OVERVIEW

 

HARVONI delivered high cure (SVR12) rates in a broad range of GT 1 subjects1

  • The HARVONI clinical trial program enrolled the most challenging subjects, regardless of GT 1a or 1b subtype, prior experience with HCV therapy, or presence of compensated cirrhosis1

Study Designs: randomized, open-label trials in GT 1 subjects1

ION-1: TN subjects (N=865) with or without cirrhosis were randomized to receive HARVONI for 12 weeks, HARVONI + RBV for 12 weeks, HARVONI for 24 weeks, or HARVONI + RBV for 24 weeks.

ION-2: TE subjects (N=440) with or without cirrhosis were randomized to receive HARVONI for 12 weeks, HARVONI + RBV for 12 weeks, HARVONI for 24 weeks, or HARVONI + RBV for 24 weeks.

ION-3: TN subjects (N=647) without cirrhosis were randomized to receive HARVONI for 8 weeks, HARVONI + RBV for 8 weeks, or HARVONI for 12 weeks.

These studies did not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients.

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR is considered a virologic cure.5

Cirrhosis = compensated cirrhosis (Child-Pugh A), RBV = ribavirin, TE = treatment-experienced (patients who have failed a peginterferon alfa + RBV–based regimen with or without an HCV protease inhibitor), TN = treatment-naïve

HARVONI is the only HCV treatment that offers an 8-week course of therapy1

  • The dosing information listed here does not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients
  • 97% (n=119/123) overall cure rate among TN HCV GT 1 subjects without cirrhosis who had baseline HCV RNA <6 million IU/mL and who received HARVONI for 8 weeks1
  • Many patients may qualify for an 8-week HARVONI regimen
    • In the ION-3 clinical trial, 59% of subjects taking HARVONI had baseline HCV RNA <6 million IU/mL1
    • In an independent chart review, more than half (53%) of GT 1 patients (n=2814) were TN without cirrhosis and had baseline HCV RNA <6 million IU/mL6,b
These data are derived from a study conducted by IPSOS. The study consisted of over 2100 patient chart reviews per quarter by approximately 150 HCV-treating physicians from April 2015-March 2016.

IMPORTANT SAFETY INFORMATION

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

HARVONI was safe with low rates of discontinuations and adverse events (AEs) across clinical trials1

  • Adverse reactions (all grades) reported in ≥5% of GT 1 subjects receiving 8, 12, or 24 weeks of treatment with HARVONI (in ION-3, ION-1, and ION-2): fatigue (13%-18%), headache (11%-17%), nausea (6%-9%), diarrhea (3%-7%), and insomnia (3%-6%)1

No baseline resistance testing is required with HARVONI1

  • HARVONI is RBV-free for the majority of TN and TE patients with or without cirrhosis, regardless of GT 1a or 1b subtype1
  • No hepatic or hematologic monitoring is required when HARVONI is used alone1
  • HARVONI has been prescribed to more than 260,000 patients9,d
IMS Weekly NPA™ Market Dynamics™ from week-ending 11/14/14–4/1/16.
This information is derived from IMS NPA, IMS NSP™, and IntegriChain® data; data reflect estimated patient starts for HARVONI from October 2014–February 2016.

HARVONI was safe with low rates of discontinuations and adverse events (AEs) across clinical trials1

  • Adverse reactions (all grades) reported in ≥5% of GT 1 subjects receiving 8, 12, or 24 weeks of treatment with HARVONI (in ION-3, ION-1, and ION-2): fatigue (13%-18%), headache (11%-17%), nausea (6%-9%), diarrhea (3%-7%), and insomnia (3%-6%)1

No baseline resistance testing is required with HARVONI1

  • HARVONI is RBV-free for the majority of TN and TE patients with or without cirrhosis, regardless of GT 1a or 1b subtype1
  • No hepatic or hematologic monitoring is required when HARVONI is used alone1
References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.
  2. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898.
  3. Kowdley KV, Gordon SC, Reddy KR, et al; for the ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.
  4. Afdhal N, Reddy KR, Nelson DR, et al; for the ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
  5. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  6. Data on file. IPSOS Healthcare. IPSOS HCV USA, April 2015-March 2016.
  7. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14–4/1/16. Gilead Sciences, Inc.
  8. Data on file. HCV Weekly Sales Reports, 11/14/14–1/1/16. Gilead Sciences, Inc.
  9. Data on file. HARVONI Patient Starts from October 2014–February 2016. Gilead Sciences, Inc.

