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About
Zokinvy®

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Zokinvy adds years to the lives of young people with progeria or processing-deficient progeroid laminopathies (PDPL), empowering them to do more.1

At least 75% of patients in the United States already have substantial experience taking Zokinvy through Boston Children’s Hospital and/or the Eiger Managed Access Program, with nearly 50% of the patients taking Zokinvy in the 2 clinical studies on treatment for at least 5 years, and nearly 10% for more than 10 years.1,2

The world’s only disease-modifying treatment for progeria and PDPL3

Zokinvy is a farnesyltransferase inhibitor that prevents the accumulation of cellular progerin and progerin-like proteins. For the very first time, you can help enable patients to live longer lives.1

By inhibiting farnesylation, Zokinvy targets a key step in the pathophysiology of progeria and PDPL.1

Image Normal cell2

Lamin A, a normal LMNA protein product, is critical to many cellular functions.3

Image Progeria cell2

Left untreated, farnesylated protein will incorporate into the inner nuclear membranes of cells.3,4

Image Progeria cell after treatment with Zokinvy2

Zokinvy inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.1

Photos courtesy of The Progeria Research Foundation
Zokinvy prevents the accumulation of progerin and progerin-like proteins, resulting in restoration of nuclear morphology.1

Zokinvy reduces the risk of mortality, adding years to patients’ lives1

The efficacy of ZOKINVY was determined based on results from the Observational Cohort Survival Study, which retrospectively compared survival data from two phase 2 studies in patients with progeria with those from an untreated cohort.1

  • The primary end point was all-cause mortality compared with historical control patient data matched by age at start of treatment, gender, and continent.1,2
  • At last follow-up, treatment with Zokinvy resulted in increased mean survival of 2.5 years and a 60% reduction in risk of mortality. 1
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At a 3-year follow-up, there was a 70% reduction in risk of mortality. At last follow-up, the reduction was 60%.1

  • Study 1

    Phase 2, open-label, single-arm trial that evaluated the efficacy of Zokinvy in 28 patients1:

  • Among the 28 patients, 27 had progeria and 1 had PDPL.
  • Patients received Zokinvy for 24 to 30 months.
  • Patients initiated treatment with Zokinvy at 115 mg/m² twice daily.
  • After 4 months of treatment, patients who tolerated treatment increased dosage to 150 mg/m² twice daily.
  • Among the 28 patients treated, 27 patients with progeria were included in the survival assessment.
  • The median age at treatment initiation for the 27 patients was 7.5 years (range, 3 to 16 years).
  • Body weight range was 6.6 to 17.6 kg and body surface area (BSA) range was 0.38 to 0.7 m².
  • Study 2

    Another phase 2, open-label, single-arm trial, consisting of 2 study periods, in 26 patients1:

  • In the first period, patients received Zokinvy with additional therapies for about 5 years.
  • In the second period, patients received Zokinvy 150 mg/m² twice daily for up to 3 years.
  • An additional 35 treatment-naïve patients with progeria enrolled in the second period of Study 2.
  • The median age was 6 years (range, 2 to 17 years).
  • Body weight range was 6.7 to 22.0 kg and BSA range was 0.42 to 0.90 m².
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    Although ProLon1 (Study 1) had a lower starting dosage than ProLon2 (Study 2), adverse reactions were reduced in both studies over time.1

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    Only 4 patients (or 6.3%) withdrew from the studies due to nausea and vomiting.1

Zokinvy improves cardiovascular outcomes in patients with progeria or PDPL2,3,5

In clinical studies, Zokinvy was shown to reduce2,3,5

  • Carotid artery echodensity, suggestive of a reduction in vascular wall inflammation and fibrosis
  • Pulse wave velocity, a measure of arterial stiffness

Zokinvy has a well-studied safety profile1

In clinical studies, the most commonly reported adverse reactions were gastrointestinal (such as vomiting, diarrhea, and nausea).1

