Novartis manufacturing associate checking punches at compressing machine.
Source: Novartis
In 2010, a volcano erupted in Iceland. For Dr. Oliver Sartor, a cancer research professor at the Tulane University School of Medicine, it was a problem.
Ash from the eruption disrupted flights across Europe — including a time-sensitive shipment of experimental radioligand therapy that Sartor was expecting from Norway.
Radioligand therapy, also called radionuclide or radiopharmaceutical therapy, is a targeted form of cancer treatment that delivers radiation directly to cancer cells. While other forms of cancer treatment can target any rapidly dividing cells in the body, radioligand therapy’s precision helps limit damage to healthy, surrounding tissue.
It’s an effective form of treatment that many experts and patients are excited about, but there’s a significant catch — the medication expires within days after it’s manufactured.
A radioligand is made of a radioisotope, which emits radiation that damages cells, and a targeted ligand — a molecule that binds to specific markers on cancer cells. The radioactive component has a very short half-life, or the time it takes for the radioactivity to decrease by 50%. Once the radioactivity decays, it can no longer kill the cancer cells as effectively, which means radioligand therapy has a limited window of viability. By the time it is packaged and ready to ship, the treatment has to reach patients in a matter of days.
“It takes planning,” Sartor told CNBC. “It’s not something you just sort of walk in and say ‘Oh, I think I’ll give you [this] today.'”
Pharmaceutical company Novartis believes the returns will be worth the challenge of mastering this race against time.
Novartis currently produces two radioligand therapy treatments called Lutathera, which treats neuroendocrine tumors, a rare form of cancer in the digestive tract, and Pluvicto, for patients with a specific type of prostate cancer. They were both approved by the Food and Drug Administration.
As of October, Novartis had treated more than 16,000 neuroendocrine patients and 4,000 prostate cancer patients in the U.S. Pluvicto was approved only last March and demand is increasing. As many as 60,000 U.S. patients could ultimately benefit from the medicine, said Jeevan Virk, head of radioligand therapy at Novartis.
The drugs are expensive. The list price (wholesale acquisition cost) of Pluvicto is around $42,500, while Lutathera is around $53,200, and most patients require between four to six doses. Novartis, which generated more than $50 billion in net sales last year, believes Pluvicto holds multibillion-dollar peak sales potential.
But in order to realize that potential, Novartis has to move the medication through the supply chain seamlessly.
Expensive to produce and ship fast
Nuclear medicine has been used to treat cancer for decades, and radioligand therapy itself is not new. The therapy has previously been used to treat cancers like lymphoma, but it was not always widely accepted or used by members of the medical community.
“I think it was challenging for it to find its place,” said Dr. Delphine Chen, director of molecular imaging and therapy at Fred Hutchinson Cancer Center in Seattle.
Dr. Leo I. Gordon, a professor of cancer research at Northwestern University’s Feinberg School of Medicine, said the hesitation often comes down to finances.
Producing radioligand therapy is expensive, and companies have to be willing to shoulder the costs and navigate a challenging supply chain in the hope that they can eventually make a profit.
“I’m not sure it’s a great message to send that everything is based on profit mode and all,” he said, “but it certainly does exist in medicine, oncology and the world.”
For lymphoma, it’s not a long-term investment any company has been willing to make, Gordon said. But since Pluvicto and Lutathera outperform existing treatments available for certain prostate and neuroendocrine cancers, they are being seen to have significant commercial promise.
“There’s a lot of excitement around it,” said Chen, who has administered both drugs to patients. “A lot of patients feel better on it, so that’s really exciting and gratifying to me as a physician to be able to offer something that actually is helpful with minimal toxicity.”
Novartis engineers in packaging facility.
Source: Novartis
Novartis manufactures radioligand therapy at three sites in Italy, Spain and New Jersey, and has a fourth facility slated to open in Indiana next year. Virk said between 70 to 150 people work in each facility, and the site in Indiana will be Novartis’ largest to date.
For both Pluvicto and Lutathera, the manufacturing process begins with a mineral. The minerals are enriched into a stable isotope and exposed to radiation in nuclear reactors, where they ultimately become radioactive after around two to three weeks. During the irradiation, the enriched isotopes are placed into capsules to keep them secure.
The strength of the radiation starts to decay as soon as the capsules are taken out of the reactors, which means Novartis begins a race against a ticking clock. The radioactive atoms have a half-life of just six and a half days.