IMPORTANT SAFETY INFORMATION

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.
  2. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  3. Data on file. IPSOS Healthcare. IPSOS HCV USA, April 2015-March 2016.
  4. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14–4/1/16. Gilead Sciences, Inc.
  5. Data on file. HCV Weekly Sales Reports, 11/14/14–1/1/16. Gilead Sciences, Inc.
  6. Data on file. HARVONI Patient Starts from October 2014–February 2016. Gilead Sciences, Inc.

STUDY RESULTS

HARVONI delivered high cure (SVR12) rates in GT 1 treatment-naïve adult subjects with or without cirrhosis1,a

% SVR12 in treatment-naïve GT 1 subjects in ION-11

RBV was not shown to increase the response rates observed with HARVONI in ION-1. Therefore, the HARVONI + RBV arm is not presented.1

aSVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR is considered a virologic cure.2

One tablet taken once daily without IFN or RBV1

  • The recommended treatment duration for treatment-naïve patients with or without cirrhosis is HARVONI once daily for 12 weeks. HARVONI for 8 weeks can be considered in GT 1 treatment-naïve patients without cirrhosis with pre-treatment HCV RNA <6 million IU/mL1
    • The dosing information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • No on-treatment virologic failure occurred in subjects treated with HARVONI for 12 weeks in ION-11

HARVONI delivered high cure (SVR12) rates in GT 1 treatment-naïve adult subjects without cirrhosis1,a

% SVR12 in treatment-naïve GT 1 subjects without cirrhosis in ION-31,b

RBV was not shown to increase the response rates observed with HARVONI in ION-3. Therefore, the HARVONI + RBV arm is not presented.1

aSVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR is considered a virologic cure.2

bThe treatment difference between the 8-week treatment of HARVONI and 12-week treatment of HARVONI was -2.3% (97.5% confidence interval [-7.2% to 2.5%]).1

One tablet taken once daily without IFN or RBV

  • The recommended treatment duration for treatment-naïve patients with or without cirrhosis is HARVONI once daily for 12 weeks. HARVONI for 8 weeks can be considered in GT 1 treatment-naïve patients without cirrhosis with pre-treatment HCV RNA <6 million IU/mL1
    • The dosing information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • No on-treatment virologic failure occurred in ION-31

Relapse rates are affected by baseline host and viral factors and differ between durations for certain subgroups1

Relapse rates by baseline viral load in ION‑31

aHCV RNA values were determined using the Roche TaqMan® Assay; a subject's HCV RNA may vary from visit to visit.

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

IMPORTANT SAFETY INFORMATION

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

HARVONI delivered high cure (SVR12) rates in GT 1 treatment-experienced adult subjects1,a

% SVR12 in GT 1 treatment-experienced subjects in ION‑21

RBV was not shown to increase the response rates observed with HARVONI in ION-2. Therefore, the HARVONI + RBV arms are not presented.1

aSVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR is considered a virologic cure.2

One tablet taken once daily without IFN or RBV

  • The recommended treatment duration for treatment-experienced patients without cirrhosis is 12 weeks1
  • The recommended treatment duration for GT 1 treatment-experienced patients with cirrhosis is 24 weeks1
    • HARVONI + RBV for 12 weeks can be considered in treatment-experienced GT 1 patients with cirrhosis who are eligible for RBV. The daily dosage of RBV is weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in 2 divided doses with food. Refer to the RBV prescribing information1
  • The dosing information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • No on-treatment virologic failure occurred in subjects receiving HARVONI alone for 12 or 24 weeks1
  • SVR rates in other subgroups were 86% in subjects with cirrhosis treated with HARVONI for 12 weeks (n=22) and 99% in subjects without cirrhosis treated with HARVONI for 24 weeks (n=86)1
  • Among subjects with available SVR12 and SVR24 data (206/218), all subjects who achieved SVR12 in the ION-2 study also achieved SVR241
  • In subjects with cirrhosis, relapse rates were 14% with HARVONI for 12 weeks (n=22) and 0% with HARVONI for 24 weeks (n=22)1

Relapse rates are affected by baseline host and viral factors and differ between durations for certain subgroups1

Relapse rates for selected subgroups in ION-21

aSubjects with missing cirrhosis status were excluded from this subgroup analysis.

bThese 4 non-cirrhotic relapsers all had baseline NS5A resistance-associated polymorphisms.

cNS5A resistance-associated polymorphisms include any change at NS5A positions 24, 28, 30, 31, 58, 92, or 93.

