Much is said about cardiac SPECT imaging programs becoming less reliable because of challenges in the global supply chain of Molybdenum-99, the parent nucleus of Technetium-99. Reinforcing the pessimistic outlook is the fact that a new shortage of Technetium-99, the main cardiac SPECT radiopharmaceutical, seems to be looming on the nuclear cardiology marketplace, similar to the last major one from 2009-2010.
The planned shutdown on March 31, 2018 of the NRU nuclear reactor of Chalk River in Canada – anecdotally the world’s longest-operating, with 60 years in the running – is reviving worries of market unavailability and price volatility of these agents, and steering some cardiac SPECT providers to take a closer look, again, at cardiac PET for myocardial perfusion imaging procedures.
Will the projected Technetium shortages be a boon for cardiac PET?
Perhaps, but one must keep in mind the Rubidium supply chain is not much more diversified. The degree of industry concentration, and the dependence on a fairly limited number of actors in the supply chain, are just as high for Strontium-82, the parent nucleus of Rubidium-82, as they are with Molybdenum-99. Indeed a comparable number of accelerators is available globally to produce, as a small part of their diversified production, Strontium-82 for the medical industry. Namely, these are Brookaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL) in the U.S., iThemba labs in South Africa, INR in Russia, Triumf in Canada, and Arronax in France.
However, the industry concentration in source supply may diminish, if many new commercial cyclotron providers see the light. In September 2015, Indiana-based Zevacor Molecular announced it had installed the first strontium-82 cyclotron in the U.S., manufactured in Belgium by Ion Beam Applications, who was awarded the contract in 2013. As of this day, the company has not publicly announced a launch of commercial production.
Bracco Diagnostics: 28 Years of Owning the Rubidium Generator Market
As the first company to invest heavily in cardiac PET MPI, Bracco has been, since 1989, the only company with an FDA-approved generator-based perfusion agent available for cardiac PET: CardioGen-82 (Rubidium-82). Starting in 2017, however, Bracco will have to face a newcomer to the U.S. Rubidium-82 scene: Jubilant DraxImage. The next few years will tell whether this represents a new competitive threat for Bracco, or a new opportunity for cardiac PET’s market growth.
Today, the uncontested leadership position the Bracco organization has built over almost three decades puts the company in an ideal position to focus on addressing the challenges intrinsic to the cardiac PET supply chain, and breaking some of the barriers to adoption that still exist. The company continues its work to enhance the distribution network, contain operational costs, simplify the logistics, sponsor clinical research, and provide training to a gradually growing population of cardiac PET providers.
Jubilant DraxImage: Breaking News Signals End of the Single-Vendor Play in Rubidium
The latest breaking-news came days after the ASNC 2016 meeting wrapped up: the FDA has approved Jubilant DraxImage’s RUBY-FILL complete generator-elution system for PET MPI (October 2016). This is a major industry development for the U.S. market, where Bracco’s single-vendor play was perceived by some as a “monopoly.” This FDA nod practically signals the advent of a new “generic” version of CardioGen-82 in the U.S., which will likely provide a competitive and cost-effective option to the cardiac PET market.
In its Canadian home market, the Rubidium -82 generator has already obtained Health Canada approval for clinical use, however the associated elution system, which in Canada is looked at separately, is not yet approved for use. “ARMI” and “REST-PET”, two ongoing clinical trials of the company, as well as the latest U.S. FDA approval, may help accelerate the path of RUBY-FILL towards commercial availability in Canada.
Ionetix: Ammonia Cyclotrons for High Volume Facilities?
In February 2016, Ionetix was the first vendor to announce it had produced doses of N-13 Ammonia for clinical use, in its new University of Michigan Health System cyclotron. The N-13 Ammonia radiopharmaceutical performs well compared to Rubidium-82 but has a radically different operational model. It has a 10-minute half-life and can only be produced in a nearby cyclotron, compared to Rubidium-82 which has a shorter half-life of 70 seconds, but can be produced using a much less expensive on-site generator.
These logistic constraints mean that N13 Ammonia has very high start-up costs that could fall in $1 million territory, followed by relatively low fixed costs for the production of clinical doses. In contrast to Rubidium-82, which offers low start-up costs but high ongoing costs upwards of $30,000 per month for the replacement of on-site generators, it is clear that N13 Ammonia can only be financially viable for high-volume facilities. Therefore, Ionetix needs to experiment with alternative business models, possibly around managed equipment services, to be able to break into the market.
Lantheus Medical Imaging: Active F-18 Investments to Deliver Soon?
In May 2015, Lantheus Holdings, Inc. announced the results of the first of two phase III trials for the flurpiridaz F-18 PET MPI agent it has under investigation. Currently, the company is preparing to commence the second phase III trial, which it plans to conduct through partnership. Like every other imaging technique, F-18 is differentiated with some powerful, but perhaps also some limiting attributes. On the upside, F-18 has a half-life of 110 minutes, appears to perform extremely well on obese patients, have high sensitivity compared to the SPECT MRI, and improve on absolute quantification of myocardial blood flow (MBR) compared to Rubidium-82 PET. The latest trial results have shown flurpiridaz F-18 to be compatible with exercise-stress testing, and not entirely dependent on pharmacologic stress-testing (eg, with adenosine, dipyridamole [Persantine], or dobutamine).
On the flipside, given Lantheus and its prospective partner would most likely be the first to enter the market with a flurpiridaz F-18 agent, they will probably need to implement a brand new operational and commercialization model for the new agent, once it is ready to enter the marketplace.