Radiopharmaceuticals

Editor’s note: This story was published in August 2023 and, since then, the radiopharmaceuticals field has advanced quickly. We’re including this story in the trendline you’re reading as it provides a useful snapshot of when the field started to take off. 

When the Food and Drug Administration approved a new prostate cancer drug in 2022, it validated a bet made by Novartis to acquire the drug’s maker, Endocyte. The decision was also another step forward for a long-studied research field that appears to finally be coming of age.

The medicine, Pluvicto, is known as a “radiopharmaceutical.” Unlike the small molecule or biologic medicines drugmakers use to flip cellular switches on or off, radiopharmaceuticals are designed to precisely deliver radioactive material into the body. The result is a targeted punch of radiation that can knock out tumors in a way other drugs can’t.

However, since Pluvicto’s approval, Novartis has struggled to meet demand, highlighting one of the many issues that has slowed development of radiopharmaceuticals. They’re difficult to produce, distribute and administer. The earliest examples never lived up to commercial expectations, hamstrung by manufacturing problems, competition, high costs and safety concerns. GSK stopped making one, known as Bexxar, in 2014. Another, named Zevalin and originally developed by Idec Pharmaceuticals, never became a big seller.

A group of companies, from biotechnology startups to pharmaceutical giants, think they’ve solved these problems. Borrowing from progress in another cancer drug field, they’re leaning on technical advancements that have enabled researchers to design medicines capable of safely delivering a radioisotope to just the right spot.

Novartis is the most invested, having spent $6 billion on acquisitions of Endocyte and Advanced Accelerator Applications. Right alongside Novartis is Bayer, which has also brought a radiopharmaceutical to market and is testing others.

Behind them are a handful of publicly traded companies and at least a dozen biotech startups, making radiopharmaceuticals a hotly competitive area of drug research. Here’s where things stand:

What are radiopharmaceuticals, and how do they work?

Born shortly after the discovery of the X-ray, radiation therapy has more than a century of history in cancer treatment. It’s a way of using high-energy particles or waves to damage the DNA of cancer cells, preventing division and growth.

Along with surgery, radiation therapy is a mainstay of cancer care, used to treat or prevent the recurrence of tumors in more than half of people with the disease, according to the American Cancer Society.

But radiation therapy is a blunt force. Rays beamed from outside the body can damage healthy tissue, while a more targeted, inside-the-body approach is costly and complex.

By comparison, radiopharmaceuticals can deliver the destructive power of radiation directly into tumors. They are akin to microscopic smart bombs — radioactive material guided by a molecular courier to cells with specific protein flags.

With Novartis’ drug Pluvicto, a radioisotope known as lutetium is chemically fused to a small molecule that binds to PSMA, a protein overexpressed in most prostate cancers. Novartis’ other radiopharmaceutical, Lutathera, delivers radioactive lutetium to SSTR, a target found on certain neuroendocrine tumors.

The drugs are complex, made of hand-picked parts. Different radioactive materials may weigh more or less, last longer or pack a bigger punch. Some radiopharmaceuticals may require a “chelator,” a molecule that keeps the radioactive material intact as it’s carried through the body.

Drugmakers also have to design chemical “linkers” that hold their therapies together, but don’t stick around too long after reaching their target. A molecular guide that seeks out malignant cells is another necessary component.

Once designed, radiopharmaceuticals are tricky to produce at scale. Supplies of radioactive materials are limited, and their transport is controlled. The drugs must be made and delivered quickly, before the radioactive components decay too much.

Why are radiopharmaceuticals a hot area of investment?

Interest in radiopharmaceuticals mirrors the ascent of another class of targeted cancer medicines, known as antibody-drug conjugates, or ADCs.

Like radiopharmaceuticals, ADCs deliver a toxic substance, usually a chemical, directly to a tumor. After years of slow progress, they’ve undergone a renaissance catalyzed by technical advances, regulatory approvals and interest from large drugmakers. Venture investors are in turn backing new startups.

Radiopharmaceuticals are now in the spotlight, too. Despite the poor sales of the field’s first medicines, newer drugs are performing better. Studies supporting some, like Pluvicto, have shown radiopharmaceutical drugs can extend survival and, in some cases, outperform other types of treatments.

Radiopharmaceutical drugs are “now being recognized as an effective, safe, and economically and logistically viable treatment modality,” wrote physicians from Johns Hopkins University School of Medicine and Memorial Sloan Kettering Cancer Center, in a 2020 article in Nature Reviews Drug Discovery.