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

HARVONI delivered high cure (SVR12) rates in treatment-naïve and treatment-experienced subjects with HCV/HIV-1 co-infection1,a

% SVR12 in HCV GT 1 or 4 subjects with HCV/HIV-1 co‑infection in ION‑41

aSVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR is considered a virologic cure.2

  • HARVONI delivered consistently high cure rates regardless of prior HCV treatment experience or cirrhosis status (94% in subjects with cirrhosis and 98% in treatment-experienced subjects with cirrhosis)1
  • No subjects had HIV-1 rebound during this study1
  • The relapse rate in Black subjects was 9% (10/115) and all 10 were IL28B non-C/C genotype. The relapse rate in non-Black subjects was 0% (0/220). In the ION-1, ION-2, and ION-3 HCV mono-infection studies, relapse rates were 3% (10/305) in Black subjects and 2% (26/1637) in non-Black subjects1
  • The safety profile in HCV/HIV-1 co-infected subjects was similar to that observed in HCV mono-infected subjects. See the Drug Interactions section of the HARVONI Prescribing Information for potentially significant drug interactions with HIV antiretrovirals1
  • For patients with HCV/HIV-1 co-infection, follow the dosage recommendations listed in the Dosage and Administration section. Refer to the Drug Interactions section of the HARVONI Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs1
References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.
  2. U.S. Department of Health and Human Services, Center for Drug Evaluation and Research. Draft guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.

IMPORTANT SAFETY INFORMATION

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.
  2. U.S. Department of Health and Human Services, Center for Drug Evaluation and Research. Draft guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. Published October 2013.

STUDY DESIGNS

ION-1: GT 1 treatment-naïve adults with or without cirrhosis1

ION-1: GT 1 treatment-naïve adults with or without cirrhosis1

A Phase 3, randomized, open-label clinical trial (N=865)1

Subjects were randomized in a 1:1:1:1 ratio for each treatment arm, and randomization was stratified by the presence or absence of cirrhosis and HCV genotype (1a vs 1b).1

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA ≥25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • 16% had compensated cirrhosis
  • Median age: 54 years (range: 18 to 80)
  • 59% were male; 41% were female
  • 85% were White; 12% were Black; 12% were Hispanic or Latino
  • Mean BMI was 27 kg/m2 (range: 18 to 48 kg/m2)
  • 79% had baseline HCV RNA levels ≥ 800,000 IU/mL
  • 67% had HCV GT 1a
  • 70% had IL28B non-C/C alleles (CT or TT)

ION-3: GT 1 treatment-naïve adults without cirrhosis1

ION-3: GT 1 treatment-naïve adults without cirrhosis1

A Phase 3, randomized, open-label clinical trial (N=647)1,4,a,b

aSubjects were randomized in a 1:1:1 ratio to 1 of the 3 treatment groups and stratified by HCV genotype (1a vs 1b).1

bSVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • Median age: 55 years (range: 20 to 75)
  • 58% were male; 42% were female
  • 78% were White; 19% were Black; 6% were Hispanic or Latino
  • Mean BMI was 28 kg/m2 (range: 18 to 56 kg/m2)
  • 81% had baseline HCV RNA levels ≥ 800,000 IU/mL
  • 80% had HCV GT 1a
  • 73% had IL28B non-C/C alleles (CT or TT)

IMPORTANT SAFETY INFORMATION

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

ION-2: GT 1 previously treated adults with or without cirrhosis1

ION-2: GT 1 previously treated adults with or without cirrhosis1

A Phase 3, randomized, open-label clinical trial (N=440)1

Subjects were randomized in a 1:1:1:1 ratio to each of the treatment arms, and randomization was stratified by the presence or absence of cirrhosis, HCV genotype (1a vs 1b), and response to prior HCV therapy (relapse/breakthrough vs nonresponse).1

