The Food and Drug Administration (FDA) has approved ZokinvyTM (lonafarnib; Eiger BioPharmaceuticals) in patients 12 months of age and older with a body surface area of 0.39m2 and above to reduce the risk of mortality in Hutchinson-Gilford progeria syndrome (HGPS) and for the treatment of processing-deficient progeroid laminopathies with either (1) heterozygous LMNA mutation with progerin-like protein accumulation; (2) homozygous or compound heterozygous ZMPSTE24 mutations.
Zokinvy works by preventing farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane. The approval was based on data from an Observational Cohort Survival Study, which retrospectively compared survival data from two phase 2 studies (NCT00425607 and NCT00916747) in 62 patients with HGPS to those from a natural history cohort (N=81).
Results showed that treatment with Zokinvy reduced the incidence of mortality by 60% (hazard ratio [HR] 0.40; 95% CI, 0.21-0.77; P =.0064). The lifespan of HGPS patients treated with Zokinvy increased by an average of 3 months through the first 3 years of follow-up and 2.5 years through the last follow-up time (11 years) compared with untreated patients.
As for safety, the most common adverse reactions (incidence greater than or equal to 25%) reported with Zokinvy included vomiting, diarrhea, infections, nausea, decreased appetite, fatigue, upper respiratory tract infection, abdominal pain, musculoskeletal pain, electrolyte abnormalities, decreased weight, headache, myelosuppression, increased AST/ALT, decreased blood bicarbonate, cough, and hypertension.
Zokinvy is contraindicated with concomitant use of strong or moderate CYP3A inhibitors or inducers, midazolam, lovastatin, simvastatin or atorvastatin. Additionally, coadministration with other drugs (CYP2C9 inhibitors, CYP3A substrates, loperamide, CYP2C19 substrates, P-gp substrates) may result in clinically significant interactions that may reduce the efficacy of Zokinvy and increase the risk of adverse reactions from Zokinvy or the coadministered drug.
Zokinvy will be supplied as 50mg and 75mg strength capsules and is expected to be available January 2021. For patients unable to swallow, the capsule contents can be mixed with Ora Blend SF®, Ora-Plus®, orange juice, or applesauce.
For more information visit zokinvy.com.
- FDA approves first treatment for Hutchinson-Gilford Progeria Syndrome and some progeroid laminopathies. [press release]. Silver Spring, MD: US Food and Drug Administration; November 20, 2020.
- Eiger BioPharmaceuticals announces FDA approval of Zokinvy™ (lonafarnib): the first treatment for Hutchinson-Gilford Progeria Syndrome and processing-deficient progeroid laminopathies. [press release]. Palo Alto, CA: Eiger BioPharmaceuticals; November 20, 2020.
- ZokinvyTM [package insert]. Palo Alto, CA: Eiger BioPharmaceuticals; 2020.