Phillip Koo: Hello, and welcome to UroToday. Today, we're very fortunate to have with us again, Dr. Johannes Czernin, who is the Director of the Ahmanson Translational Imaging Division at UCLA, and also the Editor in Chief of the Journal of Nuclear Medicine. For those who aren't aware, Dr. Czernin was one of the early pioneers who started this whole process of getting gallium-68 PSMA approved here in the United States, and as we're all aware, on December 1st, this radiopharmaceutical received FDA approval. So welcome, Dr. Czernin.

Johannes Czernin: Thank you very much for having me.

Phillip Koo: So this idea of academic institutions applying for an NDA, something that's very unique. Could you tell us a little bit about that journey and that process and how it must feel now that you've reached the finish line?

Johannes Czernin: Well, first of all, it feels good to reach the finish line. It's a bit like when you... I don't know whether you've ever run a marathon, but that's the best moment when you reach the finish line. But the start dates back to probably close to eight years ago, seven, eight years ago, when we recruited a colleague from Germany and named Ken Herrmann, who is now chief of a major nuclear medicine operation in Germany, and who then brought two very talented young investigators, Matthias Eiber and Wolfgang Fendler from Germany. And when he convinced me that we should try to go for an NDA and an approval, not only for the diagnostic portion but also to start some work on the therapeutic application of PSMA ligands. So we were trained by the people who had quite a bit of experience, and then about, I would say four and a half years ago, Jeremie Calais joined our team and he then led the UCLA portion of this effort.

That was a partnership with the UCSF, Tom Hope, whom you know very well, and together they created a really exciting and exceptional clinical research program and conducted a study that I think was very, very well-designed and extremely well-executed, and it led to the key and pivotal publications required for convincing the FDA. I do want to also say that one of the nice learning experiences there was that the FDA is actually a highly collaborative institution. They were positive and supportive from the get-go. They had nothing but positive feedback and ideas on how we can improve the process and how we can improve the study design and how we can improve the data collection. There was never any obstruction or any bureaucratic hurdle that was unreasonable. So that was a very, very pleasant and very good experience.

Phillip Koo: So now that you've reached the finish line, I think a lot of people throughout the United States are very curious about access. I think the listeners are familiar with the fact that this was approved for UCSF and UCLA specifically. So I guess one two-part question, what will access look like at UCLA and UCSF, including a timeline, and what do you think access will start looking like nationwide, including a timeline for that as well?

Johannes Czernin: So I think there are two components to that. One is that if sites apply for an NDA that is associated or affiliated with our NDA, they can cross-reference all of our data, but they need to come up with their own production report. They need to report how they produce the compound. It's called the CMC section. And that's essentially the exchange of manufacturing production description. And that can be done, but imagine now if, say, 20 or 50 or 100 sites would submit their applications to the FDA, it will take time to get these approved. And there was no way around it because if you submit an academic NDA to the FDA, you cannot accommodate all sites that can produce it. It's different. So each site needs to be responsible and responsive to the request for the CMC section.

There is a time frame that I would think would probably be 8 to 10 months until sites can get approval from the FDA. I don't know the exact time, but that's approximately what I think it would be. One should always also keep in mind that in the meantime, fluorinated compounds have been submitted like PyL, the compound that was originally developed by Marty Pomper, was clinically developed by Progenics and now Lantheus, which has been submitted as in NDA to the FDA. And it is quite likely that this will be approved if the data are well done, which I cannot control by them, but by which I assume.

So I would think that in a year, probably a fluorinated compound will be available on the market. That would be my guess. I have no detailed insight into that, but that would be my guess. So for this one-year timeframe, there still will be a bottleneck in getting access to PSMA imaging, no question about it. And it's unfortunately unavoidable. But I think that is kind of the answer to your question about availability. So it still will be probably 8 to 10 months, maybe a year to the broad availability of one piece of PSMA ligand or two PSMA ligands for imaging.

Phillip Koo: Great. So then locally at UCLA and UCSF, how soon will patients be able to go to those two facilities and get this and have it reimbursed or covered by Medicare, let's say, or maybe even private insurance?

Johannes Czernin: So there is of course an attempt on our side to make it as accessible as possible to our patients. For an interim period, we will still have to charge patients, and then the patients can communicate with their private insurances, or we can try to get as soon as possible Medicare to pay a portion of the study. We don't know yet how that will work. We will definitely try. The problem is that insurance companies as well as Medicare will have to come up with codes that are procedure codes, and then the codes then will only allow for billing and reimbursement. As long as we don't have the codes, nothing can be really done about it. So our next steps are to get in contact with each of the major private insurances, but also with, of course, the Medicare regional representatives so that we can start to work on educating the insurance community about what we have, what we can do, why it is clinically relevant, and why it should be reimbursed.

