The power to treat X-linked hypophosphatemia (XLH) at its source

Dr. Ginsberg: Hi, I’m Dr. Charles Ginsberg. I'm a nephrologist, and I’ve been managing phosphate-related disorders, including X-linked hypophosphatemia—or XLH—for nearly a decade.

Dr. Smeryage: And I’m Bonnie Smeryage. I’m a nurse practitioner, and I’ve been caring for patients with XLH for 12 years.

Dr. Ginsberg: And this is XLH in Focus. Today, we’re breaking down what “mild XLH” really means—and when and how treatment may be appropriate.

Disclaimer: Dr. Charles Ginsberg is a consultant, and Bonnie Smeryage is a speaker for Kyowa Kirin. Both receive compensation from Kyowa Kirin for their engagements.

TOPIC 1

Dr. Smeryage: Do X-linked hyposphosphatemia symptoms stop in adulthood?

Dr. Ginsberg: I think that’s one of the biggest misconceptions we deal with—that XLH only impacts children and the disease stops once growth is complete.

Dr. Smeryage: In pediatrics, we focus on growth and symptoms like rickets and bowing. But I always tell families that XLH is not just about childhood growth.

Dr. Ginsberg: Exactly. Bones are dynamic—they're constantly renewing themselves to stay healthy, and one of the things they need to do that is phosphate.

Dr. Smeryage: So even after growth plates close, the need for phosphate continues, and the pathophysiology of phosphate wasting doesn’t stop.

TOPIC 2

Dr. Smeryage: What does “mild XLH” mean?

Dr. Ginsberg: I really don’t like the term “mild.” It tells patients to attribute their symptoms to something else because their disease is just “mild.”

Dr. Smeryage: I agree. Clinicians might describe XLH as “mild” based on labs.

Dr. Ginsberg: Right. Maybe a patient’s phosphorus isn’t that low, but duration matters. A week or a month may not mean much, but if phosphorus levels remain low over a long period of time, that’s something we should manage.

Dr. Smeryage: Patients may call their XLH “mild” because that’s how a provider described it to them, or because they’ve become accustomed to their symptoms and see them as mild compared to challenges they had while they were growing up.

Dr. Ginsberg: Exactly. Mild compared to what? Compared to when they were 9? That’s a very different benchmark than looking at the full impact of the disease today.

TOPIC 3

Dr. Ginsberg: How do you assess true disease burden in XLH?

Dr. Smeryage: So in my practice, I’ve seen parents normalize their child’s limitations. They might say, “Well, they’re just not as fast as the other kids on the playground.”

Dr. Ginsberg: Humans adapt. Over time, patients may start to see those limitations as just what’s normal for them.

Dr. Smeryage: I really believe in regular assessments with my patients. I think it’s important to not only look at biochemical markers, but also at how the XLH is impacting their daily lives.

Dr. Ginsberg: I agree. Regular assessments help track the change in disease burden over time and can give us a clearer picture of how patients are progressing.

TOPIC 4

Dr. Ginsberg: Should “mild” cases of XLH be considered for treatment?

Dr. Smeryage: I think too many people think about XLH on a severity scale. The impact of the disease can look different from person to person, but it's a genetic condition—you either have it or you don’t.

Dr. Ginsberg: When I’ve put these types of patients on treatment, there’s kind of a perspective change. What they once called “mild,” they may realize was something they had normalized or just learned to live with.

Dr. Smeryage: And that’s why ongoing assessment is so important. It helps us better understand what "mild” means for each patient, which can help inform treatment decisions.

Dr. Ginsberg: Phosphate wasting doesn’t change from 12 years old to 16 to 20 to 40. And if phosphate wasting remains, that warrants looking into treatment. You only get one skeleton—you can’t get a skeleton transplant.

TOPIC 5

Dr. Ginsberg: Why do you recommend CRYSVITA?