As is often the case, large pharma investment is sparking a chain reaction of activity. Novartis’ acquisitions of Advanced Accelerator and Endocyte yielded Lutathera and Pluvicto, which, despite production challenges, are seeing strong demand. Bayer reached close to $500 million in peak yearly sales with its radiopharmaceutical Xofigo; it’s now working on newer medicines and, in 2021, acquired two startups.

Diagnostics company Lantheus Holdings bought the maker of Azedra, another radiopharmaceutical recently approved by the FDA for rare neuroendocrine tumors.

Those deals, along with radiochemistry advances and a “greater ability to innovate in ‘complex’ therapeutic modalities,” have spurred a wave of investments in new radiopharmaceutical companies, wrote Faisal Khurshid, an analyst with Leerink Partners, in a report.

Some, like the publicly traded biotech Fusion Pharmaceuticals and startup RayzeBio, are going after the same targets as Pluvicto and Lutathera, but with different radioactive components or guiding molecules.

Others are pursuing different cancer-associated proteins. Belgian biotech Precirix, for example, is evaluating a radiopharmaceutical for tumors driven to growth by HER2, a well-known cancer gene.

As far as cancer treatments go, radiopharmaceuticals are conceptually simple. After all, radioactive isotopes are very good at killing cancer cells. And as targeting technology improves, large pharma companies are paying closer attention to the drug field and the many smaller biotechnology firms within it.

This radio-renaissance belies the long history of radiation-based drugs, the idea for which has been around for more than half a century, said Jack Hoppin, CEO of Ratio Therapeutics, one of those small biotechs.

“It’s not a novel concept to put a radioisotope into patients,” Hoppin said, describing research into the radioisotope iodine-131 in the 1950s.

Decades later in the early 2000s, GSK’s Bexxar and Idec Pharmaceuticals’ Zevalin both won approvals to treat lymphoma, but their use never took off due to logistical and other issues. While radioisotopes became commonplace in diagnostic imaging, the current boom in radiopharmaceuticals was brought on by two drugs now owned by Novartis: Lutathera for neuroendocrine tumors and Pluvicto for prostate cancer.

“There have been a couple other successes in the space, but those are the two driving forces that caught everyone’s eye,” said Hoppin. “When a buyer like Novartis steps in and starts building infrastructure, and oncologists are willing to prescribe and treat directly with these drugs, it builds momentum.”

Ratio is still early in its own development journey. But backed by another pharma giant, Bristol Myers Squibb, the company has a front row seat to the field’s rapid expansion.

“I think you’ll see these drugs evolve in the way that antibody-drug conjugates have” said Hoppin. “It took time to adopt and come to fruition, but we’re now in an era where companies are looking for fit-for-purpose molecules for radioligand therapy and the characteristics required to be successful.”

Merging fields

One of the challenges in developing radiopharmaceuticals is balancing the drugs’ potency with their safety. The isotope the drugs contain must be linked securely enough to a targeting compound that it reaches the target tumors, but loosely enough that it can be deposited upon arrival.

To get that balance right requires more than just biology and chemistry, said Hoppin, who holds a Ph.D. in mathematics. For example, understanding the way radioactive isotopes — actinium-225 in Ratio’s case — populate into a tumor is as much a math problem as it is biological.

“People in pharmaceutical sciences underestimate nuclear medicine, and people in nuclear medicine underestimate pharmaceutical sciences,” said Hoppin. “We try to acknowledge that you’re only as good as the weakest disciplinarian within your group.”

Ratio uses actinium-225 with a combination of targeting and linking platforms to ensure a calculated dose for its treatments, one of which is close to entering Phase 1 testing.

While biotechnology advances can come in seemingly overnight breakthroughs, Hopping credits the steady accumulation of better targets and biomarkers for the growth in therapeutic radiopharmaceuticals.

“There wasn’t a clear-cut smoking gun that changed the market,” he said. “[It was] more an evolution of medicinal chemistry and biomarker technology to image these agents faster and more quantitatively.”

Building a market

Ratio is one of more than a dozen small- to mid-sized startups exploring radiopharmaceuticals. Acquisitions by large pharma companies have boosted the field, encouraging the formation of new companies and funding for those already established.

Bristol Myers Squibb announced a $4.1 billion acquisition of RayzeBio at the end of 2023. Around the same time, Eli Lilly made a $1.4 billion purchase of Point Biopharma. Both companies have radiopharmaceutical candidates in clinical trials.

