DUPA’s origins trace back to the late 1990s in Low’s lab, known for designing “smart molecules.” His team created DUPA to bind tightly to a protein found in prostate cancer cells, prostate-specific membrane antigen (PSMA). Initially, they attached a radioactive tracer detectable by PET scans and launched a study with IU in 2008. Although the images were promising, flaws in the study design led IU to shut it down early.
“The images turned out beautifully,” Low recalled. “Unfortunately, they’ve never seen the light of day.”
Endocyte pivoted, exploring fluorescent dyes to make cancer glow during surgery. But development was slow, and faculty struggled to find a clinical use. By 2019, DUPA was rarely discussed in research meetings. “It just sort of petered out,” Cary recalled.
Quietly, though, the molecule had found a second life in Europe. A small German company discovered DUPA’s patent in 2014 and had a fresh idea: What if the molecule were used as a missile to deliver a radioactive payload to cancer? All it required was a modest tweak of adding four atoms.
“If I were to put the chemical structures in front of you,” Low said, “it might take you several minutes to notice a difference. Fortunately, however, our earlier Purdue University patents still covered the modified molecule, so the final Pluvicto molecule still belonged to us.”
Endocyte saw the potential and acquired the clinical data from the German company for $12 million, gaining access to the safety, efficacy and optimal dosing information. In 2018, after strong Phase 1 trial results, Novartis bought Endocyte for $2.1 billion. “Pretty good return,” Low joked.
When the therapy reached a Phase 3 study, called the VISION Trial, IU School of Medicine was at the forefront. The cancer center enrolled 12 patients — one of the largest volumes — that helped Pluvicto win FDA approval in March 2022.
Nabil Adra, MD, left, helped put Pluvicto through its paces during clinical trials. Clint Cary, MD, MPH, the Chair of the Department of Urology, arrived at IU when the molecule behind the drug was being tested as a tool to help with prostate cancer surgery.
Unlike chemotherapy or radiation, both of which harm healthy tissue, Pluvicto is precise in ferrying a radioactive isotope to cancer. The drug entered testing with tempered expectations for benefiting patients with advanced disease. The results stunned seasoned oncologists.
Pluvicto worked broadly, across many stages. Roughly half of patients experienced “deep and durable remissions,” said Adra, who oversaw IU’s trial site. One of his patients is still cancer-free almost four years later. Data from the main study and a follow-up analysis reported minimal and tolerable side effects. “It’s not stuff we normally see with prostate cancer,” Adra said.
It’s why Novartis spent $169 million to put a 700,000-square-foot facility in Indianapolis. It opened in 2023 in a former FedEx hub near the airport — strategically placed to manufacture the doses, which have a short half-life, and quickly ship them nationwide.
Each dose is made to reach a patient on a specific time and day,” said James Fredette, who oversees operations at the facility. “Often within days or hours of being manufactured.”
To protect handlers, doses are sealed in lead-lined containers. They are shipped immediately, equipped with GPS tags, to one of 650 treatment sites across the United States. That precise supply chain, Fredette said, has an on-time rate of almost 99%.
At IU, operations are tailored to this reality. A tumor board meets weekly to evaluate patients and coordinate care. Pluvicto recipients undergo a streamlined process — consultation, labs and infusion all in one visit. If a patient can’t receive a dose, others are ready to step in. “We almost never waste a dose,” Adra said.
For a time, IU was the only site in Indiana offering Pluvicto. Patients traveled from Illinois, Kentucky and Ohio. Over the past three years, Adra estimates IU has treated around 300 patients — among the highest clinical volumes in the country.
IU’s role continues to evolve. Researchers at the IU Simon Comprehensive Cancer Center are leading trials to test Pluvicto earlier in the disease course, including before chemotherapy or even as an alternative to surgery. Investigators are studying biomarkers to predict which patients will benefit most, aiming to personalize treatment and avoid unnecessary therapy of prostate cancer.
“It was a dream come true,” Adra said. “I’ve seen the drug move from early development to Phase 3 clinical trials to FDA approval, and now will likely become a frontline therapy.”
To support prostate cancer research and the development of innovative therapies, such as Pluvicto, at the IU Simon Comprehensive Cancer Center, please contact Liz Standiford at estandi@iu.edu.