—Alan Franciscus, Editor-in-Chief
It’s always difficult coming up with the top news
items, but in the last few years it has been even more difficult
because of the accelerated rate of HCV drug development and the
increased attention given to hepatitis C in the news. This translates
to a lot of really good news. The “Good News,” however was
confined to the development of drugs, the Baby Boomer testing
recommendation, the discovery of another HCV genotype and the
development of a structural picture of an HCV protein that may be the
key to the creation of an HCV vaccine. There were also some news items
about HCV outbreaks in 2013 and verdicts from trials of people who
were accused of contributing to HCV outbreaks in the past.
It is usually difficult to come up with
the number 1 item and this year was no exception; so we decided that
two different news items topped our list—the Food and Drug
Administration’s (FDA) approval of sofosbuvir combination therapy to
treat HCV genotypes 1,2,3, and 4 and the recommendation that the
United States Preventive Services Task Force (USPSTF) made for a
one-time test for everyone born from 1945 to 1965 for hepatitis C.
recommendation from the USPSTF for a one-time test for everyone born
from 1945 to 1965 (based on the CDC recommendations) has the potential
to save many thousands of lives by identifying over 800,000 people with
hepatitis C and, hopefully, getting the people who are diagnosed into
medical care and treatment. Although the uptake on testing has been
slow it will hopefully increase in 2014. New York State took the USPSTF
and CDC recommendations to heart and passed legislation that a
one-time test had to be offered to baby boomers when seeing their
primary care doctor or when receiving hospital inpatient and outpatient
care. Way to go New York!
December Gilead’s blockbuster drug received FDA approval. The
combination of Sovaldi (once-a-day pill), pegylated interferon (weekly
injection) and ribavirin (dosed twice-a-day based on body weight) was
approved to treat HCV genotypes 1 and 4. The cure rates of 89% for
people with HCV genotype 1 and 96% for HCV genotype 4 were achieved
after only 12 weeks treatment duration. Furthermore, the FDA approved
the first interferon-free therapy—Sovaldi plus ribavirin to treat HCV
genotypes 2 and 3. The cure rates for HCV genotype 2 were up to 93%
for people who were treated for 12 weeks and 84% for HCV genotype 3 who
were treated for 24 weeks. The FDA also approved Sovaldi for the
treatment of people who are coinfected with HIV/HCV and for people with
kidney impairment. Patients with liver cancer who are waiting for a
liver transplant can be treated with Sovaldi plus ribavirin. The FDA
approved the treatment of Sovaldi plus ribavirin (without interferon)
for people who are HCV genotype 1 interferon ineligible—the recommended
treatment duration is 24 weeks.
The side effects of the triple therapy (PEG/RBV and Sovaldi)
was mostly from interferon—fatigue, headache, nausea, insomnia and
anemia. The side effects from Sovaldi plus ribavirin (no interferon)
for genotype 2 and 3 therapy were fatigue and headache.
November, Janssen’s new protease inhibitor triple combination therapy
was approved to treat HCV genotype 1. Olysio, pegylated interferon
plus ribavirin therapy cured up to 80% of treatment-naïve patients and
79% of prior relapsers. Olysio is a once-a-day pill.
a study of the combination of Sovaldi and Olysio with and without
ribavirin results showed very high cure rates (in one group 100%) in
HCV genotype 1 people with cirrhosis. Although FDA approval of this
combination therapy is highly unlikely, the off-label use may be an
option for those who have no other treatment options.
All of drugs awarded “Breakthrough Therapy” status by the
FDA made our list this year—the award is for potential treatments for
serious medical conditions for drugs that have been shown to provide a
substantial improvement compared to drugs that are currently
To date there have been two (out of six) Phase 3 study results released
of AbbVie’s interferon-free therapy. The topline results in the first
trial (631 treatment-naïve patients) reported cure rates of 95% in HCV
genotype 1a and 98% in HCV genotype 1b for patients who were treated
for 12 weeks. The second trial (394 treatment-experienced patients)
reported cure rates of 96% for genotype 1a and 97% for genotype 1b.
