You’ve recently been diagnosed with metastatic cancer. You started the recommended first-line therapy, but it isn’t cutting it. There is another available treatment, but your hopes are crushed upon learning that you will have to wait at least three months before the life-extending medication can be produced for you and reach your location. All the while, your cancer will continue to grow and spread, slowly eating your body from the inside out. This scenario isn’t hypothetical — it’s happening now.
Lutetium Lu 177 vipivotide tetraxetan, manufactured by Novartis under the trade name Pluvicto, has been approved since March of 2022 for the treatment of metastatic prostate cancer refractory to chemical castration. Yet at the time of this writing, over a year later, there exists only one site approved by the U.S. Food and Drug Administration (FDA) to manufacture the drug for commercial use, and it’s all the way in Ivrea, Italy!
To make matters worse, there is a narrow five-day window for the product to reach the patient. Any interruption to production or shipping that delays the process beyond this window results in the destruction of the dose and a longer postponement in the patient’s treatment and that of the many others piling onto the waiting list. And it isn’t simply a matter of patience. A recent estimate suggested that one in 20 patients die during the waiting period.
At this point, the demand for Pluvicto exceeds the supply, and federal regulation is limiting the speed with which industry can respond. Novartis does, in fact, own an additional production site in Millburn, NJ, but the manufacturing at this site is limited to research purposes and not for commercial market distribution.
With backing from the Society of Nuclear Medicine and Molecular Imaging (NSMMI), Novartis has submitted a request to FDA for expedited review to approve commercial manufacturing in Millburn, but the process will likely last several months before any final decisions are made. In the meantime, NSMMI continues to advocate for increased awareness of the crisis and to urge FDA and Novartis leadership to investigate other options, such as increasing enrollment in trials for experimental therapies like SPLASH (NCT0464752) or ECLIPSE (NCT05204927).
However, this raises the question of whether we really want our prostate cancer patients to have to enroll in clinical trials to get the treatment they need. If the current trend continues, patients in the U.S. will be left with no other option.
Of course, the Pluvicto shortage affects only a subset of male cancer patients. But these patients are more than one might think. Of the over 3 million men diagnosed with prostate cancer in 2020 and a 12 percent incidence of castrate resistance, at least 360,000 patients per year, hardly a negligible number.
To these patients, time is a precious resource, and what is currently being done for them is not enough.
Maybe our hands really are tied until the FDA grants Novartis more manufacturing freedom, but we cannot afford to overlook this issue. At the end of the day, we need to seriously examine how we ended up in the middle of this supply crisis and focus more effort on preemptively addressing logistical challenges for novel radiopharmaceuticals. Who knows, perhaps the developers of one of the up-and-coming compounds will launch their product with an improved supply chain, seizing the opportunity to cash in on the unmet demand and easing the growing burden imposed on these patients.
Since the writing of this article, significant developments have come to light, warranting an update. In late April, Novartis was indeed approved by the FDA to manufacture Pluvicto for U.S. commercial use at their Radioligand Therapy (RLT) facility in Millburn, New Jersey. We are pleased to report that production has already begun. This remarkable milestone is a breakthrough for patients relying on Pluvicto for their treatment and is expected to help stabilize the supply as production capacity is further increased throughout the rest of this year. We thank Novartis and the FDA for their commitment to resolving the Pluvicto shortage and for their efforts to ensure a stable supply of this vital treatment option for patients in need.
Matt Drewes is a medical student.