And that, of course, will require time and good nerves because as you know, this is sometimes not an easy thing to do. The other thing we will do is we'll try to get pre-authorization from all the private insurance companies for those patients who don't have Medicare. And if we get pre-authorization, then we can do the scans. The demand is incredibly high. We currently have a demand, we could accommodate probably eight patients a day, and I'm sure that UCSF has the same demand issue. We will try to accommodate six to eight patients a day within the foreseeable future. And of course, we will try to work as hard as possible to get reimbursement going as quickly as possible.

I am also using the bully pulpit, as they know it, in this case the Journal of Nuclear Medicine that is educating, and at times also criticizing insurance companies for not paying or reimbursing what they should be reimbursing because it is the standard of care. And PSMA imaging, for instance, is standard of care in Europe and is part of the guidelines, especially in managing prostate cancer patients with biochemically recurrence, but also expanding beyond this one indication.

Phillip Koo: Great. So you alluded to using the JNM as your bully pulpit, but for some of the people out there who haven't read JNM, you wrote a very powerful editorial about PET reimbursement and how it's become a target for insurance companies to deny patients access to PET. What message do you have for some of the urologists and medical oncologists and other listeners out there when it comes to the power of PET, let's say.

Johannes Czernin: So I think the first one is to be vocal. If you have the opportunity to communicate with local and regional politicians, then do this. Contact your congressmen or women, contact your representatives, and do grassroots lobbying. Part of it is really a misunderstanding of what PET is. PET still has the reputation of being expensive. We actually did an analysis many years ago, I think 2011 or so, showing that PET imaging, for instance, probably accounts only 1% of Medicare cancer care costs. So it is really not where Medicare should try to save money over private insurance. It should try to save money because it's something that the control of which probably costs more than the actual expense for the imaging. That's one thing.

The second thing is there are pseudo arguments that always used against PET imaging. One is it exposes patients to dangerous radiation, which is a completely ridiculous argument. And in fact has discouraged people from getting those tests that help them to actually improve the outcomes, namely high-quality diagnostic tests. And the second thing is to suggest that PET images should be done with just low radiation CT scan portions, and get a separate diagnostic CT scan, which then, in fact, increases the radiation dose, total radiation dose to patients. So it's kind of the arguments that have been made were always arguments, a dogma that people heard about, but really didn't think through it carefully and didn't look at the appropriate cost-effectiveness analysis. Didn't look at all the literature that suggests how many downstream costs can be avoided if you do best patient management that includes high-end imaging.

Phillip Koo: So the final question I have, a lot of people out there, now that we have PSMA approved in the US, are wondering when bone scans and CTs might become obsolete? So I guess question one is, will it become obsolete, and if so, how do you predict the future will turn out?

Johannes Czernin: First of all, in prostate cancer, there's currently no prospective study comparing bone scans with PSMA scans. Empirically I would say that many, many of the bone scans will go away, but we actually will start the prospective study comparing bone scans with PSMA scans because I don't think it can be done retrospectively and we secured the funds to do the prospective study, so I think that will be important to do. And then I think that will rewrite the bone imaging criteria in prostate cancer in all kinds of different disease states. About CT scans, CT scans in conjunction with PET will always be important and they should be high quality, diagnostic quality contrast CT studies. And the reason is we see sometimes now two- or three-millimeter lymph nodes with PSMA scans that have visible expression of PSMA. So we see it on the scan.

It is so much easier to see that stuff and discriminate it from the adjacent structures with a good CT scan. You know it, when you read many CT scans, you know how that is, it's just no contest. Now the pelvis is not the easiest area to read. There can be very many small lymph nodes and small structures that can be quite misleading what you read off if you just read a non-contrast CT. So I think high quality always trumps, and every scan should be done at the best quality that is achievable. The reason is it's not dangerous, it's not killing patients with radiation. That's complete nonsense. It has not shown to be any risk for any subsequent malignancies, and will, in the end, achieve the best outcome for patients because the most appropriate diagnosis will result in the best patient management.

Phillip Koo: Yeah, I agree. I mean, high-quality imaging is something oftentimes our referring providers don't necessarily appreciate, and I think this is something that really, really does make a difference. So I thank you for bringing that to the surface and the light. Just want to thank you very much for your time. Congratulations. And also thank you very much from the prostate cancer community for the work that you and your team have put in over the past eight years. So thank you very much.

Johannes Czernin: It was for us a great experience to do that. And I think we also, along the way, learned a lot about designing high-quality prospective trials, but also how to best interact with the FDA, which is actually a wonderful agency. And in getting something done together with another academic institution, that helps everyone. That was kind of rewarding. Well, thanks so much for having me.

Phillip Koo: Thank you.