Then in 2024, AstraZeneca bought Fusion Pharmaceuticals for $2.4 billion, continuing the dealmaking trend. There were 86 licensing, partnering or acquisition deals in the radiopharmaceuticals field over the last five years, according to a Nature report, with the number of deals nearly tripling between 2021 and 2022.

There are still challenges in the field, as Hoppin can attest, from manufacturing of radioactive materials to supply chain and storage. But the future looks bright.

“Some of these things can’t be instantly solved, but looking out a decade, there are going to be multiple approvals and really exciting times,” Hoppin said.

Mariana Oncology arrived at the J.P. Morgan Healthcare Conference in 2024 with momentum. The radiopharmaceutical drug developer had secured $175 million in fresh funding four months prior and, in the time since, seen two competitors in its field acquired via multibillion-dollar acquisitions.

The result was a full calendar of meetings for Mariana’s executive team. “The inbound interest was broad and almost frenetic,” said company CEO Simon Read in an interview. “The business development deals in the run-up to J.P. Morgan had really conditioned the marketplace.”

One of those conversations led to Mariana’s own deal, a $1 billion buyout by Novartis.

According to Read, Mariana saw the chance to combine with Novartis, a radiopharmaceutical leader that sells two of the targeted radiation drugs, as a “perfect marriage.”

“If you want to maximize the value of [your pipeline], it helps to be able to add scale. You can carry on raising more and more money, but having a party that can add scale, knows how to commercialize these drugs, that's probably a better strategy,” Read said.

Novartis has a good claim at being expert. The company invested heavily in radiopharmaceuticals, acquiring its approved drugs Pluvicto and Lutathera through a pair of acquisitions several years ago and building out the manufacturing to support them since.

Novartis’ success with Pluvicto in prostate cancer has motivated others, Mariana among them, to follow into the field. “We began thinking in mid-2020 about the makeup of the company. We had been struck by the compelling efficacy that was coming out the clinic with Pluvicto,” Read said.

Eli Lilly’s $1.4 billion purchase of Point BioPharma, meanwhile, gave Lilly a potential competitor to Pluvicto, as well as an entry point into radiopharmaceuticals.

Radiopharmaceuticals combine an isotope, like lutetium or actinium, with a targeting molecule meant to shepherd the cell-killing radiation directly to the tumor. Essentially, the drugs offer a more precise way to target cancers with less risk of harming healthy tissue, as beamed or implanted radiation can.

But they’re tricky to manufacture and, because radioactive isotopes degrade over time, require a precisely choreographed supply chain to get doses to patients in just the right window.

Even Novartis has run into challenges, temporarily pausing production in 2022 to resolve certain quality issues and then struggling to keep up with demand for Pluvicto.

The company has added new factories and scaled up capacity in response. A plant in Indianapolis came on line in 2024, for example, increasing the number of doses Novartis can make annually.

“It was a significant investment for the organization,” said Jeevan Virk, therapeutic area strategy head for radiopharmaceuticals at Novartis, in a February interview. “We now feel we’re in a space where we’re able to deliver on the promise of unconstrained supply.”

Novartis has additional radiopharmaceutical facilities in New Jersey, Italy and Spain, and is planning to open sites in Japan and China.

Mariana had its own manufacturing already set up. That distinguished its deal with Novartis from other recent acquisitions of RayzeBio by Bristol Myers Squibb and of Fusion Pharmaceuticals by AstraZeneca, Read said.

“The narrative of those deals were about, ‘let’s secure supply chain, let’s secure manufacturing as table stakes to get into this space,” added Read. “[Mariana’s deal] was slightly different in so much as this was about a fantastic pipeline and portfolio complementarity.”

Radiopharmaceutical drug developer Aktis Oncology raised $318 million from an initial public offering this past January.

Aktis priced 17.65 million shares at $18 each, more than what it planned to sell. It upsized the offering after Eli Lilly, which previously partnered with the cancer drugmaker, stepped in to purchase $100 million, or a third of the shares. 

The company, which is based in Boston, is developing a twist on specialized cancer drugs that it says can hit tumor targets “outside the scope” of other radiopharmaceuticals. 

AKY-1189, its most advanced prospect, is a “miniprotein radioconjugate” targeting Nectin-4, the same protein that Pfizer’s bladder cancer drug Padcev binds to. Aktis is studying what other cancers it could be used in, with Phase 1 study results expected in the first quarter of 2027. 

