Lonafarnib

Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.

• ZOKINVY is indicated in patients 12 months of age and older with a body surface area (BSA) of 0.39 m 2 and above: To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS) For the treatment of processing-deficient Progeroid Laminopathies with either: Heterozygous LMNA mutation with progerin-like protein accumulation Homozygous or compound heterozygous ZMPSTE24 mutations ZOKINVY is a farnesyltransferase inhibitor indicated in patients 12 months of age and older with a body surface area of 0.39 m 2 and above: ( 1 ) To reduce risk of mortality in Hutchinson-Gilford Progeria Syndrome. For treatment of processing-deficient Progeroid Laminopathies with either: Heterozygous LMNA mutation with progerin-like protein accumulation.

• ZOKINVY is contraindicated in patients taking: Strong CYP3A inhibitors [see Drug Interactions ( 7.1 )] Strong or moderate CYP3A inducers [see Drug Interactions ( 7.1 )] Midazolam [see Drug Interactions ( 7.2 )] Lovastatin, simvastatin, or atorvastatin [see Drug Interactions ( 7.2 )] Strong CYP3A inhibitors. ( 4 ) Strong or moderate CYP3A inducers.contraindicated

Start at 115 mg/m 2 twice daily with morning and evening meals. ( 2.1 ) After 4 months, increase to 150 mg/m 2 twice daily. ( 2.1 ) Round all total daily doses to nearest 25 mg increment. ( 2.1 ) See full prescribing information for dosage modifications due to adverse reactions. ( 2.2 ) See full prescribing information for preparation and administration instructions. ( 2.4 ) 2.1 Recommended Dosage The starting dosage of ZOKINVY for patients with a BSA of 0.39 m 2 and above is 115 mg/m 2 twice daily with morning and evening meals (see Table 1 ) to reduce the risk of gastrointestinal adverse reactions [see Adverse Reactions ( 6.1 )] . An appropriate dosage strength of ZOKINVY is not available for patients with a BSA of less than 0.39 m 2 [see Indications and Usage ( 1 )] . After 4 months of treatment, increase the dosage to 150 mg/m 2 twice daily with morning and evening meals (see Table 2 ). Round all total daily dosages to the nearest 25 mg increment (see Table 1 and Table 2 ). If a dose is missed, take the dose as soon as possible with food, up to 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next scheduled dose, skip the missed dose, and resume taking ZOKINVY at the next scheduled dose. Table 1 provides the BSA-based dosage recommendations for the starting dosage of 115 mg/m 2 twice daily.

QTc Interval Prolongation : Increases the QTc interval. Avoid use in patients with symptomatic bradycardia, hypokalemia, or hypomagnesemia, and in combination with other drugs known to prolong the QTc interval. ( 5.1 ) Risk of Reduced Efficacy or Adverse Reactions Due to Drug Interactions : Prior to and during treatment, consider potential for drug interactions and review concomitant medications; monitor for adverse reactions. ( 5.2 , 7 ) Laboratory Abnormalities: Monitor for changes in electrolytes, complete blood counts, and liver enzymes. ( 5.3 ) Nephrotoxicity: Caused nephrotoxicity in rats. Monitor renal function at regular intervals. ( 5.4 , 13.2 ) Retinal Toxicity: Caused rod-dependent, low-light vision decline in monkeys. Perform ophthalmological evaluation at regular intervals and at the onset of any new visual changes. ( 5.5 , 13.2 ) Impaired Fertility: Caused impaired fertility in female rats, impaired fertility and testicular toxicity in male rats, and toxicity in the male reproductive tract in monkeys. Advise females and males of reproductive potential of the animal fertility findings. ( 5.6 , 13.1 , 13.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 QTc Interval Prolongation ZOKINVY prolongs the QTc interval. Prolongation of the QTc interval increases the risk of Torsade de pointes, other serious arrhythmias, and sudden death.

The most common adverse reactions (incidence ≥25%) are vomiting, diarrhea, infection, nausea, decreased appetite, fatigue, upper respiratory tract infection, abdominal pain, musculoskeletal pain, electrolyte abnormalities, decreased weight, headache, myelosuppression, increased aspartate aminotransferase, decreased blood bicarbonate, cough, hypertension, and increased alanine aminotransferase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sentynl Therapeutics, Inc. at 1-888-507-5206 or zokinvysafety@sentynl.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 84 subjects were treated with at least one dose of ZOKINVY with or without additional therapy, of which 8 were treated at a dosage of at least 115 mg/m 2 twice daily for greater than or equal to 10 years. The safety profile of ZOKINVY is based on 128 patient-years of treatment exposure (62 patients with HGPS and 1 patient with processing-deficient Progeroid Laminopathy with LMNA heterozygous mutation) and pooled results from two Phase 2 open-label, single-arm trials (n=63: 28 patients from Study 1 and 35 treatment naïve patients from Study 2).

