1. Harvoni® ledipasvir/sofosbuvir
Manufacturer: Gilead Sciences
FDA Approval Date: 10/10/2014

2. 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

3. 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.

4. Harvoni® - ledipasvir/sofosbuvir Clinical Application
Pregnancy:
Category B
Lactation:
It is not known whether Harvoni can be found in human breast milk.

5. Harvoni® - ledipasvir/sofosbuvir Drug Facts
Pharmacology:
Ledipasvir – inhibits the HCV NS5A protein necessary for viral replication
Sofosbuvir – prodrug converted to its active form (GS ), which inhibits NS5B RNA-dependent RNA polymerase and acts as a chain terminator

6. Harvoni® - ledipasvir/sofosbuvir Drug Facts
Pharmacokinetics: A
Cmax hours
Well absorbed D
>99.8% protein bound M
Slow oxidative metabolism via an unknown mechanism E
87% feces, 1% urine
T1/2 47 hours

7. Harvoni® - ledipasvir/sofosbuvir Drug Interactions
Drug Interactions – Object Drugs:
 digoxin
 tenofovir
 simeprevir
 rosuvastatin

8. 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

9. Harvoni® - ledipasvir/sofosbuvir Adverse Effects
8 weeks
12 weeks
24 weeks
Fatigue
16%
13%
18%
Headache
11%
14%
17%
Nausea 6% 7% 9%
Diarrhea 4% 3%
Insomnia 5%

10. 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

11. 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

12. 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

13. 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:

14. 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:

15. 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:

16. Harvoni® - ledipasvir/sofosbuvir Literature Review
ION-1
12 week treatment
24 week treatment
Afdhal N, et al. N Engl J Med. 2014;370:

17. Harvoni® - ledipasvir/sofosbuvir Literature Review
ION-1
*Subgroup results do not include patients who withdrew consent or were lost to follow-up
12 week treatment
24 week treatment
Afdhal N, et al. N Engl J Med. 2014;370:

18. 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:

19. 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

20. Harvoni® - ledipasvir/sofosbuvir References
Harvoni package insert. Gilead. October nes/liver-disease/harvoni/harvoni_pi.pdf
November 2014.
UPDATE 2 - US FDA approves Gilead’s $94,500 hepatitis C drug. Reuters. October ( fda-hepatitis-idUSL2N0S51WN )
Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370: