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Spotlight Series on Hepatitis C

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Hepatitis C Drug Pipeline Update

June 2016

pipeline

Credit: scherbet for iStock via Thinkstock


The current drugs to treat hepatitis C have high cure rates and minimal side effects (compared to the older therapies). This has created a dilemma for drug developers who must develop new drugs that somehow improve upon the current drugs. This is a difficult task, but not impossible. Probably the biggest achievement will be shorter treatment duration and lower cost. There is a percentage of patients who are the more difficult to treat, such as those with genotype 3 who have cirrhosis and have not achieved a cure with a previous course of therapy. The race is on for new, better and cheaper therapies -- this is very good news for people living with chronic hepatitis C.

You will see below that the need for these new therapies has narrowed the pharmaceutical companies to a number that you can count on your fingers! As a result I have decided to rework our pipeline and list it by the pharmaceutical company. I am also just listing the major studies. This is also a new pipeline that will grow as information is released. The pipeline is a brief overview. More extensive information is listed in our newsletters and in our blog.

A brief overview of how this pipeline is laid out:

Date: The Pipeline will be updated on a monthly basis and will be included with the HCV Advocate Newsletter

Genotype(s): This lists the drugs or combination of drugs and the particular gentoype or genotypes that the drug is active against.

Comments: This section will list the study results. Within this section, I will list the genotype(s) being studied and the phase of the study with a brief recap of the study.

You will note that many of the drugs or combinations of drugs are pan-genotypic -- that is they work on many or most of the HCV genotypes.

Note: Many of the drugs listed below have been updated with the latest information from the Liver Meeting 2015 and and the International Liver Congress 2016. More detailed information about drugs in development is available in our blog and reported in the HCV Advocate newsletters.


AbbVie

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Genotype(s): 1, 2, 3, 4, 5, 6 (Pan-genotypic)

Comments

Genotype 1 -- Phase 2 Study: Information from the International Liver Congress 2016: AbbVie's once-daily therapy of ABT-493 (protease inhibitor) and ABT-530 (NS5A inhibitor).

Non-cirrhotic patients Treatment period -- 8 weeks:

  • Genotype 1: 85% were treatment-navie; 15% were pegylated interferon(PEG)/ribavirin (RBV) experienced, cure rates -- 97% (33 of 34 patients)
  • Genotype 2: 87% were treatment-navie: 87% were PEG/RBV treatment experienced: cure rate -- 98% (53 of 54 pts)
  • Genotype 3: 100% were treatment-navie: cure rate -- 97% (28 of 29 pts)

Treatment period 12 weeks:

Cirrhotic treatment-naive patients, genotype 3 -- cure rate -- 100% (24 of 24 patients) Non-cirrhotic treatment-navie patients (85%), PEG/RBV (15%); genotype 4 (22 pts), genotype 5 (1 pt), genotype 6 (11 pts) -- cure rate -- 100% (34 of 34 pts)

Bottom line: cure rates were 97% to 100%.


Gilead

Genotype 1,2,3,4,5,6, (Pan-genotypic)

Comments

  • Genotype 1 -- Phase 3: Sofosbuvir plus velpatasvir (GS-5816) In Phase 3 clinical trials (ASTRAL-1-4), the cure rates in genotypes 1 through 6 ranged 97% to 100%. Gilead has applied for marketing approval to the Food and Drug Administration, (FDA) and approval is expected in 2016. The most common side effects were headache, fatigue, sore throat, runny nose, and nausea. In January 2016 the combination received priority review status and Gilead stated that FDA approval is expected by June 28, 2016. To view the Phase 3 data go here.
  • Genotype 1 and 3 -- Phase 2: Information from ILC 2016: In the group of treatment-navie patients treated for 6 weeks the cure rate was 79% (53 of 67 pts); the treatment-navie group that was treated for 8 weeks the cure rate was 96% (95 of 99 pts).

In another study to treat people who are treatment experienced genotype 1 through 6 and who had been treated with a previous course treatment -- prior NS5A-experienced (27%); non-NS5A-experienced (52%), direct-acting antiviral-experienced (DAA (52%), and 21% that failed an interferon-based therapy without a DAA. The cure rate was 99% (127 of 128 pts).

