Gilead Will Keep Hepatitis C Dominance In Its Grip With Recent Trial Results

| About: Gilead Sciences, (GILD)

Summary

Harvoni may attain preferred status for HCV genotype 4 patients, and be recommended for genotype 5 patients.

Gilead’s oral triple drug combo (3DAA) was promising for the most common genotype at 6-week treatment durations, which is shorter than the current standard 8 weeks.

The 3DAA could be as successful in trials of other genotypes, and if approved could rake in more revenue than Sovaldi alone.

Gilead Sciences, Inc. (NASDAQ:GILD) reached a market cap of $154.44 billion by dominating the hepatitis C virus (HCV) market with Sovaldi ($10.3 billion in 2014, $8.51 billion in the U.S.; $1.73 billion in Q4 2014, $1.18 billion in the U.S.) and Harvoni (launched in Q4 with $2.11 billion in worldwide sales, mostly U.S.). In U.S. practice, Gilead's two lead products are the sole or among the treatments of choice for every HCV genotype (see Appendix), though officially Sovaldi is approved for patients with genotypes 1-4, while Harvoni is only for patients with genotype 1. Last week, Gilead reported data from several studies of HCV regimens of marketed products Sovaldi, Harvoni, as well as investigational agents GS-9857 (NS3/4A protease inhibitor) and GS-5816 (NS5A inhibitor). The trials covered HCV genotypes 1 through 5, representing more than 99% of HCV patients (see Table 1).

Table 1. Hepatitis C Virus Prevalence in the United States

Genotype 1

70%

Genotype 1a

55% of Genotype 1

Genotype 1b

35% of Genotype 1

Genotype 2

15-20%

Genotype 3

10-12%

Genotype 4

1%

Genotype 5

< 1%

Genotype 6

< 1%

The HCV market is extremely competitive (see Table 2). Abbvie (NYSE:ABBV), Enanta Pharmaceuticals (NASDAQ:ENTA) and Bristol-Myers Squibb (NYSE:BMY) also have commercially available products. In addition, Achillion Pharmaceuticals (NASDAQ:ACHN), Bristol-Myers Squibb and Merck (NYSE:MRK) are working on shorter-duration treatments. Shorter treatments mean the trials will only take a few months, not years. The high prevalence of HCV also makes for rapid enrollment completion. The potential for better treatments in the quickly-evolving space would be blessings for patients, prescribers, and even payors, but they present real threats to Gilead and its shareholders. These new results can help Gilead bolster its leading position in HCV.

Table 2. HCV Combinations (Marketed Products Are in BOLD).

Company/Product

NS3/4A Protease Inhibitors

+

NS5A Inhibitors

+

NS5B (NYSE:NUC) Polymerase Inhibitors

+

NS5B (Non-NUC) Polymerase Inhibitors

Gilead/Harvoni

   

Ledipasvir

 

Sovaldi

   

Gilead

GS-9857

 

GS-5816

 

Sovaldi

   

AbbVie/Viekira Pak

Paritaprevir

 

Ombitasvir

     

Dasabuvir

Bristol-Myers Squibb

Sunvepra

 

Daklinza

     

Beclabuvir

Merck

Grazoprevir

 

Elbasvir

 

MK-3682

   

Achillion

Sovaprevir

 

ACH-3102

 

ACH-3422

   

A Phase 2 trial of Gilead's all-oral triple direct-acting antiviral (3DAA) fixed-dose combination of Sovaldi, GS-9857 and GS-5816 among genotype 1 patients delivered mixed results (see Table 3) as far as rates of sustained virologic response 12 weeks after treatment (SVR12).

Table 3. Results of Sovaldi + GS-5816 + GS-9857 Phase 2 Trial.

Genotype

N

Duration

SVR12

Patient Population

Genotype 1

30

6 weeks

90.0%

Treatment-naïve patients

Genotype 1

15

6 weeks

93.3%

Treatment-naïve, non-cirrhotic patients

Genotype 1

15

6 weeks

86.7%

Treatment-naïve, cirrhotic patients

Genotype 1

30

6 weeks

66.7%

Patients who failed therapy with two or more DAAs

Genotype 1

15

4 weeks

26.7%

Treatment-naïve patients

The 4-week regimen had sub-optimal SVR12, but the 6-week regimen had comparable SVR12 to Harvoni's longer treatments (see Table 4). Gilead believes in this regimen's pan-genotypic potential, and has recently initiated additional Phase 2 studies for patients of the other genotypes, including those with cirrhosis and those who have failed prior therapy with DAAs.

