Kyowa Kirin, North America (KKNA) is gearing up for a clinical trial on a new FGF23 antibody, called KK8123 (like burosumab used to be KRN23). The purpose of the trial is to study the new antibody’s safety and effectiveness as doses are increased, presumably to establish an ideal dosage. (The same process was followed in the early stage of studying KRN23, which became burosumab.) I assume KK8123 works on the same basic principles as burosumab, and my guess is that the intent is to find an alternative that lasts longer than 4 weeks (in adults; 2 weeks in kids). If the proposed new product is safe and effective, it will likely replace burosumab on the market in another ten years or so.
This is just a very tiny initial step, with only 24 patients being recruited across 8 locations (in the U.S.: California, Connecticut, Indiana, and Tennessee; and globally in France, Germany, and Spain). Assuming that this trial produces positive results for safety and effectiveness, there would still need to be a larger study that would take at least two or three more years, and then a significant amount of time would pass while it winds its way through the FDA bureaucracy.
The odds are pretty good that if KK8123 makes it through this early study, it will likely make it all the way to FDA approval. Usually, the odds of success in clinical drug development are very low; it’s commonly said that something like 90% of all new drug development fails along the way and never reaches the market. Treatments for rare disorders tend to do a bit better, with only 75% of them failing. That number is a little misleading in the context of biologics (like burosumab and KK8123), because most of the drugs that fail are what’s referred to as a “small molecule” — basically a naturally-occurring (or modified) compound that researchers are guessing will fix a symptom. Biologics are far more targeted than that, and so are less likely to fail in the early stages, making the odds of success at least twice as good as for small molecules.
If you’re interested in the study or know someone who might be interested, here’s the link to the full listing at clinicaltrials.org. At present, only one location is reported to be recruiting, with contact info, but if you’re interested and have a contact at another location that’s more convenient for you, it wouldn’t hurt to reach out now to be added to a wait list.
The trial is open only to adult XLH patients (which I think is a mistake — why not take the opportunity to test it on the other FGF-23 mediated hypophosphatemias at the same time, so as to avoid the problem we have now of ultra-rare hypophosphatemias probably able to benefit from burosumab, but unable to get it because the clinical trials were limited to one kind of FGF-23 mediated hypophosphatemia?). It also excludes anyone who has been on burosumab for seven months before starting the study. There are a variety of other exclusion criteria, but not currently being on burosumab is probably the biggest barrier to recruitment. I don’t know of many patients on burosumab who’d be willing to go off treatment for a big chunk of year, just to go on a different treatment that may or may not work as well (and probably won’t initially, since it will start at the lowest imaginable dose and work up to an effective one).
I should note that I think this is a poorly thought-out misstep on the part of KKNA. This is just my personal opinion, but I don’t think they’ve gotten a real feel for what matters to patients/caregivers, and they may be wasting money on work that won’t actually make a significant difference to patients’ lives. Even a small, Phase I/II trial like this one is extremely expensive, and I think the money could be better spent, in terms of both KKNA’s return on investment and benefits to patients. I would love to see more dosing-adjustment research done with respect to burosumab, that would enable better tailoring of dosages, rather than starting over with another product that would not really resolve the main unknowns of burosumab. We also need more research on the question of why our bones secrete too much FGF23, so we can look for a target even earlier in the process. Other things that would benefit patients would be a self-injectable option, a shelf-stable option (especially good for people in temporary quarters like the military or dorm rooms), and something like a patch for needle-phobic patients or those who have significant injection-site reactions.
While I don’t think this study is a good next step for the chronic hypophosphatemia community in general (and is more about extending KKNA’s monopoly on XLH treatment than benefiting patients), this study may be worth enrolling in for certain patients who are not currently on burosumab and would like to see if this new antibody will benefit them. There’s no reason to think the new antibody is unsafe (although anyone who enrolls should of course do their due diligence by reading the study materials and carefully considering the risks and benefits). I just don’t see it as sufficiently beneficial to patients to justify the time, money, and attention of a five-to-ten-year pursuit of FDA approval. I’d like to be proven wrong though, so I’ll be looking forward to seeing the data that comes out of the study!
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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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