Drugmakers bet billions that targeted radiation could be the next breakthrough in cancer treatment – ​​NBC New York

• Bristol Myers Squibb, AstraZeneca, Eli Lilly and other pharmaceutical companies have spent about $10 billion on radiopharmaceutical acquisitions and partnerships over the past year.
• Drugmakers are trying to replicate the success Novartis has achieved with Pluvicto and Lutathera.
• Radiopharmaceuticals are currently available for some neuroendocrine tumors and prostate cancer. They may one day be used for many cancers.

Drugmakers are betting that delivering radiation directly to tumors will prove to be the next breakthrough in cancer treatment.

Bristol Myers Squibb, AstraZeneca, Eli Lilly and other pharmaceutical companies have spent about $10 billion on deals to acquire or collaborate with radiopharmaceutical makers, taking over smaller companies to acquire technology that, while in its infancy, could treat many cancers.

“Any large company that has a presence in oncology or for which oncology is an important therapeutic category will likely need exposure to this space in one way or another,” said Michael Schmidt, an analyst at Guggenheim Securities.

Two Novartis radiopharmaceuticals are already available. Schmidt estimates that dozens more are in development. The overall market opportunity is hard to estimate because there are so many possible cancers the drugs could treat, he said.

Schmidt predicts that the category could grow to the low $5 billion range if the technology is limited to treating a few types of cancer, such as prostate and neuroendocrine cancers. even tens of billions if it turns out to be so effective for more cancers.

The drugs work by attaching radioactive material to a target molecule that seeks out and attaches to a specific marker on cancer cells. The trick is finding the markers that occur on cancer cells but not on healthy cells. This may allow the treatment to deliver radiation to the cancer cells and spare the rest of the body from the harm caused by the use of many cancer drugs.

It took some time to prove the technology could work both scientifically and financially. The first radiopharmaceuticals were approved in the early 2000s. But interest from large pharmaceutical companies didn’t pick up until recently.

The production of drugs requires complicated production and logistics, which are two major drawbacks. The radioactive material degrades quickly, so patients must be treated within days of the drug being prepared.

Pharmaceutical companies had already proven they could manage complex, time-sensitive drugs, such as CAR-T for blood cancers or gene therapies for rare diseases. Novartis then showed that these strategies could be applied to radiopharmaceuticals.

The Swiss pharmaceutical giant received approval in 2018 to use a radiopharmaceutical called Lutathera to treat a rare type of pancreatic and gastrointestinal cancer. Then in 2022, Novartis won another approval for prostate cancer treatment Pluvicto. Combined, the drugs are expected to achieve sales of about $4 billion by 2027, according to FactSet consensus estimates.

These successes sparked wider interest in radiopharmaceuticals.

“We put all this together and thought we have to do something, we have to make deals here,” said Jacob Van Naarden, president of Eli Lilly’s oncology division.

Lilly acquired radiopharmaceutical maker Point Biopharma last year for about $1.4 billion, and has also signed several partnerships with companies developing these treatments. One of the most important factors in Lilly’s initial search was whether the companies were ready to manufacture the drugs, Van Naarden said. Radiopharmaceuticals are not easy to manufacture, and Lilly wanted to make sure any initial acquisition would be able to manufacture the drugs itself, rather than outsource the work.

Manufacturing was also a key part of Bristol Myers Squibb’s $4.1 billion acquisition of RayzeBio, said Ben Hickey, RayzeBio’s chief executive. At the time of the acquisition, RayzeBio was nearing completion of a plant in Indiana and had secured its own supply of radioactive materials needed to develop experimental drugs in its process.

“That was clearly one of the criteria to ensure that our fate was in our own hands,” Hickey said.

Novartis has shown why this is so important, as the company initially struggled to produce enough doses of Pluvicto. It is investing more than $300 million to open and expand radiopharmaceutical manufacturing facilities in the U.S. to produce the drug and get it to patients quickly. The company is now able to keep up with demand for the treatment, which means carefully planning distribution.

