Burosumab approved for pediatric use in UK

We are absolutely thrilled to announce this morning that burosumab has been APPROVED for routine use on the UK’s NHS for children from 1 years old up to young adults aged 16/17 years.

This news completely changes the landscape for the estimated 250 children living with XLH in the UK. Burosumab will be the first and only treatment that targets the cause of the hypophosphatemia in the body. The treatment helps reduce symptoms during childhood and by reducing bone damage during childhood growth it could mean the potential for a better quality of life for children later in their lives too.

We want to say a MASSIVE thank you to all those individuals who shared their experiences with us and with NICE so that decision-makers could understand what this treatment will really mean to patients and their families. Without all of your input this decision to approve burosumab may not have been made.

For those that can’t quite believe their eyes this morning, please visit NICE for the full guidance on children with XLH. If you have further questions about the treatment and whether it is right for your child then please do speak to their paediatrician that manages their XLH.

Since this news is so important, we at XLH UK have put together a press release. See link.
https://www.dropbox.com/s/o97z8m8nswd79m2/PR_xlhuk.pdf?dl=0

Whilst access to burosumab on the NHS will just be for children for now, let me assure you that the fight for the adult license has begun.

Meanwhile please please do stay tuned and encourage other XLHers in the UK & their families to join our XLH-UK facebook page because we’re so much stronger together.

https://www.nice.org.uk/…/gid-hst1…/documents/html-content-2

Last chance to comment on UK decision about burosumab

There are only a few days left to speak up about the benefits of burosumab before the regulatory agency makes its final decision, possibly denying this life-changing treatment to patients in the UK. To comment, you must register at NICE using this link. 

The evaluation committee is interested in receiving comments on the following:

a)How do symptoms (both physical and psychological) and treatments (including any surgery) you or your child experienced in childhood affect you in adult life?

b) For children on standard treatment (phosphate and calcitriol), what are the side effects of taking current treatment (phosphate, calcitriol)? How is that a burden for the child and your family?

c) If you have a child who is 1-12 years old and on burosumab, please explain how this treatment is currently helping in the short-term and how you expect that it will help in the long-term.

d) If you have a child who is 13-17 years old and on burosumab, please explain how this treatment is currently helping in the short-term and how you expect that it will help in the long-term.

If you have any questions at all, please don't hesitate to get in touch. Comment below or email us at Oliver.gardiner@xlhnetwork.org

Help ensure access to life-saving treatment!

The regulating authority in England is set to decide, incorrectly we believe, that even though burosumab is safe and effective, it will not be made available to patients in the UK for financial reasons. There is a short window of opportunity (just until July 6) for patients' voices to be heard (from anywhere in the world, but especially from the UK), so speak up now! And share this post and ask your friends in the XLH community to act too!

To comment, you must register at NICE using this link.

The evaluation committee is interested in receiving comments on the following:

• How do symptoms (both physical and psychological) and treatments (including any surgery) you or your child experienced in childhood affect you or your child in adult life? 
• For children on standard treatment (phosphate and calcitriol), what are the side effects of taking current treatment (phosphate, calcitriol)? How is that a burden for the child and your family?
• If you have a child who is 1-12 years old and on burosumab, please explain how this treatment is currently helping in the short-term and how you expect that it will help in the long-term.
• If you have a child who is 13-17 years old and on burosumab, please explain how this treatment is currently helping in the short-term and how you expect that it will help in the long-term.

We believe in the power of our combined voices, and there is a reason NICE provides a window for discussion. It is imperative that we stand up for children and families in the UK and that we do so now. Please join us.

Finally, if you have any questions, feel free to email: oliver.gardiner@xlhnetwork.org

#PowerInNumbers #XLHStrong #SetTheRecordStraight

Burosumab approved by European Medicines Agency

The European Medicines Agency has approved the use of burosumab in children (age 1 and up) and adolescents with XLH.

There is, of course, more work to be done in individual European countries to ensure access and to educate both the patient and medical communities.

According to the press release:

The European Marketing Authorization is valid in the 28 countries of the European Union and in Norway, Iceland and Liechtenstein. The first commercial launch of Crysvita is expected to take place in Germany in the second quarter of 2018, followed by other European countries.

You can read the whole release here: http://ir.ultragenyx.com/news-releases/news-release-details/kyowa-kirin-and-ultragenyx-announce-crysvitar-burosumab-receives

Questions about burosumab?

You know that the new treatment for XLH, the antibody to FGF23, and known as burosumab, is under consideration by the U.S. Food & Drug Administration and by the European Medicines Agency with (we hope) approval due sometime in the next few months.

You must have questions about what happens after the approval. We're working on some resources that will answer as many questions as possible about burosumab and how to discuss it with your doctor, your insurer and your pharmacist.