The capsules are transferred to an isotope-precursor production facility where they are further purified and concentrated into a radioactive liquid salt solution. At the end of this stage, which takes around 48 hours, there is enough radioactivity in one vial to treat between 30 and 50 patients.
The final step takes place in a labeling facility where the radioactive atoms are attached to targeting molecules, or the medicine itself, and that takes around 24 hours. After the final product has been packaged and inspected for quality, it is ready to be shipped.
The drugs have different shelf lives depending on how much radiation Novartis can load into one vial. Pluvicto expires five days after it’s packaged at the factory, while Lutathera has a 72-hour shelf life.
“We basically need to get the product distributed around the world, just in 72 hours, from those three production sites,” Virk said. “This includes anywhere from Tokyo to Anchorage, so it’s an incredible distance that needs to be covered.”
Novartis scientist in lab packing materials for transportation.
Source: Novartis
Pluvicto and Lutathera are packaged inside a small lead container, roughly the size of a credit card. Lead is a strong insulator, so it doesn’t allow the radiation to escape. The drugs are also placed inside an additional container called a Type-A container, which is made of Styrofoam and helps with temperature control.
The risk of radiation exposure is so minimal that radioligand therapy is often transported via commercial airlines and cargo planes. When doses have to be transported on the ground, Virk said Novartis often uses a private courier van service to ensure they reach their destination as quickly as possible.
The process is timed to the minute, said Virk, and there’s a team of around 30 to 40 people at Novartis who oversees the complex logistics.
“It’s a 24/7 operation as you might imagine, because we really have customers around the globe that depend on ensuring that patients get their doses,” he said. “That’s really the fuel that keeps us going.”
Mistakes can happen, and things do go wrong in the supply chain occasionally, Virk said. But errors are costly, because if the shipments do not reach patients in time, the doses can’t be salvaged, and the manufacturing process has to start over.
Patients feel the difference
Radioligand therapy is administered through an IV infusion, and though it does help limit damage to healthy tissue, patients can experience some side effects.
Chen of the Fred Hutchinson Cancer Center said patients who receive Pluvicto can experience some nausea, vomiting, diarrhea, constipation, and fatigue in the short term. “Most of them have had only mild nausea that we’ve observed, and so Pluvicto is very well tolerated compared to chemotherapy,” she said.
Chen said patients can experience many of the same symptoms with Lutathera, but the diarrhea can be exacerbated, and some patients contend with worsening bowel obstruction. In rare cases, patients may be unable to maintain their blood pressure.
But for many patients, these side effects are worth it.
Vanue Lacour Jr. was first diagnosed with prostate cancer in 2007, and underwent a “tough” surgery to remove his prostate after his diagnosis. He stayed cancer-free for eight years, but in 2015, he learned he had relapsed with an advanced form of prostate cancer that had spread into his bones.
“I was determined to win,” the 80-year-old told CNBC. “I’m determined to live.”
Lacour began a grueling round of chemotherapy that he described as a “very, very hard, harsh medicine.” He incurred painful damage to nerves in his foot and leg that he still lives with today.
The chemotherapy helped stabilize his cancer, but Lacour said his doctors were not satisfied. In 2018, Lacour enrolled in a clinical trial for Pluvicto and received six doses over eight months. Now, he is officially in remission.
“I had no real side effects,” Lacour said. “I’m getting back to doing a lot of the things I like to do.”
Radioligand therapy has also helped Josh Mailman, who learned he had a softball-sized neuroendocrine tumor of the pancreas in 2007. The cancer had also spread to his liver.
“I didn’t know how much time I had,” the 61-year-old Oakland, California, resident told CNBC. “There were very few treatments for pancreatic neuroendocrine tumors at the time.”
Mailman decided to join a support group, and he said the other members encouraged him to learn as much as possible about his disease. In 2008, he traveled to a medical conference in Toronto where he heard about radioligand therapy for the first time. As his symptoms worsened over the next six months, his doctor agreed to give Mailman his first dose of radioligand therapy under compassionate care in 2009.
Mailman received three doses of radioligand therapy in 2009 and 2010, and he said it kept his cancer stable for the next six years. He has since had two follow-up treatments — one in 2016 and one in 2020, after the FDA approved Lutathera.
“I’m still here 15 years later,” he said. “It’s been a game-changer in the neuroendocrine tumor space.”
Because of his success with radioligand therapy, Mailman has become deeply involved in patient advocacy, where he works to raise awareness about nuclear medicine and neuroendocrine tumors.
