90Y-TheraSphere

⁹⁰Y-TheraSphere is a type of radioembolization therapy used in the treatment of liver cancer. It involves the use of small beads called TheraSphere that are loaded with the radioactive isotope Yttrium-90 (⁹⁰Y). These beads are delivered directly into the blood vessels that supply the tumor in the liver, where they release radiation to target and destroy cancer cells.

This therapy is considered a minimally invasive treatment option for liver cancer patients who are not eligible for surgery or other forms of treatment. It is often used in cases where the cancer has spread to the liver from other parts of the body.

⁹⁰Y-TheraSphere works by delivering high doses of radiation directly to the tumor site while minimizing exposure to healthy liver tissue. This targeted approach helps to destroy cancer cells while reducing the risk of damage to surrounding organs.

Overall, ⁹⁰Y-TheraSphere has shown promising results in improving outcomes for patients with liver cancer and is an important option in the treatment of this disease.

Description

TheraSphere^® is a therapy for transarterial radioembolization (TARE) in hepatic neoplasia including HCC. The product is a suspension of insoluble ⁹⁰Y-labeled glass microspheres (20–30 µm in diameter, about 50,000 microspheres per mg or 1,200,000 particles per vial of 3.0 GBq; 2,500 Bq per particle). ⁹⁰Y is an integral constituent of the glass and cannot dissolve in body fluids. The product has a density of about 3.6 g/ml. This product was filed as a brachytherapy drug and as such still to be considered as a medical device.

TheraSphere^® was initially owned and developed by Nordion. On July 13, 2013, BTG completed the acquisition of the Targeted Therapies Division of Nordion, Inc., which includes the product TheraSphere^®. TheraSphere^® is still manufactured by Nordion (Canada), and the name is a trademark of the Theragenics Corporation. In 2019, BTG was acquired by Boston Scientific.

Clinical applications

⁹⁰Y-TheraSphere (TheraSphere^®) is approved for locoregional therapy of HCC, with or without portal vein thrombosis (PVT). The microparticles embolize the liver’s capillary and concentrate the radiation in the malignancy. The treatment has shown a 77% response rate in patients who would otherwise have no therapeutic option. In a previous study, patients treated with TheraSphere^® survived a median of 800 days compared with 258 days for a population of high-risk patients. Treatment procedure is described in several hospital patient leaflets (e.g., see UW Health).

Additional development

A large Phase III study, STOP-HCC, involving more than 500 patients was initiated in March 2012 and was completed by beginning of 2020.

In the Dosisphere-01 trial (data published ASCO 2020), TheraSphere patients treated with the personalized dosimetry approach reached an overall survival rate of 26.7 months versus 10.7 months for those patients receiving standard, single-compartment dosimetry. The US clinical trials database reports 58 studies performed with TheraSphere, but only four new studies have been initiated since January 2019. By mid-2020, there were still 14 studies open and recruiting patients.

Availability

The product is available from Boston Scientific which provides a full description page.¹

In France, the level of reimbursement of the product was fixed at EUR 11,417 in March 2020.²

Competition

TheraSphere became the second radiolabeled microparticle on the market following SIR-Spheres. Both are labeled with ⁹⁰Y and are now in competition with the third player QuiremSpheres, another microparticle also intended for HCC patients but labeled with ¹⁶⁶Ho.

Head-to-head clinical comparisons have never been performed between TheraSphere^® and SIR-Sphere^®, thus it is difficult to rank both products. It is also surprising that similar comparisons were so far not requested by authorities for new products coming on the market (e.g., QuiremSpheres). Next to the difference in type of spheres, there are, however, some small differences between the two presently major players:

TheraSphere^® microspheres have a high level of activity per particle compared with SIR-Spheres (2,500 vs 50 Bq) and, therefore, need a smaller number of particles to be injected, or a higher dose to the target tumor with less amount of product is allowed.
There is no guarantee that 100% of the particles stay in the liver, as some can migrate. The percentage of migrating microspheres is highly dependent upon the type of particle and the skill of the operator. As ⁹⁰Y is not a gamma emitter, it remains quite difficult to follow and estimate the proportion of particles that do not remain in the target tissue. This number of migrating particles seems, however, to be quite low in both cases.
The migration potential is also depending upon the difference in microsphere surfaces and the density of the particle (i.e., polymer vs. glass).

QuiremSpheres’ main difference is the radionuclide 166Ho which brings as advantage the possibility to image the distribution of the particles.

Since microspheres are not available in developing countries and anyway too expensive for these markets, the Russian company BEBIG LLC launched a project of development of microspheres based on glass, first for the domestic market, but with the aim to sell this product in CIS countries and some Asian countries.

In Iran there is also a project initiated by AEOI (Tehran) to develop and sell resin microspheres for the domestic market.

Comments

TheraSphere is the second largest player in the field of HCC therapy with microparticles, next to Sir-Spheres. The market is now jeopardized by QuiremSpheres and the distribution of market share may change if a price competition starts.

It has always been surprising that particles, such as SIR-Sphere^® microspheres or TheraSphere^® microspheres, are considered as medical devices and not as drugs. In fact, these materials did fit exactly with the official definition of an implantable medical device, and their description is in accordance with the criteria set by authorities.

Radioactive particles, nanospheres, and microspheres can be considered as medical devices

if their owner claims and demonstrates that they are internal radiotherapy tools,
if they are chemically neutral and their surface does not interact with the body’s cells, fluids, and tissues,
if they are active in part through a mechanical action (e.g., particles leading to embolization, size allows trapping in an organ or tissue, form forbidding migration, etc.) without any interaction with a biological fluid.

However, recently authorities started to reconsider this definition, limiting it to devices that can in a second stage be removed from the body. Of course, neither microparticles, nor gels, all of them used as neutral carrier for radionuclides can be taken from the body. Even if this material is not yet to be considered as a drug, authorities have requested additional clinical trials which are identical to the ones needed to obtain a MA for a drug. Eventually microparticles will not be considered as medical devices but as true drugs and newcomers in this field should take in account this evolution when developing such pharmaceuticals.