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • 20% of subjects had compensated cirrhosis
  • Median age: 57 years (range: 24 to 75)
  • 65% were male; 35% were female
  • 81% were White; 18% were Black; 9% were Hispanic or Latino
  • Mean BMI was 28 kg/m2 (range: 19 to 50 kg/m2)
  • 89% had baseline HCV RNA levels ≥ 800,000 IU/mL
  • 79% had HCV GT 1a
  • 88% had IL28B non-C/C alleles (CT or TT)
  • 53% failed prior therapy with an HCV protease inhibitor + Peg-IFN + RBV regimen (62% were relapse/breakthrough; 38% were nonresponder)
  • 47% of subjects failed prior therapy with Peg-IFN + RBV (49% were relapse/breakthrough; 51% were nonresponder)

ION-4: GT 1 or 4 treatment-naïve and treatment-experienced subjects with HCV/HIV-1 co-infection1

ION-4: GT 1 or 4 treatment-naïve and treatment-experienced subjects with HCV/HIV-1 co-infection1

A Phase 3, open-label clinical trial (N=335)1

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA ≥25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • Median age: 52 years (range: 26 to 72)
  • 82% of the subjects were male; 18% were female
  • 61% were White; 34% were Black
  • Mean BMI was 27 kg/m2 (range: 18 to 66 kg/m2)
  • 75% had HCV GT 1a infection
  • 76% had non-C/C IL28B alleles (CT or TT)
  • 20% had compensated cirrhosis
  • 55% of subjects were treatment-experienced; 45% of subjects were treatment-naïve

Subjects were on stable HIV-1 antiretroviral therapy that included emtricitabine + tenofovir disoproxil fumarate, administered with efavirenz, rilpivirine, or raltegravir.

HARVONI was studied in a range of subjects1

Select baseline characteristics in HCV HARVONI clinical trials (ION‑1, ION‑3, ION‑2, ION‑4)1,3-8
References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.
  2. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  3. Afdhal N, Zeuzem S, Kwo P, Chojkier M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1889-1898.
  4. Kowdley KV, Gordon SC, Reddy KR, Rossaro L, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(16):1879-1888.
  5. Afdhal N, Reddy KR, Nelson DR, Lawitz E, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
  6. Afdhal N, Reddy KR, Nelson DR, Lawitz E, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16)(suppl).
  7. Naggie S, Cooper C, Saag M, et al; for the ION-4 Investigators. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705-713.
  8. Naggie S, Cooper C, Saag M, et al; for the ION-4 Investigators. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8)(suppl).

IMPORTANT SAFETY INFORMATION

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

DOSAGE AND ADMINISTRATION

 

HARVONI is a once-daily single-tablet regimen for HCV GT 1, 4, 5, or 6 patients built on a sofosbuvir backbone1

Recommended treatment duration for HARVONI1

The dosing information listed here does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients.

aHARVONI + RBV for 12 weeks can be considered in TE GT 1 patients with cirrhosis who are eligible for RBV. The daily dosage of RBV is weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in 2 divided doses with food. Refer to the RBV prescribing information.

Cirrhosis = compensated cirrhosis (Child‑Pugh A), IFN = interferon, RBV = ribavirin, TE = treatment-experienced (patients who have failed a Peg-IFN alfa + RBV–based regimen with or without an HCV protease inhibitor), TN = treatment-naïve

HARVONI is IFN- and RBV-free for TN and TE patients with or without cirrhosis, regardless of GT 1a or 1b subtype1

  • The dosing information listed here does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • For patients with HCV/HIV-1 co-infection, follow the dosage recommendations listed above. Refer to the Drug Interactions section of the HARVONI Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs1
  • Relapse rates are affected by baseline host and viral factors and differ between treatment durations for certain subgroups1
  • No dosage adjustments are required based on advanced age, mild or moderate renal impairment, or mild, moderate, or severe hepatic impairment1
  • No dosage recommendations can be given for patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) or with end stage renal disease (ESRD) due to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite1
  • Each HARVONI tablet contains 90 mg of ledipasvir and 400 mg of sofosbuvir1
Reference:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.

IMPORTANT SAFETY INFORMATION

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Reference:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.

SAFETY INFORMATION

CONTRAINDICATIONS

  • If HARVONI is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin.

WARNINGS & PRECAUTIONS

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

To learn more about counseling and the cardiac monitoring of patients, as well as the signs and symptoms of bradycardia, click here.

