The pharmaceutical industry is witnessing a significant shift in oncology treatment paradigms as radiopharmaceuticals emerge as a powerful new approach to precision medicine. After years of relying on traditional chemotherapy and radiation therapy, companies are now leveraging advanced targeting technologies to deliver radiation directly to tumors while sparing healthy tissue.
Market Leaders and Emerging Competitors
Novartis currently dominates the radiopharmaceutical landscape with two FDA-approved therapies: Lutathera for gastroenteropancreatic neuroendocrine tumors and Pluvicto for metastatic castration-resistant prostate cancer (mCRPC). These products generated over $2.1 billion in combined sales in 2024, establishing Novartis as the clear frontrunner.
"We've built industry-leading radioligand research and production sites globally," said Geoff Towle, vice president of Novartis's radioligand therapy solid tumor strategy. The company aims to "realize the $10 billion business potential of our candidates in clinical trials or pre-clinical trials," he added.
Bayer, despite having the first-to-market advantage with Xofigo (approved in 2013), has struggled to maintain competitive positioning. Meanwhile, pharmaceutical giants including AstraZeneca, Eli Lilly, and Bristol Myers Squibb (BMS) are making aggressive moves to capture market share in a sector projected to reach $16 billion by 2033.
Strategic Acquisitions Fuel Rapid Growth
The past 18 months have seen a flurry of high-value acquisitions as companies race to establish themselves in the radiopharmaceutical space:
AstraZeneca acquired Fusion Pharmaceuticals for up to $2.4 billion in March 2024, gaining FPI-2265, an actinium-225-based therapy targeting PSMA in prostate cancer.
BMS purchased RayzeBio for $4.1 billion in December 2023, securing a platform of actinium-225-based radiotherapeutics including RYZ-101, which targets somatostatin receptor type 2.
Eli Lilly entered the arena with its $1.4 billion acquisition of Point Biopharma in October 2023, followed by deals with Aktis Oncology (up to $1.1 billion) and Radionetics Oncology ($140 million upfront with $1 billion acquisition rights).
Novartis strengthened its leading position by acquiring Mariana Oncology for $1 billion in May 2024, adding MC-339, an actinium-based therapy for small cell lung cancer.
Technological Innovation Drives the Field Forward
Alpha vs. Beta Emitters
A significant trend in radiopharmaceutical development is the shift from beta-emitting isotopes like lutetium-177 (used in Novartis's approved products) to more powerful alpha-emitting isotopes, particularly actinium-225.
"Actinium-225 holds the promise of being a next-generation radioisotope in cancer treatment," explained Puja Sapra, AstraZeneca's senior vice president for Biologics Engineering and Oncology Targeted Discovery. "It delivers greater radiation dose over shorter distance, with potential for more targeted delivery and potential to reduce damage to surrounding healthy tissue compared to beta emitters."
Ben Hickey, president of RayzeBio under BMS, emphasized that "alpha-emitting isotopes represent the next generation of therapeutic radionucleotides due to their higher potency as compared to beta-emitting isotopes."
According to Oliver Sartor, director of Radiopharmaceutical Clinical Trials at the Mayo Clinic, alpha particles are nearly 8,000 times larger than beta particles, contributing to their stronger cancer-killing activity.
Targeting Mechanisms
Companies are also focusing on optimizing the targeting component of radiopharmaceuticals, which directs the radioactive payload to cancer cells. Three main approaches are being explored:
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Peptides: Novartis favors peptide-based targeting due to their "favorable pharmacokinetic properties," according to Shiva Malek, Novartis's global head of Oncology. "They're rapidly cleared from the body. You don't want an RLT [radioligand therapy] sitting in your bone marrow or circulating for a long time."
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Small molecules: Used in several developmental therapies including AstraZeneca's FPI-2265.
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Biologics (including antibodies): Offer another targeting approach with potential for high specificity.
Daniel Pryma, Eli Lilly's vice president for Global Clinical Development in Radioligand Therapy, noted that "the optimal ligand will be the one that has excellent performance for a specific target," emphasizing the importance of "rational pairing" between "target, ligand, isotope and patient populations."
Expanding Clinical Applications
Moving to Earlier Treatment Settings
Radiopharmaceuticals are increasingly being studied for use in earlier treatment settings. Novartis recently won a label expansion for Pluvicto, allowing its use in prostate cancer before chemotherapy—a move that William Blair analysts note would "basically triple the total addressable market for Pluvicto."
New Indications Beyond Prostate Cancer
While prostate cancer remains the primary focus for many radiopharmaceutical programs, companies are actively exploring other indications:
Bayer and BMS are both developing GPC3-targeted, actinium-225-based therapies for hepatocellular carcinoma.
BMS is pursuing a CA9-targeted approach for renal cell carcinoma.
AstraZeneca's AZD2068 targets EGFR and cMET for various solid tumors.
Novartis aims to expand radioligand therapies to breast and lung cancer.
Combination Approaches
Combining radiopharmaceuticals with other therapies represents another frontier. Novartis is conducting studies pairing its radiotherapies with standard of care and immunotherapies in prostate cancer.
AstraZeneca is exploring combinations that can "attack a tumor from multiple angles," according to Sapra. She suggested that targeted radiotherapies could complement antibody-drug conjugates (ADCs) by accessing tumor types or locations that ADCs cannot reach, while the DNA damage caused by radioconjugates might synergize with therapies that inhibit DNA repair mechanisms.
Challenges and Limitations
Despite their promise, radiopharmaceuticals face several challenges:
Supply constraints: "Having access to radioisotope[s] has been rate limiting in many instances even for clinical trials," noted Andrew Tsai, an analyst at Jefferies.
Toxicity concerns: Radiation accumulation in organs "could limit the dosing potential" of these therapies, according to Tsai.
Clinical adoption barriers: Both patients and physicians remain uninformed or uncomfortable with the technology, requiring improved awareness and education.
Looking Ahead
Key upcoming milestones include:
- AstraZeneca's Phase II AlphaBreak study readout for FPI-2265 in mCRPC expected in the second half of 2025
- BMS's RYZ-101 data in small cell lung cancer later this year and pivotal GEP-NETs results in 2026
- Novartis's FDA decision on Pluvicto's expanded indication in the first half of 2025
- Regulatory filings for Lilly's PNT2002 for mCRPC
While the field is still in its infancy, the substantial investments by major pharmaceutical companies signal strong confidence in radiopharmaceuticals as a transformative approach to cancer treatment. As Jefferies analysts predicted in February, companies will likely "explore more modalities, isotopes, and $1B+ cancer targets" throughout the year, further accelerating innovation in this rapidly evolving therapeutic area.
