Harvoni ® ledipasvir/sofosbuvir Manufacturer: Gilead Sciences FDA Approval Date: 10/10/2014.
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Transcript of Harvoni ® ledipasvir/sofosbuvir Manufacturer: Gilead Sciences FDA Approval Date: 10/10/2014.
Harvoni®
ledipasvir/sofosbuvir
Manufacturer: Gilead Sciences
FDA Approval Date: 10/10/2014
Harvoni® - ledipasvir/sofosbuvir
Clinical Application
• Indication:• Treatment of chronic hepatitis C (CHC)
genotype 1 infection in adults.
• Place in therapy:• One pill a day for convenient dosing and
increased compliance
• Less adverse effects than the current treatment options for genotype 1
Harvoni® - ledipasvir/sofosbuvir
Clinical Application
• Contraindications:• None
• Warnings and Precautions:• P-gp inducers may reduce therapeutic
effect of Harvoni.
• The use of Harvoni with other products containing sofosbuvir (Sovaldi) is not recommended.
Harvoni® - ledipasvir/sofosbuvir
Clinical Application
• Pregnancy:• Category B
• Lactation:• It is not known whether Harvoni can be
found in human breast milk.
Harvoni® - ledipasvir/sofosbuvir
Drug Facts
• Pharmacology:• Ledipasvir – inhibits the HCV NS5A
protein necessary for viral replication
• Sofosbuvir – prodrug converted to its active form (GS-461203), which inhibits NS5B RNA-dependent RNA polymerase and acts as a chain terminator
Harvoni® - ledipasvir/sofosbuvir
Drug Facts
• Pharmacokinetics:
ACmax 4-4.5 hoursWell absorbed
D >99.8% protein bound
M Slow oxidative metabolism via an unknown mechanism
E87% feces, 1% urineT1/2 47 hours
Harvoni® - ledipasvir/sofosbuvir
Drug Interactions
• Drug Interactions – Object Drugs: digoxin tenofovir simeprevir rosuvastatin
Harvoni® - ledipasvir/sofosbuvir
Drug Interactions
• Drug Interactions – Precipitant Drugs: • Acid reducing agents solubility of
ledipasvir
• Anticonvulsants Harvoni
• Antimycobacterials Harvoni
• HCV products ledipasvir
• St. Johns wort Harvoni
Harvoni® - ledipasvir/sofosbuvir
Adverse Effects
Harvoni8 weeks
Harvoni12 weeks
Harvoni 24 weeks
Fatigue 16% 13% 18%
Headache 11% 14% 17%
Nausea 6% 7% 9%
Diarrhea 4% 3% 7%
Insomnia 3% 5% 6%
Harvoni® - ledipasvir/sofosbuvir
Monitoring Parameters
• Efficacy Monitoring:• Signs of clinical improvement
• HCV RNA (viral load) at weeks 4 and 12
• Toxicity Monitoring:• CBC, basic chemistry panel, liver enzyme
levels, bilirubin levels at weeks 1-2, 4, and then monthly during treatment
Harvoni® - ledipasvir/sofosbuvir
Prescription Information
• Dosing:• One tablet (90mg ledipasvir/400mg
sofosbuvir) taken orally once daily with or without food
• Treatment-naïve with or without cirrhosis: 12 weeks
• Treatment-experienced without cirrhosis: 12 weeks
• Treatment-experienced with cirrhosis: 24 weeks
Harvoni® - ledipasvir/sofosbuvir
Prescription Information
Duration of Treatment Estimated Cost
8 Weeks $63,000
12 Weeks $94,500
24 Weeks $189,000
*Estimated cost based on Wholesaler Acquisition Cost of $1125 per pill
Harvoni® - ledipasvir/sofosbuvir
Literature Review
ION-1
•Design: open-label, randomized, phase 3 trial
• 99 sites in the United States and Europe
•Interventions• Fixed-dose combinations of
ledipasvir/sofosbuvir +/- ribavirin for 12 or 24 weeks in treatment-naïve patients with genotype 1 HCV
Afdhal N, et al. N Engl J Med. 2014;370:1889-98.
Harvoni® - ledipasvir/sofosbuvir
Literature Review
ION-1
•Primary Endpoint: SVR at 12 weeks after the end of treatment
• Assessed in all patients who were randomized and received treatment
Afdhal N, et al. N Engl J Med. 2014;370:1889-98.
Harvoni® - ledipasvir/sofosbuvir
Literature Review
ION-1
•Inclusion Criteria:• Chronic HCV Genotype I (n=865)
• 18 years or older
• No prior HCV treatment
• Patients with cirrhosis accepted (up to 20% of patients)
Afdhal N, et al. N Engl J Med. 2014;370:1889-98.
Harvoni® - ledipasvir/sofosbuvir
Literature Review
ION-1
Afdhal N, et al. N Engl J Med. 2014;370:1889-98.
12 week treatment
24 week treatment
Harvoni® - ledipasvir/sofosbuvir
Literature Review
ION-1
Afdhal N, et al. N Engl J Med. 2014;370:1889-98.
12 week treatment
24 week treatment
*Subgroup results do not include patients who withdrew consent or were lost to follow-up
Harvoni® - ledipasvir/sofosbuvir
Literature Review
ION-1
•Conclusions:• “Once daily ledipasvir/sofosbuvir with or
without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection.”
Afdhal N, et al. N Engl J Med. 2014;370:1889-98.
Harvoni® - ledipasvir/sofosbuvir
Summary
• Harvoni® is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults
• The use of Harvoni® with P-gp inducers is not recommended
• Harvoni® has a convenient dosing schedule which may increase compliance
Harvoni® - ledipasvir/sofosbuvir
References
1. Harvoni package insert. Gilead. October 2014. http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf
2. http://www.harvoni.com/ November 2014.
3. UPDATE 2 - US FDA approves Gilead’s $94,500 hepatitis C drug. Reuters. October 2014. (http://www.reuters.com/article/2014/10/10/gilead-fda-hepatitis-idUSL2N0S51WN20141010)
4. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889-98.