“I would say I’m retired, my wife disagrees,” Mailman joked.
Mailman also runs virtual patient groups twice a week, where patients, friends and family members can come together to discuss their diagnosis and treatments. Mailman said radioligand therapy is discussed in more than 90% of the sessions.
“Either someone’s going to have it, someone had it, someone wants to know more about it,” he said.
During one session CNBC observed in early November, more than a dozen patients met and discussed their experiences with and concerns about radioligand therapy. Patients who had already received it answered questions about their side effects and shared tips about how to overcome fear about needles and radiation.
It is common for patients to express unease about the radiation, said Chen, but there are clear precautions in place to limit exposure and protect others.
Completion was expected in the second half of next year, the Swiss pharma group said.
Arnd Wiegmann | Reuters
The road ahead
As demand for radioligand therapy increases, Novartis’ challenge is to scale up access and awareness about the medication.
Virk, head of radioligand therapy at Novartis, said the company is working with health care systems, governments and other regulatory agencies around the world to improve its operations.
“From my perspective, [radioligand therapy] as a platform is still very much in its infancy,” he said. “So [we’re] really excited about the drug, [but] very acutely aware that we’re just at the beginning of this radioligand therapy revolution.”
Sartor at the Tulane University School of Medicine said there is still work to be done, particularly in terms of optimizing the supply chain but that radioligand therapy makes a real difference for patients.
“I think radioligand therapy has arrived in a way that is meaningful for patients today,” he said. “I’m anxious for patients to be able to receive the therapy in an FDA-approved manner, and also to do the next generation of clinical trials to ensure that even more people will have access in the future.”
Apple’s iPhone 16 at an Apple Store on Regent Street in London on Sept. 20, 2024.
Rasid Necati Aslim | Anadolu | Getty Images
Apple has made moves to diversify its supply chain beyond China to places like India and Vietnam, but tariffs announced by the White House are set to hit those countries too.
China will face a 34% tariff, but with the existing 20% rate, that brings the true tariff rate on Beijing under this Trump term to 54%, CNBC reported. India faces a 26% tariff, while Vietnam’s rate is 46%.
Apple was not immediately available for comment when contacted by CNBC.
Here’s a breakdown on Apple’s supply chain footprint that could be affected by tariffs.
China
The majority of Apple’s iPhones are still assembled in China by partner Foxconn.
China accounts for around 80% of Apple’s production capacity, according to estimates from Evercore ISI in a note last month.
Around 90% of iPhones are assembled in China, Evercore ISI said.
While the number of manufacturing sites in China dropped between Apple’s 2017 and 2020 fiscal year, it has since rebounded, Bernstein said in a note last month. Chinese suppliers account for around 40% of Apple’s total, Bernstein said.
Evercore ISI estimates that 55% of Apple’s Mac products and 80% of iPads are assembled in China.
India
Apple is targeting around 25% of all iPhones globally to be made in India, a government minister said in 2023.
India could reach about 15%-20% of overall iPhone production by the end of 2025, Bernstein analysts estimate. Evercore ISI said around 10% to 15% of iPhones are currently assembled in India.
Vietnam
Vietnam has emerged in the past few years as a popular manufacturing hub for consumer electronics. Apple has increased its production in Vietnam.
Around 20% of iPad production and 90% of Apple’s wearable product assembly like the Apple Watch takes place in Vietnam, according to Evercore ISI.
Other key countries
Malaysia is a growing manufacturing location for Apple for Macs and is facing a 25% tariff. Thailand is also a small hub for Mac production and will be hit with a 36% levy.
Apple also sources components from South Korea, Japan, Taiwan and the United States. Components may be shipped from one country to another before assembly takes place in China or elsewhere.
In February, Apple announced plans to open a new factory for artificial intelligence servers in Texas as part of a $500 billion investment in the U.S.
However, Apple does not have mass production in the United states. It produces only the Mac Pro in Texas.
A Xiaomi store in Shanghai, China, on March 16, 2025.
Qilai Shen/Bloomberg | Bloomberg | Getty Images
Chinese electric carmakers Xiaomi, Xpeng and Leapmotor each delivered nearly 30,000 or more cars in March, roughly twice several of their fellow startup competitors.
It’s a sign of how some automakers are pulling ahead, while BYD remains the market leader by far.
Xiaomi delivered a record number of electric vehicles in March, exceeding 29,000 units, the company announced on social media. That topped its prior run of delivering more than 20,000 vehicles in each of the past five months.