  • The overall safety profile of Zokinvy in patients with progeria or PDPL is based on 414 patient-years of treatment exposure.
  • More than 90 young people participated in clinical studies of Zokinvy; only 4 patients (6%) discontinued due to adverse reactions.2
  • ~46.4% of patients with progeria have received Zokinvy for ≥5 years.1,2
  • ~9.5% of patients with progeria have received Zokinvy for ≥10 years.1,2
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  • a Adverse reactions greater than or equal to a lower threshold of 5% are provided for greater context.
  • b One patient had progeroid laminopathy with LMNA heterozygous mutation.
  • c Abdominal pain includes stomach pain and abdominal pain.
  • d Infection includes abdominal infection, candidiasis, chicken pox, Clostridium difficile colitis, colitis, croup, dengue fever, flu syndrome, flu-like symptoms, fungal infection, gastroenteritis, gastrointestinal infection, Helicobacter pylori infection, infection, infection viral, influenza, nail infection, otitis media, parotitis, perirectal abscess, pneumonia, small intestine infection, submandibular lymphadenitis, tonsillitis, and viral infection.
  • e Upper respiratory infection includes bronchial infection, bronchitis, sinus infection, and upper respiratory infection.
  • f Electrolyte abnormalities includes hypermagnesemia, hypokalemia, hyperkalemia, hyponatremia, hypercalcemia, hypokalemia, hyperphosphatemia, hypocalcemia, and hypernatremia.
  • g Myelosuppression includes absolute neutrophil count decreased, low total white blood cells, lymphopenia, decreased hemoglobin, and hematocrit low.
  • h Musculoskeletal pain includes arthritis, back pain, bone pain, foot pain, intercostal pain, joint pain, knee pain, leg pain, musculoskeletal pain, pain in ankle/extremity/ fingers/hip/leg/limb/lower limbs/left arm, shoulder pain, unilateral leg pain. Excluded is musculoskeletal pain for abdomen.
  • i Cerebral ischemia includes central nervous system hemorrhage and ischemia cerebrovascular.
  • j Ocular changes includes visual acuity change, corneal clouding, conjunctivitis, watering eyes, keratitis.
Although ProLon1 (Study 1) had a lower starting dosage than ProLon2 (Study 2), adverse reactions were reduced in both studies over time2

Analysis of clinical data from both studies indicates that2

  • After the first 4 months of treatment, adverse reactions decreased by 70%-80%
  • 94% of patients treated with Zokinvy continued beyond the initial 4-month period
  • The longest treatment duration is ≥10 years
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Adverse reactions can be managed with supportive care2

Adverse reactions, including gastrointestinal issues, can be successfully managed with supportive care and generally decrease over time.2

  • Prophylactic administration of loperamide is allowed.1
    • When Zokinvy is coadministered with loperamide, do not exceed loperamide 1 mg once daily when first coadministered.1
    • Slowly increase loperamide dosage with caution in accordance with its approved product labeling.1
Get More Dosing Information

During the 4-month period after dosage increase 150 mg/m2, adverse events may be reduced by reverting to the starting dosage of 115 mg/m2 twice daily of Zokinvy.1

IMPORTANT SAFETY INFORMATION

Contraindications

ZOKINVY is contraindicated in patients taking:

  • Strong or moderate CYP3A inhibitors or inducers
  • Midazolam
  • Lovastatin, simvastatin, and atorvastatin

Warnings and Precautions

Laboratory Abnormalities

Some patients treated with ZOKINVY developed laboratory abnormalities. These included:

  • Electrolyte abnormalities (43%), such as hyperkalemia, hypokalemia, hyponatremia, or hypercalcemia
  • Myelosuppression (35%), such as reductions in absolute neutrophil count, white blood cell counts, lymphopenia, hemoglobin, or hematocrit
  • Increased liver enzymes, such as aspartate aminotransferase (35%), or alanine aminotransferase (27%)

These laboratory abnormalities often improved while continuing ZOKINVY, but it is not possible to exclude ZOKINVY as a cause of the abnormalities. Periodically monitor electrolytes, complete blood counts, and liver enzymes, and manage abnormalities accordingly.

