Nuclear Medicine: The First Billion-Dollar Molecule is Born!

The first billion-dollar molecule in the nuclear medicine field has been born.

Recently, Novartis announced its 2024 financial report. The data shows that its radiolabeled drug (RDC) product Pluvicto (177Lu-PSMA-617) achieved annual sales of $1.392 billion, surpassing the $1 billion mark for the first time.

This marks the first billion-dollar molecule in the global nuclear medicine field. From the late 19th century when Marie Curie first extracted the radioactive element radium, to the 20th century when radioactive iodine was first used to treat thyroid cancer, and later with the rise of targeted radionuclide therapy (RLT), the development of therapeutic nuclear medicine has accelerated. This field has gradually attracted the attention of multinational corporations (MNCs). Since 2010, companies like Bayer and Novartis have started entering the nuclear medicine market. However, despite the interest of well-funded MNCs, the field has not seen significant breakthroughs, and no single product with large commercial potential has emerged until now.

The milestone achievement of Pluvicto was anticipated in the industry, and based on Novartis' current strategy for the product, its sales are expected to continue to rise. Recently, iSpot.TV, a platform specializing in TV advertising tracking and analysis, reported that in January 2025, Novartis spent over $47 million on advertising for Pluvicto, surpassing AbbVie's Skyrizi to take the top spot. Other data shows that in December 2024, Pluvicto's advertising expenditure ranked fifth, and in November, it ranked seventh, whereas before, its advertising spend had never made the top ten. The increasing advertising spend may signal Novartis' intent and determination to focus resources on further boosting Pluvicto.

The Journey of the First Billion-Dollar Nuclear Medicine Molecule

Readers familiar with Pluvicto may know that it was not developed in-house by Novartis but was acquired from Endocyte. However, Pluvicto itself was not originally developed by Endocyte either, but was acquired by Endocyte from the German company ABX in 2017. Thanks to this acquisition, Endocyte's stock price soared, increasing about tenfold within a year.

In October 2018, when Endocyte's stock price had reached its peak, Novartis acquired all of Endocyte's outstanding common shares for $24 per share, totaling approximately $2.1 billion. Through this acquisition, Novartis gained access to Pluvicto and 225Ac-PSMA-617. At the time, the Phase III VISION trial for Pluvicto in metastatic castration-resistant prostate cancer (mCRPC) was already underway, and the FDA had agreed to use radiographic progression-free survival (rPFS) as a surrogate primary endpoint for overall survival (OS) in the trial.

In March 2022, the FDA approved Pluvicto for the treatment of adult patients with PSMA-positive mCRPC. This approval was based on positive results from the Phase III VISION trial. The study showed that patients treated with Pluvicto in combination with standard therapy had a significantly improved overall survival, with a 38% reduction in the risk of death, and a statistically significant improvement in rPFS. As the first FDA-approved RLT product for mCRPC, Pluvicto set an example for other players in the nuclear medicine field.

From its initial approval to the end of the 2024 fiscal year, Pluvicto has contributed $2.643 billion in revenue to Novartis, already recouping the cost of the acquisition. According to Novartis, in its first year on the market (2022), Pluvicto achieved total sales of $271 million, and in 2023, its total sales were $980 million (a 261% year-over-year increase). In 2024, Pluvicto's total sales reached $1.392 billion, a 42% increase from the previous year.

According to Novartis' pipeline disclosures, there are still four indications in development for Pluvicto, including a Phase III trial for metastatic hormone-sensitive prostate cancer (mHSPC), which is expected to be completed in 2025 with a filing submission planned. With Pluvicto's strong growth momentum and Novartis' further investment in expanding indications, geographical access, and commercialization, the product has a promising future.

Nuclear Medicine: The Trend Continues to Rise

In the 1940s, doctors used radioactive iodine to treat thyroid cancer, marking the earliest clinical application of nuclear medicine (therapeutic). In the 21st century, scientists added targeting structures to radioactive isotopes, creating antibody-targeted radiopharmaceuticals, such as Zevalin and Bexxar.

After 2010, with the rapid development of RLT, multinational corporations (MNCs) quickly entered the nuclear medicine space. Among them, Bayer was one of the earliest entrants, developing Radium-223 chloride [223Ra] in collaboration with Algeta. This product was approved by the FDA and EMA in 2013 for the treatment of symptomatic bone metastases from castration-resistant prostate cancer (CRPC) without known visceral metastases, bringing therapeutic nuclear medicine into the public eye. At the time, many analysts predicted that the annual sales of Radium-223 would reach about $670 million. In recent years, Bayer has continued to strengthen its nuclear medicine pipeline, acquiring Noria Therapeutics, PSMA Therapeutic, and Bicycle Therapeutics.

Currently, besides Novartis and Bayer, other companies such as Eli Lilly, AstraZeneca, BMS, Merck, and Johnson & Johnson have entered the nuclear medicine space through acquisitions, licensing, and equity investments. Notable transactions include:

1. In October 2023, Eli Lilly acquired Point Biopharma for $1.4 billion (87% premium), gaining the core asset PNT2002 (β-radioisotope).
2. In December 2023, BMS acquired RayzeBio for $4.1 billion, with its core pipeline designed around actinium-based payloads.
3. In March 2024, AstraZeneca acquired Fusion Pharmaceuticals for $2.4 billion, focusing on actinium-based payloads.
4. In May 2024, Novartis acquired Mariana Oncology for $1.75 billion, focusing on actinium-based payloads.

From these significant transactions, it is clear that the current hot spot in nuclear medicine is α-emitting radiopharmaceuticals, particularly Actinium-225. Compared to β-emitting radioisotopes, α-emitting isotopes have a shorter range, cause minimal damage to normal tissue, and have almost no side effects, making them safer and suitable for treating small tumors or micro-metastases.

However, due to the unique nature of nuclear medicine, the field also faces several challenges, one of the most frequently mentioned being transportation limitations. Radioactive isotopes decay over time, meaning they must be delivered and administered to patients within a specific window. The logistics of nuclear medicines often require strict consideration of transport distance and robust upstream and downstream industry support. Novartis, with multiple nuclear medicine pipelines in development, has already established several radiopharmaceutical production facilities in Italy, Spain, and the United States. In mid-2024, it also launched China's first radioligand therapy production facility in Haiyan County, Zhejiang, attempting to overcome product shelf-life challenges with an extensive production network and further expand market access.