FOR HEALTHCARE PROFESSIONALS
ABOUT VILTEPSO
VILTEPSO is an exon-skipping therapy studied in children as young as 4 years
VILTEPSO is designed to bind to and induce skipping of exon 53 of the dystrophin pre-mRNA, resulting in the production of a shortened dystrophin protein that contains essential functional portions
An estimated 10% of patients with DMD would be amenable to treatment with an exon 53 skipping therapy such as VILTEPSO*
VILTEPSO was discovered through an innovative triple-screening approach designed to identify antisense oligonucleotides with the highest possible exon-skipping efficiency
mRNA=messenger RNA.
For children with DMD, early diagnosis can be instrumental to inform the management of progressive muscle deterioration and motor function decline
EXON-SKIPPING THERAPY
VILTEPSO is for DMD patients with a confirmed mutation that is amenable to exon 53 skipping
Exon skipping is a genetic technique that, in essence, “skips over” an exon next to the deleted exon(s) in patients with DMD.
- There are nearly 50 DMD gene mutations that can be treated with VILTEPSO, including, but not limited to, 45-52, 47-52, 48-52, 49-52, 50-52, and 52 of the dystrophin gene
- An estimated 10% of patients with DMD are amenable to treatment with VILTEPSO
- In the United States, about 2% of patients with DMD have an exon 52 deletion that is amenable to treatment with VILTEPSO
Deletions amenable to exon 53 skipping
SEE HOW EXON SKIPPING WORKS
EFFICACY
VILTEPSO provided significant improvements in dystrophin expression
Study 1: Mean increase in dystrophin expression to nearly 6% of normal with VILTEPSO (80 mg/kg/wk) vs 0.6% at baseline
- Efficacy was assessed by validated Western blot (normalized to myosin heavy chain) based on the change from baseline in dystrophin protein level, measured as percentage of the dystrophin level in healthy subjects at week 25
-
Mean change in dystrophin was 5.3% (SD 4.5) of normal levels (P=0.01)
- Median change from baseline was 3.8%
*
P-value for change from baseline at week 25 was statistically significant.
Study design: A 2-period, North American dose-finding study with ambulant males aged 4 to <10 years with a confirmed mutation of the DMD gene amenable to exon 53 skipping who were receiving a stable dose of corticosteroids for ≥3 months (N=16). Primary study endpoints were safety, tolerability, and dystrophin protein production (Western blot). Secondary study endpoints were other dystrophin measures (RT-PCR, MS, and IFS) and timed motor function tests (6MWT, TTCLIMB, TTRW, TTSTAND) and NSAA. Patients were treated for 24 weeks, and then all patients elected to continue in an open-label, up to 192-week extension study for further assessment.
IFS=immunofluorescence staining; MS=mass spectrometry; NSAA=North Star Ambulatory Assessment; QMT=quantitative muscle testing;
RT-PCR=reverse transcriptase-polymerase chain reaction; 6MWT=6-minute walk test; SD=standard deviation; TTCLIMB=time to climb 4 stairs;
TTRW=time to run/walk 10 meters; TTSTAND=time to stand from supine.
DYSTROPHIN WHERE IT MATTERS: Immunofluorescence staining showed VILTEPSO-induced increases in dystrophin levels were correctly localized to the muscle cell membrane, where dystrophin is needed to support muscle health.
100% of patients showed an increase in dystrophin levels with VILTEPSO
Study 1: Dystrophin levels at 25 weeks vs baseline
Dystrophin expression (% of normal) normalized to myosin heavy chain
- In a clinical study of patients aged 4 to <10 years, 100% of patients showed an increase in dystrophin levels with VILTEPSO, with a mean increase in dystrophin expression to ~6% of normal vs 0.6% at baseline
- The statistically significant increase in dystrophin expression was measured by Western blot analysis, which is a validated, highly sensitive, and reproducible methodology
In the same 24-week study,
Secondary endpoint results provided additional evidence of dystrophin production
†
Mean dystrophin levels as assessed by mass spectrometry (normalized to filamin C) increased from 0.6% (SD 0.2) of normal at baseline to 4.2% (SD 3.7) of normal by week 25, with a mean change in dystrophin of 3.7% (SD 3.8) of normal levels (nominal P=0.03, not adjusted for multiple comparisons); the median change from baseline was 1.9%.
