Originally Published July 15, 2015
The current standard of care for treating HCV is
currently Harvoni and Viekira PAK for genotype 1, Sovaldi plus ribavirin
to treat genotype 2 and 3, and Sovaldi plus pegylated
interferon/ribavirin to treat genotype 4. There are a couple of
combinations of drugs submitted to, and likely to be approved by, the
Food and Drug Administration (FDA) by the end of this year or early
next year. Additionally, many more drugs are being developed that are
in early to mid-stage development. These medications hold the promise
to cure even more people with HCV genotypes 1 through 6. This month’s
“The Five” will discuss the most promising drugs in development.
Grazoprevir/Elbasvir (one pill/once-a-day) in treatment-naïve and
treatment-experienced patients infected with HCV genotype 1, 4 or 6 and
treated for 12 weeks. The cure rates were up to 100%. There were
issues with NS5A resistance, but Merck is conducting more clinical
trials with NS5A inhibitors to overcome this problem. Merck has filed
a New Drug Application earlier this year. Merck was awarded
Breakthrough Therapy Designation by the FDA for genotype 4 and to treat
those with severe kidney disease—the studies above included patients
with genotype 4 and severe kidney problems. FDA approval is expected
by year end.
- Bristol-Myers Squibb (BMS): BMS has two drug combinations that are being tested to treat hepatitis C.
Daclatasvir plus sofosbuvir has been awarded Breakthrough Therapy
Designation for patients with advanced cirrhosis and those with HCV
genotype 1 with HCV post-liver transplant. In the Ally-1 study, the
cure rates of the patients with advanced cirrhosis were 82% for
genotypes 1 and 94% for the post-patients with genotype 1.
has completed their phase 3 clinical trials of daclatasvir plus
sofosbuvir and submitted their data to the FDA for approval. In the
trials treatment naïve people treated for 12 weeks with the combination
of daclatasvir/sofosbuvir achieved cure rates of 90%, and 86% in
people who are treatment experienced. In people who did not have
cirrhosis, the cure rates were 96%. These are very high cure rates.
BMS also has a fixed-dose
single-pill regime (daclatasvir, asunaprevir, beclabuvir) to treat HCV
genotype 1a and 1b that is taken twice daily for 12 weeks. There were
two separate studies that included treatment naïve and treatment
experienced patients with and without cirrhosis. The studies also
included arms with and without ribavirin. The overall cure rates were
up to 98% with ribavirin and 93% without ribavirin. Breaking it down
by subtype—genotype 1b had approximately 10% higher cure rates than
genotype 1a. The cure rates observed in the ribavirin groups were not
The second single-pill
combination listed above hasn’t been submitted to the FDA but it is
expected to be submitted soon, and approval is expected mid-2016.
plus GS-5816 with and without ribavirin. In a phase 2 study of 104
genotype 3 patients treated for eight weeks the cure rates were up to
100%. GS-5816 is active against genotypes 1-6 (pangenotypic). It is
listed in www.clinicaltrials.gov as a phase 3 trial that is active but
not recruiting. The phase 3 study will be a fixed
dose of one pill with both drugs given once a day to treat genotypes 1
through 6. The treatment duration will be either 8 or 12 weeks.
Olysio made a big splash last year as a combination with sofosbuvir
with major prescriptions and high cure rates. They have acquired
Vertex’s HCV drugs in development (ALS-2200). This year Janssen signed
an agreement to codevelop and commercialize Achillion’s inhibitors
(ACH-3102, ACH-3422 and sovaprevir). Although no data is available,
it should make for a very interesting 2015-2016. If I can steal a
common term, they seem to have a very robust pipeline. As listed
above, Janssen many opportunities to develop and commercialize HCV drugs
for the short term and long term. Keep on eye on Janssen.
In cooperation with Enanta, AbbVie is testing ABT-493, plus ABT-530
with and without ribavirin to treat genotypes 1 through 6 for 8 to 12
weeks. The drugs are in phase 2 studies.
The Merck approval is expected
soon. The BMS plus sofosbuvir is also expected to be approved soon.
The new Gilead drugs are likely to be approved by next year and will be
followed by the second BMS combination, Janssen’s combinations, and
AbbVie’s. Hopefully, more agents will be discovered that will show
even more promise, and we just may have a market that is flooded with
excellent drugs that will work for everyone.
Be sure to keep an eye out for the return of the HCV Advocate Drug Pipeline in September!