Companies are in discussion with advocates about other
access arrangements, but many advocates fear that the lack of data on the use
of new hepatitis C drugs in people with cirrhosis and in those who have
received liver transplants will prove a barrier to access.
Professor Thomas Berg, head of the Division of Hepatology at
the University Hospital, Leipzig, warned that some hepatitis C drugs have shown
unexpected serious toxicities, resulting in deaths in several studies. Professor
Berg suggested that compassionate access to new HCV drugs would be best
organised through specialised centres that have the capacity to manage serious
adverse events and to monitor patients carefully.
“Physicians may not be well trained in the use of HCV drugs.
Physicians also need to have long-term experience of managing the relevant
patient population,” he said.
Physicians are also
concerned about the lack of drug interaction data, particularly in patients
taking immunosuppressive drugs after liver transplantation. Some are also
concerned about the risk of serious side-effects if the drugs are used in
people with decompensated cirrhosis who are on the waiting list for a liver
“I think it is unethical at this moment not to do a study in people on the transplant waiting list,” said
Luis Mendão of the Portuguese activist group GAT. Treating patients with
cirrhosis and those on the waiting list has the potential to avoid the need for
liver transplantation, said Tracy Swan, Hepatitis/HIV
Project Director of the Treatment Action Group.
The rate of progression from compensated to decompensated
cirrhosis is high – approximately 5-7% of people with compensated cirrhosis
will progress to decompensation each year, Ivan Gardini pointed out. (Patients
with higher hepatic venous gradients are at greater risk of decompensation).
Yet data from
the French ATU programme and from Austrian liver centres show the high risk
of serious adverse events in patients with cirrhosis, said Prof. Pratis. Patients
with highest risk of decompensation were also at the highest risk for severe
infections during triple therapy, Austrian researchers found.
Drug-drug interactions remain a particular concern in people
with cirrhosis. Unlike in HIV, where companies had no option but to study drugs
in the sickest patients first, hepatitis C drugs are being tested first in
trials that either exclude cirrhotics or recruit small numbers. This makes it
difficult to draw conclusions about safety and drug-drug interactions.
“Drug-drug interactions should not be an exclusion criteria
for cirrhotics,” said Luis Mendão.
The other population who need compassionate access are
people with HV and HCV co-infection.
“People with HIV and hepatitis C co-infection are likely to
form a disproportionate part of the population needing new drugs because of
faster progression of liver disease,” said Luis Mendão, who is living with HIV
and hepatitis C.
Ivan Gardini urged that compassionate access programmes
should exclude as few patients as possible, and that patients rather than
doctors should make the final decision about the degree of risk they are
prepared to accept. “We need doctors to have the courage to try something that
they don’t know,” he said.