From the first successful Phase III CRISPR trial to promising advancements in Alzheimer’s treatment, 2023 was a pivotal year for clinical research.
According to GlobalData’s Pharmaceutical Intelligence Centre, 22,338 clinical trials were initiated in 2023, with oncology being the most common focus area, followed by central nervous system disorders. The majority (36%) of these were Phase II trials. Additionally, 7,183 clinical trials concluded, including 6,234 completed studies and 777 terminated trials.
“The proportion of terminated to completed trials increased by 2.7% from 2022 to 2023, as rising inflation and geopolitical factors created funding challenges across the industry. Despite these difficulties—along with trial initiations reaching a five-year low—several innovative drugs successfully reached the market,” said Sonnika Lamont, Clinical Trials Intelligence Analyst at GlobalData.
Eli Lilly Advances in Alzheimer’s Treatment with Donanemab
Eli Lilly has made significant strides in Alzheimer’s treatment with the successful results of its Phase III trial (NCT04437511) for donanemab. This investigational therapy targets deposited amyloid plaque, leading to substantial plaque clearance in treated patients. On average, donanemab reduced amyloid plaque by 84% over 18 months, compared to just a 1% decrease in the placebo group.
Dr. Dennis Selkoe, neurologist and co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, commented: “It’s taken a long time to get to lecanemab and donanemab, and I attribute that to the complexity of finding disease-modifying treatments that work well and can be given safely. We are now giving mild AD patients lecanemab (donanemab is not yet FDA-approved) and are carefully monitoring the safety of these antibodies to the amyloid protein.”
Donanemab demonstrated a significant slowing of cognitive and functional decline in patients with amyloid-positive early symptomatic Alzheimer’s disease, reducing their risk of disease progression. Nearly half of early-stage participants showed no clinical progression after one year of treatment.
Despite these promising results, donanemab is still awaiting approval from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
Exa-cel Shows Promise as a One-Time Functional Cure
One of the most groundbreaking advancements in 2023 came from Vertex Pharmaceuticals and CRISPR Therapeutics with their gene therapy exagamglogene autotemcel (exa-cel). Marketed as Casgevy, exa-cel has been developed to treat sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).
Preliminary data from three Phase III trials—CLIMB-111 (NCT03655678), CLIMB-121 (NCT03745287), and CLIMB-131 (NCT04208529)—included 75 patients (44 with TDT and 31 with SCD) with follow-up of up to 37.2 months. The results continue to support exa-cel’s potential as a one-time functional cure for these blood disorders. The Institute for Clinical and Economic Review (ICER) has estimated a health-benefit price benchmark (HBPB) for exa-cel between $1.35 million and $2.05 million.
Following regulatory reviews, exa-cel has now been approved by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
Dr. Rodolphe Barrangou, Editor-in-Chief of The CRISPR Journal, remarked on the significance of these approvals: “I think it's extremely exciting and truly momentous. It’s an anticipated milestone; maybe for some people, it's more relief than anything else. I think it was a foregone conclusion, and once the UK gave that approval, it was the first in a pending series.”
Eli Lilly Enters the Obesity Market with Zepbound
Eli Lilly continues to make waves in the pharmaceutical industry with Zepbound (tirzepatide), its obesity treatment that has shown superior efficacy compared to Novo Nordisk’s Wegovy (semaglutide). As a glucagon-like peptide-1 receptor agonist (GLP-1Ra), tirzepatide demonstrated impressive weight loss results across multiple Phase III trials in 2023.
The SURMOUNT-3 clinical trial (NCT04657016) evaluated tirzepatide in adults with obesity or overweight with weight-related comorbidities (excluding type 2 diabetes). The study found that, after 12 weeks of intensive lifestyle intervention, patients experienced a 21.1% reduction in body weight from baseline. Over 84 weeks, total weight loss reached an average of 26.6% from study entry.
