A volcano erupted in Iceland in 2010 and for Dr. Oliver Sartor, a professor at the Tulane University School of Medicine who specializes in cancer research, this was an issue. Ashes from the eruption hampered planes across Europe, including Sartor’s consignment of time-sensitive radioligand therapy from Norway.
As per CNBC, radioligand therapy, also known as radionuclide therapy and radiopharmaceutical therapy, is a targeted cancer treatment that delivers radiation directly to cancer cells. While conventional cancer treatments can target any rapidly dividing cells in the body, the accuracy of radioligand therapy helps to reduce collateral damage to good tissue.
Many professionals and patients are enthusiastic about this therapeutic method, but there is a huge catch: the drug expires within days after its production.
A radioligand is comprised of a radioisotope, which produces radiation that destroys cells, and a targeted ligand, which binds to specific markers on cancer cells. The radioactive component has an extremely short half-life, or the amount of time it takes for the radioactivity to decrease by half. Once the radioactivity decays, it is no longer as efficient in killing cancer cells, hence radioligand therapy has a limited window of viability. The therapy must reach patients within a few days from the moment it is packaged and prepared for shipment.
“It requires preparation,” Sartor told CNBC. “You can’t just come in and say, ‘I guess I’ll give you [this] today’.” Novartis, a pharmaceutical corporation, feels the benefits will justify the difficulty of winning this race against time. Lutathera addresses neuroendocrine tumors, a rare form of digestive system cancer, and Pluvicto cures a specific type of prostate cancer. The Food and Drug Administration has authorized both of them.
Novartis had treated more than 16,000 neuroendocrine patients and 4,000 prostate cancer patients in the United States as of October. The approval of Pluvicto occurred only in March of last year, although the drug’s popularity is rising. According to Jeevan Virk, head of radioligand therapy at Novartis, as many as 60,000 patients in the United States could eventually benefit from the medication.
The medications are pricey. Pluvicto’s list price (wholesale acquisition cost) is approximately $42,500, whereas Lutathera’s is approximately $53,200, and the majority of patients require four to six doses. Novartis, which produced more than $50 billion in net sales in 2014, believes Pluvicto has peak sales potential in the multibillion-dollar range.
In order to maximize this promise, however, Novartis must transfer the drug efficiently through the supply chain. For decades, nuclear medicine has been utilized to treat cancer, and radioligand therapy is also not new. The therapy has been utilized in the past to treat diseases such as lymphoma, but it has not always been universally acknowledged or utilized by the medical community.
Dr. Delphine Chen, director of molecular imaging and therapy at the Fred Hutchinson Cancer Center in Seattle, stated, “I believe that it was difficult for it to find its position.” According to Dr. Leo I. Gordon, a professor of cancer research at the Feinberg School of Medicine of Northwestern University, the reluctance is frequently a financial issue.
The production of radioligand therapy is costly, and enterprises must be willing to absorb these expenses and traverse a complex supply chain in the hopes of generating a profit in the long run. “I’m not sure if it’s a nice message to give that everything is profit-driven,” he said, “but it exists in medicine, oncology, and the globe.”
For lymphoma, no firm has been willing to make a long-term commitment, according to Gordon. Due to the fact that Pluvicto and Lutathera outperform conventional treatments for some prostate and neuroendocrine tumors, it is believed that they hold substantial commercial potential.
Chen, who has delivered both medications to patients, remarked, “There’s a lot of buzz about it.” As a physician, I find it quite exciting and gratifying to be able to deliver something that is actually beneficial with minimal toxicity to a significant number of patients.
Novartis manufactures radioligand treatment at three locations in Italy, Spain, and New Jersey, with a fourth facility scheduled to open in Indiana in the coming year. According to Virk, between 70 to 150 individuals work in each facility, and the Indiana location will be Novartis’ largest to date.
For both Pluvicto and Lutathera, production begins with the extraction of a mineral. The minerals are enhanced with a stable isotope and then exposed to radiation in nuclear reactors, where they become radioactive after approximately two weeks. During irradiation, the enriched isotopes are sealed in capsules to maintain their integrity.
As soon as the capsules are removed from the reactors, the power of the radiation begins to deteriorate, putting Novartis in a race against time. Six and a half days is the half-life of radioactive atoms. The capsules are moved to a facility for the manufacturing of isotope precursors, where they are purified and condensed into a radioactive liquid salt solution. At the conclusion of this phase, which takes around 48 hours, one vial has enough radioactivity to treat 30 to 50 patients.
The final stage takes around 24 hours and takes place in a labeling facility, where radioactive atoms are bonded to targeting molecules or the actual drug. After packaging and quality inspection, the final product is ready to be dispatched. Depending on how much radiation Novartis can load into a vial, the medications have varying shelf life. Lutathera has a shelf life of 72 hours compared to Pluvicto’s five days.
Virk stated, “We need to get the product delivered globally within 72 hours from these three production facilities.” This ranges from Tokyo to Anchorage, requiring a tremendous distance to be traveled.
