The PROTAC oncology market is projected to capture $3.7 billion by 2030
Proteolysis targeting chimeras (PROTACs) are a promising approach to cancer treatment, yet after over two decades of research, not a single PROTAC has gained FDA approval. PROTACs are novel bifunctional compounds that promote the degradation of a protein of interest (POI) by connecting a POI ligand to an E3 ubiquitin ligase (E3) ligand through a linker. Despite the current lack of approved PROTAC therapies, the PROTAC oncology market is projected to capture $3.7 billion by 2030, according to GlobalData, a leading data and analytics company.
GlobalData’s analyst consensus forecasts reveal that PROTACs will enjoy lucrative sales, especially Arvinas/Pfizer’s vepdegestrant, which is being studied as a single agent for HER2-negative breast cancer in the second-line setting in the ongoing Phase III VERITAC-2 clinical trial and as a first-line therapy in combination with Pfizer‘s Ibrance (palbociclib) in the Phase III VERITAC-3 clinical trial.
Vepdegestrant is anticipated to account for over 34 per cent of the global PROTACs market, generating more than $1.2 billion in sales by 2030. Arvinas is also aiming to capture a higher market share by developing several PROTACs, including bavdegalutamide and ARV-393, targeting various cancers.
Biswajit Podder, PhD, Oncology and Hematology Analyst at GlobalData, states, “PROTACs represent a promising strategy for selectively eliminating ‘undruggable’ proteins, offering new therapeutic possibilities not only in cancer but also in neurodegenerative diseases, immune disorders, and viral infections. By degrading rather than merely inhibiting target proteins, PROTACs can overcome acquired resistance to conventional targeted therapies.”
Currently, 39 Phase I-III clinical trials are testing various PROTAC molecules globally, with only two, which include vepdegestrant reaching Phase III. In addition, Arvinas’s bavdegalutamide, which targets the androgen receptor, is in Phase II clinical trial for metastatic castration-resistant prostate cancer as a third-line therapy. This indicates Arvinas is positioned well in the PROTACs oncology market with multiple pipeline products.
“Arvinas’ collaboration with Novartis on ARV-766, a next-generation PROTAC, showcases the potential of PROTACs and the interest from big pharma. Novartis’ resources and experience could hasten its approval as a first-in-class prostate cancer treatment. Successfully progressing these agents through clinical development could position Arvinas as a leader in the PROTACs oncology market,” Podder adds.
“However, the development of PROTACs is not without challenges. Their large molecular size can hinder their ability to enter cells and reach the protein of interest. Hence, enhancing their cell permeability and solubility is critical. Moreover, the variability in E3 ligase expression across different cancer types complicates their widespread application,” he concludes.