First, the good. It looks like burosumab can help patients with another rare bone disorder, fibrous dysplasia (FD), which includes hypophosphatemia as a symptom in at least some patients. The report on an NIH phase 2 trial, “A phase 2 trial of burosumab for treatment of fibroblast growth factor-23-mediated hypophosphatemia in children and adults with fibrous dysplasia” concludes, “Burosumab has the potential to lead to functional improvements and ambulation gains in severely affected patients and is a valuable tool to reduce the impact of FD-related disability.” There’s also a case report, “Burosumab use in fibroblast growth factor-23-mediated hypophosphatemia in McCune-Albright syndrome/fibrous dysplasia” showing it was helpful for one patient.
Not only is this good news for FD patients, but I think it’s good for the chronic hypophosphatemia community in general. It gives scientists some additional information about the role of FGF23, putting the emphasis squarely on the hypophosphatemia (where it belongs), rather than on “rickets” or any specific cause of the hypophosphatemia.
Now, for the less good. A small company developed an enzyme to treat one of the ultra-rare variants of genetic hypophosphatema, which causes earlier and more extensive soft-tissue calcification (previously called Generalized Arterial Calcification of Infancy, but now referred to by the name of the relevant gene, ENPP1, that causes the problem). Early trials showed promise for a virtual cure (so long as treatment continued), but the most recent trial produced mixed results. The patients’ blood phosphorus levels normalized, but unlike with XLH/TIO patients, the ENPP1 patients’ bones didn’t heal significantly. No decision has been announced with respect to whether the pharma company will continue developing this potential treatment.
These results are disappointing for the affected patients, and my heart goes out to them. It’s important to remember the big picture though, and a negative result in science is still useful information. Logically, you’d expect that normalizing blood-phosphorus levels would also normalize bone mineralization. After all, that’s the theory that led to the development of burosumab once scientists realized that FGF23 was the culprit behind phosphate-wasting. What the ENPP1 trial tells us though is that not all ways of normalizing phosphorus levels have the same benefits (I believe some ENPP1 patients benefit from burosumab treatment), and we need to look for other factors in the pathway phosphorus takes from the blood to the bones.
It’s now clear that just getting the phosphorus into the blood may not be enough to get it where it needs to go, so there must be something else happening in the pathway. Let’s hope that realization leads to new and innovative treatment options, possibly even a cure, for all forms of chronic hypophosphatemia!
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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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