Within 15 years, it may be possible to cure hepatitis C for
$100-200 for a 12-week treatment course using two direct-acting antivirals plus
ribavirin produced by generic manufacturers, according to an analysis of the
potential for cost savings through generic drug production presented by Dr
Andrew Hill of the University of Liverpool earlier this month at the 7th
International AIDS Society Conference on HIV Pathogenesis, Treatment and
Prevention (IAS 2013) in Kuala Lumpur, Malaysia.
Current costs for hepatitis C triple therapy comprising
pegylated interferon, ribavirin and a first-generation direct-acting antiviral
range from $38,568 for a boceprevir-containing regimen in the United Kingdom to
around $67,000 for a course of treatment containing telaprevir in the United
States.
Improvements in hepatitis C therapy are likely to remain out
of the reach of many people who need them. In India, for example, it is
estimated that around 18 million people have hepatitis C, while in Indonesia 9 million people have hepatitis C.
Although prices for pegylated interferon and ribavirin have
fallen as a result of negotiation in some lower middle-income countries, the
cost of direct-acting antivirals is likely to remain unaffordable for most people in low- and middle-income countries. Although manufacturers have given no indication of the prices they will charge for interferon-free regimens, financial analysts expect to see pricing in the region of $60,000-70,000 in the United States.
Since 2000, the cost of antiretroviral drugs (drugs used to treat HIV) in low- and
middle-income countries has declined as generic manufacturers in India have
begun to produce versions of branded products. Although this move was at first
fiercely resisted by some pharmaceutical companies, almost all drugs used in
HIV treatment in low- and middle-income countries are now manufactured in India
or South Africa by generic producers, often on license from the patent owner.
As a result of these changes, the cost of antiretroviral
therapy for these countries has fallen from more than $10,000 a year in 2000 to
less than $200 a year in 2013 (although middle-income countries outside Africa
continue to pay considerably more).
This process of price reduction has been assisted by the
expiry of patent protection on some key products, together with the lack of
patent protection on older products. Patent protection on direct-acting
antivirals currently in development will begin to expire from 2025, although opportunities
for generic production as a result of voluntary licensing may exist before
patents on some products expire.
The cost of drugs is also determined by the chemicals
required to manufacture them, and the complexity of the chemical processes
involved.
Using data on antiretroviral drug costs gathered by Médecins Sans Frontières, the researchers were able to define price ranges for the
production of drugs of similar chemical structure, complexity and total weight.
They used these price ranges to estimate the cost of a number of direct-acting
antivirals now in phase III development, and to estimate the costs of a number
of interferon-free combinations of these drugs already tested in phase II studies.
Analysis of the chemical structure of direct antivirals for
hepatitis C treatment reveals that they are similar in molecular weight,
complexity and structure to antiretroviral drugs used in HIV treatment. This
means that similar chemical products and processes will be required to
manufacture both classes of drug, allowing the researchers to estimate that the
cost of new direct-acting antivirals for hepatitis C will be no more than ten times
higher than the cost of manufacturing antiretroviral drugs.
Potential product
cost
|
Agent
|
Dose
|
Estimated cost for 12-week
course
|
|
Ribavirin
|
1000mg
|
$21-63
|
|
Ribavirin
|
1200mg
|
$25-76
|
|
Daclatasvir
|
NS5a inhibitor
|
$10-30
|
|
Sofosbuvir
|
Nucleotide analogue, complex synthesis
|
$68-136
|
|
Faldaprevir
|
Protease inhibitor
|
$100-210
|
|
Simeprevir
|
Protease inhibitor: more complex structure
|
$130-270
|
Potential regimen
costs
|
Regimen
|
Duration
|
Estimated cost
|
|
Daclatasvir & sofosbuvir
|
12 weeks
|
$78-166
|
|
Daclatasvir & sofosbuvir
|
24 weeks
|
$156-332
|
|
Sofosbuvir & ribavirin
|
12 weeks
|
$89-199
|
|
Sofosbuvir & ribavirin
|
16 weeks
|
$119-265
|
|
Sofosbuvir & simeprevir & ribavirin
|
12 weeks
|
$219-469
|
|
Sofosbuvir & simeprevir
|
12 weeks
|
$198-406
|
The authors caution that more precise estimates of
production costs will require production of pilot batches of products, as well
as more detailed process chemistry. They also note that, as in the case of HIV,
further reductions in cost could be achieved through work to optimise chemical
synthesis and cheaper sourcing of raw materials. In the case of antiretroviral
drugs for HIV, the Clinton HIV Access Initiative worked with generic
pharmaceutical manufacturers in India, and raw material manufacturers in China,
to re-engineer manufacturing processes to bring down the production costs of
some newer antiretrovirals by 20 to 30%.