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



• 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.



• Pregnancy:• Category B

• Lactation:• It is not known whether Harvoni can be

found in human breast milk.


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


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


Drug Interactions

• Drug Interactions – Object Drugs: digoxin tenofovir simeprevir rosuvastatin


Drug Interactions

• Drug Interactions – Precipitant Drugs: • Acid reducing agents solubility of

ledipasvir

• Anticonvulsants Harvoni

• Antimycobacterials Harvoni

• HCV products ledipasvir

• St. Johns wort Harvoni


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%


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


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


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


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.


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



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)



Literature Review

ION-1


12 week treatment

24 week treatment


Literature Review

ION-1


12 week treatment

24 week treatment

*Subgroup results do not include patients who withdrew consent or were lost to follow-up


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.”



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


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.

harvoni ® ledipasvir/sofosbuvir manufacturer: gilead sciences fda approval date: 10/10/2014

Documents