  • Risk of Reduced Therapeutic Effect Due to P-gp Inducers: The concomitant use of HARVONI and P-gp inducers (e.g., rifampin, St. John's wort) may significantly decrease ledipasvir and sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect of HARVONI. Therefore, the use of HARVONI with P-gp inducers is not recommended.
  • Risks Associated with Ribavirin Combination Treatment: If HARVONI is administered with ribavirin, the warnings and precautions for ribavirin, in particular the pregnancy avoidance warning, apply to this combination regimen. Refer to the ribavirin prescribing information for a full list of the warnings and precautions for ribavirin.
  • Related Products Not Recommended: HARVONI is not recommended for use with other products containing sofosbuvir.

HARVONI demonstrated tolerability with low discontinuation rates and does not require IFN or RBV1

Adverse reactions (all grades) reported in ≥5% of subjects receiving 8, 12, or 24 weeks of treatment with HARVONI (ION-1, -3, -2)1

Direct comparison across trials should not be made due to differing trial designs.1

  • Based on pooled data from three Phase 3 clinical trials in GT 1 subjects with compensated liver disease with or without cirrhosis1
  • The majority of the adverse events presented in the table occurred at a severity of grade 1 (mild, transient, and did not require treatment modification)1
  • The safety profile in HCV/HIV-1 co-infected subjects was similar to that observed in HCV mono-infected subjects. See the Drug Interactions section of the HARVONI Prescribing Information for potentially significant drug interactions with HIV antiretrovirals1
    • The most common adverse reactions occurring in ≥10% of subjects in ION-4 were headache (20%) and fatigue (17%)1

Discontinuations due to adverse events for HARVONI were 1% or less1

Discontinuations due to adverse events in GT 1 subjects treated with HARVONI (ION-1, -3, -2)1

HARVONI is IFN- and RBV-free for GT 1 treatment-naïve and treatment-experienced patients with or without cirrhosis1

HARVONI drug interaction profile1

HARVONI is not recommended with the following medications1,a

Concomitant
Drug Class
and Drug Names

Coadministration
Is Not
Recommended

Clinical Considerations

Antiarrhythmics

amiodarone

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

Antimycobacterials

rifabutin, rifampin,b rifapentine

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Herbal Supplements

St. John's wort

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

HCV Protease Inhibitors

simeprevirb

Concentrations of ledipasvir and simeprevir are increased when simeprevir is coadministered with ledipasvir.

Anticonvulsants

carbamazepine, phenytoin, phenobarbital, oxcarbazepine

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

HIV Antiretrovirals

STRIBILD® (elvitegravir/cobicistat/ emtricitabine/tenofovir DF)

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Statins

rosuvastatin

May significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

HARVONI use with HIV antiretrovirals1,a

Concomitant Drug
Class and
Drug Names

Coadministration
Is Not
Recommended

Potentially Significant Interaction

No Clinically Significant Interaction

Clinical Considerations

HIV Antiretrovirals

STRIBILD® (elvitegravir/
cobicistat/emtricitabine/
tenofovir DF)

   

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir

   

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Regimens containing tenofovir DF and an HIV protease inhibitor/ritonavir or cobicistat:

  • atazanavir/ritonavir or cobicistat + emtricitabine/ tenofovir DFb
  • darunavir/ritonavir or cobicistat + emtricitabine/ tenofovir DFb
  • lopinavir/ritonavir + emtricitabine/tenofovir DF

   

The safety of increased tenofovir concentrations in this setting has not been established. Consider alternative HCV or antiretroviral therapy. If coadministration is required, monitor for tenofovir-associated adverse reactions. Refer to VIREAD® or TRUVADA® prescribing information for recommendations on renal monitoring.

Regimens containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat

   

Monitor for tenofovir-associated adverse reactions. Refer to VIREAD or TRUVADA prescribing information for recommendations on renal monitoring.

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir (darunavir/ritonavir),
Tivicay® (dolutegravir),
Sustiva® (efavirenz),
GENVOYA® (elvitegravir/ cobicistat/emtricitabine/
tenofovir alafenamide),
EMTRIVA® (emtricitabine),
Epivir® (lamivudine),
Isentress® (raltegravir),
Edurant® (rilpivirine)

   

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI may be coadministered with acid-reducing agents1,a

Concomitant
Drug Class
and Drug Names

Potentially
Significant

Interaction

Clinical Considerations

Acid-Reducing Agents

 

Ledipasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of ledipasvir.

