared Racism a 'Serious Public Health Threat'. https://blackhealthmatters.com/general-health/cdc-declares-racism-public-health-threat/