Clinical trials 2021 report reveals double-rate growth from pre-pandemic levels

Pharma Intelligence has recently published the “2021 Completed Trials” report, indicating apparent green shoots of COVID-19 recovery in clinical trials across the pharma industry.

As the COVID-19 pandemic stretched through a second year, its impact continued to reshape the clinical trials landscape. According to market numbers and the “2021 Completed trials” report, 4,109 industry-sponsored clinical trials have moved from phase-I through to phase-III/IV and have either reached completed trial status or reported primary endpoints during 2021. This exceeds the 3,777 trials in 2020 and represents an 8.8 per cent annual increase, and doubles the growth rate observed in the pre-pandemic period from 2017 through 2019 (3.0-4.3 per cent).

Despite the turbulence caused by the pandemic, the leading clinical trial sponsors achieved success rates comparable to those in 2019 in trials conducted across a wide array of rare and prevalent diseases, where the top three therapeutic areas are oncology, infectious diseases and autoimmune/inflammation. These companies continue to focus on global trials, although the increased domestic trial activity by Chinese sponsors is now making a mark on overall completed trial trends.

The report further indicates that oncology continued to be at the top spot among rankings of therapeutic areas for completed trial activity in 2021. For the first time, infectious diseases (ID) shot from fifth into second place owing to considerable COVID-19 pandemic-related trial activity.

The autoimmune/inflammation attained the third rank, while Central Nervous System (CNS) and metabolic/endocrinology (met/endo) dropped into fourth and fifth places, respectively. Cardiovascular (CV) has been seen to decline in completed trials observed since 2018. Vaccines, which often overlap with ID trials, retained their seventh position while completing substantially more trials in the past year. The smallest therapeutic areas, Ophthalmology and Genitourinary (GU), are trending in opposite directions with modest changes in their trial counts.

Even as notable increases in completed trials were observed in infectious diseases (49.7 per cent), vaccines (47.1 per cent), and oncology (8.3 per cent), both infectious diseases and vaccines also reported the highest termination rates, with year-on-year changes of 42 per cent and 111 per cent, respectively. It should be noted that despite this high percentage change in vaccines, the absolute numbers remain low with only 19 trials terminated, compared with nine in 2020, these trials also are classified in the infectious disease therapeutic areas as COVID-19 studies.

In autoimmune/inflammation therapy, trial completions increased by 5.3 per cent, while terminations decreased modestly (-2%; 137 versus 140). Terminations also decreased, year-over-year, for metabolic/endocrinology (-53%; 57 versus 122), cardiovascular (-54%; 39 versus 85), and CNS( -34%; 89 versus 134).

The expected distribution of trial counts by phase was observed with fewer later phase trials completing than those of earlier phases across therapeutic areas. This trend towards growth in earlier phases of research and reductions in larger clinical trial completions indicates that the pandemic recovery is still ongoing, with the multi-year timelines of phase-III trials in particular more prone to disruption.

Historically, oncology completes a two-fold lower proportion of phase-III trials (~12-13 per cent for the past three years) than other therapeutic areas (~21-25 per cent for autoimmune/inflammation and cardiovascular). Oncology’s profile is similar in 2021 as compared to 2020, including nearly identical phase-I and phase-III trial counts, indicating that the growth in oncology can be traced to increased phase-I/II and phase-II activity (~15.8 per cent each). The dramatic jump in completed infectious disease trials (49.7 per cent) comprised roughly proportional increases across all phases.

The 2021 counts were also augmented by increased activity captured from Chinese registries. These trials are generally run exclusively in China. Most of these trials, ranging from 67.5 per cent to 82.1 per cent for mid-sized therapeutic areas and 55 per cent for oncology, are phase-I or phase-I/II studies, a factor that accounts for most of the growth in that phase observed during this period.

Substantially, fewer diseases achieved at least 25 successful trials in 2021 (14) compared with 2020 (21) and 2019 (17). COVID-19 dominated the field by this metric, with 120 trials reporting that primary endpoints were achieved. Respiratory vaccines made this list for the first time based on 26 positive trials that included 22 for COVID-19 vaccines. Despite their relatively high trial counts, success ratings for these diseases are sixth and 13th, respectively, with oncology indications taking the top five positions. The increasing trial activity in NSCLC, noted previously, has yielded 87 successful trials, and it both achieved the top ranking (42 per cent) and outperformed success rates in both 2020 (39.6 per cent) and 2019 (36.5 per cent).

Although the top 20 pharma increased its overall completed trial counts (1,612 versus 1,575), the relative contribution to overall completed trials dropped from 41.6 per cent to 39.6 per cent. Within the individual clinical stages, the proportion of All Other Pharma (AOP) sponsorship in phase-I was higher than observed in earlier analyses. These shifts are mainly driven by the increased influx of Chinese phase-I trials. Despite the shift towards smaller clinical trial sponsors, Bristol Myers Squibb, AstraZeneca, Merck & Co., Pfizer and Novartis continues to occupy the top five rankings for annual completed trial activity.

Bristol Myers Squibb (BMS) has moved steadily upwards since 2018 and is ranked at the top spot in 2021 with 177 completed trials. Twelve other sponsors completed 50 or more trials, comprising Eli Lilly (121), Roche (115), Johnson & Johnson (110), Sanofi (82), GlaxoSmithKline (80), AbbVie (76), Takeda (70), Boehringer Ingelheim (69), Jiangsu Hengrui Pharma (63), Otsuka (56), Bayer (53) and Amgen (52). Most of these sponsors met this criterion in 2020 but completed fewer trials in 2021.

Balancing the relative contributions of the top pharma companies, it can be concluded that these sponsors remain essential for the development of novel medicines at a global level. Nevertheless, the remaining smaller pharma companies possess an increasing share of clinical activity and are important for domestic approvals. In recent years, there is a growing list of larger US- and EU-headquartered organisations that are completing fewer studies, only to be replaced by emerging companies in China and Japan with narrower therapeutic and geographic focusses.