Table 4. Results of Harvoni's Pivotal Trials.

Trial

Genotype

N

Duration

SVR12

Patient Population

ION-3 (Study 0108)

Genotype 1

214

8 weeks

93.9%

Treatment-Naïve Adults without Cirrhosis

ION-3 (Study 0108)

Genotype 1a

171

8 weeks

93.0%

Treatment-Naïve Adults without Cirrhosis

ION-3 (Study 0108)

Genotype 1b

43

8 weeks

97.7%

Treatment-Naïve Adults without Cirrhosis

ION-3 (Study 0108)

Genotype 1

216

12 weeks

96.3%

Treatment-Naïve Adults without Cirrhosis

ION-3 (Study 0108)

Genotype 1a

172

12 weeks

95.9%

Treatment-Naïve Adults without Cirrhosis

ION-3 (Study 0108)

Genotype 1b

44

12 weeks

97.7%

Treatment-Naïve Adults without Cirrhosis

ION-1 (Study 0102)

Genotype 1

213

12 weeks

98.6%

Treatment-Naïve Adults with or without Cirrhosis

ION-2 (Study 0109)

Genotype 1

109

12 weeks

93.6%

Previously-Treated Adults with or without Cirrhosis

ION-2 (Study 0109)

Genotype 1

109

24 weeks

99.1%

Previously-Treated Adults with or without Cirrhosis

BOSON, a randomized Phase 3 study of Sovaldi in combination with ribavirin (RBV) or with pegylated interferon (NYSE:PEG)/RBV in 592 patients with genotypes 2 and 3, was remarkable for the highest cure rates observed among treatment-experienced, cirrhotic genotype 3 patients in any Phase 3 clinical trial to date (compare Tables 5 and 6). Treatment-experienced Genotype 2 patients also demonstrated high SVR12 rates across all treatment arms. Among genotype 3 patients, rates of SVR12 were highest for those receiving Sovaldi plus PEG/RBV. However, these new data only serve to confirm current practice, as prescribers aren't likely to go back to interferon-containing regimens.

Table 5. Results of BOSON (Study 153) Phase 3 Trial.

Genotype

N

Regimen

Duration

SVR12

Patient Population

Genotype 2

16

SOF + PEG/RBV

12 weeks

93.8%

Treatment-experienced patients

Genotype 2

17

SOF + RBV

24 weeks

100.0%

Treatment-experienced patients

Genotype 2

15

SOF + RBV

16 weeks

86.7%

Treatment-experienced patients

Genotype 3

181

SOF + PEG/RBV

12 weeks

92.8%

 

Genotype 3

182

SOF + RBV

24 weeks

84.1%

 

Genotype 3

181

SOF + RBV

16 weeks

70.7%

 

Genotype 3

35

SOF + PEG/RBV

12 weeks

85.7%

Treatment-experienced patients with cirrhosis

Table 6. Results of Sovaldi's Pivotal Trials.

Trial

Genotype

N

Regimen

Duration

SVR12

Patient Population

NEUTRINO (Study 110)

Genotype 1

291

SOF + PEG/RBV

12 weeks

89.3%

Treatment-Naïve Adults

NEUTRINO (Study 110)

Genotype 1a

225

SOF + PEG/RBV

12 weeks

91.6%

Treatment-Naïve Adults

NEUTRINO (Study 110)

Genotype 1b

66

SOF + PEG/RBV

12 weeks

81.8%

Treatment-Naïve Adults

NEUTRINO (Study 110)

Genotype 4

28

SOF + PEG/RBV

12 weeks

96.4%

Treatment-Naïve Adults

FISSION (Study 1231)

Genotype 2

73

SOF + RBV

12 weeks

94.5%

Treatment-Naïve Adults

FISSION (Study 1231)

Genotype 3

183

SOF + RBV

12 weeks

55.7%

Treatment-Naïve Adults

POSITRON (Study 107)

Genotype 2

109

SOF + RBV

12 weeks

92.7%

Interferon Intolerant, Ineligible or Unwilling Adults

POSITRON (Study 107)

Genotype 3

98

SOF + RBV

12 weeks

61.2%

Interferon Intolerant, Ineligible or Unwilling Adults

FUSION (Study 108)

Genotype 2

39

SOF + RBV

12 weeks

82.1%

Previously Treated Adults

FUSION (Study 108)

