bottlenecksBottleneck

Clinical trial capacity for radioligand therapy

There are so many new radioactive cancer drugs now being tested that the trials themselves compete with each other, and with approved treatments, for the same scarce radioactive material, the same specially licensed hospital rooms, and the same trained staff. Sometimes a trial has to pause enrolling new patients simply because the isotope has run out.

Radioligand therapy's clinical pipeline has grown faster than the trial infrastructure needed to run it: industry analyses describe more than 200 lutetium-177-based radiopharmaceutical therapy trials of all phases in progress, including a large share of all active phase 3 radiopharmaceutical therapy trials underway worldwide. Because trial doses and commercial doses are drawn from the same limited isotope supply, a shortage hits trials directly: in June 2024, Bristol Myers Squibb's RayzeBio paused new-patient enrolment in the phase 3 ACTION-1 trial of RYZ101 (225Ac-DOTATATE) because it could not secure enough actinium-225, with a trial investigator noting there was only one Ac-225 supplier for the entire global study; patients already enrolled continued treatment while the company worked to bring on-site production online.

Site-level capacity compounds the isotope constraint. A clinical-operations guide to radiopharmaceutical trials notes that qualifying a site can take several months longer than for a conventional drug trial, because sites need an active radioactive-materials licence, shielded rooms, dedicated patient toilets, imaging-camera qualification (dose calibrator checks, dummy deliveries), and pharmacy staff specifically trained to receive time-critical, non-reschedulable shipments; some radiopharmaceuticals also require ordering a month or more in advance, so a patient's slot can be blocked by another patient's ongoing treatment cycle. The same nuclear medicine departments that run these trials are also treating growing numbers of commercial Pluvicto and Lutathera patients, so trial and standard-of-care patients increasingly compete for the same limited administration slots at the same centres.

Because a no-show wastes a dose that can cost tens of thousands of dollars and cannot be re-used, site readiness guidance now stresses building slack into scheduling and engaging nuclear medicine leadership early, on top of the underlying isotope-supply constraint that no amount of site-level planning alone can fix.

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Scale of the problem

>200

Lutetium-177 radiopharmaceutical therapy trials of all phases reported in progress (industry analysis)

source

June 2024, cited cause: actinium-225 shortage, single global supplier

RayzeBio (BMS) paused new-patient enrolment in phase 3 ACTION-1 trial

source

Root causes

Trial doses and commercial doses are drawn from the same constrained global isotope supply (particularly actinium-225 and, to a lesser extent, lutetium-177), so a supply shortfall hits both simultaneously.
Radiopharmaceutical trial sites typically take several months longer to qualify than conventional drug trial sites, because of radioactive-materials licensing, shielded-room construction, and imaging-equipment qualification requirements.
Nuclear medicine departments running trials are also treating a growing volume of approved standard-of-care patients, creating direct scheduling competition for the same hot labs and administration slots.
A missed or cancelled patient appointment wastes an individually manufactured, non-reschedulable dose that can cost tens of thousands of dollars, so scheduling slack has to be built in at a cost most conventional trials do not bear.

Current efforts

BMS/RayzeBio advancing on-site accelerator-based actinium-225 production specifically to de-risk ACTION-1 and its wider RYZ101 programme after the 2024 enrolment pause.
Novartis and other sponsors building dedicated, multi-site radioligand therapy manufacturing capacity ahead of pivotal trial readouts, partly to protect trial as well as commercial supply.
Specialist clinical-operations guidance for radiopharmaceutical trial site readiness, recommending early engagement with nuclear medicine leadership and explicit resource-allocation planning between trial and standard-of-care caseloads.

Success criteria

Isotope allocation and site capacity for clinical trials are planned and, where necessary, ring-fenced separately from commercial supply, so a manufacturing or feedstock shortage no longer forces a phase 3 trial to pause enrolment.