Patisiran

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Structural formula
(5'-3 ') G- U -AA- C - C -AAGAG- U -A- U - U - C - C -A- U -dT-dT
(3'-5') dT-dT-CA - U -UGGUUCUCA- U -AAGGUA


G = guanosine -, U = uridine -, U = O -methyl-uridine-, A = adenosine- , C = cytidine- , C = O -methyl-cytidine-, dT = thymidine residues in a nucleic acid double strand (5 '-3') // (3'-5 '): direction

General
Non-proprietary name Patisiran
other names

RNA duplex from guanylyl- (3 '→ 5') - 2'- O -methyluridylyl- (3 '→ 5') - adenylyl- (3 '→ 5') - adenylyl- (3 '→ 5') - 2 '- O -methylcytidylyl- (3' → 5 ') - 2'- O -methylcytidylyl- (3' → 5 ') - adenylyl- (3' → 5 ') - adenylyl- (3' → 5 ') - guanylyl - (3 '→ 5') - adenylyl (3 '→ 5') - guanylyl (3 '→ 5') - 2'- O -methyluridylyl (3 '→ 5') - adenylyl (3 '→ 5 ') -2'- O -methyluridylyl- (3' → 5 ') -2'- O -methyluridylyl- (3' → 5 ') -2'- O -methylcytidylyl- (3' → 5 ') -2 '- O -methylcytidylyl- (3' → 5 ') - adenylyl- (3' → 5 ') - 2'- O -methyluridylyl- (3' → 5 ') - thymidylyl- (3' → 5 ') - thymidine and
thymidylyl (5 '→ 3') - thymidylyl (5 '→ 3') - cytidylyl (5 '→ 3') - adenylyl (5 '→ 3') - 2'- O -methyluridylyl- (5 '→ 3') - uridylyl (5 '→ 3') - guanylyl (5 '→ 3') - guanylyl (5 '→ 3') - uridylyl (5 '→ 3') - uridylyl (5 '→ 3') - cytidylyl (5 '→ 3') - uridylyl (5 '→ 3') - cytidylyl (5 '→ 3') - adenylyl (5 '→ 3') - 2'- O -methyluridylyl- (5 '→ 3') - adenylyl- (5 '→ 3') - adenylyl- (5 '→ 3') - guanylyl- (5 '→ 3') - guanylyl- (5 '→ 3') -uridylyl- (5 '→ 3') - adenosine

Molecular formula C 412 H 480 N 148 O 290 P 40
External identifiers / databases
CAS number 1420706-45-1
Wikidata Q40441442
Drug information
Drug class

RNAi therapeutic

Mechanism of action

Transthyretin protein synthesis inhibitor

properties
Molar mass 13384.11 g mol −1
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Patisiran ( Onpattro , manufacturer Alnylam Pharmaceuticals ) is a drug used to treat hereditary ATTR amyloidosis (hATTR). It is a representative of a comparatively new class of active ingredients based on RNA interference (RNAi or RNA silencing) or gene silencing . In the life sciences, RNA interference has established itself as an experimental possibility for the temporary shutdown of genes (“ gene knockdown ”). This class of substances is referred to as RNAi therapeutics .

Patisiran is a siRNA and binds to the 3 ′ end of the hATTR mRNA . There is a catalytic breakdown of the TTR mRNA in the liver and, as a result, a reduction in the TTR protein in the serum. The root word -siran the generic name of the drug is "small interfering RNA".

In the United States Patisiran was from the August 10, 2018 FDA approved, followed on 27 August 2018 the European Union approval for the treatment of hATTR amyloidosis in adult patients with polyneuropathy of stages 1 or 2 by the European Commission . Patisiran was assessed as part of an expedited process as there are few treatment options. It is the third drug for the treatment of hATTR amyloidosis after Tafamidis ( Vyndaqel ) and Inotersen ( Tegsedi ), which was approved in July 2018 .

Studies

  • APOLLO (Phase 3): The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR) -Mediated Amyloidosis.
  • OLE (Phase 2): The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR) -Mediated Amyloidosis in Patients Who Have Already Been Treated With ALN-TTR02 (Patisiran)

literature

  • Ole B. Suhr, Teresa Coelho, Juan Buades, Jean Pouget, Isabel Conceicao, John Berk, Hartmut Schmidt, Márcia Waddington-Cruz, Josep M. Campistol, Brian R. Bettencourt, Akshay Vaishnaw, Jared Gollob and David Adams: Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study . In: Orphanet Journal of Rare Diseases . tape 10 , 2015, p. 109 , doi : 10.1186 / s13023-015-0326-6 , PMID 26338094 .

