Purdue University legend Dr. Philip Low admits he could buy a yacht and sail into the sunset, but that would ignore the call he feels to continue life-saving work: “If you can help a lot of people, I think it would be misdirected time not to do it,” he says. Men with advanced stage prostate cancer are the latest group of patients to benefit from one of Dr. Low’s discoveries; the FDA approved Pluvicto just weeks ago, offering newfound hope for men who have run out of treatment options. The precision targeted drug is based on an approach that Low is confident will kill not only other cancers, but a long list of terrible diseases—and so, the yacht can wait.
Based on FDA approval in late March, Novartis is now selling Pluvicto; the healthcare giant picked up the therapy when it purchased Low’s Purdue-based startup Endocyte in 2018 for the staggering price tag of $2 billion—the largest-ever acquisition of an Indiana life sciences company.
Pluvicto is designed to treat metastatic castration-resistant prostate cancer (mCRPC), which is cancer that has spread (metastasized) beyond the prostate gland and is no longer responding to the few treatment options available.
Pluvicto is based on a molecule that Low discovered in his Purdue lab years ago; the team designed the molecule to “home in very specifically on prostate cancer cells” and bind to the surface of those cells.
“We used this homing molecule kind of as a smart molecule—like a smart bomb, in defense terminology,” says Low, Purdue’s Presidential Scholar for Drug Discovery. “We attached to it what’s called a radioactive nuclide; the smart molecule carries the attached radionuclide very selectively to prostate cancer tissue, avoiding uptake by healthy tissue. Therefore, it concentrates this lethal radioactivity almost exclusively in the cancer cells.”
The approach enhances the potency of the drug, while also reducing the off-target toxic effects to healthy tissues. The FDA designated it a “Breakthrough Therapy,” an unusual move that expedites the approval process. Pluvicto’s Phase 3 trial found it to reduce the risk of death by 38% “which is enormous,” says Low, and reduce the risk of disease progression by 60%, compared to standard therapies.
Novartis has announced plans to test Pluvicto in increasingly earlier stages of prostate cancer, followed by other cancers that also express PSMA—the target that the drug is directed to. Other cancers that seem to express PSMA include colon, breast and bladder.
Low says the success of Pluvicto validates the overall approach of targeting drugs exclusively to diseased cells—a method that his team “pioneered and explored for 35 years or more” at Purdue.
“And this validation…has attracted enormous attention to our work, so that now it’s becoming financially possible to develop many other applications for this targeting approach,” says Low. “As a consequence, we’re developing targeted medicines to treat many, many different diseases, including viral infections, autoimmune diseases like multiple sclerosis and rheumatoid arthritis, many other cancers…and even central nervous system diseases like Alzheimer’s, Parkinson’s and so forth.”
Low describes Pluvicto as a major milestone in his 46-year career at Purdue, which includes two FDA approvals in less than six months for his discoveries, the creation of seven startups and the $2 billion sale of Endocyte. Another significant piece of his professional legacy is the training of close to 80 PhD students at Purdue to “perpetuate the skill and art of discovering drugs.”
“It’s great to suddenly see a lot of the fruits of your labors being validated and becoming available to people, so you’re actually doing something that matters and helps mankind, rather than just increasing the number of pages of scientific papers in the library,” says Low. “There’s a great deal of satisfaction knowing we’ve been able to reduce pain and suffering on the planet.”
With five children and 18 grandchildren, Low acknowledges that he and his wife often discuss retirement. While Pluvicto marks a “major pivot point” in his career, Low says it’s too soon to hang up his hat, because he’s even more excited about what lies ahead.
“Rather than seeing the greatest contributions behind me, I actually see many more exciting opportunities ahead. If I can continue to execute on some of these ideas and move them into human clinical trials, I think we’ll see an awful lot of benefit from this basic approach,” says Low. “These ideas are strategies for treating a lot of important diseases. If I have the health, physical capability and financial support to complete the development of these ideas, I plan to do so.”
Low says, already approved for advanced stage prostate cancer, Pluvicto has the potential to be a blockbuster drug if also approved for earlier stages of the disease.
Low says his next FDA approval will likely be for a malaria drug; Low repurposed a cancer drug to create the malaria therapy.