The SU7, Xiaomi’s flagship model, was involved in a crash on a highway on Tuesday that left three dead. The automaker on Tuesday afternoon released a statement on Chinese social media that the vehicle was in navigation on autopilot mode before the accident.
Based on preliminary information, the road was obstructed because of construction. The driver took control of the car but collided with construction infrastructure. Xiaomi added in the release that investigations were underway.
That came two weeks after the automaker announced on March 18 its goal to deliver 350,000 vehicles this year. There are also talks of the automaker expanding its second EV factory in Beijing to meet demand, Bloomberg reported on March 18. Xiaomi did not immediately respond to CNBC’s request for comment.
Its competitor Xpeng in March delivered 33,205 vehicles, the fifth consecutive month it has delivered over 30,000 units per month and reflecting a 268% surge in deliveries from the same month last year. March is also the fifth consecutive month the company has delivered over 15,000 units of the Mona M03.
Li Autodelivered 36,674 vehicles in March, a 26.5% year-over-year increase, but fewer than every month in the second half of 2024. The company’s cars had gained early traction with Chinese consumers since most come with a fuel tank for charging the vehicle’s battery, reducing anxiety about driving range.
BYD sold 371,419 passenger vehicles in March, reflecting a year-over-year growth of 57.9%. Its overseas sales volume also hit a record high of 72,723 units in March.
Across the board, major companies across China’s electric car industry reported deliveries rose last month, indicating a pick-up in demand from the seasonally soft first two months of the year.
U.S. automaker Tesla sold 78,828 electric vehicles in China in March, marking a 11.5% year-over-year decline in growth.
Other Chinese carmakers saw growth in deliveries but some still struggled to break through the 20,000-unit mark.
Niodelivered 15,039 vehicles, a 26.7% year-over-year growth, but well below the number of cars delivered in the months of May to December last year. Nio-owned Onvo, which markets its electric vehicles as family-oriented, in March recorded 15,039 units in deliveries.
Aito, as of April 2, has not published its delivery numbers for March. The automaker, which uses Huawei tech in its vehicles, on social media had reported monthly deliveries of 34,987 and 21,517 in January and February, respectively.
Quarterly performance
On a first-quarter basis, BYD remained in the lead with 986,098 vehicles sold. The automaker, which overtook Tesla in annual sales last year, surpassed the U.S. EV giant in battery electric vehicles sales this quarter.
Tesla sold 172,754 vehicles in China in the first quarter this year, according to monthly delivery numbers published by the China Passenger Car Association.
Xpeng also reported strong growth, with a total of 94,008 vehicles delivered in the quarter ending in March, reflecting a 331% year-over-year growth.
Leapmotor saw quarterly deliveries more than double to 87,552 units from 33,410 units the same period in 2024, according to publicly available numbers the company published.
However, Li Auto and Nio reported weaker growth than their competitors in the first quarter of the year.
Nio saw 42,094 vehicles delivered in the three months ended March 2025, an increase of 40.1% year over year. Li Auto saw a slower year-over-year growth of 15.5%, with a total of 92,864 vehicles delivered.
Wednesday’s announcement, which came alongside a set of sweeping new tariffs, gives customs officials, retailers and logistics companies more time to prepare. Goods that qualify under the de minimis exemption will be subject to a duty of either 30% of their value, or $25 per item. That rate will increase to $50 per item on June 1, the White House said.
Use of the de minimis provision has exploded in recent years as shoppers flock to Chinese e-commerce companies Temu and Shein, which offer ultra-low cost apparel, electronics and other items. The U.S. Customs and Border Protection has said it processed more than 1.3 billion de minimis shipments in 2024, up from over 1 billion shipments in 2023.
Critics of the provision say it provides an unfair advantage to Chinese e-commerce companies and creates an influx of packages that are “subject to minimal documentation and inspection,” raising concerns around counterfeit and unsafe goods.
The Trump administration has sought to close the loophole over concerns that it facilitates shipments of fentanyl and other illicit substances on the claims that the packages are less likely to be inspected by customs agents.
Temu and Shein have taken steps to grow their operations in the U.S. as the de minimis loophole has come under greater scrutiny. After onboarding sellers with inventory in U.S. warehouses, Temu recently began steering shoppers to those items on its website, allowing it to speed up deliveries. Shein opened distribution centers in states including Illinois and California in 2022, and a supply chain hub in Seattle last year.