• Effect of burosumab on pre-existing pseudofracture healing will be monitored by centrally read targeted X-Ray [ Time Frame: Targetted X-Rays at ongoing fracture sites will be taken at the End of Study Visit, approximately week 144. ]
  Targeted radiography at locations pre-determined by the skeletal survey performed during UX023-CL303 or UX023-CL304 will be taken to monitor healing of pseudofractures and/or fractures.
• Effect of burosumab on patients walking ability measured using the 6 Minute Walk Test. [ Time Frame: The 6MWT will be measured at Baseline and then every 12 weeks for the first 48 weeks and then every 24 weeks for up to 144 weeks ]
  Patient's motor function by sustained walking will be evaluated using the 6 Minute Walk Test. (6MWT). The percent predicted values for the 6MWT will be calculated using published normative data based on age, gender and height.
• Effect of burosumab on Patient mobility assessed using the Timed Up and Go Test (TUG). [ Time Frame: The TUG Test will be assessed at Baseline and then every 12 weeks for the first 48 weeks and then every 24 weeks for up to 144 weeks ]
  The TUG assesses transitions during ambulatory activity incorporating strength, agility and dynamic balance assessments. The TUG score will be reported as the time (in seconds) that a subject takes to rise from a chair, walk three meters (approximately 10 feet), turn around, walk back to the chair and sit down.
• Effect of burosumab on stiffness and physical function will be assessed using WOMAC. [ Time Frame: The WOMAC questionnaire will be administered at Baseline and then every 12 weeks for 48 weeks and every 12 weeks for up to 48 weeks and then every 24 weeks for up to 96 weeks ]
  The patient's impression of their stiffness and physical function will be assessed by administering the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire- a 24 item patient reported questionnaire. The WOMAC will be administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe and extreme corresponding to an ordinal scale of 0 to 4. Higher scores on the WOMAC indicate worse stiffness and functional limitations.
• Effect of burosumab on patient's pain severity and the impact of pain on functioning will be assessed using the Short-form Brief Pain Inventory questionnaire. [ Time Frame: The BPI will be administered at Baseline and then every 12 weeks for 48 weeks and then every 24 weeks for up to 144 weeks ]
  The patient's recall of pain over a 24 hour period will be captured by administering the short form of the Brief Pain Inventory (BPI) questionnaire. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others and sleep).
• Effect of burosumab on patient's fatigue and the interference of fatigue on daily life over a 24 hour period. [ Time Frame: The BFI will be administered at Baseline and then every 12 weeks for up to 48 weeks and then every 12 weeks for up to 144 weeks ]
  The patient's recall of fatigue will be captured by administering the Brief Fatigue Inventory (BFI) questionnaire. The BFI is a self-reported questionnaire consisting of nine items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Two dimensions are measured: fatigue and the interference of fatigue on daily life. The change from baseline to post-baseline visits will be assessed.
• Effect of burosumab on bone metabolism and phosphate homeostasis using urinary phosphorus as PD marker. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks ]
  Pharmacodynamic assessment.
• Effect of burosumab on enthesopathy will be monitored by centrally read targeted X-Ray. [ Time Frame: Lateral foot views (bilateral) will be obtained at screening and at End of Study, approximately week 88. ]
  Lateral foot views (bilateral) will be obtained in all subjects at Screening (as part of skeletal survey) and at End of Study (EOS). Size of enthesopathy spurs at both the superior and inferior calcaneus will be measured in two dimensions.
• Effect of burosumab on bone metabolism and phosphate homeostasis using Serum Phosphorus as PD marker. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks. ]
  Pharmacodynamic assessment.
• Effect of burosumab on bone metabolism and phosphate homeostasis using serum 1, 25(OH)2D as PD marker. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks. ]
  Pharmacodynamic assessment.
• Effect of Burosumab on phosphate reabsorption as measured by the ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtrate [TmP/GFR]. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks. ]
  Pharmacodynamic assessment.
• Effect of burosumab on health related quality of life as measured by SF-36v2 [ Time Frame: The SF-36v2 will be administered at Baseline and then every 12 weeks for 48 weeks and then every 24 weeks for up to 144 weeks ]
  Patients will answer questions around their physical functioning, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and mental health