Dr. Smeryage: I recommend CRYSVITA because in my pediatric patients, I’ve seen it help heal rickets or reduce rickets severity, improve leg abnormalities, increase growth, and increase phosphorus levels into the normal range.

Dr. Ginsberg: In adult patients, CRYSVITA can help normalize phosphorus levels, improve osteomalacia, and improve healing of fractures and pseudofractures.

We’ll get into how to talk about CRYSVITA with patients in a moment. But first, let’s take a look at who CRYSVITA is indicated for and when it’s contraindicated.

Indication

CRYSVITA^® (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.

Important Safety Information

CONTRAINDICATIONS

CRYSVITA is contraindicated:

• In concomitant use with oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia.
• When serum phosphorus is within or above the normal range for age.
• In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.

TOPIC 6

Dr. Ginsberg: How do you start the conversation about CRYSVITA with patients?

Dr. Smeryage: I explain why XLH is not able to correct itself, and how CRYSVITA addresses the problem at the source. So here's a model of our DNA double helix showing a section of the PHEX gene, highlighting a variant. Variants such as these result in excess FGF23. That drives phosphate wasting, and CRYSVITA targets that pathway.

Dr. Ginsberg: And here is our CRYSVITA molecule bound to FGF23. CRYSVITA targets FGF23 to address the root cause of XLH.

It’s about giving them the information—what the disease is doing, what the data show, what to expect from a safety standpoint, and what their options are. And then deciding together what makes sense for them.

CLOSING

Dr. Smeryage: We’re glad we could help put XLH in focus today.

Dr. Ginsberg: Before we wrap up, please continue watching for additional Important Safety Information for CRYSVITA.

WARNINGS AND PRECAUTIONS

Hypersensitivity

• Hypersensitivity reactions (e.g., rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment.

Hyperphosphatemia and Risk of Nephrocalcinosis

• Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient’s serum phosphorus levels.

Hypercalcemia

• Increases in serum calcium have been reported in patients treated with CRYSVITA. Patients with risk factors such as pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment, are at higher risk of hypercalcemia. Monitor these patients for serum calcium and parathyroid hormone levels before and during CRYSVITA treatment for moderate to severe hypercalcemia. In patients with moderate to severe hypercalcemia, CRYSVITA should not be administered until hypercalcemia is adequately managed.

Injection Site Reactions

• Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment.

ADVERSE REACTIONS

Pediatric Patients

• Adverse reactions reported in 10% or more of CRYSVITA-treated pediatric XLH patients across three studies are: pyrexia (55%, 44%, and 62%), injection site reaction (52%, 67%, and 23%), cough (52%), vomiting (41%, 48%, and 46%), pain in extremity (38%, 46%, and 23%), headache (34% and 73%), tooth abscess (34%, 15%, and 23%), dental caries (31%), diarrhea (24%), vitamin D decreased (24%, 37%, and 15%), toothache (23% and 15%), constipation (17%), myalgia (17%), rash (14% and 27%), dizziness (15%), and nausea (10%).

Adult Patients

• Adverse reactions reported in more than 5% of CRYSVITA-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain (15%), headache (13%), tooth infection (13%), restless legs syndrome (12%), vitamin D decreased (12%), dizziness (10%), constipation (9%), muscle spasms (7%), and blood phosphorus increased (6%).
• Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if CRYSVITA therapy exacerbates spinal stenosis or spinal cord compression.

USE IN SPECIFIC POPULATIONS

• There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544.
• There is no information regarding the presence of CRYSVITA in human milk or the effects of CRYSVITA on milk production or the breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CRYSVITA and any potential adverse effects on the breastfed infant from CRYSVITA or from the underlying maternal condition.

PATIENT COUNSELING INFORMATION

• Advise patients not to use any oral phosphate and/or active vitamin D analog products.
• Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless legs syndrome induction or worsening of symptoms occur.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Kyowa Kirin, Inc. at 1-844-768-3544.

For important risk and use information, please see the full Prescribing Information for CRYSVITA in the link provided.