Lumasiran for PH1 in Infants and Young Children

Among the late-breaking abstract presentations at the National Kidney Foundation Spring Clinical Meetings 2025 was “Lumasiran for Primary Hyperoxaluria Type 1 in Infants and Young Children.” Co-author Mini Michael, MD, an associate professor of renal pediatrics at Baylor College of Medicine who practices at Texas Children’s Hospital, joined Joel Topf, MD, on site for a conversation about her abstract and the phase 3 ILLUMINATE-B trial that produced the results.

Dr. Topf: Joel Topf with Nephrology Times. I’m here with Dr. Mini Michael. She’s at the Baylor School of Medicine and Texas Children’s Hospital, and she is studying primary hyperoxaluria type 1 and has a phase 3 clinical trial that’s presenting here today on lumasiran. This is a microRNA interference, is that right?

Dr. Michael: Yes, mRNA. It acts in the liver, and it blocks an enzyme, which actually produces substrate for the oxalate. So basically, one step before the PH1 enzyme defect.

Dr. Topf: That relieves the pressure, and these patients do well—it looks like. There were 18 patients enrolled in [the] trial. Or is it 14?

Dr. Michael: Yes, 18 patients in this poster; and it’s children under 6 years of age. It’s a multinational study.

Dr. Topf: How often do these patients get this medication?

Dr. Michael: Initially, they get [it] monthly for 3 months, and then depending on the weight, if it’s less than 10 kilos, they get monthly injections. If they’re over 10 kilos, every 3 months. It’s subcutaneous, and they can take it at home.

Dr. Topf: It’s just a sub-Q, and they can do it at home. That’s great. You’re a site PI [principal investigator] for this study. How many patients from your site were enrolled?

Dr. Michael: Just one. It’s a multi[national study] and it’s an ultra-rare condition.

Dr. Topf: I get the sense that it’s a very rare disease. Did any site have more than one?

Dr. Michael: As I said, it was a multinational study, so [in] Europe and [at] other centers, they may have more than one. It’s an autosomal recessive condition, so [in] places where they have more consanguinity, they would have more patients.

Dr. Topf: Right. But that’s not Texas. This trial had already been completed for people that were over the age of 6. Is that right?

Dr. Michael: Yes, it’s actually under the age of 6 and over the age of 6 with the maintained renal function. That’s ILLUMINATE-A and -B. Both are completed.

Dr. Topf: It’s all completed, but the drug’s not yet approved?

Dr. Michael: Yes. It was approved in 2020.

Dr. Topf: It was approved forever ago. We’re finally getting our data. You only have one patient with PH1. I have zero patients with PH1. I’ve never even seen the disease. [laughs]

Dr. Michael: My patient is now on the commercial medication.

Dr. Topf: I was just looking at the abstract. It looks like the drug was a tremendous success. Nobody had any progression of renal failure. GFR [glomerular filtration rate] went up as you’d expect as they got older and bigger, and stone risk was really low.

Dr. Michael: Yes, that’s correct.

Dr. Topf: Are we done with this disease? Have we figured this out? Is this a cure or close enough?

Dr. Michael: There’s more research going on.

Dr. Topf: What are the questions that are outstanding with PH1? You’ve got a drug that seems to block the production of this early on, allows the kidneys to continue to grow. What are the outstanding questions that you’re interested in?

Dr. Michael: I think if there is a permanent solution, like gene therapy.

Dr. Topf: And they’re working on that?

Dr. Michael: Yes.

Dr. Topf: Excellent. What other message do you want to give about PH1?

Dr. Michael: I think early diagnosis because, from comparing different trials of different age groups, if you look at the GFR, the ILLUMINATE-B, which included young children under 6, they had the better GFR than the older children in ILLUMINATE-A.

Dr. Topf: It’s the same message that we always have: Get this diagnosis early, get them treated early, and they get better outcomes. How do you make this diagnosis?

Dr. Michael: Anyone with any children with more than one kidney stone, you should be doing. Now the genetic testing is easily available. You can do that. You can use oxalate levels as the first step, but you can also concurrently do the genetic testing if you’re suspecting that, especially if there’s a family history. You don’t have to wait for one to come back.

Dr. Topf: It’s recessive. That family history probably is not that powerful?

Dr. Michael: There is, like siblings [in which it could appear].

Dr. Topf: Siblings, sure. If there’s a big family. Anything else, any other final thoughts on the lumasiran in PH1?

Dr. Michael: If you treat early, if you pick up early, then you can avoid—the previously standard therapy was liver-kidney transplant. Liver transplant hopefully can be avoided…. If your patient presents late with decreased GFR, you can still treat with lumasiran and get them stable. If they have advanced CKD [chronic kidney disease], then you can do kidney-only transplant.

Dr. Topf: Kidney only because you’re not going to trash the new kidney with the hyperoxaluria. It eases up the surgical burden.

Dr. Michael: But they have to remain on lumasiran.

Dr. Topf: Dr. Michael, thanks for joining us at Nephrology Times.

Dr. Michael: Thank you.