In the same 24-week study,
Secondary endpoints included several motor function tests
Functional tests were secondary endpoints of study 201 and were compared to Duchenne natural history data, which is not considered an adequate comparator arm. Functional data are not in the US Prescribing Information, and therefore definitive conclusions should not be drawn.
‡
The control subjects for this trial were matched for age and corticosteroids from the CINRG-DNHS registry.
§
Negative velocity means lower rate of velocity; positive velocity means higher rate of velocity.
‖
Negative time means less time; positive time means more time.
¶
Negative number means less distance traveled; positive number means greater distance traveled.
#
Negative number means a lower score relative to baseline; positive number means a higher score relative to baseline.
CINRG=Cooperative International Neuromuscular Research Group; DNHS=Duchenne Natural History Study.
SAFETY
Safety profile evaluated in two 24-week clinical studies
Adverse reactions reported in ≥10% of DMD patients treated with VILTEPSO 80 mg/kg once weekly
*
Upper respiratory tract infection includes the following terms: upper respiratory tract infection, nasopharyngitis, and rhinorrhea.
†
Injection site reaction includes the following terms: injection site bruising, injection site erythema, injection site reaction, and injection site swelling.
DOSING
VILTEPSO offers a choice of treatment location—at home or at a treatment center
VILTEPSO is given as an 80-mg/kg weekly intravenous infusion
The appropriate dose of VILTEPSO is calculated based upon patient weight, at a recommended weekly dose of 80 mg/kg
VILTEPSO is infused for 60 minutes by a healthcare professional, either at the patient’s home or at a treatment center
HOW TO DOSE AND ADMINISTER A VILTEPSO INFUSION
Determining dosing for VILTEPSO infusion
VILTEPSO is available as single-dose vials containing 250 mg/5mL (50 mg/mL) solution. The appropriate dose is based on patient’s body weight, with the recommended dosage of VILTEPSO 80 mg/kg administered once weekly as a 60-minute intravenous infusion.
Weekly dosing chart
Only odd kg body weight provided for illustrative purposes.
If volume of VILTEPSO required is <100 mL, dilution in 0.9% sodium chloride for injection, USP, is required such that the total volume in the infusion bag is 100 mL. If the volume of VILTEPSO to be infused is ≥100 mL, dilution is not required.
†
The actual number of theoretical vials required is 15.04.
When less than 100 mL of VILTEPSO is required:
1.
Withdraw from the 100‑mL infusion bag a volume of 0.9% sodium chloride for injection, USP, equivalent to the calculated volume of VILTEPSO solution that will be added.
2.
Withdraw the calculated volume of VILTEPSO solution from the appropriate number of vials, and inject into the infusion bag, such that the total volume in the bag is 100 mL.
When 100 mL or more of VILTEPSO is required:
Withdraw the calculated volume of VILTEPSO solution from the appropriate number of vials, and inject into an empty infusion bag. Further dilution is not required if the volume of VILTEPSO is 100 mL or more.
After preparation, VILTEPSO infusion
should begin as soon as possible
Infusion should begin no more than 5 hours after preparation of VILTEPSO and be completed within 6 hours of preparation (allowing for 1 hour of infusion time) if diluted solution is stored at 20°C to 26°C (68°F to 79°F).
VILTEPSO is administered via intravenous infusion using a peripheral or central venous catheter. Flush the intravenous access line with 0.9% sodium chloride for injection, USP, after infusion. Filtration of VILTEPSO is not required.
Do not mix other medications with VILTEPSO or infuse other medications concomitantly via the same intravenous access line.
VILTEPSO Pocket Dosing Guide
This guide serves as a quick reference for information on appropriate VILTEPSO dose and number of corresponding VILTEPSO vials, as well as corresponding volumes of saline, VILTEPSO, and total volume of VILTEPSO solution, for select patient body weights.
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Product Order Form
Complete this form and fax or mail it to NS Support to order VILTEPSO for your appropriate patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping.
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