Pluvicto and Lutathera are contained within a credit card-sized lead container. Lead is an excellent insulator, therefore, it prevents the escape of radiation. In addition, the medications are placed within a Type-A container, which is composed of Styrofoam and aids in temperature regulation.
Because the risk of radiation exposure is so low, radioligand treatment is frequently transported through commercial airplanes and cargo planes. Virk indicated that when medicines must be conveyed on the ground, Novartis frequently employs a private courier van service to guarantee that they arrive at their destination as promptly as feasible. According to Virk, the process is timed to the minute, and a 30-person to 40-person team at Novartis manages the logistics.
“It’s a 24-hour business, as you might expect, because we have customers all around the world who rely on us to ensure patients receive their medications,” he explained. This is the very fuel that keeps us going. Virk stated that mistakes are possible and that supply chain issues do occur on occasion. If shipments do not reach patients on schedule, doses cannot be recovered, and the production process must be restarted.
Radioligand therapy is provided via intravenous infusion, and although it limits harm to healthy tissue, patients may experience adverse effects. Patients using Pluvicto may experience nausea, vomiting, diarrhea, constipation, and exhaustion, according to Dr. Chen of the Fred Hutchinson Cancer Center. Pluvicto is very well tolerated compared to chemotherapy, as the majority of patients have just mild nausea.
Chen stated that individuals could suffer many of the same symptoms while using Lutathera; however, diarrhea can be worsened, and some patients may experience severe intestinal obstruction. In extremely rare instances, people may be unable of maintaining their blood pressure.
However, many patients find these adverse effects to be worthwhile. Vanue Lacour Jr. was initially diagnosed with prostate cancer in 2007 and subsequently underwent a “difficult” surgery to remove his prostate. In 2015, he discovered he had relapsed with an aggressive form of prostate cancer that had spread to his bones. He had been cancer-free for eight years.
The 80-year-old man told CNBC, “I was determined to win.” “I’m determined to live.” Lacour started an arduous round of chemotherapy, which he described as “very, extremely difficult and severe treatment.” The nerve damage he sustained in his foot and leg continues to cause him pain today.
His cancer was stabilized by the chemotherapy, but Lacour’s doctors were not pleased. In 2018, Lacour participated in a Pluvicto clinical trial and received six doses over the course of eight months. Now, his cancer is in remission.
Lacour stated, “I had no significant negative effects.” “I’m returning to doing many of the activities I enjoy.” Josh Mailman, who in 2007 discovered he had a neuroendocrine tumor of the pancreas the size of a softball, has also benefited from radioligand therapy. His cancer had also metastasized to his liver.
The 61-year-old Oakland, California resident stated to CNBC, “I did not know how much time I had.” At the time, virtually few treatments were available for pancreatic neuroendocrine tumors.
Mailman opted to join a support group, and he reported that his other members urged him to learn as much as possible about his illness. In 2008, he came to Toronto for a medical conference where he first learned about radioligand therapy. In 2009, as Mailman’s symptoms worsened over the course of the next six months, his physician agreed to administer him his first dosage of radioligand therapy as part of compassionate care.
In 2009 and 2010, Mailman underwent three doses of radioligand therapy, which he stated stabilized his cancer for the following six years. Since the FDA’s approval of Lutathera in 2016, he has received two further treatments: one in 2016 and one in 2020.
“I’m still here after 15 years,” he said. It has been a game-changer in the field of neuroendocrine tumors. Mailman has become heavily involved in patient advocacy as a result of his success with radioligand therapy, where he strives to increase knowledge of nuclear medicine and neuroendocrine tumors.
“I would claim that I’m retired, but my wife disagrees,” laughed Mailman. Additionally, Mailman hosts twice-weekly virtual patient groups where patients, friends, and family can discuss their diagnosis and treatments. According to Mailman, radioligand treatment is discussed in over 90% of the sessions. He stated, “Either someone is going to have it, someone now has it, or someone wants to learn more about it.”
During a session observed by CNBC at the beginning of November, more than a dozen patients recounted their experiences with and worries regarding radioligand therapy. Patients who had previously undergone the treatment responded to inquiries about their side effects and provided advice for overcoming needle and radiation phobia.
According to Chen, it is normal for patients to voice apprehension regarding the radiation, but there are obvious procedures in place to restrict exposure and protect others. As the demand for radioligand therapy rises, Novartis faces the problem of expanding access to and awareness of the medication.
Novartis’ global head of radioligand therapy, Virk, stated that the business is collaborating with health care systems, governments, and other regulatory authorities to enhance its operations. In his opinion, radioligand treatment as a platform is still in its infancy. “Therefore, [we are] really enthusiastic about the medicine, [yet] keenly aware that the radioligand therapy revolution is just beginning.”
Radioligand therapy makes a significant difference for patients, according to Dr. Sartor of the Tulane University School of Medicine. However, there is still work to be done, especially in terms of streamlining the supply chain.
“I believe that radioligand therapy has arrived in a meaningful way for patients,” he stated. “I am eager for patients to be able to receive the therapy in an FDA-approved manner, as well as to conduct the next phase of clinical trials to ensure that in the future, even more individuals will have access.”