So this case, published in the beginning, really triggered the interest and really held promise that overcoming beta-resistant with alpha emitters might become true reality and that we might have a much more effective drug in our hands. So after 10 years, multiple retrospective case series, more than 1,000 patients. In summary, also phase I to III clinical trials have been initiated, but yet no agent is proved so far. So what I'm going to do is to give you an outline on the different aspects of Actinium PSMA. And I would like to start and show you the developmental status of the so-called first-generation PSMA-ligands used for actinium, which is basically PSMA-617. Novartis is now the main driver for it. ML phase I trial was completed and two phase II/III or phase III trials are initiated finally last year and are currently running one post-lutetium and one pre-taxane similar to PSMAfore, only slightly different. Control arm plus and combo treatment together with ARPIs.
There is PSMA-I&T, an unpatented agent developed at the Technical University in Munich. And Fusion and now AstraZeneca has committed themselves to develop lutetium PSMA, Actinium PSMA-I&T. Two phase II studies have been performed or are still ongoing, TATCIST and AlphaBreak. Final data I have not found published. There is also one study announced in clinical trials, a combination with PARP inhibitors. The current status is unclear. And there was even another company, POINT, which is also active in the PSMA-I&T field. However, due to different developments after takeover by Lilly, they have dropped the Actinium PSMA program. So if you look to lutetium versus actinium, you see major differences in the speed of the development. So if you look on both timelines, you see that basically after PSMA-I&T and 617 have been developed, both treatments with lutetium as well as with actinium have been initiated and published.
I have to say that the body of evidence for lutetium and the intensity of the compassionate use initially in Germany than in other countries, for example, Australia, have a greater and much broader body of evidence, which led to the fact that then a phase II trial could be initiated followed by the phase III VISION trial in 2018 and then the FDA approval in 2022. Actinium PSMA was moving much, much slower with compassionate use in different centers first in Germany then in other parts of the world, for example, Australia, but also India and Asia. A phase I trial, the action trial was started in 2020 and another one with PSMA-I&T, the TATCIST trial was started in 2021 and phase III trial needed for drug registration only started or two phase III trials only started in 2025. So I think it is a clear difference. However, if you look on the average time of drug development, which is usually between 10 and 15 years from discovery to approval, I would say lutetium PSMA was exceptionally fast developed.
And there was this level of body of evidence generated in Germany and other parts of the world, which really accelerated and kickstarted the development of lutetium and actinium more following the usual speed of drug development. So I would say it's not a slow development, it's more unusual development, what we are seeing with actinium. And what we're seeing also now that there are new agents coming in phase I trials. And this is what I also would like to talk about, new agents for Actinium PSMA treatments, improved agents, how I would improve generation agents, how I would call them plus the antibodies hanging around for a while. So improved agents, for example, in the way of reduced salivary gland uptake PSMA-R2 is in candidate, I show you later the status. There is also a bio compound trillium, which has a higher albumin binding. There is not much to be found. There's currently a phase I trial has been published a couple of weeks ago at ASCO. There is Blue Earth Therapeutics working on the family of rhPSMA ligands also developed in Munich and there's also one with an improved tumor-to-background ratio, potential candidate for Actinium PSMA, and there are the antibodies hanging around for a while and now also being explored for actinium treatment, both academically as well by a company.
So if you look on the status of efficacy and toxicity, we have a broad range which is published PSA50, 50 to 70%, depending on pre-treatments, mPFS and OS, different ranges, reasonable hematotoxicity, main toxicity which hurts the development of actinium PSMA or which slows it is xerostomia. So I think there is documented high efficacy, but dose-limiting toxicity and the superiority compared to lutetium PSMA is still not proven. Xerostomia is a significant problem. You see this in a case like this. We treated this patient together with Dr. Morris. He received two cycles of Actinium PSMA. In Munich, you see decrease of salivary gland uptake in the PET. And this patient really suffered from great xerostomia with tube feeding, food intolerance, pneumonia, and finally death due to the side effects or indirectly to the side effects. So this is a significant issue, xerostomia.
Xerostomia is difficult to deal with. There are multiple strategies have been tested to mitigate effects. So far it is really no clear path could be found. There has been trials to look where the monosodium glutamates could do that job. However, it both reduces uptake in salivary gland as well as in tumor lesions. It is known that biodistribution of the antibody regarding salivary gland is much better than for small molecules. And there's also the alpha recoil, I think, which might contribute to salivary gland toxicity because the preclinical studies now that the redistribution of daughter nuclide like bismuth is, for example, very prominent to the salivary glands. There are a lot of data on dosimetry, and it looks like the different agents can differ themselves in dosimetry, especially if you look in salivary gland, you see that PSMA-R2 has a very low salivary gland uptake. So this was really an idea of developing in that direction. Actinium PSMA-R2 was developed in fact by Novartis in two phase I/II clinical trials.
Safety was very promising. You see here only 21% xerostomia rate, much lower than published for PSMA-617. However, end of last year, probably due to the portfolio setup of Novartis, general development of this agent was stopped. As I told you, there are other new novel agents like rhPSMA-10.1, which also shows low salivary gland uptake and retained high tumor uptake and is now soonly investigated in a phase I clinical trial. There are also different combinations tested now, and I think this is definitely a way to go. And I think if you look to actinium from outside, I think it follows a little bit the so-called hype cycle. There was really an innovation rigor with these early cases. Then there was a peak of inflated expectations where there was this, it can overcome better resistant. There's extensive antitumor effect, but then this disillusionment with xerostomia.
And I think now we are following the path of the slope of enlightenment and hopefully getting to the plateau of productivity that we get something finally also potentially approved. Where are we currently? Actinium PSMA, I think is more like in real world of drug development compared to lutetium PSMA. Despite challenges, there are many players still active in the field. I told you about Novartis, their program, and lutetium PSMA-I&T Fusion at AstraZeneca, and there are also other novel agents being explored in phase I clinical trials. It is still interesting to adapt strategy, ligand engineering to optimize salivary gland uptake and also to find ideal combinations to reduce actinium PSMA dose. And I think the success will probably not be determined by the most potent drug but the optimal therapeutic window. And I have one last slide despite the music is already running.
So this I created today in the morning by ChatGPT, and I have to say it really summarizes what I've told you the last 10 minutes. ChatGPT needed 15 seconds to create this, and I needed more than the flight time from Munich to Germany to create the rest of my slides. Thank you very much.