Transcript harvoni
® 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: A D M E Cmax 4-4.5 hours Well absorbed >99.8% protein bound Slow oxidative metabolism via an unknown mechanism 87% feces, 1% urine T1/2 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 Harvoni 8 weeks Harvoni 12 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 12 week treatment 24 week treatment Afdhal N, et al. N Engl J Med. 2014;370:1889-98. 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;370:1889-98. 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/medici nes/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/gileadfda-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.