We've been wracking our brains to anticipate all your questions, starting with the belief that they're the same questions we have ourselves. But everyone's experience with XLH is different and everyone has different concerns, so we need your help to make sure we haven't missed any important topics.

So here's your chance to tell us what you've been wondering about for the future of XLH treatment. We won't be answering your questions right now (and we can't advise you on whether treatment is right for you or your family specifically), but we'll try our best to make sure that the materials we'll be publishing this spring will contain enough information to answer all your non-patient-specific questions.

You can send your questions privately to info@xlhnetwork.org, or post them in a comment at our official facebook page, https://www.facebook.com/xlhnetwork/

Wanted: XLH-experienced clinicians

Do you remember how hard it was to find a doctor who knew something about XLH, either for yourself or your child? For many XLHers, it's a time-consuming and frustrating experience, waiting months for an appointment, only to find out that the health care provider is the wrong one, so you have to start over. Or perhaps you stick with the doctor, only to find out months or years later that the advice being offered wasn't based on the most recent science, and your health declined as a result.

Wouldn't it be great if that didn't have to happen to others? If you have a good, XLH-experienced health care provider, you can help other XLHers avoid all that frustration, wasted time, and inadequate treatment by sending that health care provider's name and contact information (just city and state is enough if that's all you have at hand) to us at info@xlhnetwork.org.

The Network is hard at work making sure you'll have all the information and resources you'll need when, assuming all goes as well as we hope, the new treatment for XLH is available in a few months. One of the first questions that many patients will be asking is "where can I find a doctor who knows about burosumab?"

We already have a database of clinicians who have experience treating XLH, but it's got some pretty huge gaps in it. That's where you come in. You can help to fill in the gaps and save some fellow XLHers from the frustrating, time-wasting, health-endangering experience of dealing with a health care provider who's never heard of XLH before. Just send your doctor's name and contact info to info@xlhnetwork.org.

Thank you for your help!

Latest data on KRN23/burosumab trials

The latest data from 48 weeks into the adult Phase 3 trials are really encouraging. They show continuing improvement in terms of pain reduction, stiffness reduction and improved fracture healing. Perhaps most impressive was the drop in painkiller medications that would seem to be an objective corroboration of the reported pain reduction (and especially encouraging insofar as pain medications carry with them some serious consequences):

[quote]The patient frequency of reported opioid use decreased by 76% from 17 patients (25%) at baseline to four patients (6%) at week 48 in the burosumab group, and by 70% from 13 patients (20%) to four patients (6%) in the crossover group [patients who started on placebo and therefore had only been on burosumab for 24 weeks instead of the full 48]. The patient frequency of reported nonsteroidal anti-inflammatory drugs (NSAIDs) use decreased by 72% from 47 patients (69%) at baseline to 13 patients (19%) at week 48 in the burosumab group, and by 74% from 43 patients (65%) to 11 patients (17%) in the crossover group. [/quote]

You can read the full report here: http://ir.ultragenyx.com/releasedetail.cfm?ReleaseID=1050531

Positive European Medicines Agency recommendation for KRN23/burosumab

Excellent news for the European members of our community!

According to a press release today from Ultragenyx and Kyowa Hakko Kirin, "the Committee for Medicinal Products for Human Use (CHMP), the European Medicines Agency's (EMA) scientific committee, has adopted a Positive Opinion recommending the conditional marketing authorization of burosumab, an anti-FGF23 human monoclonal antibody, for the treatment of X-linked hypophosphatemia (XLH) with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons."

There's more work to be done before the treatment will be available to patients in Europe, but this is a huge leap forward! A final decision needs to be made by the European Commission, and is expected in the first quarter of 2018. It will apply to all 28 countries of the European Union, Norway, Iceland and Liechtenstein, but individual countries will still need to do additional reviews, largely with respect to payment issues, rather than safety and efficacy issues.

You can read the entire press release here: http://ir.ultragenyx.com/releasedetail.cfm?ReleaseID=1051923

What should the FDA know about XLH?

The XLH Network, Inc. will be meeting with the U.S. Food  & Drug Administration on  December 4, 2017 [previously set for January 2018], to make sure that the patients' (and their families') voices are heard as the FDA considers the safety and efficacy of KRN23/burosumab and whether to approve it for treatment of both children and adults.

As we're planning our presentation, we want to do our best to cover the entire spectrum of what it means to live with XLH. As we all know, XLH affects so many systems of the body, and there's a wide variation in symptoms and severity. We know what we ourselves have experienced (or what our family members have experienced), what we've read on our listserv, forum or Facebook page, and what we gathered from XLH Day attendees this year.

But we still don't have the full story. We don't have your story.

What would you tell the FDA  if you had just two minutes to give them your message?