Genotype 3

64

SOF + RBV

12 weeks

29.7%

Previously Treated Adults

FUSION (Study 108)

Genotype 3

63

SOF + RBV

16 weeks

61.9%

Previously Treated Adults

VALENCE (Study 133)

Genotype 2

73

SOF + RBV

12 weeks

93.2%

Treatment-Naïve and Previously Treated Adults

VALENCE (Study 133)

Genotype 3

250

SOF + RBV

24 weeks

84.0%

Treatment-Naïve and Previously Treated Adults

Finally, a French open-label Phase 2 study demonstrated the efficacy of Harvoni (ledipasvir/Sovaldi) in both treatment-naïve and treatment-experienced patients with genotypes 4 or 5 infection, half of whom had cirrhosis. This new evidence will strengthen the recommendation level for Harvoni in genotype 4 and should make Harvoni the gold standard for genotype 5. Data from all 4 studies were presented at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, which ended Sunday.

Table 7. Results of Phase 2 (Study 1119).

Genotype

N

Regimen

Duration

SVR12

Genotype 4

44

Harvoni

12 weeks

93.2%

Genotype 5

41

Harvoni

12 weeks

95.1%

Looking forward, Gilead revenues will incrementally increase as more genotypes 4 and especially 5 patients are put on Harvoni. Gilead's 3DAA is definitely worth watching as they are shorter than current treatments. Of the 3 Phase 2 trials, Study 1468 will furnish results the earliest. SVR12 may not be available until October, but SVR at 4, 6, and 8 weeks will come sooner. Positive results for the preliminary looks are largely predictive of success for the longer observation periods.

Appendix

Summary of Recommendations for Patients Who are Initiating Therapy for HCV Infection or Who Experienced Relapse after Prior PEG/RBV Therapy, by HCV Genotype

HCV Genotype 1a: Three options with similar efficacy in general are recommended.

  1. Harvoni for 12 weeks*.
  2. Viekira Pak plus twice-daily dosed dasabuvir (250 mg) and weight-based RBV for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis).
  3. Sovaldi (400 mg) plus Olysio (150 mg) daily with or without weight-based RBV for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis).

HCV Genotype 1b: Three options with similar efficacy in general are recommended.

  1. Harvoni for 12 weeks*.
  2. Viekira Pak plus twice-daily dosed dasabuvir (250 mg) for 12 weeks. The addition of weight-based RBV is recommended in patients with cirrhosis.
  3. Sovaldi (400 mg) plus Olysio (150 mg) daily for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis).

HCV Genotype 2: Recommended regimen.

  1. Sovaldi (400 mg) daily and weight-based RBV for 12 weeks. Extending treatment to 16 weeks is recommended in patients with cirrhosis.

Alternative regimens.

None.

HCV Genotype 3: Recommended regimen.

  1. Sovaldi (400 mg) daily and weight-based RBV for 24 weeks.

Alternative regimens.

  1. Sovaldi (400 mg) daily and weight-based RBV plus weekly PEG-IFN for 12 weeks for IFN-eligible, treatment-naive patients with HCV Genotype 3 infection.

HCV Genotype 4: Three options with similar efficacy in general are recommended.

  1. Viekira Pak and weight-based RBV for 12 weeks.
  2. Sovaldi (400 mg) daily and weight-based RBV for 24 weeks.
  3. Harvoni for 12 weeks.

Alternative regimens.

  1. Sovaldi (400 mg) daily and weight-based RBV plus weekly PEG-IFN for 12 weeks.
  2. Sovaldi (400 mg) plus Olysio (150 mg) daily with or without weight-based RBV for 12 weeks.

HCV Genotype 5: Recommended regimen.

  1. Sovaldi (400 mg) daily and weight-based RBV plus weekly PEG-IFN for 12 weeks.

Alternative regimen.

  1. Weekly PEG-IFN plus weight-based RBV for 48 weeks for IFN-eligible, treatment-naive patients with HCV Genotype 5 infection.

HCV Genotype 6: Recommended regimen.

  1. Harvoni for 12 weeks.

Alternative regimen.

  1. Sovaldi (400 mg) daily and weight-based RBV plus weekly PEG-IFN for 12 weeks for IFN-eligible, treatment-naive patients with HCV Genotype 6 infection.

Disclosure: The author is long GILD, ENTA.

The author wrote this article themselves, and it expresses their own opinions. The author is not receiving compensation for it (other than from Seeking Alpha). The author has no business relationship with any company whose stock is mentioned in this article.

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