Zokinvy (lonafarnib)

Zokinvy (lonafarnib) is approved for use in certain types of genetic disorders such as:

• Hutchinson-Gilford progeria syndrome (HGPS) to lower the risk of death
• certain health problems called processing-deficient Progeroid Laminopathies (PLs)

Both HGPS and PLs are extremely rare and fatal genetic premature aging diseases. Zokinvy (lonafarnib) is not indicated for other Progeroid Syndromes or processing-proficient Progeroid Laminopathies. Based upon its mechanism of action, it is unlikely to be effective in these populations.

Definitions

"Body Surface Area" is a measure of the total surface area of the body used to calculate drug dosages.

"Genetic mutation" is a permanent alteration in the sequence, number, structure, or function of the unit of inheritance, also known as a gene.

"Heterozygous" describes a genetic disorder inherited from one parent.

"Homozygous" describes a rare genetic disorder inherited from both parents.

Medical Necessity Criteria for Initial Authorization

The Plan considers Zokinvy (lonafarnib) medically necessary when ALL of the following criteria are met:

1. Prescribed by or in consultation with a geneticist, metabolic disorder specialist, or progeria specialist; AND
2. The member meets ALL of the following:
   • Is 12 months of age or older; and
   • Has a body surface area (BSA) of 0.39 m2 or above; and
   • Has a confirmed diagnosis of ONE of the following:
     • Hutchinson-Gilford Progeria Syndrome (HGPS) with confirmatory mutational analysis showing G608G mutation in the lamin A gene; or
     • processing-deficient Progeroid Laminopathies with either:
       1. Heterozygous LMNA mutation with progerin-like protein accumulation;or
       2. Homozygous or compound heterozygous ZMPSTE24 mutations;
3. The member is NOT currently taking ANY of the following:
   • Strong or moderate CYP3A inhibitors or inducers; or
   • b. Midazolam; or
   • c.Lovastatin, simvastatin, or atorvastatin; AND
4. Is being prescribed within the manufacturer’s published dosing guidelines or falls within dosing guidelines found in a compendia of current literature; AND
5. Chart documentation and supporting laboratory test results are provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, Zokinvy (lonafarnib) will be approved for 6 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if BOTH of the following are met:

1. The member still meets the applicable initial criteria; AND
2. Recent chart documentation (within the last 6 months) shows the member has experienced a positive clinical response to therapy (e.g., weight gain rate ≥ 50% higher than the pre-therapy estimated rate, weight gain instead of pre-therapy estimated weight loss).

Experimental or Investigational / Not Medically Necessary:

Zokinvy (lonafarnib) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. Borthakur G, Kantarjian H, Daley G, et al. Pilot study of lonafarnib, a farnesyl transferase inhibitor, in patients with chronic myeloid leukemia in the chronic or accelerated phase that is resistant or refractory to imatinib therapy. Cancer. 2006;106(2):346-352. doi:10.1002/cncr.21590
2. Gordon LB, Kleinman ME, Massaro J, et al. Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 12 July 2016. 134(2):114-25.
3. Gordon LB, Shappell H, Massaro J, et al. Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients with Hutchinson-Gilford Progeria Syndrome. JAMA. 24 April 2018. 319(16):1687-1695.
4. Lonafarnib. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. 7 Jan 2021.
5. Wong NS, Morse MA. Lonafarnib for cancer and progeria.. Expert Opin Investig Drugs. July 2012. 21(7):1043-55.
6. Zokinvy (lonafarnib) [prescribing information]. Palo Alto, CA: Eiger BioPharmaceuticals Inc; November 2020.

Clinical Guideline Revision / History Information

Original Date: 03/11/2021
Reviewed/Revised: 12/01/2021, 03/17/2022, 12/08/2022, 12/14/2022