Treatment of rare metabolic diseases, excellent data in the third phase of research new drugs

Treatment of rare metabolic diseases, excellent data in the third phase of research new drugs

December 05, 2017 Source: WuXi PharmaTech

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Ultragenyx Pharmaceutical, Kyowa Hakko Kirin, and Kyowa Kirin International today disclosed the results of an active phase 3 clinical trial of burosumab (KRH23) in adult X-linked hypophosphatemia (XLH) patients. After 48 weeks of treatment with burosumab, the study observed that the patient's serum phosphorus levels were normal and maintained, as well as further improvements in body stiffness, body function and pain were observed.

XLH is a hereditary disease that affects every 20,000 people. XLH is carried on the X chromosome, and although almost all X-linked diseases are recessive, XLH is one of the few dominant inheritance diseases. XLH is also the most common hypophosphatemia. The kidneys of XLH patients do not properly treat Vitamin D and phosphorus, but this is not caused by kidney problems, but some substances in the blood circulation cause the kidneys to treat phosphorus as waste, not enough to circulate it for bones and teeth.

Burosumab, discovered by Kyowa Hakko Kirin, is a recombinant humanized monoclonal IgG1 antibody directed against fibroblast growth factor 23 (FGF23). FGF23 reduces serum and active vitamin D levels in serum by regulating phosphate excretion and the production of active vitamin D in the kidney. Ultragenyx and Kyowa Hakko Kirin are developing burosumab for the treatment of XLH and tumor-induced osteomalacia (TIO), which are characterized by an excess level of FGF23. Excessive consumption of phosphate is caused by excessive activity of FGF23 in XLH and TIO diseases, and burosumab mAb is effective in binding to FGF23 and inhibiting the biological activity of FGF23. By blocking excess FGF23 in XLH and TIO patients, burosumab aims to increase phosphate reabsorption from the kidneys and increase vitamin D production, thereby also enhancing the absorption of phosphate and calcium ions in the gut.

The clinical study enrolled 134 patients with a random dose of 1 mg/kg dose of burosumab or placebo, once every 4 weeks for 24 weeks. After 24 weeks, patients from both groups continued the open-label trial, during which they received 1 mg/kg of budoutumab once every 4 weeks.

After 24 to 48 weeks of treatment, patients who received burosumab treatment since the start of the study (n = 68), 84% achieved and maintained serum phosphorus levels above the lower limit of normal (2.5 mg/dL). 89% of patients who crossed from placebo to patients who received 24-week burosumab (n = 66) achieved and maintained serum phosphorus levels above the lower limit of normal. According to the measurement of the Osteoarthritis Index WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), the body stiffness and physiological function of patients receiving burosumab continued to improve. The stiffness score varied from an average of 7.42 points in 24 weeks to 16.03 points in 48 weeks. Patients who crossed from placebo to burosumab had an average change of 15.82 points between 24 and 48 weeks. The body function score increased from 2.78 points in 24 weeks to an average of 7.76 points in 48 weeks. For the crossover group, body function changed by an average of 8.18 points from 24 weeks to 48 weeks.

Burosumab also reduces patient pain through the Concise Pain Assessment Scale 3 (BPI Q3, the most severe pain in the last 24 hours). For patients receiving burosumab, the pain score improved from an average of 0.81 at week 24 to 1.09 at week 48. Patients who crossed from placebo to burosumab had an average change of 1.18 points from 24 weeks to 48 weeks. Treatment with burosumab also improved fracture healing (active fractures and pseudo-fractures) compared with placebo for 48 weeks. The fracture healing rate of the burosumab group was 43% at 24 weeks and increased to 63% at 48 weeks. In the crossover group with a fracture healing rate of 8% at 24 weeks, it increased to 35% at 48 weeks. The fracture healing results of the patients in the cross group were consistent with the results of the first 24 weeks of the burosumab group.

â–² Dr. Emil D. Kakkis, CEO and President of Ultragenyx (Source: Ultragenyx Official Website)

"Long-term data on symptom improvement and fracture healing support the potential value of burosumab in treating severe disease symptoms and promoting bone healing in XLH adult patients," said Dr. Emil D. Kakkis, CEO and President of Ultragenyx: "Continuous clinical improvement and The new data show that the use of painkillers is significantly reduced after treatment with burosumab, which provides further support for the potential value of burosumab in treating XLH adult patients."

"This study provides valuable additional long-term data for adult XLH patients," said Mitsuo Satoh, vice president and executive officer of Kyowa Hakko Kirin's R&D department. "I believe that burothumab may be an effective treatment option for XLH patients."

â–²Ultragenyx focuses on the development of new drugs for rare diseases (Source: Ultragenyx official website)

Dr. Tom Stratford, President and CEO of Kyowa Kirin International, said: "The long-term data from this adult phase 3 study suggests that burosumab may have a positive impact on the lives of XLH patients and we look forward to discussions with regulators in Europe and the United States."

We hope that the review of this new drug will go smoothly and help patients with this rare genetic disease to relieve body pain and restore body function.

Reference materials:

[1] Ultragenyx Stock Booms After Burosumab Continues to Impress in Phase III Study

[2] Ultragenyx and Kyowa Kirin Announce Positive 48-Week Data from Adult Phase 3 Study of Burosumab (KRN23) in X-Linked Hypophosphatemia

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