Individual evidence

  1. ^ A b World Health Organization: International Nonproprietary Names for Pharmaceutical Substances (INN) - Recommended International Nonproprietary Names: List 71 . In: WHO Drug Information . 28, No. 1, 2014.
  2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  3. ↑ a b The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR) -Mediated Amyloidosis , clinicaltrials.gov, accessed July 24, 2017.
  4. ↑ a b The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR) -Mediated Amyloidosis in Patients Who Have Already Been Treated With ALN-TTR02 (Patisiran) , clinicaltrials.gov, accessed on 24 July 2017.
  5. ↑ OUR PIPELINE ( Memento from August 7, 2017 in the Internet Archive ), website of the manufacturer Alnylam, accessed on July 24, 2017.
  6. ↑ Ken Garber: Alnylam's RNAi therapy targets amyloid disease. In: Nature Biotechnology. 33, 2015, p. 577, doi: 10.1038 / nbt0615-577a .
  7. ↑ WHO: Addendum to "The use of stems in the selection of International Nonproprietary names (INN) for pharmaceutical substances" - WHO / EMP / RHT / TSN / 2013.1 , INN Working Document 17.418 of May 25, 2017.
  8. ↑ FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease
  9. ↑ Onpattro | Authorization details. European Medicines Agency, accessed February 2, 2019 .
  10. ↑ Summary of Product Characteristics. EMA, accessed February 2, 2019 .
  11. ↑ European Medicines Agency: Vyndaqel. Retrieved February 25, 2020 .
  12. ↑ European Medicines Agency: Tegsedi . Retrieved February 25, 2020
  13. ↑ Data Monitoring Committee Recommends Continuation of APOLLO Phase 3 Clinical Trial of Patisiran for Hereditary ATTR Amyloidosis with Polyneuropathy (hATTR-PN) ( Memento of October 9, 2017 in the Internet Archive ), PM Alnylam of October 10, 2017, accessed on July 24 2017
  14. ↑ Alnylam Reports New Results from Investigational RNAi Therapeutic Programs for Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy (hATTR-PN) and Cardiomyopathy (hATTR-CM) ( Memento from September 21, 2017 in the Internet Archive ), PM Alnylam from July 1, 2016, accessed on July 24, 2017.
  15. ↑ Alnylam Completes Enrollment in APOLLO Phase 3 Study with Patisiran, an Investigational RNAi Therapeutic for Patients with Transthyretin (TTR) -Mediated Amyloidosis (ATTR Amyloidosis) ( Memento from September 21, 2017 in the Internet Archive ), PM Alnylam from February 1, 2016, accessed on July 24, 2017.
  16. ↑ Alnylam and Sanofi Report Positive Topline Results from APOLLO Phase 3 Study of Patisiran in Hereditary ATTR (hATTR) Amyloidosis Patients with Polyneuropathy ( Memento of September 21, 2017 in the Internet Archive ), PM Alnylam of September 20, 2017, accessed on October 8 2017.
  17. ↑ Alnylam Reports New Clinical Results from the APOLLO Phase 3 Study of Patisiran at the American Academy of Neurology 2018 Annual Meeting , PM Alnylam, April 24, 2018, accessed May 20, 2018.
  18. ↑ Alnylam Reports New Results from Investigational RNAi Therapeutic Programs for Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy (hATTR-PN) and Cardiomyopathy (hATTR-CM) ( Memento from September 21, 2017 in the Internet Archive ), PM Alnylam from July 1, 2016, accessed on July 24, 2017.
  19. ↑ Alnylam Reports Complete 18-Month Data from Ongoing Phase 2 Open-Label Extension Study of Patisiran, an Investigational RNAi Therapeutic Targeting Transthyretin for the Treatment of Hereditary ATTR Amyloidosis with Polyneuropathy (hATTR-PN) ( Memento from August 6, 2017 in the Internet Archive ), PM Alnylam, April 20, 2016, accessed July 24, 2017.
  20. ↑ Alnylam Reports Final 24-Month Results from Phase 2 Open-Label Extension Study of Patisiran, an Investigational RNAi Therapeutic in Development for the Treatment of Hereditary ATTR (hATTR) Amyloidosis ( Memento June 6, 2017 in the Internet Archive ), PM Alnylam from April 26, 2017. Retrieved July 24, 2017.
  21. ↑ Alnylam Reports Complete 18-Month Data from Ongoing Phase 2 Open-Label Extension Study of Patisiran, an Investigational RNAi Therapeutic Targeting Transthyretin for the Treatment of Hereditary ATTR Amyloidosis with Polyneuropathy (hATTR-PN) ( Memento from August 6, 2017 in the Internet Archive ), PM Alnylam, April 20, 2016, accessed July 24, 2017.
  22. ↑ Alnylam Completes Enrollment in APOLLO Phase 3 Study with Patisiran, an Investigational RNAi Therapeutic for Patients with Transthyretin (TTR) -Mediated Amyloidosis (ATTR Amyloidosis) ( Memento from September 21, 2017 in the Internet Archive ), PM Alnylam from February 1, 2016, accessed on July 24, 2017.