Impactful Clinical Trials of 2024
In 2024, the clinical trials landscape is experiencing a significant transformation driven by technological innovations, regulatory changes, and a growing emphasis on patient-centered approaches. As medical research progresses, keeping up with the latest trends in clinical trials is essential.
This report examines a few impactful clinical trial trends for 2024 that are set to drive advancements in the field and shape the future of medicine.
1. Skyscraper-01
Roche’s Skyscraper-01 trial, a major oncology study in 2024, focuses on TIGIT, a key target for cancer immunotherapy. It evaluates Roche’s tiragolumab with Tecentriq versus Tecentriq alone in advanced lung cancer patients. Although tiragolumab missed one main goal related to disease progression, it still aims to extend patient survival.
2. Heart-1
Heterozygous familial hypercholesterolemia, which affects approximately 1 in 300 individuals, is caused by mutations in the PCSK9 gene, leading to ineffective breakdown of LDL receptors and often poor response to statins. VERVE-101 is an innovative in vivo base-editing therapy designed to inactivate PCSK9 in the liver using a lipid nanoparticle to deliver mRNA that encodes an adenine base editor and a guide RNA. This approach has the potential to provide a one-time treatment for lowering LDL cholesterol.
The Heart-1 trial is the first global study to test in vivo DNA base editing in humans, serving as a significant proof of concept for PCSK9-targeted base-editing strategies to manage LDL cholesterol levels.
3. LixiPark
This clinical trial highlighted the potential of lixisenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, to slow the motor disability associated with the progression of Parkinson’s disease. Parkinson’s disease is a debilitating neurological disorder that affects nearly 10 million people worldwide, with no known cure, emphasizing the urgent need for disease-modifying therapies. After the onset of the disease, patients experience symptoms such as tremors, slowed movement, and impaired speech, all of which progressively worsen over time. GLP-1 agonists like lixisenatide are commonly used in the management of diabetes and obesity; by mimicking a gut hormone, this class of drugs may provide neuroprotective benefits for patients with Parkinson’s disease. In this trial, patients treated with lixisenatide showed no worsening of their movement symptoms after a year of follow-up, in contrast to the placebo group. However, as this is the first study to clearly demonstrate the neuroprotective effects of a drug on Parkinson’s symptom progression, further research is necessary to confirm its safety and efficacy.
4. CLIMB-121
In december 2023, Casgevy, an innovative CRISPR gene-editing therapy, made history by becoming the first therapy of its kind to receive approval from the United States Food and Drug Administration (US FDA) for the treatment of sickle cell disease (SCD). In SCD, patients have misshapen or "sickled" red blood cells that can block blood vessels, leading tno severe pain, organ damage, and even stroke. Casgevy utilizes CRISPR-Cas9 gene-editing technology to modify a patient’s hematopoietic stem cells, which are then reinfused into the patient. The modified cells produce higher levels of fetal hemoglobin, which is more efficient at carrying oxygen than adult hemoglobin. In pivotal clinical trials, an impressive 94.1% of the 17 evaluated patients met the primary endpoint of not experiencing a vaso-occlusive crisis for at least 12 consecutive months. The approval of this CRISPR-based therapy in the U.S., and likely in Europe and Canada in the future, validates the safety and effectiveness of gene-editing technologies in addressing challenging genetic diseases.
5. DESTINY-Breast12
Despite advancements in diagnosis and treatment, 10–15% of women diagnosed with metastatic breast cancer have tumors that have spread to the brain, a figure that may be higher among those with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. DESTINY BREAST-12 is a Phase IIIb/IV study aimed at evaluating the treatment benefits of trastuzumab deruxtecan (T-DXd) in adult patients with unresectable or advanced metastatic HER2-positive breast cancer, regardless of whether they have brain metastases. Results from DESTINY-Breast-12 support the use of T-DXd for patients with HER2-positive metastatic breast cancer, whether or not they have stable or active brain metastases.