8.1 Pregnancy Risk Summary Based on findings from animal studies, ZOKINVY can cause embryofetal harm when administered to a pregnant woman. There are no human data on ZOKINVY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the risk to a fetus. In animal reproduction studies, oral administration of lonafarnib to pregnant rats during organogenesis produced embryo-fetal toxicity at exposures that were 1.2-times the human exposure at the recommended dose of 150 mg/m 2 twice daily. In pregnant rabbits, oral administration of lonafarnib during organogenesis produced skeletal malformations and variations at exposures lower than the human exposure at 150 mg/m 2 twice daily, and maternal toxicity at 26 times the human exposure at 150 mg/m 2 twice daily (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Metabolism

The pharmacokinetics of lonafarnib at steady state in patients with HGPS following oral administration of lonafarnib twice daily with food are summarized in Table 7 . Table 7: Summary of Pharmacokinetic Parameters of Lonafarnib at Steady State after Oral Administration Twice Daily to Patients with HGPS Lonafarnib Dose Median (range) t max (hr) Mean (SD) C max (ng/mL) Mean (SD) AUC 0-8hr (ng*hr/mL) Mean (SD) AUC tau (ng*hr/mL) 115 mg/m 2 N 23 23 23 15 Results 2 (0, 6) 1777 (1083) 9869 (6327) 12365 (9135) 150 mg/m 2 N 18 18 18 8 Results 4 (0, 12) 2695 (1090) 16020 (4978) 19539 (6434) Absorption …

• Nov 20, 2020NDANDA213969Sentynl Theraps Inc

1. 1Product Dose Omission Issue2330%
2. 2Diarrhoea1621%
3. 3Vomiting1216%
4. 4Death45.3%
5. 5Headache45.3%
6. 6Abdominal Pain Upper33.9%
7. 7Asthenia33.9%
8. 8Cardiac Operation33.9%
9. 9Fatigue33.9%
10. 10Malaise33.9%
11. 11Nausea33.9%
12. 12Product Supply Issue33.9%
13. 13Abdominal Discomfort22.6%
14. 14Anaemia22.6%
15. 15Aortic Stenosis22.6%

The 10 most recently updated of 39 ClinicalTrials.gov registrations naming Lonafarnib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Once Daily Dosing of Lonafarnib Co-administered With Ritonavir for Treatment of Chronic Hepatitis D Virus Infection
  Completed · Phase 3 · Interventional · 10 enrolled · Soroka University Medical Center
  NCT05229991updated 2026-04-30
• Phase I/II Trial of Everolimus in Combination With Lonafarnib in Progeria
  Enrolling by invitation · Phase 1 · Phase 2 · Interventional · 80 enrolled · Boston Children's Hospital
  NCT02579044updated 2026-04-02
• Study to Determine Optimal Dose and Evaluate Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS)
  Active not recruiting · Phase 2 · Interventional · 10 enrolled · PRG Science & Technology Co., Ltd.
  NCT06775041updated 2026-02-09
• Lonafarnib and Temozolomide in Treating Patients with Glioblastoma Multiforme That is Recurrent or Did Not Respond to Previous Treatment with Temozolomide
  Active not recruiting · Phase 1 · Interventional · 34 enrolled · M.D. Anderson Cancer Center
  NCT00102648updated 2024-10-17
• Peginterferon Lambda and Lonafarnib Boosted With Ritonavir 48-Week Combination Therapy for Delta Hepatitis
  Withdrawn · Phase 2 · Interventional · 0 enrolled · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  NCT05953545updated 2024-05-23
• Titrating-Dose of Lonafarnib in Combination With Ritonavir
  Completed · Phase 2 · Interventional · 15 enrolled · Eiger BioPharmaceuticals
  NCT02527707updated 2023-06-22
• Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a
  Completed · Phase 3 · Interventional · 407 enrolled · Eiger BioPharmaceuticals
  NCT03719313updated 2023-04-14
• Lonafarnib Boosted With Ritonavir With and Without Peginterferon Alfa-2a (PEG IFN-a) in HDV (LOWR-2)
  Completed · Phase 2 · Interventional · 55 enrolled · Eiger BioPharmaceuticals
  NCT02430194updated 2023-03-03
• Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
  Unknown · Phase 2 · Interventional · 85 enrolled · Boston Children's Hospital
  NCT00916747updated 2023-02-27
• Lonafarnib With and Without Ritonavir in HDV (LOWR-1)
  Completed · Phase 2 · Interventional · 21 enrolled · Eiger BioPharmaceuticals
  NCT02430181updated 2022-11-29

Frequently asked questions

How does Lonafarnib work?

Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.

What is Lonafarnib used for?

According to FDA labeling, Lonafarnib carries indications including: ZOKINVY is indicated in patients 12 months of age and older with a body surface area (BSA) of 0.39 m 2 and above: To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS) For the treatment of processing-deficient Progeroid Laminopathies with either: Heterozygous LMNA mutation with progerin-like protein accumulation Homozygous or compound heterozygous ZMPSTE24 mutations ZOKINVY is a farnesyltransferase inhibitor indicated in patients 12 months of age and older with a body surface area of 0.39 m 2 and above: ( 1 ) To reduce risk of mortality in Hutchinson-Gilford Progeria Syndrome. For treatment of processing-deficient Progeroid Laminopathies with either: Heterozygous LMNA mutation with progerin-like protein accumulation.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lonafarnib?

Lonafarnib is classified as Various alimentary tract and metabolism products, Farnesyltransferase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2C19 Inhibitors, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 3A Inhibitors, Farnesyltransferase Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, P-Glycoprotein Inhibitors.

What are the brand names for Lonafarnib?

Lonafarnib is marketed under brand names including Zokinvy.

What are the contraindications for Lonafarnib?

Lonafarnib labeling lists contraindications including: ZOKINVY is contraindicated in patients taking: Strong CYP3A inhibitors [see Drug Interactions ( 7.1 )] Strong or moderate CYP3A inducers [see Drug Interactions ( 7.1 )] Midazolam [see Drug Interactions ( 7.2 )] Lovastatin, simvastatin, or atorvastatin [see Drug Interactions ( 7.2 )] Strong CYP3A inhibitors. ( 4 ) Strong or moderate CYP3A inducers.. Always consult the full prescribing information and a clinician.