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child diagnosed with Progeria playing ball

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 Sentynl Cares | Zokinvy Access and Support 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

normal cell Normal cell2

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

Progeria cell Progeria cell2

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

Progeria cell after treatment with Zokinvy 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 continent1,2
  • At last follow-up, treatment with Zokinvy resulted in increased mean survival of 2.5 years and a 60% reduction in risk of mortality1
survival probability curve of Zokinvy compared to untreated control

At a 3-year follow-up, there was a 70% reduction in risk of mortality. At last follow-up (11 years), the reduction was 60%.1

  • ProLon1

    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
  • ProLon2

    A second phase 2, open-label, single-arm trial, consisting of 2 study periods1:

  • In the first period, 26 patients from ProLon1 received Zokinvy with additional therapies for about 5 years
  • In the second period, those 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 ProLon 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
  • Play

    Although ProLon 1 had a lower starting dosage than ProLon 2, adverse reactions were reduced in both studies over time1

  • Play

    Only 4 patients (or 6.3%) withdrew from the studies due to nausea and vomiting1

Zokinvy improves cardiovascular outcomes in patients with Progeria or PDPL.2,3,5

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 100 young people participated in clinical studies of Zokinvy; only 4 patients (6%) discontinued due to adverse reactions2
  • ~46.4% of patients with Progeria have received Zokinvy for ≥5 years1,2
  • ~9.5% of patients with Progeria have received Zokinvy for ≥10 years1,2
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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 include hypermagnesemia, hypokalemia, hyperkalemia, hyponatremia, hypercalcemia, hypocalcemia, hyperphosphatemia, and hypernatremia.
  • g Myelosuppression includes decreased absolute neutrophil count, low total white blood cells, lymphopenia, decreased hemoglobin, and low hematocrit.
  • 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, and 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 allowed1
    • When Zokinvy is coadministered with loperamide, do not exceed loperamide 1 mg once daily when first coadministered1
    • Slowly increase loperamide dosage with caution in accordance with its approved product labeling1

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

References:

  • 1. ZOKINVY [prescribing information]. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=956a142f-35d6-4fe3-8aef-7e4878d275ed. 2. Data on file. Sentynl Therapeutics, 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. 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. 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.
person with PDPL riding bicycle

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

IMPORTANT SAFETY INFORMATION

Contraindications

ZOKINVY is contraindicated in patients taking:

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