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Pharmaceuticals: Some General Aspects
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The three latest orphan medical products designated by the EMA early 2018 (EMA, 2018b) via accelerated assessment after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended marketing approval are Crysvita (burosumab), Prevymis (letermovir), and Jorveza (budesonide). The active substance of Crysvita (Kyowa Hakko Kirin Co. Ltd., Kyowa Kirin International PLC and Ultragenyx Pharmaceutical) is burosumab, a recombinant fully humanized monoclonal IgG1 antibody that binds to and inhibits the activity of fibroblast growth factor 23. The drug is indicated for the treatment of X-linked hypophosphataemia (XLH, a chronic progressive musculoskeletal disorder) with radiographic evidence of bone disease in children 1 year of age and older. The antiviral agent Prevymis (letermovir), a non-nucleosidic, inhibitor is used for prophylaxis of cytomegalovirus (CMV) infection and disease in adults and acts by inhibiting the human CMV viral terminase by a mechanism that remains to be elucidated (Ligat et al., 2018). CMV may cause life-threatening infections in immuno-compromised patients and serious congenital malformations. Prevymis is marketed by Merck & Co., Inc. (or Merck Sharp & Dohme (kurz MSD)) and was developed by AiCuris up to the clinical phase 2b. AiCuris received from Merck €30 million in addition to €105 million that became due after approval of Prevymis by the FDA in November 2017. Jorveza (with the glucocorticosteroid budesonide), marketed by Dr. Falk Pharma GmbH, Germany, is a medicine used to treat adults with the rare inflammatory disease eosinophilic esophagitis, a designation stemming from the fact that in the tissue of the esophagus in patients with this disease numbers of white blood cells called eosinophils are very high. Budesonide acts by preventing antigen-stimulated secretion of proinflammatory signal molecules such as thymic stromal lymphopoeitin (TSLP, a protein belonging to the cytokine family and produced mainly by non-hematopoietic cells (its expression is linked not only to eosinophilic esophagitis but also to other diseases, e.g., asthma, inflammatory arthritis, atopic dermatitis, etc.), interleukin-13 (the IL-13 protein is associated primarily with the induction of airway diseases), and eotaxin-3 (or chemokine (C-C motif) ligand 26 (CCL26) in the esophageal epithelium. Eotaxin-3 is a small cytokine belonging to the CC chemokine family and chemotactic for eosinophils (and basophils); for the regulatory role of this human chemokine in connection with attracting eosinophils and basophils, see Petkovic et al. (2004).
Value-based decision-making for orphan drugs with multiple criteria decision analysis: burosumab for the treatment of X-linked hypophosphatemia
Published in Current Medical Research and Opinion, 2021
Björn Vandewalle, Miguel Amorim, Diogo Ramos, Sofia Azevedo, Inês Alves, Telma Francisco, Helena Pinto, Sérgio Sousa
The majority of the expert panel (four out of five) classified burosumab as a drug directed to the underlying cause of XLH and with curative properties (functional cure) and all five experts thought it was a highly innovative drug that would provide a substantial improvement on health equity for these patients, leading to notable difference in valuation between burosumab and conventional therapy. Additionally, all panellists classified burosumab’s ‘Level of uncertainty regarding the available evidence’ as minimal (n = 3, 60%) or reduced to moderate (n = 2, 40%), meaning they strongly believe results from phase II and III clinical trials will translate into clinical practice. Regarding economic burden related criteria, burosumab valued slightly higher on two of the three criteria as experts thought burosumab would result in an improvement of the patients’ condition and consequently in fewer hospital visits and hospitalizations, resulting in lower transportation costs (direct non-medical cost) and lower absenteeism (indirect cost).
Antibodies to watch in 2019
Published in mAbs, 2019
Hélène Kaplon, Janice M. Reichert
On February 19, 2018, the EC issued a conditional marketing authorization in the EU for burosumab (Crysvita) as a treatment for X-linked hypophosphatemia (XLH) in children 1 year of age and older, and adolescents with growing skeletons. Burosumab is a human IgG1 mAb that binds to and inhibits the activity of fibroblast growth factor 23, thereby reducing loss of phosphate from the kidney and other metabolic abnormalities, and ameliorating bone changes that are a hallmark of the disease.25 In a double-blind, placebo-controlled, Phase 3 study of symptomatic adults with XLH administered SC burosumab 1 mg/kg (n = 68) or placebo (n = 66) every 4 weeks, across midpoints of dosing intervals, 94.1% of burosumab-treated participants attained mean serum phosphate concentration above the lower limit of normal compared with 7.6% of those receiving placebo (p < 0.001).26 Burosumab was granted Orphan Drug designations in the EU and US, and FDA granted the drug Breakthrough Therapy designation for pediatric XLH. Burosumab-twza was approved by the FDA on April 17, 2018.27
Antibodies to watch in 2018
Published in mAbs, 2018
Hélène Kaplon, Janice M. Reichert
Burosumab (KRN23) is a human IgG1 mAb targeting fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate excretion and active vitamin D production by the kidney. Discovered by Kyowa Hakko Kirin, burosumab is being developed by Ultragenyx and Kyowa Hakko Kirin to treat X-linked hypophosphatemia (XLH), which is characterized by skeletal defects resulting from excess levels of FGF23, as well as tumor-induced osteomalacia. Marketing applications have been submitted in the EU and US. Burosumab was granted Breakthrough Therapy designation in the US, and the BLA was granted a priority review. FDA's Prescription Drug User Fee Act (PDUFA) date is April 17, 2018.