Forty-nine percent of the patients in the second trial were prior null
responders—the most difficult patient population to treat. The
medications in the studies included ABT-333 plus ribavirin (both dosed
twice daily) plus a fixed dose of ABT-450/ritonavir co-formulated with
ABT-267 (one pill of ABT-450/ritonavir plus ABT-257 taken once-daily).
has interferon-free studies in Phase 3 that included 1,952 HCV genotype 1
patients who received Sovaldi (sofosbuvir) plus ledipasvir without
ribavirin, or sofosbuvir, ledipasvir with ribavirin and who were
treated for 8, 12 or 24 weeks. The results reported were from the 8 and
12-week treatment duration arms. The cure rates were 93% to 99%. The
study results from the 24-week treatment duration arm (434 patients)
are not yet available. The study included 1,512 treatment-naïve and
440 treatment-experienced patients; 224 patients had cirrhosis.
there is a 3-drug combination being developed by BMS to treat hepatitis
C currently in Phase 3 studies. The combination of daclatasvir,
asunaprevir and BMS-791325 in an early dose-ranging study of 166
patients: HCV genotype 1a (82%) and genotype 1b (18%). The cure rate
was 92% in patients regardless of subtype.
was recently awarded “Breakthrough Therapy” status for the
combination of MK-5172, MK-8742 and ribavirin. In a small phase 2
study that reported on 58 patients cure rates were 96 to 100% These
drugs are currently in early studies.
Although not awarded ‘Breakthrough Therapy’ Boehringer
Ingelheim’s faldaprevir has been granted accelerated assessment from
the European Medicines Agency. The Phase 3 studies of faldaprevir, BI
207127 and ribavirin were begun in November 2013. In a small
dose-ranging Phase 2 study cure rates of up to 47% in HCV genotype 1a
and up to 75% in the HCV genotype 1b group were reported. The study
included different treatment durations and different dosing schedules.
It has been theorized for some time that there are more than
the six genotypes of HCV we know about. This year, a seventh genotype
was discovered—genotype 7. In addition to the identification of another
genotype the researchers also identified another 67 subtypes.
Scientists at the Scripps Research Institute developed a
structural picture of the HCV protein known as E2 envelope
glycoprotein. It is believed that this protein may be the key to
developing an effective vaccine to protect against hepatitis C. It is
estimated that 170 to 200 million people worldwide are infected with
hepatitis C. This discovery of a vaccine to prevent HCV and
medications to cure HCV could potentially eradicate HCV.
Treatment & Disease Progression
There was finally a verdict in the largest hepatitis C
outbreak in the United States—64,000 people who had procedures at a Las
Vegas, NV endoscopy center were exposed to blood borne pathogens. Of
those who were tested, 7 were diagnosed with HCV and, sadly, one person
died. Dr. Dipak Desai was found guilty of second-degree murder for
the death of the patient—Rodolfo Meana. He was also convicted on 26
criminal counts and convicted of insurance fraud. Desai was sentenced
to life in prison. The anesthetist Ronald Lakeman was found guilty of
16 counts and sentenced to 8 to 21 years in prison.
Another tragic outbreak—David
Kwiatkowski, a traveling medical technician who infected at least 45
people with hepatitis C was found guilty of 16 federal charges of drug
theft and tampering. Kwiatkowski was caught switching out syringes
filled with pain medication for the syringes he used when he injected
himself with the stolen pain medication. Kwiatkowski pleaded guilty and
was sentenced to 39 years in prison.
Was justice served? I will leave it up to our readers to decide, but personally I’m not so sure.
Waiting for Justice?
In 2013, unfortunately, another large outbreak of HCV
occurred at a medical center. The outbreak was at a dental practice in
Tulsa, Oklahoma. Dr. Harrington exposed 7,000 people to hepatitis C,
hepatitis B and HIV due to unsafe safety practices. Of the 4,202 who
have been tested so far, 89 tested positive for hepatitis C, 4 for HBV
and 1 for HIV. The investigation and testing continues. Harrington
has been charged with 17 criminal counts.
This was the first documented outbreak that has occurred at a dental practice.
In yet another large HCV outbreak, this
time in a long-term care facility in Minot, North Dakota. So far 500
people have been tested and of those 35 cases of HCV have been
confirmed. The state health department and the CDC are investigating
the outbreak, but have not yet found the cause of the exposure.
Note: It’s important to be clear
about these outbreaks. The exposures occurred because someone (or
many someone’s) didn’t follow universal or safety precautions.
On October 27, 2013 we lost a true pioneer in the music
field—Lou Reed died of complications from hepatitis C. Reed was a
founding member of the avant-garde rock band, Velvet Underground, and
later had a successful solo career. One of his most popular songs and
one that became an anthem for many was “Take a Walk on The Wild Side.”
Source: HCV Advocate Newsletter: January 2014