Antacids (eg, aluminum and magnesium hydroxide)

It is recommended to separate antacid and HARVONI administration by 4 hours.

H2-receptor antagonistsb (eg, famotidine)

H2-receptor antagonists may be administered simultaneously with or 12 hours apart from HARVONI at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Proton-pump inhibitorsb (eg, omeprazole)

Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions.

HARVONI use with antiarrhythmics and statins1,a

Concomitant
Drug Class
and Drug Names

Coadministration
Is Not
Recommended

Potentially Significant Interaction

No Clinically Significant Interaction

Clinical Considerations

Antiarrhythmics

amiodarone

   

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

digoxin

   

Coadministration may increase the concentration of digoxin. Therapeutic concentration monitoring of digoxin is recommended when coadministered with HARVONI.

Statins

rosuvastatin

   

Coadministration may significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

pravastatin

   

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI does not have clinically signifcant interactions with the following medications1,a

Concomitant
Drug Class
and Drug Names

No Clinically
Significant

Interaction

Clinical Considerations

Immunosuppressants

cyclosporine, tacrolimus

No clinically significant drug interactions have been observed or are expected with HARVONI.

Opioids

methadone

No clinically significant drug interactions have been observed or are expected with HARVONI.

Oral Contraceptives

oral contraceptives

No clinically significant drug interactions have been observed or are expected with HARVONI.

Calcium Channel Blockers

verapamil

No clinically significant drug interactions have been observed or are expected with HARVONI.

HIV Antiretrovirals

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir (darunavir/ritonavir),
Tivicay® (dolutegravir),
Sustiva® (efavirenz),
GENVOYA® (elvitegravir/ cobicistat/emtricitabine/
tenofovir alafenamide),
EMTRIVA® (emtricitabine),
Epivir® (lamivudine),
Isentress® (raltegravir),
Edurant® (rilpivirine)

No clinically significant drug interactions have been observed or are expected with HARVONI.


See "HARVONI use with HIV antiretrovirals" table, above, for additional information on the use of HARVONI with certain HIV antiretroviral regimens.

Statins

pravastatin

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI is not recommended with the following medications1,a

Coadministration Is Not Recommended

amiodarone - Antiarrhythmics

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

rifabutin, rifampin,b rifapentine - Antimycobacterials

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

St. John's wort - Herbal Supplements

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

simeprevirb - HCV Protease Inhibitors

Concentrations of ledipasvir and simeprevir are increased when simeprevir is coadministered with ledipasvir.

carbamazepine, phenytoin, phenobarbital, oxcarbazepine - Anticonvulsants

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

STRIBILD® (elvitegravir/cobicistat/ emtricitabine/tenofovir DF) - HIV Antiretrovirals

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir - HIV Antiretrovirals

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

rosuvastatin - Statins

May significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

HARVONI use with HIV antiretrovirals1,a

Coadministration Is Not Recommended

STRIBILD® (elvitegravir/
cobicistat/emtricitabine/tenofovir DF)
- HIV Antiretrovirals

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir - HIV Antiretrovirals

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Potentially Significant Interaction

Regimens containing tenofovir DF and an HIV protease inhibitor/ritonavir or cobicistat - HIV Antiretrovirals

  • atazanavir/ritonavir or cobicistat + emtricitabine/ tenofovir DFb
  • darunavir/ritonavir or cobicistat + emtricitabine/ tenofovir DFb
  • lopinavir/ritonavir + emtricitabine/tenofovir DF

The safety of increased tenofovir concentrations in this setting has not been established. Consider alternative HCV or antiretroviral therapy. If coadministration is required, monitor for tenofovir-associated adverse reactions. Refer to VIREAD® or TRUVADA® prescribing information for recommendations on renal monitoring.

Regimens containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat - HIV Antiretrovirals

Monitor for tenofovir-associated adverse reactions. Refer to VIREAD or TRUVADA prescribing information for recommendations on renal monitoring.

No Clinically Significant Interaction

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir (darunavir/ritonavir), Tivicay® (dolutegravir), Sustiva® (efavirenz), GENVOYA® (elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide), EMTRIVA® (emtricitabine), Epivir® (lamivudine), Isentress® (raltegravir), Edurant® (rilpivirine) - HIV Antiretrovirals

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI may be coadministered with acid-reducing agents1,a

Potentially Significant Interaction

Ledipasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of ledipasvir.

