Betalutin Update

The makers of Betalutin provided an update this week on their phase 2 clinical trial called PARADIGME. 

There wasn't much to report, which is I guess kind of the story. 

Some reminders about what Betalutin is:

Betalutin (also known as ¹⁷⁷Lu lilotomab satetraxetan) is a RadioImmunoTherapy (RIT) treatment being developed in Norway. RIT is kind of an exciting treatment, in my opinion. In general, RIT works by bringing radiation directly to lymphoma cells. Radiation can be very effective in treating cancer, though it works a lot better on solid tumors than liquid tumors like those in blood cancers, since blood cancer cells don't stay still. RIT works by attaching a tiny bit of radiation to something like a Rituxan molecule. The Rituxan finds the CD20 protein on the surface of the lymphoma cell, attaches itself to the cell, and then delivers the tiny bit of radiation directly to the cell. In theory, it's a great system -- fewer side effects because the radiation is delivered right to the cancer cells.

There have already been two RIT treatments approved for Follicular Lymphoma, and that approval happened years ago -- Zevalin and Bexxar. I was personally very excited at the idea of Zevalin when I was first diagnosed, because I had heard from a few people who had been given Zevalin and had very long remissions from it (even longer than my now almost 14 years). 

There are still some stories in the news about Zevalin, but no longer about Bexxar -- it was discontinued by the manufacturer because so few people used it. 

And that's the problem with RIT, at least in the United States. Very few people use it, despite it helping so many people. 

The reasons don't have much to do with effectiveness or safety, both of which are very good for Zevalin. Instead, they have more to do with rules for how it gets used. Because it is radioactive, any doctors administering Zevalin have to go through a large amount of training before they can be approved. That means regular oncologists won't be able to give the treatment, though they can refer patients to specialists who can give it. But with few doctors who have had that training, and lots of other options available, most oncologists just try a different treatment that they themselves can give to the patient. There has also been some question about how doctors are reimbursed for the treatment, creating enough of a hassle to just not use it. 

It's really too bad. I think RIT can offer an alternative that could help a lot of people, if it were easier to get to patients.

So the press release about Betalutin pointed out a different problem -- Covid-19 has made it harder to recruit patients into the trial. Like many FL treatments, one of the side effects of RIT is lowered immunity. That's not so good while Covid is around, especially with the new variant. 

The good news is, they have managed to recruit 106 patients, which is great for a phase 2b trial (their goal is 120). And they announced last August that they had made some changes to the trial that had helped it. Last February, they released data that showed good effectiveness and safety, with 65% of Relapsed/Refractory FL patients in the trial having a response, including 30% Complete Response.

So I'm hoping things continue to go well for Betalutin. I have an emotional attachment to RIT, given how excited I was about it many years ago. But I do think, even with a a rational head, RIT is a good approach to dealing with FL, and gives a different way of dealing with the problem. One of the studies that I was excited about many years ago was one that used RIT as a salvage treatment. That is, patients were given R-CHOP and then followed up with Zevalin, which cleaned up any cancer cells that Rituxan and chemo didn't get to. That approach made sense to me then, and still does -- it's the basic idea behind the combination treatments that are so popular these days. Cancer cells find ways to stay alive, so going after them in different ways (chemo + antibodies + radiation; or antibodies + inhibitors; or chemo + CAR-T) may catch those cells that the other treatments missed.  

And maybe some success from a new RIT will inspire change in the way it is administered in the U.S. and allow more people to get it. I don't know what the rules are in Europe and elsewhere, but maybe they are different enough that it would be easier to administer there.

I'm hoping maybe we'll get another update by ASCO. I'm looking forward to hearing more.