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Harvoni: Why hepatitis C focus is a plus for Benitec
With Gilead’s announcement in October of FDA approval for Harvoni, Benitec’s
Senior Vice President of Research & Development, Dr David Suhy, explains why
putting Hepatitis C in the spotlight is good for Benitec.
Hepatitis C: snapshot
Hepatitis C is a liver disease caused by the hepatitis
C virus (HCV). According to the World Health
Organisation, 130-150 million people suffer from
the disease worldwide with 350,000 to 500,000
dying each year1.
There are about 13 million sufferers in the Americas
and Europe, with the highest disease prevalence in
the Middle East, Africa and Asia2. In the USA, over
50% of intravenous drug users suffer hepatitis C3,
which is spread via the blood.
Harvoni: what Gilead says
Harvoni is a once-a-day tablet treatment for
Hepatitis C Genotype 1, which was approved by the
US FDA in October 20144. Harvoni combines
ledipasvir and sofosbuvir (trade name Sovaldi) to
block replication of the virus.
Harvoni eliminates the need to also take Ribavirin
and Interferon, previously part of double or triple
therapies with Sovaldi, and is currently prescribed to
be taken over 12-24 weeks5. Treatment
combinations containing Ribavirin and Interferon
have been noted to cause fatigue, headache,
nausea, insomnia and anemia6 which increased
patient withdrawal and decreased cure rates.
Harvoni has cure rates of between 99.1% and 94%7
and a treatment period of eight, 12 or 24 weeks. The
duration of prescribed treatment depends on the
patients’ treatment history, cirrhosis status and viral
load; the eight week period could be applied to
treatment-naïve patients without cirrhosis and with
a low baseline HCV viral load8.
While the side effects of Harvoni are said to be less
severe than the Ribavirin, Interferon and Sovaldi
treatment, the Prescribing Information confirms
they still include fatigue, headache, nausea, diarrhea
and insomnia9.
Contact us:
www.benitec.com
(02) 9555 6986
When considering the
impact of Harvoni on the
potential hepatitis C
market for TT-034,
factors such as cost,
compliance, re-infection
and mode of action need
to be examined.
A sizeable price tag
In the USA, a 12-week
course of Harvoni will
cost US $94,500 or US
$1,125 per day10
compared to Gilead’s
predecessor Sovaldi (US
$84,000).
“...present focus on
hepatitis C serves to hint
at the scale of the
opportunity for Benitec”
For those with private health insurance, the
Journal of the American Medical Association
estimates that the cost of new HCV therapeutics
could increase each person’s premium by up to US
$300 per year over the next five years11.
For the uninsured in the United States, about
750,000 hepatitis C sufferers receive state-funded
healthcare through Medicaid or the prison
system. Based on Sovaldi pricing, earlier this year
Express Scripts estimated that the USA would foot
a bill of US $55.2 billion if all States made that
regimen available12. Given the higher price for
Harvoni, one would assume the bill for the newer
treatment would also be higher.
1.Hepatitis C Key Facts; WHO
2.Ibid
3.High Risk Groups Hepatitis C in the USA; Epidemic.org
4.U.S. Food and Drug Administration Approves Gilead’s Harvoni;
Gilead; Oct 10, 2014
5.Ibid
6.Patient Information; Sovaldi; Gilead Sciences; Dec 2013
7.Gilead; Op Cit
8.Gilead; Op Cit
9.Prescribing Information for Harvoni; Gilead; Oct 2014
10.Harvoni wins FDA Approval; New York Times; Oct 10, 2014
11.The Journal of the American Media Association; reported by Seattle
Post-Intelligencer
12.State Governments May Spend $55 Billion on Hepatitis C Medications
1
Express Scripts; Jul 17 2014.
Harvoni: Why hepatitis C focus
is a plus for Benitec
Because it has only recently gained regulatory
approval, it’s not clear how many US insurance
companies will offer reimbursement for the Harvoni
treatments. With Sovaldi, some insurers offer
cheaper alternatives that have more side effects and
less efficacy, and offer the more expensive drug only
to the most severe cases13.