If  you don't know where to start, here are some things to think about: Perhaps you'd want them to know about your biggest XLH-related challenge in your career or personal life. Or maybe there's one particular XLH symptom that, if treated, would improve your life dramatically. How would your life be different if you didn't have that particular symptom, even if you still experienced other symptoms? Is there something you've always wanted to do, but felt you couldn't because of your XLH? Or, for those of you who have XLH and also a child with XLH, is there one thing in particular that you wish your child wouldn't have to experience the way you did?

Send your message no later than November 1, 2017 to ExecutiveDirector@XLHNetwork.org  Our time with the FDA is going to be brief, so we need to ask you to keep your message concise, no more than one hundred words (that's about half of a double-spaced page) and focused on the one XLH-related challenge for which you would particularly like a medical solution.

Thank you for helping us tell our community's story. Together we can make a difference and help the FDA understand the need for this new treatment, as well as for additional research.

FDA due to rule by April 17, 2018

The U.S. Food and Drug Administration has set the calendar for its review of KRN23/burosumab, the promising new treatment for XLH, and granted "priority review" status that will expedite the process. A decision is due from the FDA by April 17, 2018.

You can read the press release here:http://ir.ultragenyx.com/releasedetail.cfm?ReleaseID=1043322

KRN23/burosumab trial data presented at ASBMR

Some data from the clinical trials of KRN23/burosumab were shared with clinicians and researchers during the recent conference of the American Society for Bone and Mineral Research. Dr. Karl Insogna presented about the treatment of adults, and Dr. Michael Whyte presented for pediatric issues. 

The data were summarized in an article by MedPage Today, which you can read here: https://www.medpagetoday.com/meetingcoverage/asbmr/67919

Of particular interest is the lack of significant adverse effects reported in the adult study, as reported by MedPage Today:  

"The safety profile of burosumab was similar to what was seen for placebo, with no serious drug-related adverse events and no events leading to study discontinuation.
"We conclude that burosumab represents an exciting new therapy for XLH," Insogna said."

And for the pediatric study, as reported by MedPage Today, the improvement in the rickets score (lower is better), even though at least some of the patients had previously been treated with the current therapy (phos and calcitriol): "the most substantial improvements [in rickets scores] being seen for children who had more severe rickets (RSS of 1.5 or higher at baseline). In that subgroup, RSS decreased from a baseline score of 2.46 to 1.01 .... "

Also, side effects in the pediatric study were considered either insignificant or unrelated to the new treatment: "Renal function remained normal and there was no evidence of ectopic mineralization of the myocardium. The most common adverse events were transient injection site reactions, and only one child had a serious adverse event, which was considered unrelated to the therapy. "The favorable benefit-risk profile of burosumab holds promise for long-term outcomes for these children," Whyte concluded."

FDA to consider both pediatric and adult issues

According to a recent Ultragenyx press release, the company has had a meeting with the FDA to discuss the planned submission for approval of KRN23/burosumab, with encouraging results. 

The press release states: "At the meeting, the FDA agreed that the BLA [Biologics License Agreement] can be submitted based on available clinical data and confirmed that both pediatric and adult indications would be included in the review. Based on the agreement, the submission of the burosumab BLA is planned for the second half of 2017."

Of particular importance to the XLH community is the FDA's decision to consider both pediatric and adult indications for the use of KRN23/burosumab, since previously it appeared that the FDA might only consider pediatric use of the new therapy during its review under the Breakthrough Therapy designation. Without FDA approval for adults, insurance companies might only cover the treatment for children, not for adults. Anecdotal evidence suggests that the treatment can be extremely beneficial for adults, not just for children.

The Network is investigating a variety of ways to provide the FDA with information from the patient perspective, particularly with respect to adult issues that need treatment, which have not been addressed as widely in the medical literature as the pediatric issues. We'll let you know  how you can help too as soon as we have more information.

You can read the entire press release here: 
http://ir.ultragenyx.com/releasedetail.cfm?ReleaseID=1031181

Additional results from KRN23/burosumab studies

The latest press release from Ultragenyx Pharmaceutical, primarily addressed to investors, includes some new data on the healing of fractures in the adult XLHers in the Phase 3 clinical trial of KRN23/burosumab:

"At study entry, 52% of patients (comprising 48% of patients randomized to burosumab and 56% of patients randomized to placebo) presented with either active fractures (12%) or pseudofractures (47%) or both. At week 24, 37% of active fractures or pseudofractures in patients treated with burosumab were completely healed compared to 10% on placebo. Additionally, at week 24, 3% of existing active fractures or pseudofractures treated with burosumab worsened compared to 11% on placebo." 

It's worth noting that the study, in addition to showing apparent benefits for healing, also documents just how widespread the occurrence of fractures and pseudofractures is within the adult XLH community, with roughly half of the study participants having a fracture or pseudofracture! 

You can read the entire press release here:
http://ir.ultragenyx.com/releasedetail.cfm?ReleaseID=1024922