Dr. Louis Aronne, an obesity specialist and medical director of the Comprehensive Weight Control Center at Weill Cornell Medicine, sees tirzepatide as a major contender: “I think it will be a major player—I don't see why not, given the level of efficacy we're seeing and the improvement in comorbidities. The thing that will really determine GLP-1Ra’s success are the studies where we're looking at what happens when you give this to people for five years. When you look at the positive results from the first CVOT in semaglutide, SELECT, we have every reason to be optimistic about the future of GLP-1Ra’s and obesity treatment.”
However, Novo Nordisk is preparing to challenge Zepbound’s dominance. The company has announced a head-to-head trial between its investigational therapy CagriSema and Zepbound. According to ClinicalTrials.gov, the Phase III trial will enroll 800 participants with obesity but without diabetes, with relative change in body weight at 72 weeks as the primary endpoint.
Merck’s Sotatercept Shows Strong Results in PAH Treatment
Merck’s investigational therapy sotatercept has delivered impressive results in its Phase III trial (NCT04576988) for pulmonary arterial hypertension (PAH). Patients treated with sotatercept demonstrated an average improvement of 40 meters in the six-minute walk test, surpassing expectations. The activin signaling inhibitor successfully met its primary endpoint and achieved eight out of nine secondary endpoints, with trial results released in April 2023.
Dr. Stephen Chan, Director of the Vascular Medicine Institute at the University of Pittsburgh, praised the findings: “The Phase III data is very impressive in terms of being that first entrance into this sort of new era of drug treatment and management for this patient population.”
With a PDUFA date set for March 2024, sotatercept is poised to become a groundbreaking advancement in PAH treatment, potentially transforming the standard of care for patients with this rare and life-threatening condition.
Dupixent Shows Promise as First Biologic for COPD
Regeneron Pharmaceuticals and Sanofi have announced promising results from their Phase III NOTUS trial (NCT04456673) evaluating dupixent (dupilumab) for chronic obstructive pulmonary disease (COPD). The trial demonstrated that dupixent significantly reduced exacerbations, reinforcing the positive findings from the earlier BOREAS trial.
Additionally, the NOTUS trial confirmed that patients experienced rapid and significant improvements in lung function within 12 weeks, with benefits sustained through 52 weeks. If approved, dupixent could become the first biologic therapy for COPD, representing a major breakthrough for patients with this chronic and debilitating disease.
From Success to Setback: Challenges in 2023 Clinical Trials
The clinical trials landscape in 2023 has been marked by both significant breakthroughs and notable failures, with several highly anticipated studies not meeting their expected outcomes or being terminated prematurely.
The year began on a difficult note when Janssen, a subsidiary of Johnson & Johnson, terminated its pivotal Phase III trial (NCT03964415) of an HIV vaccine in January. An independent data and safety monitoring board (DSMB) concluded that the vaccine was ineffective in preventing HIV infection when compared to a placebo. While no safety concerns were identified, the lack of efficacy led to the trial’s early termination.
Similarly, Gilead Sciences faced setbacks with magrolimab, an investigational therapy being tested for acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). Both Phase III trials (NCT04313881 and NCT04778397) were terminated in 2023. The AML trial was paused in August by the FDA, and ultimately terminated after a report indicated that magrolimab was "unlikely to demonstrate a survival benefit" over the current standard of care. Gilead acquired Forty Seven, the company behind magrolimab, for $4.9 billion in 2020.
Bayer also faced disappointment when its Phase III trial of the anti-coagulant drug asundexian was terminated early due to a lack of efficacy. The OCEANIC-AF trial (NCT05643573) aimed to evaluate asundexian for preventing strokes and systemic embolisms in atrial fibrillation patients. The Independent Data Monitoring Committee (IDMC) found that asundexian was inferior in efficacy compared to the control, though it recommended continuing a related trial, OCEANIC-STROKE (NCT05686070), for stroke patients.
Lastly, Sarepta Therapeutics experienced a mixed year after its Duchenne muscular dystrophy (DMD) treatment, Elevidys, was granted accelerated approval by the FDA in June. However, in October, the company’s Phase III trial (NCT05096221) failed to meet its primary endpoint, as the data did not show statistical significance in improving motor function compared to the placebo. Despite the initial success, this setback cast a shadow over Sarepta’s prospects for the year.