Each dose has a GPS tracker to ensure it gets to the right patient at the right time, according to Victor Bulto, president of Novartis’ U.S. business. Novartis is delivering doses to sites up to nine hours away from the plant to minimize the risk of disruptions from storms, Bulto said.

Doctors and patients also experience this complexity.

Bassett Healthcare Network in upstate New York had to update its medical license to handle radioactive materials before administering Lutathera and Pluvicto, said Dr. Timothy Korytko, Bassett’s chief radiation oncologist. The drugs, which are administered intravenously, must be administered by a certified specialist.

It can take several weeks from the time a radiopharmaceutical is prescribed to when it is administered. With Pluvicto, patients come back once every six weeks for a maximum of six treatments.

Radiopharmaceuticals begin to break down after they are manufactured, so they are only suitable for use for a few days.

Ronald Coy knows how important it is to get to an appointment. Coy, a retired firefighter who has been battling prostate cancer since 2015, drives more than an hour across upstate New York to pick up Pluvicto in Bassett. Coy has had no problems so far, but he worries that a snowstorm could ruin his plans for an appointment between now and the end of January.

“Hopefully there won’t be any major storms by then, and if there are, I’ll be able to leave in a week,” Coy said.

When Coy returns home from treatment, he has to take precautions, such as staying away from his wife Sharon so she is not exposed to radiation. He drinks a lot of water to remove the extra radiation from his body. He doesn’t mind being a little uncomfortable for a few days if it means fighting cancer.

For Novartis, investing in infrastructure to manufacture and distribute radiopharmaceuticals would be worthwhile for Pluvicto and Lutathera alone, Bulto said. But it is even more attractive because of its potential to treat a wider range of cancers. He cites Novartis’ work to develop a drug for the marker which occurs in 28 different cancers, including breast, lung and pancreatic cancer.

“If we could take all of these lessons that we learned from manufacturing distribution and apply them to lung cancer patients, breast cancer patients, and potentially demonstrate these levels of significant efficacy and tolerability, we’re talking about a very large potential impact on cancer care. And of course, a very profitable business as well,” he said.

At this stage, it’s still an “if.” The field is in its early days, executives say, and the promise of radiopharmaceuticals beyond the current cancers they treat still needs to be proven.

“If we can expand the repertoire of targets and cancer types, this could be a very large class of drugs,” Eli Lilly’s Van Naarden said, adding that at this point it’s hard to say whether the class will be “super important” or “just important.”

One possibility Bristol Myers Squibb sees is combining radiopharmaceuticals with existing cancer drugs, such as immunotherapy, said Robert Plenge, Bristol’s chief research officer. AstraZeneca shares that vision.

AstraZeneca spent $2 billion to acquire Fusion Pharmaceuticals earlier this year. Susan Galbraith, executive vice president of oncology research and development, points to existing treatment regimens that combine immunotherapy with radiation therapy.

How big AstraZeneca’s radiopharmaceutical portfolio ultimately becomes depends on its initial prostate cancer program and other undisclosed targets it is already working on, Galbraith said. But she believes the technology will become an important part of cancer medicines over the next decade.

It could take years to understand the true potential of the technology, because many experimental drugs are still in early stages of development. One unresolved question is whether other radiopharmaceuticals are as safe and well-tolerated as Novartis’ Pluvicto, especially those that use different types of radioactive materials, Guggenheim analyst Schmidt said.

Big pharma isn’t waiting to jump into the race. Stories like Coy’s encourage them that the work will pay off.

For nearly 10 years, Coy underwent multiple treatments for prostate cancer that had spread to his bones. After just one Pluvicto treatment earlier this year, blood tests showed that Coy’s cancer levels had plummeted.

Not everyone responds so well to Pluvicto, and for Coy that could always change. But for now, Coy feels lucky to be part of a group that responds well to Pluvicto. It’s worth the drive and the precautions for him.

“I feel very lucky every day to be – as it is now – part of this third group where everything works really well for me,” he said.

—CNBC Leanne Miller contributed to this report.