Switzerland-based Novartis AG spent $100 million on a 70,000-square-foot manufacturing plant that makes Pluvicto, a radiopharmaceutical medication to treat advanced-stage prostate cancer. (Photo courtesy of Novartis)
Switzerland-based Novartis AG spent $100 million on a 70,000-square-foot manufacturing plant that makes Pluvicto, a radiopharmaceutical medication to treat advanced-stage prostate cancer. (Photo courtesy of Novartis)

Inside a large manufacturing building on the northwest side, officials at Cardinal Health are busy at work on their latest expansion project, yet another clean room for nuclear medicine.

Already, workers have erected massive walls of thick lead weighing hundreds of tons to shield technicians against radiation.

“There’s still one more layer [of lead] to go on,” said Shane Thrasher, vice president of nuclear manufacturing. “That’s for the appropriate amount of radioactive shielding from what’s inside.”

What’s inside, when the project is completed, will be large commercial batches of actinium 225, an isotope that can be infused into a patient in small doses with the goal of destroying or shrinking cancer cells with more precision than chemotherapy and with fewer side effects.

Already, Cardinal Health has spent more than $50 million in the past three years on the plant, named the Center for Theranostics (a combination of “therapeutics” and “diagnostics”), to meet huge demand for nuclear medical products that are known as radiopharmaceuticals.

It’s a booming industry, with a large cluster in central Indiana. And the roster of players has surged in the past few years to include some of the world’s leading pharmaceutical companies, attracted by the potential for significant growth.

Companies as far away as France, Switzerland and Israel have invested billions of dollars in radiopharmaceutical manufacturing assets in central Indiana. They are attracted by the region’s central location, workforce talent and long history in pharmaceutical drug-making.

Last year, Indianapolis-based Eli Lilly and Co.—better known for its long history in insulins, antidepressants and traditional cancer drugs—jumped into the radiopharmaceutical business by buying Point Biopharma Global Inc., an Indianapolis-based startup, for $1.4 billion. Point had recently built a 77,000-square-foot manufacturing plant off Georgetown Road to develop radioactive compounds.

“We’re really excited about bringing radiopharmaceuticals into the portfolio by way of the acquisition of Point Biopharma,” Jacob Van Naarden, president of Lilly’s oncology business, said during an earnings conference call last month. “We are supplementing that acquisition with additional work through our discovery labs and the ability to make these medicines ourselves.”

In April, Switzerland-based Novartis AG held an open house for its new, 70,000-square-foot manufacturing plant near the Indianapolis International Airport that cost $100 million. Just a few months earlier, federal regulators approved the facility to make Pluvicto, a radiopharmaceutical medication to treat advanced-stage prostate cancer.

Novartis acquired the rights to Pluvicto when it bought West Lafayette-based startup Endocyte Inc. for $2.1 billion in 2018. Last year, Pluvicto brought in $980 million in sales.

In February, New Jersey-based pharmaceutical giant Bristol Myers Squibb Co. jumped into the game when it acquired a San Diego startup, RayzeBio Inc., for $4.1 billion. The deal included a 64,000-square-foot manufacturing plant that RayzeBio renovated in Indianapolis to make isotopes for targeted therapy of gastroenteropancreatic and neuroendocrine tumors.

In Westfield, an Israel-based company, Isotopia, is building 28,000 square feet of clean rooms, labs and other space at a cost of $20 million. The company’s first U.S. facility will make radioactive medical isotopes for targeted cancer treatments.

And two years ago, Australia-based Telix Pharmaceuticals, with U.S. headquarters in Fishers, dosed its first patient with a new imaging agent designed to target and light up prostate cancer cells so doctors can see them. Last year alone, the drug, known as Illuccix, rang up more than $500 million in sales.

At the crossroads

Central Indiana is emerging as perhaps the largest nuclear medicine cluster in the United States, due to a wide mix of factors that include the region’s central location, which allows products to be shipped quickly across the nation. That’s critical for radiopharmaceuticals, which begin to decay immediately after being manufactured and have an extremely short shelf life. Unlike most pills, radiopharmaceuticals often last less than a week or two and need to be shipped to hospitals and clinics just-in-time for use.

Indiana’s central location, coupled with an airport that houses the second-largest FedEx hub in the world, is a tough combination to beat, officials say.

And then there’s Purdue University, about an hour northwest of Indianapolis, which houses the nation’s oldest and largest nuclear pharmacy program. The program, set up in the 1970s, trains not only pharmacists but also nuclear medicine technicians, radiation safety officers and other professionals in the nuclear industry.

The industry is growing, among other reasons, because researchers have been better able to develop drugs, called ligands, that act like self-guided missiles and seek out cancer cells based on certain biomarkers that are unique to cancer.

