Lonafarnib

Lonafarnib, sold under the brand name Zokinvy, is a medication used to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in people one year of age and older.[2][3]

Lonafarnib
Clinical data
Trade namesZokinvy
Other namesSCH 66336
License data
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.204.509
Chemical and physical data
FormulaC27H31Br2ClN4O2
Molar mass638.83 g·mol−1
3D model (JSmol)

The most common side effects included nausea vomiting, diarrhea, infection, decreased appetite and fatigue.[2]

Lonafarnib was approved for medical use in the United States in November 2020.[2][4] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[5]

Medical uses

Lonafarnib is indicated to be used to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in people one year of age and older.[2][3]

Contraindications

Lonafarnib is contraindicated for co-administration with strong or moderate CYP3A inhibitors and inducers, as well as midazolam and certain cholesterol-lowering medications.[2]

History

Lonafarnib, a farnesyltransferase inhibitor, is an oral medication that helps prevent the buildup of defective progerin or progerin-like protein.[2] The effectiveness of lonafarnib for the treatment of Hutchinson-Gilford progeria syndrome was demonstrated in 62 patients from two single-arm trials (Trial 1/NCT00425607 and Trial 2/NCT00916747) that were compared to matched, untreated patients from a separate natural history study.[2][3] Compared to untreated patients, the lifespan of Hutchinson-Gilford progeria syndrome patients treated with lonafarnib increased by an average of three months through the first three years of treatment and by an average of 2.5 years through the maximum follow-up time of 11 years.[2] Lonafarnib's approval for the treatment of certain processing-deficient progeroid laminopathies that are very rare took into account similarities in the underlying genetic mechanism of disease and other available data.[2] The participants were from 34 countries around the world, including the United States.[3]

The U.S. Food and Drug Administration (FDA) granted the application for lonafarnib priority review, orphan drug, and breakthrough therapy designations.[2] In addition, the manufacturer received a rare pediatric disease priority review voucher.[2] The FDA granted the approval of Zokinvy to Eiger BioPharmaceuticals, Inc.[2]

Research

Lonafarnib is a farnesyltransferase inhibitor (FTI) that has been investigated in a human clinical trial as a treatment for progeria, which is an extremely rare genetic disorder in which symptoms resembling aspects of aging are manifested at a very early age.[6][7]

Lonafarnib is a synthetic tricyclic halogenated carboxamide with antineoplastic properties.[8] As such, it is used primarily for cancer treatment. For those with progeria, research has shown that the drug reduces the prevalence of stroke and transient ischemic attack, and the prevalence and frequency of headaches while taking the medication.[9] A phase II clinical trial was completed in 2012, which showed that a cocktail of drugs that included lonafarnib and two other drugs met clinical efficacy endpoints that improved the height and diminished the rigidity of the bones of progeria patients.

References
  1. "Lonafarnib capsule". DailyMed. Retrieved 17 January 2021.
  2. "FDA Approves First Treatment for Hutchinson-Gilford Progeria Syndrome and Some Progeroid Laminopathies". U.S. Food and Drug Administration (FDA) (Press release). 20 November 2020. Retrieved 20 November 2020. This article incorporates text from this source, which is in the public domain.
  3. "Drug Trials Snapshots: Zokinvy". U.S. Food and Drug Administration. 20 November 2020. Retrieved 11 December 2020. This article incorporates text from this source, which is in the public domain.
  4. "Drug Approval Package: Zokinvy". U.S. Food and Drug Administration (FDA). 18 December 2020. Retrieved 17 January 2021.
  5. "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021. This article incorporates text from this source, which is in the public domain.
  6. Liu G, Marrinan CH, Taylor SA, Black S, Basso AD, Kirschmeier P, et al. (September 2007). "Enhancement of the antitumor activity of tamoxifen and anastrozole by the farnesyltransferase inhibitor lonafarnib (SCH66336)". Anti-Cancer Drugs. 18 (8): 923–31. doi:10.1097/CAD.0b013e3280c1416e (inactive 2021-01-10). PMID 17667598.CS1 maint: DOI inactive as of January 2021 (link)
  7. "The FTI Drug Lonafarnib", Progeria Research Foundation. Accessed October 3, 2017.
  8. "Lonafarnib". NCI Drug Dictionary. National Cancer Institute. 2011-02-02.
  9. Ullrich NJ, Kieran MW, Miller DT, Gordon LB, Cho YJ, Silvera VM, et al. (July 2013). "Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment". Neurology. 81 (5): 427–30. doi:10.1212/WNL.0b013e31829d85c0. PMC 3776537. PMID 23897869.
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