Next Tuesday is the fifth anniversary of the U.S. FDA’s determination that burosumab is safe and effective treatment for XLH, so it’s a good time to look at both the progress since then, and my hopes for the future.
So far, burosumab seems to have been fairly widely adopted for treatment of children with XLH (and TIO as well), once the patient finds a clinician with the right expertise. The standard advice in publiciations is to start patients on phosphate and calcitriol immediately and only move to burosumab if symptoms persist on the old, cheap treatment. In practice, that likely means that all patients transition to burosumab at some point (if it’s available), because we all know that phosphate/calcitriol is not particularly effective. I suspect we’re also seeing more specialists willing to take on XLH patients, since the treatment with burosumab is so much simpler (and with far less risk) than the old, complicated and risky treatment, and there is a fair amount of both continuing medical education and journal articles available for guidance. And, perhaps best of all, patients, young and old, are reporting significant, even life-changing, improvements in their physical health and quality of life on burosumab.
Access to burosumab in the U.S. depends on individual insurance companies’ decisions, but in theory is available to patients of all ages. In a growing number of countries, the national health system has been authorized to pay for burosumab treatment for children, if not (yet) for adults, e.g., Britain, Canada, France. In a few countries, the national health system has been authorized to pay for the treatment for adults as well, e.g., Italy.
That’s the good news. But there’s still a long way to go before all patients have access to the best possible treatment for XLH (including burosumab if it’s appropriate, plus coordinated access to a whole team of professionals, including dental care, pain management, occupational therapy, and mental health care.
Some relatively easy things things I’d like to see over the next five years include:
- Expedited publication of the five-year data collected in the followup study of patients from the phase 3 clinical trials (to satisfy the medical community’s demand for “long term” safety/efficacy data, since at least some of the patients in the study, if not most of them, will have been on burosumab for seven or more years by the end of 2023). It’s possible that this data will also show a slowing of the progression of symptoms, but given how slowly calcification occurs and how hard it is to measure, I’m not sure the data will be statistically significant yet, so I’m not getting my hopes up too high.
- Some leeway and guidance on adjusting the dosage/timing, especially for adults who find that a regimen of every four weeks leaves them with significant pain and fatigue during the last week. For some patients, a three-week or even two-week dosing regimen may be significantly more effective.
- An option for self-injection of burosumab for patients who prefer it, while maintaining the option to have the injections done by a health care provider.
- A smooth and transparent transition in the responsibility for burosumab in North America from Ultragenyx to Kyowa Kirin, NA.
Some difficult, but I think feasible goals for the next five years include:
- More access to burosumab in countries who currently do not have access for patients of any age, e.g., much of Asia and Africa.
- More access to phosphorus and calcitriol in those countries who do not even have the old treatment available (and yes, they do exist), and are therefore unlikely to have access to the much more expensive burosumab in the next five years.
- More national health systems approving payment for burosumab treatment for adults. Currently, several countries approve access only for children, e.g., Canada and France, or only conditionally for adults, e.g. England, (and I’m sure there are others in both categories).
- Bringing the phosphorus blood test back to the routine lab tests done for infants around a year old, along with an educational campaign about what to do if the phosphorus result is low (to improve early diagnosis of spontaneous XLH).
- Universal recognition of the progressive nature of XLH, and the need for preventive care, rather than reactive care, by way of a really solid natural history study, with widespread patient participation.
- An end to step therapy policies (insurers requiring the phosphorus/calcitriol treatment to fail before approving burosumab treatment), since delays in treatment can have long-term adverse consequences, especially if added to time already lost due to a delay in diagnosis or ignorance of the newer treatment option. (A one-year delay in starting burosumab for someone who is twelve years old could mean missing a key growth period, which can’t be remedied later.)
- An end to prior authorization of burosumab, or at least limiting the prior authorization to the initial prescription, and not requiring it thereafter.
- Ongoing research that recognizes that while burosumab is highly effective, it is not a cure and not all patients respond to it as well as others, so there’s more work to be done.
- Better research into the incidence of XLH. The standard estimate of one in twenty to twenty-five thousand births is old and poorly sourced, and more recent indications suggest it is much rarer, possibly one in sixty or even a hundred thousand births.
And finally, I have some pie-in-the sky dreams for the next five years. They include:
- Having at least one specialist (endocrinologist or nephrologist) with a basic understanding of XLH treatment options (or a willingness to learn from widely available continuing medical education resources) within 100 miles of every XLH patient. This requires more clinician education, especially with respect to the progressive nature of XLH (whole body, whole life, whole family), the need for transition of children to adult care, and the need for ongoing adult treatment.
- Continuing medical education programs that are endorsed by patient advocacy groups that have had a significant role in the creation of those programs, by way of either organizing the program or serving as a consultant in their creation.
- A recognition that phosphorus/calcitriol is NOT an effective treatment, and that it is undeserving of the terms “conventional” and “standard.” (I’ll have a lot more to say on this topic in a future post.)
- Consensus that burosumab is, in fact, the current standard of care and should therefore be the default treatment in the absence of contraindications.
- Establishment of regional centers of excellence for XLH (and the other chronic hypophosphatemias), where patients can get coordinated multi-disciplinary care in one location. Ideally these centers of excellence would treat both kids and adults, but if that’s too much to hope for, at least having a center of excellence for kids would be a great start!
- Better understanding of pain and pain management, especially with respect to bone pain, which is so poorly understood generally that not all clinicians know it exists independent of a fracture or other visible (on x-ray) trauma.
- Better medical school and continuing medical education of clinicians with respect to listening to patients and believing us.
- More members of the medical community who don’t just say the words, “patients are the real experts,” but believe it and act consistently with their words, i.e., consult us on study protocols before they’re set in stone, engage with us throughout the FDA approval process (not just by way of separate sessions), and include us in peer review with respect to the patient experience.
- Breakthroughs for treatments/cures for the other chronic hypophosphatemias that are not FGF23-mediated, like GACI and ENPP1, where there is promising research underway.
- Breakthroughs in understanding the mechanism of soft tissue calcification that might lead to treatment that will prevent, reverse, or, at the very least, slow/stop the progression of that calcification.
- Breakthroughs in understanding the mechanism that regulates the production of FGF23, so the overproduction can be stopped before it happens, rather than blocking it like burosumab does. (This is the holy grail for an XLH cure, and is being sought, but to no avail so far.)
I’m sure I’ve missed some goals, so please let me know if there’s something I didn’t mention that you’d like to see happen in the next five years!
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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