According to GlobalData’s Pharmaceutical Intelligence Centre, 22,338 clinical trials were initiated in 2023, with oncology being the most common focus area, followed by central nervous system disorders. The majority (36%) of these were Phase II trials. Additionally, 7,183 clinical trials concluded, including 6,234 completed studies and 777 terminated trials.
“The proportion of terminated to completed trials increased by 2.7% from 2022 to 2023, as rising inflation and geopolitical factors created funding challenges across the industry. Despite these difficulties—along with trial initiations reaching a five-year low—several innovative drugs successfully reached the market,” said Sonnika Lamont, Clinical Trials Intelligence Analyst at GlobalData.
Eli Lilly Advances in Alzheimer’s Treatment with Donanemab
Eli Lilly has made significant strides in Alzheimer’s treatment with the successful results of its Phase III trial (NCT04437511) for donanemab. This investigational therapy targets deposited amyloid plaque, leading to substantial plaque clearance in treated patients. On average, donanemab reduced amyloid plaque by 84% over 18 months, compared to just a 1% decrease in the placebo group.
Dr. Dennis Selkoe, neurologist and co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, commented: “It’s taken a long time to get to lecanemab and donanemab, and I attribute that to the complexity of finding disease-modifying treatments that work well and can be given safely. We are now giving mild AD patients lecanemab (donanemab is not yet FDA-approved) and are carefully monitoring the safety of these antibodies to the amyloid protein.”
Donanemab demonstrated a significant slowing of cognitive and functional decline in patients with amyloid-positive early symptomatic Alzheimer’s disease, reducing their risk of disease progression. Nearly half of early-stage participants showed no clinical progression after one year of treatment.
Despite these promising results, donanemab is still awaiting approval from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
Exa-cel Shows Promise as a One-Time Functional Cure
One of the most groundbreaking advancements in 2023 came from Vertex Pharmaceuticals and CRISPR Therapeutics with their gene therapy exagamglogene autotemcel (exa-cel). Marketed as Casgevy, exa-cel has been developed to treat sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).
Preliminary data from three Phase III trials—CLIMB-111 (NCT03655678), CLIMB-121 (NCT03745287), and CLIMB-131 (NCT04208529)—included 75 patients (44 with TDT and 31 with SCD) with follow-up of up to 37.2 months. The results continue to support exa-cel’s potential as a one-time functional cure for these blood disorders. The Institute for Clinical and Economic Review (ICER) has estimated a health-benefit price benchmark (HBPB) for exa-cel between $1.35 million and $2.05 million.
Following regulatory reviews, exa-cel has now been approved by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
Dr. Rodolphe Barrangou, Editor-in-Chief of The CRISPR Journal, remarked on the significance of these approvals: “I think it's extremely exciting and truly momentous. It’s an anticipated milestone; maybe for some people, it's more relief than anything else. I think it was a foregone conclusion, and once the UK gave that approval, it was the first in a pending series.”
Eli Lilly Enters the Obesity Market with Zepbound
Eli Lilly continues to make waves in the pharmaceutical industry with Zepbound (tirzepatide), its obesity treatment that has shown superior efficacy compared to Novo Nordisk’s Wegovy (semaglutide). As a glucagon-like peptide-1 receptor agonist (GLP-1Ra), tirzepatide demonstrated impressive weight loss results across multiple Phase III trials in 2023.
The SURMOUNT-3 clinical trial (NCT04657016) evaluated tirzepatide in adults with obesity or overweight with weight-related comorbidities (excluding type 2 diabetes). The study found that, after 12 weeks of intensive lifestyle intervention, patients experienced a 21.1% reduction in body weight from baseline. Over 84 weeks, total weight loss reached an average of 26.6% from study entry.
Dr. Louis Aronne, an obesity specialist and medical director of the Comprehensive Weight Control Center at Weill Cornell Medicine, sees tirzepatide as a major contender: “I think it will be a major player—I don't see why not, given the level of efficacy we're seeing and the improvement in comorbidities. The thing that will really determine GLP-1Ra’s success are the studies where we're looking at what happens when you give this to people for five years. When you look at the positive results from the first CVOT in semaglutide, SELECT, we have every reason to be optimistic about the future of GLP-1Ra’s and obesity treatment.”