A second experimental drug, dubbed AKY-2519, goes after solid tumors that express a protein called B7-H3. Tumors with high levels of B7-H3 have been hard to treat, responding poorly to other cancer therapies such as anti-PD1 drugs, according to Aktis. The collaboration with Lilly could yield additional radiopharmaceutical targets.

Prior to its IPO, Aktis banked $346 million in private funding to advance its pipeline of radiopharmaceuticals, including investments from MPM BioImpact, Vida Ventures and RA Capital. 

Last year was a slow one for biotech companies looking to raise money on the public markets, with less than a dozen firms pricing IPOs, according to BioPharma Dive data. Only one, Ascentage Pharma, was a cancer drug developer.

But radiopharma companies overall have lured major pharmaceutical firms like Lilly, Bristol Myers Squibb. and Novartis. The latter, in particular, saw major success with its radiopharmaceuticals Pluvicto and Lutathera, setting off a chain of acquisitions by other pharmas looking for more precise medicines to attack tumors. 

Eli Lilly in late 2023 joined the push to develop radiopharmaceutical drugs for cancer, announcing a deal to buy Point Biopharma and its pipeline of experimental therapies for approximately $1.4 billion.

Per acquisition terms, Lilly paid $12.50 per Point share, a premium of about 87% to what the biotechnology company’s stock closed at the day before the deal’s announcement. 

Based in Lilly’s home base of Indianapolis, Point specializes in radiopharmaceuticals, which pair a radioisotope with a targeting compound that delivers radiation directly into tumor cells. Recent improvements in manufacturing and supplying the complex treatments have boosted investment in the field, drawing interest from large pharma companies like Lilly as well as new drug startups.

The Point deal was part of a broader plan by Lilly to build a presence in radiopharma drug development.

Jacob Van Naarden, who runs Lilly’s oncology unit, described the acquisition as the “beginning” of his company’s investment in developing “multiple meaningful radioligand medicines for hard-to-treat cancers.”

“Over the past few years, we have seen how well-designed radiopharmaceuticals can demonstrate meaningful results for patients with cancer and rapidly integrate into standards of care, yet the field remains in the early days of the impact it may ultimately deliver,” he said in Lilly’s statement.

Acquiring Point gave Lilly three clinical-stage drugs, two of which are potential competitors to approved radiopharma therapies sold by Novartis. One succeeded in Phase 3 testing in metastatic castration-resistant prostate cancer in 2024. The drug is similar in construction to Novartis’ Pluvicto.

Point licensed rights to those two other therapies to Lantheus Holdings, however. Evercore ISI analyst Umer Raffat therefore saw Lilly’s interest in Point as tied to the biotech’s earlier-stage drugs, which are aimed at newer therapeutic targets and use a different radioisotope, actinium, to kill cancer cells.

“Recent interest in radiopharma has coalesced around ‘alpha emitters,’ especially actinium,” he wrote in a note to clients. He added that the isotope is potentially safer to administer and more potent than previously used isotopes.

Yet radiopharma drugs are complex to produce and supply, requiring specialized partners and just-in-time delivery to treatment centers. These challenges held back the field’s expansion until recently, as private sector isotope suppliers have emerged and companies have gotten better at constructing the therapies.

Buying Point gives Lilly an 180,000-square-foot factory in Indianapolis, as well as an research and development center in Toronto.

Novartis’ commercial success with Pluvicto and its other approved radiopharma drug Lutathera has been another important proof point. 

Along with Novartis, Bayer, AstraZeneca, Merck & Co. and Roche have also made investments in radiopharma drug development, mostly via biotech partnerships.

AstraZeneca in 2024 became yet another large pharmaceutical company to make a sizable bet on radiopharmaceutical drugs for cancer, agreeing to acquire longtime biotechnology partner Fusion Pharmaceuticals in a deal worth up to $2.4 billion.

AstraZeneca acquired all of Fusion’s shares for $21 apiece, or about $2 billion. The British drugmaker could add another $3 per share via a financial instrument known as a “contingent value right” if Fusion meets an unspecified regulatory milestone. Should Fusion hit that mark, the buyout would be worth $2.4 billion. 

AstraZeneca paid a a 97% premium for Fusion’s shares. 

The deal added to a spurt of transactions involving a maker of radiopharmaceuticals, following Eli Lilly’s $1.4 billion deal for Point Biopharma and Bristol Myers Squibb’s $4.1 billion takeout of RayzeBio. 