Nephrotoxicity
  • Lonafarnib caused nephrotoxicity in rats at plasma drug exposures approximately equal to that achieved with the human dose. Monitor renal function at regular intervals during ZOKINVY therapy.
Retinal Toxicity
  • Lonafarnib caused rod-dependent, low-light vision decline in monkeys at plasma drug exposures similar to that achieved with the human dose. Perform ophthalmological evaluation at regular intervals and at the onset of any new visual changes during ZOKINVY therapy.
Impaired Fertility
  • Based on findings in rats Zokinvy may reduce fertility. Advise males and females of reproducitve potential of the animal findings and that the impact on pubertal development and the potential for impaired fertility with Zonkivy have not been adequately evaluated.
Adverse Reactions
  • The most common adverse reactions were vomiting (90%), diarrhea (81%), infection (78%), nausea (56%), decreased appetite (53%), fatigue (51%), upper respiratory tract infection (51%), abdominal pain (48%), musculoskeletal pain (48%), electrolyte abnormalities (43%), headache (37%), decreased weight (37%), increased aspartate aminotransferase (35%), myelosuppression (35%), cough (33%), decreased blood bicarbonate (33%), hypertension (29%), and increased alanine aminotransferase (27%).
Gastrointestinal Adverse Reactions
  • Gastrointestinal adverse reactions were the most frequently reported adverse reactions. Of the 57 patients (90%) that experienced vomiting, 30 (53%) patients had mild vomiting, 26 (46%) patients had moderate vomiting, and 1 (2%) patient had severe vomiting.
  • Of the 35 patients (56%) that experienced nausea, 34 (97%) patients had mild nausea and 1 (3%) patient had moderate nausea.
  • Of the 51 patients (81%) that experienced diarrhea, the majority of patients (92%) experienced mild or moderate diarrhea; 38 (75%) patients reported mild diarrhea and 9 (18%) patients reported moderate diarrhea. Four (8%) patients reported severe diarrhea.
  • Loss of fluids and dehydration can be severe, leading to hospitalization. As a result, patients should receive therapy for diarrhea at the earliest signs in order to avoid possible severe complications.
Alanine Aminotransferase and Aspartate Aminotransferase Elevations
  • Increased alanine aminotransferase was commonly reported (17 [27%] patients). Of the 17 patients with increased alanine aminotransferase, 14 (82%) patients had mild increases, 1 (6%) patient had moderate increases, and 2 (12%) patients had severe increases.
  • Increased aspartate aminotransferase was also commonly reported (22 [35%] patients). Of the 22 patients with increased aspartate aminotransferase, 21 (95%) patients had mild increases and 1 (5%) patient had a severe increase.
Hypertension
  • Increases in blood pressure have been documented in patients treated with ZOKINVY. In clinical trials the incidence of hypertension was 8.1%.
Drug Interactions
  • Strong or moderate CYP3A inhibitors
    • ZOKINVY administration with strong or moderate CYP3A inhibitors, including herbal supplements can increase exposures of ZOKINVY resulting in risk of clinically significant adverse events.
      • Do not mix the contents of ZOKINVY with any food or juice containing grapefruit or Seville oranges.
  • Weak CYP3A inhibitors
    • Avoid coadmistration of Zokinvy with weak CYP3A inhibitors. If coadministration is unavoidable, reduce ZOKINVY dosage. Resume previous dosage 14 days after discontinuing the weak CYP3A inhibitor. Closely monitor patients for arrhythmias and events such as syncope and heart palpitations.
  • Strong or moderate CYP3A inducers
    • ZOKINVY administration with CYP3A inducers, including herbal supplements, can decrease exposure of ZOKINVY, which may impact efficacy.
  • CYP2C9 Inhibitors
    • Avoid coadministration of Zokinvy with CYP2C9 inhibitors. If coadminstration is unavoidable, closely monitor patients for arrhythmias and events such as syncope and heart palpitations because the effect of increased Zokinvy exposures on the QT interval is unknown.
  • Certain CYP3A substrates
    • When ZOKINVY is coadministered with certain CYP3A substrates where minimal concentration changes may lead to serious or life-threatening toxicities, monitor for adverse reactions and reduce the dosage of the CYP3A substrate in accordance with its approved product labeling.
  • Loperamide
    • Lonafarnib is a weak inhibitor of P-gp and strong inhibitor of CYP3A. Do not exceed loperamide 1 mg once daily when first coadministered with ZOKINVY. Slowly increase loperamide dosage with caution as needed to treat diarrhea in accordance with its approved product labeling.
  • CYP2C19 substrates
    • Lonafarnib is a moderate CYP2C19 inhibitor. Avoid coadministration of ZOKINVY with CYP2C19 substrates. If coadministration is unavoidable, monitor for adverse reactions and reduce the dosage of the CYP2C19 substrate in accordance with its approved product labeling.

Use in Specific Populations

Patients who are pregnant or lactating: Based on findings from animal studies, ZOKINVY can cause embryofetal harm. 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 females of reproductive potential to use effective contraception during treatment with ZOKINVY. There are no data on the presence of ZOKINVY in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZOKINVY and any potential adverse effects of the breastfed infant from ZOKINVY or from the underlying maternal condition.

To report SUSPECTED ADVERSE REACTIONS, contact Eiger BioPharmaceuticals, Inc. at 833-267-0545 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see accompanying full Prescribing Information.

References:

  • 1. Zokinvy [package insert]. Palo Alto, CA: Eiger BioPharmaceuticals Inc; 2020. 2. Data on file. Eiger BioPharmaceuticals Inc. 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. 2018;319(16):1687-1695. doi:10.1001/jama.2018.3264. 4. Goldman RD, Shumaker DK, Erdos MR, et al. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2004;101(24):8963-8968. doi:10.1073/pnas.0402943101. 5. Gordon LB, Kleinman ME, Miller DT, et al. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2012;109(41):16666-16671. doi:10.1073/pnas.1202529109.

INDICATION AND USAGE

ZOKINVY is indicated in adult and pediatric patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 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

Limitations of Use

ZOKINVY is not indicated for use in patients with non-HGPS Progeroid Syndromes or with Progeroid Laminopathies known to be processing-proficient. Based upon its mechanism of action, ZOKINVY would not be expected to be effective in these populations.

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IMPORTANT SAFETY INFORMATION

Contraindications

ZOKINVY is contraindicated in patients taking:

  • Strong or moderate CYP3A inhibitors or inducers
  • Midazolam
  • Lovastatin, simvastatin, and atorvastatin

INDICATION AND USAGE

ZOKINVY is indicated in adult and pediatric patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 and above:

  • To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS)
  • For the treatment of processing-deficient
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