Commercial and business aspects of alpha radioligand therapeutics

Abstract

Radioligand therapy (RLT) is gaining traction as a safe and effective targeted approach for the treatment of many cancer types, reflected by a substantial and growing commercial market (valued at $7.78 billion in 2021, with a projected value of $13.07 billion by 2030). Beta-emitting RLTs have a long history of clinical success dating back to the approval of Zevalin and Bexxar in the early 2000s, later followed by Lutathera and Pluvicto. Alpha radioligand therapeutics (ARTs) offer the potential for even greater success. Driven by ground-breaking clinical results in early trials, improved isotope availability, and better understanding of isotope and disease characteristics, the global market for alpha emitters was estimated at $672.3 million for the year 2020, with projected growth to $5.2 billion by 2027. New company formations, promising clinical trial data, and progression for many radioligand therapy products, as well as an inflow of investor capital, are contributing to this expanding field. Future growth will be fueled by further efficacy and safety data from ART clinical trials and real-world results, but challenges remain. Radionuclide supply, manufacturing, and distribution are key obstacles for growth of the field. New models of delivery are needed, along with cross-disciplinary training of specialized practitioners, to ensure patient access and avoid challenges faced by early RLT candidates such as Zevalin and Bexxar. Understanding of the history of radiation medicine is critical to inform what may be important to the success of ART–most past projections were inaccurate and it is important to analyze the reasons for this. Practical considerations in how radiation medicine is delivered and administered are important to understand in order to inform future approaches.

Multivalent DNA-encoded lectins on phage enable detecting compositional glycocalyx differences

“…Exploiting differences in the composition of cell surfaces is the foundation of modern breakthrough therapies: fourteen FDA-approved antibody-drug conjugates 1 , six CAR T-cells 58 , and two approved peptide-based targeted radiopharmaceuticals (Lutathera and Pluvicto) 59 - all these examples exploit an exclusive expression of a unique, often protein-based, antigen on cancer cells. Glycan-protein interactions enable liver-specific delivery of nucleic acid therapies (GIVLAARI and 45 modalities in Phase 1-3 clinical trials 60 ) and, again, they build on the unique overexpression of the GalNAc-binding receptor in liver cells.…”

Radiopharmaceuticals for Cancer Diagnosis and Therapy

“…One analysis of the global market for α-emitters indicates projected growth to $5.2 billion by 2027 from estimated $672.3 million in 2020. 26…”

“…1 For each approved 225 Ac RPT, there is an estimated need of 200-400GBq per year of patient need. 26 This has necessitated both public (e.g., IAEA) and private cooperation and agreement to increase stock and explore novel methods of production, including creation of entities such as PRISMAP consortium to centralize coordination and communication regarding radionuclide production. This has also engendered interest in multiple clinically useful α-emitters, for example, 227 Th/ 223 Ra, 225 Ac, 211 At, and 212 Pb/ 212 Bi, to diversify production and implementation options.…”

“…Conversely, the crossfire effect, which is the ability to deliver therapeutic ionizing radiation to cancer cells that do not express the putative target of a radioconjugate, is attributed to β-emitters because they can travel much farther than α-emitters and is thought to contribute to the therapeutic effect of β-particle–emitting conjugates. One analysis of the global market for α-emitters indicates projected growth to $5.2 billion by 2027 from estimated $672.3 million in 2020 26 …”

“…For example, in 2018, the total capacity of 225 Ac generation was 75 GBq, which is wholly inadequate to meet patient needs 1 . For each approved 225 Ac RPT, there is an estimated need of 200-400GBq per year of patient need 26 . This has necessitated both public (e.g., IAEA) and private cooperation and agreement to increase stock and explore novel methods of production, including creation of entities such as PRISMAP consortium to centralize coordination and communication regarding radionuclide production.…”