Radiopharmaceuticals are complex medicines that deliver a targeted dose of radiation directly to a tumor. Though the field has been on the industry’s radar for decades, technological advances and the success of Novartis’ prostate cancer drug Pluvicto have led to a surge in investments. Many drugmakers see radiopharmaceuticals as supplanting radiation therapy, a blunt force that’s been around for more than a century. 

“Between 30 and 50% of patients with cancer today receive radiotherapy at some point during treatment, and the acquisition of Fusion furthers our ambition to transform this aspect of care with next-generation radioconjugates,” said Susan Galbraith, AstraZeneca’s executive vice president of oncology research and development, in a statement. 

At least a dozen biotechnology startups, a handful of publicly traded companies and now multiple large drugmakers are developing radiopharmaceuticals. Some are going after the same targets as Pluvicto and another Novartis therapy, Lutathera, but with different drug components. Others are pursuing different cancer-associated proteins. 

Fusion, which had been working with AstraZeneca since 2020, was among those chasing Pluvicto. Its lead drug is being developed for a form of metastatic prostate cancer and at the time of the acquisition was in Phase 2 testing. Fusion’s drug delivers a different radioactive isotope to tumors than Pluvicto, a characteristic AstraZeneca said may make for “more potent cancer killing and targeted delivery.” 

The deal also gives AstraZeneca the capabilities to manufacture radiopharmaceuticals and supply the radioactive materials. Both are critical, given the drugs are tricky to produce at scale and supplies are limited.

“We believe the acquisition recognizes the value of Fusion’s lead program as well as strategic control over isotope supply and manufacturing,” Khurshid wrote, adding that the “depth of resources” offered by a large pharmaceutical company like AstraZeneca should “help with the execution” of a future trial. 

Actithera, a radiopharmaceutical drugmaker based in Oslo, Norway and Cambridge, Massachusetts, raised just under $76 million in Series A venture financing to build out its cancer drug pipeline.

The biotechnology company said it would use the new funds to advance into clinical development an experimental treatment targeting what are known as fibroblast activation proteins.

M Ventures, which helped found the company in 2021, co-led the Series A round with Hadean Ventures, Sofinnova Partners and 4BIO Capital. Five other firms also participated.

Radiopharmaceuticals offer a better way to send tumor-killing radiation more precisely to cancerous cells and, accordingly, they’ve drawn rising interest from drugmakers. The technology works by attaching a radioisotope to a targeting compound via a specially engineered “linker” molecule.

While radiopharmaceuticals have been around for years — Bayer’s Xofigo was approved in the U.S. in 2013 — the field has taken off since the success of Novartis’ prostate cancer treatment Pluvicto. The drug earned Novartis nearly $2 billion in 2025, giving the industry a glimpse of radiopharmaceuticals’ sales potential.

Other large companies, like Bristol Myers Squibb and Eli Lilly, have entered the field with acquisitions of earlier-stage public biotechs.

Private radiopharma companies, meanwhile, drew more than $1.1 billion since 2022 from a group of 23 venture firms tracked by BioPharma Dive.

Actithera is designing its cancer drugs so they can stay in a tumor for longer by binding tightly to proteins that help a tumor grow. Founded by Andreas Goutopoulos, a veteran of Merck KGaA’s U.S. subsidiary EMD Serono Inc., the biotech is focused first on an enzyme called fibroblast activation protein, or FAP.

The protein is expressed on cells that form connective tissue, but in cancer can support tumor growth. Actithera aims to eliminate those proteins and cancer-associated fibroblasts in “a cross-fire effect that kills nearby tumor cells,” Goutopoulos said.

“It’s a way to dismantle a critical barrier to immune and therapeutic access,” he wrote in an email to BioPharma Dive.

Radiopharmaceuticals can be tricky to develop. Manufacturing is complex and expensive, and in response, companies like Novartis have opened dedicated production facilities. The isotope they contain also degrades over time, making the logistics of their delivery critical.

Actithera is one of many up-and-coming biotechs looking to follow Novartis’ lead. Some of those, including Novartis and Ratio Therapeutics, are also targeting FAP.

“Actithera stands out as one of the most thoughtfully constructed radiopharma platforms we’ve seen, combining smart molecular design with a deep understanding of tumor biology and clinical need,” Roger Franklin, a partner at Hadean Ventures, said in a statement.