With Harvoni and other multiple-dose treatments,
if patients become re-infected, they will have to
commence a new course. This obviously increases
the cost and duration of treatment.
Benitec’s intention has always been to develop
effective drugs that will be accessible in target
markets. Whilst it is far too early to be specific, we
expect a single dose of TT-034 to be priced
competitively to 56-168 doses, the number of pills
required for a 8-week or 24-week course of Harvoni.
The mode of action of Benitec’s TT-034 is quite
different and overcomes the problem of patient
re-infection. TT-034 directs patients’ liver cells to
continuously produce their own molecules to ‘turn
off’ replication of HCV, for as long as the liver cells
live. Thus, TT-034 is designed not only to clear the
infection from the liver, but to provide prophylaxis
and protect the patient’s liver from re-infection by
HCV for months or even years, from a single dose.
Compliance: reality bites
Hep C: a hint of things to come
A key factor in treatment efficacy is compliance
(continuing to take the drug) and it has to be quite
high; for instance, with anti-retroviral drugs for HIV,
compliance needs to be 95% or above for the drugs
to be effective at suppressing AIDS14. During all
clinical trials, patients are very closely monitored, so
compliance rates and therefore cure rates are
usually very high. It is accepted that once drugs
reach the market, compliance tends to drop.
Once drugs are approved and out in the community,
a wide variety of other factors may come into play
that effect compliance: forgetting, being away from
home, being busy, changes in daily routine,
psychiatric disorders and substance use/abuse15. If
patients fail to comply yet wish to be cured, they
must wait a period and start the treatment again,
thereby potentially doubling the cost, increasing the
treatment period and, presumably, skewing the cure
rates.
For Harvoni, patients must take multiple doses (56,
84 or 168 over eight, 12 or 24 weeks) and maintain
high compliance to achieve cure. By contrast,
Benitec’s TT-034 for hepatitis C is administered in a
single infusion, thus compliance or lack thereof will
not be a factor in treatment success.
Re-infection: <25% in some populations
Another factor for success is patient re-infection.
With Hepatitis C in gay men, the re-infection rate
is up to 25%16with secondary re-infection
reported at 23%17.
Contact us: www.benitec.com
(02) 9555 6986
Approval of Harvoni has moved hepatitis C, its
prevalence and significant cost of cure into the
spotlight. However, when compliance and cure
rates are put into perspective, the benefits of a
lower cost, single dose alternative therapeutic like
TT-034 become clearer. The added benefit of
protection against re-infection is compelling.
The implications for Benitec of a successful TT-034
clinical trial are far broader than hepatitis C. Small
molecule drugs like Harvoni are designed to treat
one disease. TT-034 is too, but it’s based on
ddRNAi, Benitec’s broad platform for genesilencing. Once ddRNAi technology is proven safe in
man via the TT-034 clinical trial, it can be applied to
many more disease-causing genes, through a
simple sequence change.
Clearly, ddRNAi has sizable potential beyond
hepatitis C. In fact, present focus on that disease
serves to hint at the scale of the opportunity for
Benitec. This is already occurring: our other inhouse programs based on ddRNAi - hepatitis B,
drug resistant lung cancer, age-related macular
degeneration - are progressing towards the clinic,
by leveraging off the knowledge gained with
TT-034, the first in man Hepatitis C therapeutic.
David Suhy PhD
November, 2014
13.New York Times; Op Cit.
14.Determinants of non-compliance to ARV therapy among
adults; JBI Library of Systematic Reviews
15.Ibid
16.Hepatitis C Reinfection Rising Among HIV Patients; Medscape Medi
cal News, Jul 11, 2013
17.Hepatitis C virus reinfection incidence and treatment outcome 2
among HIV-positive MSM. PubMed. Oct 2013