Radiopharmaceuticals and Theranostics Gain Momentum in Oncology Treatment

Radiopharmaceuticals have received renewed interest over the last decade beyond their previous roles as diagnostic agents following the commercial and scientific success of the latest generation of targeted therapeutic radioligands. As the oncology market enters a new era of growth, targeted therapies across several modalities are transforming the treatment paradigm, with radiopharmaceuticals capturing the attention of big pharma companies and investors alike.

Novartis was the pioneer of this drug class, as the company became the first to gain US approval for a radioligand therapy (RLT) with Lutathera (lutetium Lu 177 dotatate) in 2018. Both Lutathera and Novartis' second approved RLT, Pluvicto (lutetium Lu 177 vipivotide tetraxetan), are blockbuster sellers, with forecasts projecting the drugs will bring in $1.1bn and $5.1bn for the company in 2031, respectively.

Other pharma titans such as Eli Lilly, AstraZeneca and Bristol Myers Squibb are trying to replicate this success across their own RLT programmes. Between 2023 and 2024, the three companies bought out Point Biopharma, Fusion Pharmaceuticals and RayzeBio, respectively, through multi-billion dollar deals to gain a footing in this niche. Lilly has, however, terminated development of AC-225-PSMA-62 in prostate cancer due to the drug failing to meet efficacy expectations.

The interest in RLTs appears to be mirrored by investors, as venture financing for radiopharmaceuticals reached a record high of $408m in 2023 – a value that continued to grow into 2024 through a 330% venture capital surge in Q1 2024 versus the first quarter of 2023.

As diagnostic and therapeutic radiopharmaceutical products garner their own individual successes, attention is turning to how these techniques can be combined to facilitate precise and image-driven treatment in oncology. From this concept, theranostic radiopharmaceuticals were born – which harness a radioligand alongside a radioactive isotope visible through an imaging scan.

By blending diagnostics with treatment, theranostic radiopharmaceuticals have broad potential across numerous solid tumour types. "The neuro-endocrine and prostate cancer markets are just the tip of the iceberg," according to a healthcare partner and nuclear medicine specialist at an investment firm.

A CMO at a radiopharmaceutical-focused biotech notes that theranostics can enhance confidence when treating patients. "With theranostics, a physician can send a patient for imaging and see the extent of their disease. They can then precisely expose tumours to radiation through the radioactive payload, which will go to the exact locations picked up on the scan."

A CEO at an RLT and diagnostics-focused biotech states that theranostics present an opportunity as oncology moves away from the one-size-fits all approach. "They offer value by facilitating better patient selection, the ability to monitor patient response dynamically to adapt therapy, and the potential for superior outcomes with fewer off-target effects."

RLTs are also differentiated from other toxic payload-based therapies like antibody-drug conjugates. "The unique aspect of radiopharmaceuticals is that they are molecular markers, which allows for strong treatment specificity," according to a CEO at a radiopharma-focused biotech.

Despite the burgeoning success of this modality, companies harnessing their potential in oncology will encounter development, regulatory, reimbursement and commercialisation hurdles that must be overcome. When developing any drug, companies must navigate a plethora of regulatory hurdles to obtain approval. However, the use of a radioisotope within a therapy adds an extra layer of complexity, as both drug and nuclear regulators must share the reins during the evaluation process.

Dosimetry is one of the most important considerations in the early clinical stage and beyond. "Dosimetry gives a sense of whether an administered dose is the right one to treat the cancer. It also helps determine a radiopharmaceutical's uptake in healthy organs to discern potential side effects," according to a CMO at a radiopharmaceutical-focused biotech.