Antacids (eg, aluminum and magnesium hydroxide) - Acid-Reducing Agents

It is recommended to separate antacid and HARVONI administration by 4 hours.

H2-receptor antagonistsb (eg, famotidine) - Acid-Reducing Agents

H2-receptor antagonists may be administered simultaneously with or 12 hours apart from HARVONI at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Proton-pump inhibitorsb (eg, omeprazole) - Acid-Reducing Agents

Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions.

HARVONI use with antiarrhythmics and statins1,a

Coadministration Is Not Recommended

amiodarone - Antiarrhythmics

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

rosuvastatin - Statins

Coadministration may significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

Potentially Significant Interaction

digoxin - Antiarrhythmics

Coadministration may increase the concentration of digoxin. Therapeutic concentration monitoring of digoxin is recommended when coadministered with HARVONI.

No Clinically Significant Interaction

pravastatin - Statins

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI does not have clinically signifcant interactions with the following medications1,a

No Clinically Significant Interaction

cyclosporine, tacrolimus - Immunosuppressants

No clinically significant drug interactions have been observed or are expected with HARVONI.

methadone - Opioids

No clinically significant drug interactions have been observed or are expected with HARVONI.

oral contraceptives - Oral Contraceptives

No clinically significant drug interactions have been observed or are expected with HARVONI.

verapamil - Calcium Channel Blockers

No clinically significant drug interactions have been observed or are expected with HARVONI.

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir (darunavir/ritonavir), Tivicay® (dolutegravir), Sustiva® (efavirenz), GENVOYA® (elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide), EMTRIVA® (emtricitabine), Epivir® (lamivudine), Isentress® (raltegravir), Edurant® (rilpivirine) - HIV Antiretrovirals

No clinically significant drug interactions have been observed or are expected with HARVONI.


See "HARVONI use with HIV antiretrovirals" table, above, for additional information on the use of HARVONI with certain HIV antiretroviral regimens.

pravastatin - Statins

No clinically significant drug interactions have been observed or are expected with HARVONI.

Reference:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016.

ACCESS AND RESOURCES

Support Path can help your patients start HARVONI and move toward treatment completion

Help your commercially insured patients lower their out-of-pocket costs

With the HARVONI co-pay coupon, an eligible patient's co-pay may be no more than $5 per fill.

To register and read full terms and conditions, click here
Or call 1-855-769-7284

  • Not valid for patients enrolled in government healthcare prescription drug programs, such as Medicare Part D and Medicaid. Patients in the coverage gap known as the "donut hole" also are not eligible
  • The HARVONI co-pay coupon program will cover the out-of-pocket costs for HARVONI prescriptions up to a maximum of 25% of the catalog price of a 12-week regimen of HARVONI

Help along the way

Support Path is ready to assist patients along the way toward treatment completion

  • Ongoing support for access and reimbursement, including help with refill authorization

Enroll


Resources to help you in the treatment of patients with HCV

Centers for Disease Control and Prevention: Hepatitis C information for health professionals

US Preventive Services Task Force: Screening for hepatitis C virus infection in adults

American College of Gastroenterology: Hepatitis C treatment resources

AASLD/IDSA HCV Guidelines

IMPORTANT SAFETY INFORMATION

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

PRESCRIBING INFORMATION

Review the HARVONI full Prescribing Information as a PDF.

This information is intended for US healthcare professionals

Continue to healthcare
professional site
Go to patient site

By following this link, you are now leaving the HARVONI® (ledipasvir 90 mg/sofosbuvir 400 mg) tablets website for healthcare professionals. The site you are entering is not controlled by Gilead Sciences, Inc., and Gilead is not responsible for its content or your use of it.

Continue Cancel

Share

Share this information about HARVONI® (ledipasvir 90 mg/sofosbuvir 400 mg) tablets with others.

*Indicates required field

From


To


Message:
Dear <Name>,
This update was sent to you by <Sender>, who thought you would be interested in receiving information about transformative treatments from Gilead.

Your information will not be stored. For further information, please view the Gilead Privacy Policy.

Unsubscribe

To unsubscribe, please enter the e-mail address with which you originally registered.