In yet another study GS-9857 with sofosbuvir/velpatasvir was tested to treat DAA experienced genotype 1 patients with cirrhosis. The treatment period was 12 weeks. The cure rate was 100% (24 of 24 pts).

The bottom line: the cure rates were in the 79% to 100% in people treated 6 to 12 weeks.

The combination of sofosbuvir, velpatasvir and GS-9857 is currently in phase 3 clinical trial (POLARIS 1,2,3 and 4). The Food and Drug Administration (FDA) has granted the combination as Breakthrough Therapy for those who have previously failed an NS5A Inhibitor-containing regimen.


Janssen (Achillion/Alios)

Genotype 1,2,3,4,5,6 (Pan-genotypic)

Comments

  • Genotype 1 -- Phase 1: In a small study of samatasvir, it was found to be safe and have antiviral properties against genotype 1, 2, 3 and 4. There is now a phase 2 study of samatasvir plus Olysio (simeprevir) in treatment-naïve patients with genotype 1b or 4.
  • Genotype 1: Janssen (Alios Pharma) has initiated a phase 2a study of AL-335, odalasvir, and simeprevir to treat HCV genotype 1 treatment-navie patients. There will be 60 patients divided into three treatment arms who are treated for 4, 6 or 8 weeks.
  • Genotype 1 -- Phase 2 Study: ACH-3422 and Odalasvir (ACH-3102) and Sovaprevir are in studies with various combinations. Recently, Johnson & Johnson Innovation -- JJDC, INC (Janssen) made an investment in Achillion for co-development and distribution.
  • Genotype 1 -- Phase 2 Study: Odalasvir plus sofosbuvir (used as a proxy drug) to treat genotype 1 patients for 6 weeks achieved 100% (12 of 12 patients) cure rates. A proxy drug is a drug used to stand in for another drug. Sofosbuvir is a polymerase inhibitor so it is assumed that odalasvir plus a polymerase inhibitor that is being developed by Achillion will produce similar cure rates.
  • Genotypes 1 through 6 -- Phase 2b Study: Odalasvir, AL-335, and simeprevir in treatment-naive and treatment-experienced patients with and without cirrhosis. The trial will enroll 400 patients for six or eight weeks. The study will include four arms with different combinations of drugs. The trial will begin in June 2016 and end in July 2017.


Merck

Genotype 1, 2, 3, 4, 5, 6 (Pan-genotypic)

Comments

  • Phase 2: The study was to evaluate the safety and efficacy of an all-oral therapy. There were three different groups that included treatment-naïve, non-cirrhotic patients. The patient population included 93 genotype 1 patients, 61 genotype 2 patients, and 86 genotype 3 patients. The treatment duration was 8 weeks. All of the treatment groups received MK-3682 (300 mg or 450 mg) combined with grazoprevir/elbasvir or grazoprevir/MK-8408.

Twenty-four percent of genotype 1 patients had resistant associated variants (RAVs): 59% had NS3 (protease) RAVs and 21% had NS5B (polymerase) RAVs.

The overall cure rates were 91 to 100% in the genotype 1 groups; 60 to 94% in the genotype 2, and 86 to 91% in genotype 3. The drugs were well-tolerated with no treatment discontinuations.

Part B of C-CREST 1 and 2 will evaluate the most effective dose to treat prior treatment failures, cirrhotic patients and treatment in people with HIV/HCV coinfection.

Bottom line: The most effective dose was associated with cure rates in the 90 to 100%.


Regulus

Genotype 1, 2, 3, 4, 6

Comments

The study included 79 treatment-naive genotype 1 and 4 patients. RG-101 is a GalNAc-conjugated anti-miR targeting miR-122, a host factor for HCV infection. It is an injectable medication given at Day 1 and Day 29 plus 4 weeks of a once-a-day direct-acting antiviral medication -- Harvoni (27 patients), Olysio (27 patients), Daklinza (25 patients). Sixty-four of the patients were evaluated through week 8 of follow-up, 41 reached 12 weeks post treatment.

The cure rate was 97% (40 of 41 pts).




This article was provided by HCV Advocate. Visit HCV Advocate's website to find out more about their activities and publications.

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