Impact of COVID-19 on Rare Disease Clinical Research

An analysis of facts and figures shows COVID-19 impacted the number of rare disease clinical trials during the peak of the pandemic (2020-2021)

Clinical trials are often multi-year affairs. When something derails their progress, like the COVID-19 pandemic, the disruption ripples through the pipeline, impacting clinical research for years to come. To explain the impact of the pandemic on rare disease studies, we conducted a clinical trial review using data from Citeline Informa Pharma Intelligence. gathered for studies initiated from 2016 through 2021.

Quick Snapshot of Rare Disease

To understand the impact of COVID-19 on rare disease clinical research, let’s start by quantifying rare disease as a therapeutic area. Rare diseases affect 400 million people worldwide. Roughly 25 million in the United States and 30 million people in Europe suffer from at least one known rare disease. There are 7,000 identified rare diseases. Of these, 85% affect no more than one person.¹

The road to receiving a rare disease diagnosis is often long and complicated. It takes a median of four years from the first symptom to receiving a diagnosis. Most rare diseases are underdiagnosed and have a lack of support. In addition, misdiagnosis is common, with sufferers frequently receiving the wrong treatments. In many cases, the condition worsens in the absence of a correct diagnosis.

Understanding the Rare Disease Pipeline

The first step to understand how covid-19 pandemic affected clinical research activities, and particularly clinical investigation in rare diseases, was analyzing the number of new clinical trials initiated per year, since 2016. When looking into clinical research in general, we can see a continuous growth between 2016 and 2019, and a significant increase in the number of studies initiated in 2020, explained by research focused on the treatment and prevention of covid-19 infection. However, in 2021 the activity has decrease to pre-pandemic levels.

In comparison, the number of rare disease clinical trials has significantly increased, year after year, with special activity noticed in 2019, but this trend with abruptly interrupted in 2020.With regards to the therapeutic areas involved in clinical trials in rare diseases initiated in the last five years, Oncology indications account for 50% of the studies,  followed by Autoimmune- inflammation (18%) and central nervous system (CNS) (14%). The rest of the therapeutic areas cover less than 10% of total number of studies in rare diseases

Drug pipeline for rare diseases looks healthy. At the end of 2021, there are 18,459 drugs being researched. 5,289 of the drugs in the pipeline (29%) are for rare diseases. Approximately 23% or 1,234 have orphan drug designation.

Current Complexities in Clinical Trials in Rare Diseases

Is the decrease in the number of new rare disease clinical trials initiated per year only related to covid-19 pandemic? We conducted a metrics comparison analysis to better analyze this question. First, rare disease trials require roughly the same number of patients (median of 62 patients per study) as most other therapeutic areas, with the exception of vaccine trials which require a median of 180 patients enrolled per study. However, enrolling this median of 62 patients per study requires an average of 34 active sites, the higher among all therapeutic areas.

In addition, the average trial duration is longer than average (15 months for rare disease trials vs 11 months for all therapeutic areas) and the total effort to recruit subjects (as evidenced by the ratio of subjects to sites) is the highest amongst all therapeutic areas. We can say, based in these metrics, which enrolling one patient in a rare disease clinical trial requires a 51% extra effort than enrolling a patient in a vaccine study, which translates into a highly cost-inefficient scenario (resources and money) for rare disease trials.

Do the rare disease metrics presented in this article translate into a higher level of clinical trials failure for rare diseases? To assess the answer to this question, we analyze the clinical trials termination rate across all therapeutic areas (14%) versus each one of them. That number is largely skewed by oncology trials, which have a termination rate around 20 percent, but excluding that therapeutic area, the range is still 6 to 11 percent, which the rare disease termination rate being the lowest (6%).

The majority of rare disease clinical trials (86%) are terminated in an early phase I or phase I/II. This could indicate an early identification of safety issues and/or lack of clinical activity. However, the main reasons cited for these studies to be terminated are different:

• 27% planned but never initiated
• 22% business decision
• 18% unknown
• 10% poor enrollment

One conclusion we can draw is that pp to 41% of clinical trials in rare disease are terminated because of lack of patients, making poor patients ‘recruitment an additional factor contributing to the decrease in number of active clinical trials in this setting.

The Impact of COVID-19 on Rare Disease Research

COVID-19 has had a dramatic effect on rare disease research, which is an add-on to the difficulties inherent to conducting clinical research in rare indications. It impacted the number of trials in progress which will have a trickledown effect to the number of rare disease treatments available in the immediate future. While this impact will be temporary, COVID-19 has also influenced our understanding of rare disease research. In our next article, we will explore the adaptations and long-term implications for rare disease trials that stem from COVID-19.

References:

1. Global Genes. RARE Disease Facts. https://globalgenes.org/rare-disease-facts/. Accessed June 17, 2022.