6. SPEARHEAD-1
In August 2024, the FDA achieved several important milestones in oncology, affecting various cancers, including sarcomas and gliomas. Among the most significant approvals was afamitresgene autoleucel (afami-cel; Tecelra), granted accelerated approval on August 1, 2024. This new treatment option targets patients with advanced synovial sarcoma, supported by results from the phase 2 SPEARHEAD-1 trial (NCT04044768). Following this, the FDA also approved the SeCore™ CDx HLA A Sequencing System as a companion diagnostic.
7. ALLIUM
The combination of β-lactam piperacillin and the β-lactamase inhibitor tazobactam is commonly used for complicated urinary tract infections (UTIs) and other serious infections. However, the rise of extended-spectrum β-lactamases limits the effectiveness of β-lactams, making piperacillin/tazobactam less suitable for diseases caused by these resistant bacteria. There is a need for new treatment options. Combining β-lactams with novel β-lactamase inhibitors can restore effectiveness against resistant pathogens. In February 2024, the US FDA approved cefepime/enmetazobactam (EXBLIFEP®) for patients 18 and older with complicated UTIs, including pyelonephritis, caused by specific susceptible microorganisms like E. coli and Klebsiella pneumoniae. This approval was based on comprehensive clinical data, including results from the phase III ALLIUM trial. Additionally, the FDA granted a five-year marketing exclusivity extension until 2032 under the GAIN Act.
8. BATURA
BATURA is the inaugural study of an inhaled asthma therapy that utilizes a fully decentralized approach, in accordance with FDA guidelines for decentralized clinical trials. This study examines the exacerbation risk and safety of albuterol-budesonide 180/160 µg compared to albuterol 180 µg in participants with mild asthma, conducted in a home-based environment. It enrolled patients aged 12 and older, who received either short-acting beta2-agonist (SABA) as needed or SABA along with low-dose inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) maintenance therapy. The notable results from the BATURA trial contribute to the growing evidence supporting Airsupra as a pioneering rescue treatment, highlighting its potential to decrease asthma exacerbation risk across varying disease severities and reduce reliance on systemic corticosteroids.
7. LBx-1001
Locus Biosciences is making headlines with its groundbreaking CRISPR-based therapy aimed at treating infections, marking the first trial of its kind and the first to utilize the Cas3 protein. This therapy targets urinary tract infections (UTIs) caused by E. coli, which is responsible for approximately 80% of such infections. The company has secured $23.9 million from the Biomedical Advanced Research and Development Authority (BARDA), a division of the U.S. Department of Health and Human Services, to further develop its CRISPR-enhanced bacteriophage therapy, LBP-EC01, specifically for treating UTIs caused by drug-resistant E. coli.
8. HARMONi-2
Merck & Co.'s Keytruda, a leading cancer immunotherapy, has generated $25 billion in global sales since its launch in 2014, securing 40 approvals and becoming the world’s top-selling medicine. So, it was surprising when Summit Therapeutics claimed in May that its drug, ivonescimab, outperformed Keytruda in a head-to-head trial. Ivonescimab, discovered by China-based Akeso and partially licensed to Summit in 2022, targets both the immune-suppressing protein PD-1 and VEGF, which is involved in tumor growth. Summit and Akeso are conducting three Phase 3 studies in non-small cell lung cancer, two of which compare ivonescimab to Keytruda. The first study, HARMONi-2, reported that ivonescimab significantly slowed tumor progression compared to Keytruda. These findings won’t definitively determine ivonescimab's competitiveness against Keytruda, but they will help assess its efficacy and inform investors ahead of the HARMONi-3 trial, which is set to report results in 2027.
11. PHOENYCS GO
Biogen has been emphasizing its focus on immunology for the past five years, a mission that has gained momentum under new CEO Chris Viehbacher, who aims to redefine the company’s historically neurology-centric approach. Viehbacher points to Biogen’s expertise in multiple sclerosis, an autoimmune disorder, as a foundation for this shift. The company is increasing its investments, including a recent $1.15 billion acquisition of immunology startup Hi-Bio. Biogen now has an opportunity to validate this pivot with results from a Phase 3 trial of dapirolizumab pegol, a drug targeting the immune protein CD40L. Developed in partnership with UCB, the drug is being tested in over 300 patients with moderate-to-severe lupus, evaluating its effectiveness over 48 weeks.
