Fosdenopterin

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Fosdenopterin
Names
Trade namesNulibry
Other namesCyclic pyranopterin monophosphate (cPMP), precursor Z, ALXN1101
  • 5-amino-11,11,14-trihydroxy-14-oxo-13,15,18-trioxa-2,4,6,9-tetraza-14λ5-phosphatetracyclo[8.8.0.03,8.012,17]octadeca-3(8),4-dien-7-one
Clinical data
Main usesMolybdenum cofactor deficiency (MoCD) type A[1]
Side effectsIntravenous line complications, fever, respiratory infections, vomiting, gastroenteritis, diarrhea[2]
Routes of
use		Intravenous
Typical dose0.9 mg/kg[1]
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
Chemical and physical data
FormulaC10H14N5O8P
Molar mass363.223 g·mol−1
3D model (JSmol)
  • NC1=NC(=O)C2=C(N[C@@H]3O[C@@H]4COP(=O)(O)O[C@@H]4C(O)(O)[C@@H]3N2)N1
  • InChI=1S/C10H14N5O8P/c11-9-14-6-3(7(16)15-9)12-4-8(13-6)22-2-1-21-24(19,20)23-5(2)10(4,17)18/h2,4-5,8,12,17-18H,1H2,(H,19,20)(H4,11,13,14,15,16)/t2-,4-,5+,8-/m1/s1
  • Key:CZAKJJUNKNPTTO-AJFJRRQVSA-N

Fosdenopterin, sold under the brand name Nulibry, is a medication used to treat molybdenum cofactor deficiency (MoCD) type A.[1] In people with this condition, it reduces the risk of death.[2] It is given by gradual injection into a vein once per day.[1]

Common side effects include complications related to the intravenous line, fever, respiratory infections, vomiting, gastroenteritis, and diarrhea.[2] Other side effects may include sunburns.[2] It is a manufactured form of cyclic pyranopterin monophosphate (cPMP), which it replaces.[1]

Fosdenopterin was approved for medical use in the United States in 2021 and Europe in 2022.[2][1] It is not approved in the United Kingdom as of 2022.[4] In the United States it costs about 1,500 USD per 9.5 mg vial; a cost of about 550,000 USD for a 10 kg child for a year.[5]

Medical uses

Fosdenopterin is used to reduce the risk of mortality in people with molybdenum cofactor deficiency (MoCD) type A.[2][3]

It is believed to decrease the risk of death from 25% to 7% during the first year of life.[1]

Dosage

The typical dose is 0.9 mg/kg.[1] Lower doses of 0.4 to 0.75 mg/kg may be used in those under the age of 3 months.[2]

Mechanism of action

People with molybdenum cofactor deficiency type A cannot produce cyclic pyranopterin monophosphate (cPMP) in their body.[3] Fosdenopterin is an intravenous medication that replaces the missing cPMP.[3][6] cPMP is a precursor to molybdopterin, which is required for the enzyme activity of sulfite oxidase, xanthine dehydrogenase/oxidase and aldehyde oxidase.[7]

History

Fosdenopterin was developed at the German universities TU Braunschweig and the University of Cologne.[8][9]

The effectiveness of fosdenopterin for the treatment of MoCD-A was demonstrated in thirteen treated participants compared to eighteen matched, untreated participants.[3][10] The participants treated with fosdenopterin had a survival rate of 84% at three years, compared to 55% for the untreated participants.[3]

The U.S. Food and Drug Administration (FDA) granted the application for fosdenopterin priority review, breakthrough therapy, and orphan drug designations along with a rare pediatric disease priority review voucher.[3] The FDA granted the approval of Nulibry to Origin Biosciences, Inc., in February 2021.[3] It is the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of molybdenum cofactor deficiency type A.[3]

Society and culture

Legal status

On 21 July 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Nulibry, intended for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A.[11] The applicant for this medicinal product is Comharsa Life Sciences Ltd.[11] Fosdenopterin was approved for medical use in the European Union in September 2022.[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "Nulibry EPAR". European Medicines Agency (EMA). 18 July 2022. Archived from the original on 14 October 2022. Retrieved 14 October 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Nulibry- fosdenopterin hydrobromide injection, powder, for solution". DailyMed. Archived from the original on 20 June 2021. Retrieved 31 March 2021.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "FDA Approves First Treatment for Molybdenum Cofactor Deficiency Type A". U.S. Food and Drug Administration (FDA) (Press release). 26 February 2021. Archived from the original on 27 February 2021. Retrieved 26 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  4. ↑ "Fosdenopterin". SPS - Specialist Pharmacy Service. 8 January 2016. Archived from the original on 2 March 2022. Retrieved 31 October 2022.
  5. ↑ "Nulibry Prices, Coupons, Copay & Patient Assistance". Drugs.com. Archived from the original on 17 May 2021. Retrieved 31 October 2022.
  6. ↑ DrugBank DB16628 . Accessed 2021-03-05.
  7. ↑ Santamaria-Araujo JA, Fischer B, Otte T, Nimtz M, Mendel RR, Wray V, Schwarz G (April 2004). "The tetrahydropyranopterin structure of the sulfur-free and metal-free molybdenum cofactor precursor". The Journal of Biological Chemistry. 279 (16): 15994–9. doi:10.1074/jbc.M311815200. PMID 14761975.
  8. ↑ Schwarz G, Santamaria-Araujo JA, Wolf S, Lee HJ, Adham IM, Gröne HJ, et al. (June 2004). "Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli". Human Molecular Genetics. 13 (12): 1249–55. doi:10.1093/hmg/ddh136. PMID 15115759.
  9. ↑ Tedmanson S (5 November 2009). "Doctors risk untried drug to stop baby's brain dissolving". TimesOnline. Archived from the original on 22 June 2021. Retrieved 6 March 2021.{{cite news}}: CS1 maint: uses authors parameter (link)
  10. ↑ Schwahn BC, Van Spronsen FJ, Belaidi AA, Bowhay S, Christodoulou J, Derks TG, et al. (November 2015). "Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study". Lancet. 386 (10007): 1955–63. doi:10.1016/S0140-6736(15)00124-5. PMID 26343839. S2CID 21954888.
  11. ↑ 11.0 11.1 "Nulibry: Pending EC decision". European Medicines Agency. 22 July 2022. Archived from the original on 28 July 2022. Retrieved 30 July 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

External links

External sites:
Identifiers:
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