However, Novo Nordisk is preparing to challenge Zepbound’s dominance. The company has announced a head-to-head trial between its investigational therapy CagriSema and Zepbound. According to ClinicalTrials.gov, the Phase III trial will enroll 800 participants with obesity but without diabetes, with relative change in body weight at 72 weeks as the primary endpoint.
Merck’s Sotatercept Shows Strong Results in PAH Treatment
Merck’s investigational therapy sotatercept has delivered impressive results in its Phase III trial (NCT04576988) for pulmonary arterial hypertension (PAH). Patients treated with sotatercept demonstrated an average improvement of 40 meters in the six-minute walk test, surpassing expectations. The activin signaling inhibitor successfully met its primary endpoint and achieved eight out of nine secondary endpoints, with trial results released in April 2023.
Dr. Stephen Chan, Director of the Vascular Medicine Institute at the University of Pittsburgh, praised the findings: “The Phase III data is very impressive in terms of being that first entrance into this sort of new era of drug treatment and management for this patient population.”
With a PDUFA date set for March 2024, sotatercept is poised to become a groundbreaking advancement in PAH treatment, potentially transforming the standard of care for patients with this rare and life-threatening condition.
Dupixent Shows Promise as First Biologic for COPD
Regeneron Pharmaceuticals and Sanofi have announced promising results from their Phase III NOTUS trial (NCT04456673) evaluating dupixent (dupilumab) for chronic obstructive pulmonary disease (COPD). The trial demonstrated that dupixent significantly reduced exacerbations, reinforcing the positive findings from the earlier BOREAS trial.
Additionally, the NOTUS trial confirmed that patients experienced rapid and significant improvements in lung function within 12 weeks, with benefits sustained through 52 weeks. If approved, dupixent could become the first biologic therapy for COPD, representing a major breakthrough for patients with this chronic and debilitating disease.
From Success to Setback: Challenges in 2023 Clinical Trials
The clinical trials landscape in 2023 has been marked by both significant breakthroughs and notable failures, with several highly anticipated studies not meeting their expected outcomes or being terminated prematurely.
The year began on a difficult note when Janssen, a subsidiary of Johnson & Johnson, terminated its pivotal Phase III trial (NCT03964415) of an HIV vaccine in January. An independent data and safety monitoring board (DSMB) concluded that the vaccine was ineffective in preventing HIV infection when compared to a placebo. While no safety concerns were identified, the lack of efficacy led to the trial’s early termination.
Similarly, Gilead Sciences faced setbacks with magrolimab, an investigational therapy being tested for acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). Both Phase III trials (NCT04313881 and NCT04778397) were terminated in 2023. The AML trial was paused in August by the FDA, and ultimately terminated after a report indicated that magrolimab was "unlikely to demonstrate a survival benefit" over the current standard of care. Gilead acquired Forty Seven, the company behind magrolimab, for $4.9 billion in 2020.
Bayer also faced disappointment when its Phase III trial of the anti-coagulant drug asundexian was terminated early due to a lack of efficacy. The OCEANIC-AF trial (NCT05643573) aimed to evaluate asundexian for preventing strokes and systemic embolisms in atrial fibrillation patients. The Independent Data Monitoring Committee (IDMC) found that asundexian was inferior in efficacy compared to the control, though it recommended continuing a related trial, OCEANIC-STROKE (NCT05686070), for stroke patients.
Lastly, Sarepta Therapeutics experienced a mixed year after its Duchenne muscular dystrophy (DMD) treatment, Elevidys, was granted accelerated approval by the FDA in June. However, in October, the company’s Phase III trial (NCT05096221) failed to meet its primary endpoint, as the data did not show statistical significance in improving motor function compared to the placebo. Despite the initial success, this setback cast a shadow over Sarepta’s prospects for the year.
