The promise of monoclonal antibodies

As KRN23 is entering what is expected to be its final clinical trial prior to submission for approval by the FDA, it may be useful for the XLH community to understand more about this potential treatment.

KRN23, rather than being a traditional drug, is similar to newer treatments on the market, commonly referred to as "biologics." KRN23 is a "monoclonal antibody." It's not the only such product. You may have seen advertisements for one currently used in the treatment of rheumatoid arthritis: abatacept (Orencia).

Monoclonal antibodies are designed to bind with another substance in the body with greater specificity than other drugs, generally rendering the substance inactive. XLH (along with the autosomal variants and tumor-induced osteomalacia) appears to be well suited to treatment by this kind of antibody.

The symptoms of XLH is are caused, in large part, by the excessive production of a hormone, Fibroblast Growth Factor 23 (FGF23), which in turn causes phosphate wasting and the decreased ability to metabolize Vitamin D into its active form. The expectation is that the antibody known as KRN23 will bind to the FGF23 and essentially render it inactive, allowing normal phosphate reabsorption and active vitamin D production.

This expectation appears to be proving true in the clinical trials to date. If you'd like to read more about it, there's a somewhat technical article that's still comprehensible to the layperson (at least if you're willing to look up the terms  you don't understand) in the Journal of Endocrinology & Metabolism, which you can read for free here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495171/

The conclusion: "KRN23 has the potential to improve biochemical and skeletal outcomes in adults and children with XLH, with greater convenience and compliance than multiple daily doses of calcitriol and phosphate."

Of course, there's still more work to be done before we'll know for sure that KRN23 will be a safe and effective treatment. Additional research is also continuing into better understanding of XLH, including searching for answers as to why and how the DNA mutations associated with XLH trigger the excessive production of FGF23.

So much has been learned about bone metabolism since the discovery of FGF23 just sixteen years ago -- that's four years after the XLH Network was founded! -- and we're increasingly hopeful about the prospects of a better quality of life for individuals with hypophosphatemia.