The year 2024 witnessed significant advancements and shifts in the pharmaceutical research and development landscape, marked by breakthroughs in drug classes like GLP-1s, the clinical debut of CRISPR-based therapies, and increased investment in antibody-drug conjugates (ADCs). These developments signal evolving strategies in tackling various diseases and improving patient outcomes.
Expanding Applications of GLP-1 Receptor Agonists
Glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), continued to make waves beyond their initial indications for diabetes and weight loss. In March, the FDA approved semaglutide to reduce the risk of cardiovascular disease in individuals with a body mass index of 25 or higher. Emerging research also suggests potential benefits in treating kidney disease, anxiety, depression, and substance use disorder. Olivier Rascol, a neurologist at Toulouse University Hospital, noted the potential impact of these drugs on mental illnesses and neurodegenerative diseases, comparing it to "some of the major breakthroughs of the history of medicine."
CRISPR Gene Editing Enters the Clinic
Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, became the first CRISPR-based drug to enter the market for treating sickle cell disease and β-thalassemia. Approved by regulators in late 2023 and early 2024, the therapy involves extracting, editing, and reinfusing a patient's cells. Despite being recognized as a top invention by Time magazine, uptake has been slow due to the requirement for patients to undergo chemotherapy and the lengthy cell editing process. As of the third quarter earnings call, Vertex executives reported that approximately 40 people had initiated cell harvesting, with only one patient outside clinical trials having received their edited cells back.
Protein-Folding Algorithms Revolutionize Drug Discovery
The Nobel Prize in Chemistry was awarded to David Baker, Demis Hassabis, and John M. Jumper for their development of protein structure prediction and design tools. These algorithms have transformed biochemical research and are increasingly integrated into pharmaceutical research. Karen Akinsanya, president of therapeutics R&D at Schrödinger, emphasized that "We are in the century of the protein." Big Pharma firms have partnered with Isomorphic Labs, a drug discovery spin-off founded by Hassabis, and Baker's lab continues to create start-ups focused on developing de novo designed proteins into medicines.
Antibody-Drug Conjugates Attract Investment
Antibody-drug conjugates (ADCs) garnered significant investment in 2024, with Syneos Health's Dealmakers' Intentions Survey listing the modality as number one on investors' radar. ADCs combine a small-molecule drug with a monoclonal antibody via a linker. While some companies prefer well-characterized linkers used in approved drugs like Enhertu (Daiichi Sankyo and AstraZeneca), others are exploring new chemistries to gain a competitive edge. ADC expert Dowdy Jackson noted, "Right now, we're at the height of the ADC hype," expressing hope for novel innovations in the field.
Amylyx Pulls ALS Drug After Trial Failure
Amylyx Pharmaceuticals voluntarily withdrew its drug for amyotrophic lateral sclerosis (ALS) after a confirmatory trial failed to demonstrate efficacy. Justin Klee, co-CEO of Amylyx Pharmaceuticals, acknowledged the impact on the ALS patient community. The company is exploring the drug for other potential uses, including Wolfram syndrome and progressive supranuclear palsy.
Addressing Global Health Disparities
Kelly Chibale of the University of Cape Town emphasized the need to recognize and support African scientists in global drug discovery, highlighting untapped potential and talent on the continent.
Viral Outbreaks Keep Virologists Busy
The virology and public health communities monitored multiple viral outbreaks, including bird flu (H5N1) in North America, Marburg virus in Rwanda, and mpox in the Democratic Republic of the Congo and other countries. These outbreaks underscored the importance of surveillance, vaccine development, and public health interventions.
Radiopharmaceuticals Gain Momentum
Radiopharmaceuticals, which contain a radioactive isotope, a chelating agent, a linker, and a targeting molecule, became attractive assets. Following Bristol Myers Squibb's acquisition of RayzeBio, Novartis acquired Mariana Oncology, and AstraZeneca acquired Fusion Pharmaceuticals. SNS Insider analysts project a 10% growth in the radiopharmaceuticals market from 2024 to 2032, driven by increased investment in manufacturing and the exploration of new isotopes.
Vaccines and Dementia Risk
Studies indicated that the shingles vaccine may protect against dementia, with prior vaccination against tetanus, diphtheria, and pneumococcus also showing protective effects. Flu vaccines also appear to reduce the risk of developing neurodegenerative diseases, though the mechanisms behind this protection remain unclear.