• Effect of burosumab on pre-existing pseudofracture healing will be monitored by centrally read targeted X-Ray [ Time Frame: Targetted X-Rays at ongoing fracture sites will be taken at the End of Study Visit, approximately week 88. ]
  Targeted radiography at locations pre-determined by the skeletal survey performed during UX023-CL303 or UX023-CL304 will be taken to monitor healing of pseudofractures and/or fractures.
• Effect of burosumab on Patient's Impression of Improvement to indicate patient's perception of efficacy of treatment. [ Time Frame: The PGI questionnaire will be administered at baseline and then every 24 weeks for up to 88 weeks. ]
  The Patient's Impression of Improvement will be captured using the Patient Global Impression of Improvement (PGI-I) scale, an instrument widely used in chronic pain trials to indicate the patient's perception about the efficacy of treatment. The PGI-I is self-administered and improvement is rated on a 7-point categorical scale ranging from "very much improved" to "very much worse."
• Effect of burosumab on patients walking ability measured using the 6 Minute Walk Test. [ Time Frame: The 6MWT will be measured at Baseline and then every 24 weeks for up to 88 weeks ]
  Patient's motor function by sustained walking will be evaluated using the 6 Minute Walk Test. (6MWT). The percent predicted values for the 6MWT will be calculated using published normative data based on age, gender and height.
• Effect of burosumab on Patient mobility assessed using the Timed Up and Go Test (TUG). [ Time Frame: The TUG Test will be assessed at Baseline and then every 24 for up to 88 weeks ]
  The TUG assesses transitions during ambulatory activity incorporating strength, agility and dynamic balance assessments. The TUG score will be reported as the time (in seconds) that a subject takes to rise from a chair, walk three meters (approximately 10 feet), turn around, walk back to the chair and sit down.
• Effect of burosumab on stiffness and physical function will be assessed using WOMAC. [ Time Frame: The WOMAC questionnaire will be administered at Baseline and then every 24 weeks for up to 88 weeks ]
  The patient's impression of their stiffness and physical function will be assessed by administering the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire- a 24 item patient reported questionnaire. The WOMAC will be administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe and extreme corresponding to an ordinal scale of 0 to 4. Higher scores on the WOMAC indicate worse stiffness and functional limitations.
• Effect of burosumab on patient's pain severity and the impact of pain on functioning will be assessed using the Short-form Brief Pain Inventory questionnaire. [ Time Frame: The BPI will be administered at Baseline and then every 24 weeks for up to 88 weeks. ]
  The patient's recall of pain over a 24 hour period will be captured by administering the short form of the Brief Pain Inventory (BPI) questionnaire. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others and sleep).
• Effect of burosumab on patient's fatigue and the interference of fatigue on daily life over a 24 hour period. [ Time Frame: The BFI will be administered at Baseline and then every 24 weeks for up to 88 weeks ]
  The patient's recall of fatigue will be captured by administering the Brief Fatigue Inventory (BFI) questionnaire. The BFI is a self-reported questionnaire consisting of nine items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Two dimensions are measured: fatigue and the interference of fatigue on daily life. The change from baseline to post-baseline visits will be assessed.
• Effect of burosumab on bone metabolism and phosphate homeostasis using urinary phosphorus as PD marker. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks ]
  Pharmacodynamic assessment.
• Effect of burosumab on enthesopathy will be monitored by centrally read targeted X-Ray. [ Time Frame: Lateral foot views (bilateral) will be obtained at screening and at End of Study, approximately week 88. ]
  Lateral foot views (bilateral) will be obtained in all subjects at Screening (as part of skeletal survey) and at End of Study (EOS). Size of enthesopathy spurs at both the superior and inferior calcaneus will be measured in two dimensions.
• Effect of burosumab on bone metabolism and phosphate homeostasis using Serum Phosphorus as PD marker. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks. ]
  Pharmacodynamic assessment.
• Effect of burosumab on bone metabolism and phosphate homeostasis using serum 1, 25(OH)2D as PD marker. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks. ]
  Pharmacodynamic assessment.
• Effect of Burosumab on phosphate reabsorption as measured by the ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtrate [TmP/GFR]. [ Time Frame: Pharmacodynamic analysis will be conducted at Baseline and every 12 weeks for up to 88 weeks. ]
  Pharmacodynamic assessment.

XLH is a rare, genetic disorder that is serious, chronically debilitating and represents an unmet medical need. XLH is the most common inherited form of rickets and the most common inherited defect in renal tubular phosphate transport. XLH is transmitted as an X-linked dominant disorder. Mutations resulting in the loss of function of PHEX form the genetic basis for XLH. More than 300 different PHEX gene mutations have been identified in patients with XLH (PHEXdb); however, few definitive correlations have been observed between specific mutations and phenotypic severity.

Patients with XLH have hypophosphatemia due to excessive serum FGF23 levels. FGF23 reduces serum phosphorus levels by two distinct mechanisms of action. The primary mechanism is to inhibit phosphate reabsorption in the proximal tubule of the kidney. The secondary mechanism is to decrease phosphate absorption by the small intestine through the inhibition of 1,25(OH)2D production in the kidney.

Burosumab has the potential to block or reduce FGF23 action and improve phosphate homeostasis in XLH patients. Burosumab binds the amino-terminal domain of FGF23 that interacts with the FGF-binding portion of the combination FGFR1/Klotho receptor, preventing FGF23 from binding to and signaling from its receptor. Both intact and fragmented FGF23 polypeptides are immunoprecipitated with burosumab. By inhibiting FGF23, burosumab restores tubular reabsorption of phosphate (as measured by the ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate [TmP/GFR]) from the kidney and increases the production of 1,25(OH)2D that also enhances intestinal absorption of phosphate. The dual action on kidney reabsorption and intestinal absorption improves serum phosphorus levels, which is expected to improve bone mineralization and reduce the diverse bone and non-bone manifestations associated with hypophosphatemia in XLH patients.

Inclusion Criteria:

1. Subjects who provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures.
2. Subjects who participated in Study UX023-CL303 or UX023-CL304. Any subjects that did not complete Study UX023-CL303 or UX023-CL304 may be included on a case-by-case basis. Subjects' enrolment is not dependent on any response to Primary or Secondary endpoints in studies UX023-CL303 or UX023-CL304.
3. Willing to provide access to prior medical records for the collection of historical growth, biochemical and radiographic data, and disease history.
4. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments.
5. Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of child-bearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy. If sexually active, male and female subjects must be willing to use one highly effective method of contraception for the duration of the study.

Exclusion Criteria:

1. Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits and deemed as clinically significant in the opinion of the investigator.
2. Presence of a concurrent disease or condition that would interfere with study participation or affect safety in the opinion of the investigator or Sponsor.
3. Use of any investigational product other than burosumab or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
4. Subjects with major protocol deviations in Study UX023-CL303 or UX023-CL304 which in the view of the investigator places the subject at high risk of poor treatment compliance or of not completing the study.
5. Subjects who discontinued treatment from Study UX023-CL303 or UX023-CL304 due to either a grade ≥3 treatment-related hypersensitivity reaction or a burosumab-related hypersensitivity reaction reported as a SAE.