After being infused, the ligands are metabolized into the bloodstream and rapidly begin traveling throughout the body, binding to cancer cells.

In the process, they carry a radioisotope that acts like a nuclear warhead on a missile. But instead of exploding, the radioisotope decays, releasing particles that cause damage to the cancer cell’s DNA, destroying the cell.

“If you look at some of the early results, this is just another treatment option for patients with cancer,” said Kara Weatherman, a Purdue clinical professor of pharmacy who leads the school’s nuclear pharmacy program. “Chemotherapy, obviously, has some significant negative aspects of treating. And so, I think as the population gets older, as the incidence of cancer goes up, having multiple options for treatment is very logical.”

Buying technology

Todd Hockemeyer, CEO of Isotopia’s U.S. operations, said he isn’t surprised that large pharmaceutical companies are scooping up radiopharmaceutical startups and their Indiana manufacturing assets.

“I think the industry is waking up to the fact that radiotherapeutics is another arrow in the quiver,” he told IBJ. “If you’re in the oncology marketplace, this is something that’s got to be in your portfolio.”

Hockemeyer, who previously built a factory in Indianapolis for Point Biopharma, said the radiopharmaceutical industry has specialized knowledge that is very different from that of traditional pharmaceutical players. As a result, those traditional companies are more likely to buy or partner with smaller companies that have developed highly promising drugs or manufacturing assets.

“I think they realized that, ‘Look, this would be very difficult for us to organically dig this out of the ground. So let’s go buy something,’” Hockemeyer said.

Even large nuclear medicine companies are joining the shopping spree. In 2020, Curium, a nuclear medicine company with headquarters in London and Paris, purchased Zevacor Molecular, one of the first radiopharmaceuticals players in central Indiana, which had built a $10 million plant in Noblesville. Curium said it would invest another $10 million at the site.

Mike Bolinder, a former Lilly executive, said the industry research and development model has shifted in the past decade or so from trying to develop all drugs in-house to working with startups that do the intensive early work of raising venture capital and developing products.

Then, if something pans out, the large pharmaceutical companies can try to buy or license the product and add it to their pipeline, said Bolinder, who is now senior vice president at BioCrossroads, an Indianapolis-based organization that promotes the state’s life sciences sector.

“And I think that, you know, given that model, and given the almost miraculous success of some of these drugs, I think [big drug companies] would be ludicrous not to try to get into this.”

‘Very fast pace’

At Cardinal Health’s manufacturing center, about 5 miles west of Ascension St. Vincent’s flagship hospital at West 86th Street and Township Line Road, the company acts as a contract manufacturing organization to numerous pharmaceutical partners, turning out isotopes for Bayer, Novartis, Bristol Myers Squibb and others.

“Some of our pharmaceutical partners choose to do their own manufacturing, which is fine,” said Mike Pintek, president of Cardinal’s nuclear and precision medicine. “But they want to partner with us for preparation, dispensing and distribution of their drug to the patient.”

The company, based in Dublin, Ohio, rang up sales last year of $1.2 billion in its nuclear and precision health division, up 41%. That made it a fairly small player in the Cardinal Health empire, which had total revenue of $205 billion. But it’s one of the fastest-growing divisions.

“We are considered one of the key growth companies within Cardinal,” Pintek said.

In an hourlong interview and tour at their Indianapolis plant, Cardinal officials played up their division’s performance, pointing out that it delivers more than 12 million doses of medicine annually, with an on-time delivery rate of 99.8%.

The manufacturing space spans about 20,000 square feet, with room for ann additional 8,000 or so square feet of clean rooms. Officials took pains to point out the safety features, including numerous radioactivity monitors and plenty of thick lead shielding.

“You’re looking at a hot cell with 10 inches thick of lead all the way around,” Thrasher said, pointing to one area. “This one big lead glass window alone is 14 inches deep, 1 ton apiece just in the windows alone.”

On this particular day, none of the clean rooms was in operation, and the manufacturing plant, with about 30 employees, seemed mostly empty.

But Thrasher said the company had been operating the rooms for various clients just a few days earlier and was busy setting up space for other clients. He said the lead time for accepting a new client that needs a new manufacturing space is about a year and a half.

“On the days the room is not used for [a certain client], we’ll clean it, we’ll clear it, and we’ll release it for a different product and different client,” he said.

Cardinal Health officials said the high demand for manufacturing space and radiopharmaceuticals means the industry is likely at its early stages and will only grow by leaps in the years ahead.

“I would say we’re still in the early days of precision medicine, but it’s moving at a very fast pace,” Pintek said. “And it’s really exciting to see what it could mean for my children, their children and future generations.”

Copyright © 2024 All Rights Reserved.