June 14, 2013
The FDA Makes Hepatitis C a Priority
by Benjamin Ryan
Recognizing that investigational
drugs from three pharmaceutical companies show advantages over existing
hepatitis C therapies, the FDA has sped up its development and review process
for the therapies.
With pharmaceutical companies clamoring to bring to market second-generation direct
acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV), the U.S.
Food and Drug Administration (FDA) has recently given a trio of companies a
significant leg up. Two promising investigational agents—Gilead Sciences’
nucleotide analogue inhibitor sofosbuvir and Janssen’s protease inhibitor
simeprevir—each received what is known as a priority review status from the FDA
over the past few weeks. And in early May, the FDA tapped AbbVie’s
interferon-free combination therapy, ABT-450/r, ABT-267 and ABT-333 (which has
been studied both with and
without ribavirin) as a “breakthrough therapy,” qualifying those drugs for an
expedited development and review process in preparation for FDA approval.
The FDA grants priority review to drugs in development that appear to
offer significant advantages over available therapies. As of now, there are two
FDA-approved DAAs to treat hep C: Incivek (telaprevir) and Victrelis
(boceprevir), each of which cures about 50 to 75 percent of those who undergo
therapy lasting between 24 and 48 weeks. Both must be taken with ribavirin and
also interferon, an injectable drug that often causes difficult, flu-like side
effects. So at this stage, the FDA’s imprimatur for the investigational
therapies, while not necessarily a promise of the final stamp of approval, marks
an official recognition that the research indicates these new drugs will likely
improve on the current crop of therapeutic options on various fronts.
Simeprevir, for one, has shown in clinical trials to have
somewhat higher cure rates than today’s DAAs, but its major advancements are in
its once-a-day dosing, its reduction of side effects and its shorter duration of
therapy. Sofosbuvir, meanwhile, has been a champion of sorts throughout the
clinical trials process, consistently boasting high cure rates when used in
combination with other drugs in development: either Bristol-Myers Squibb’s daclatasvir or Gilead’s
own ledipasvir (the company
has longer-range plans to develop sofosbuvir and ledipasvir as a fixed-dose
pill).
For practical purposes, the priority review is intended to cut
down the FDA’s review process, which begins 60 days after a new drug application
(NDA) is filed, from the standard 10 months to six. Companies that receive
priority review also get additional guidance from the FDA to expedite the
development and approval process. On March 28, Janssen filed its NDA for
simeprevir, to be taken with ribavirin and interferon for treatment of those
with genotype 1 of hep C; as such, the company expects an answer from the FDA in
late November. Gilead is just a couple
weeks behind in the same process; it’s seeking approval for sofosbuvir to be
administered as an all-oral therapy with ribavirin among those with genotype 2
or 3, and in combination with ribavirin and interferon for genotypes 1, 4, 5 and
6.
By comparison, Incivek and Victrelis each received priority review
designation in January 2011 and were approved in May that same year.
Achieving breakthrough therapy status, on the other hand, promises a more
dynamic range of benefits to AbbVie, which is the first company developing an
HCV therapy that has received the designation. Intended to expedite the
development and review of investigational drugs when clinical trial data shows
they promise at least one significant improvement over currently available
treatments, the designation means AbbVie receives, for starters, fast track
designation. This allows a pharmaceutical company to submit elements of its
marketing application before submitting its complete application for the drug.
Among other benefits, the breakthrough therapy designation also grants AbbVie
more FDA involvement in the combo therapy development—for example, by providing
increased access to the agency’s senior management, as well as giving practical
advice and helping design clinical trials that are as efficient as
possible.
Alan Franciscus, executive director of the Hepatitis C Support
Project in San Francisco, said that AbbVie’s breakthrough status was awarded
“clearly because of the less frequent dosing and pill burden, lower side effects
and high cure rates” when compared with Incivek and Victrelis.
“I
believe that this will greatly accelerate the approval process, especially if
the FDA has stated that they will provide guidance during the development and
approval process,” Franciscus says.
But even with all this extra help,
AbbVie’s combo is still running behind its competitors, not having submitted an
NDA. Furthermore, sofosbuvir and simeprevir have been researched as an interferon-free combination
therapy with one another: Taken with or without ribavirin, they were found in a
recent study to boast high cure rates among those with genotype 1 of hep C. If
both drugs receive FDA approval, clinicians are free to prescribe them together
off-label, providing yet another option outside the FDA-sanctioned uses for
people with hep C.
Daniel Fierer, MD, an assistant professor of medicine
in infectious diseases at Mount Sinai School of Medicine in New York City,
projects that “since simeprevir and sofosbuvir were already expected to hit the
market soonest, probably at the same time, the only thing I can see is that
maybe AbbVie moves up its timeline a little. But if it doesn’t move it up to
being out before [Janssen’s simeprevir and Gilead’s sofosbuvir] come to the
table, they will start eating without AbbVie, and then it’ll be leftovers for
lunch.”
Indeed, there is much excitement over these drugs in the
pipeline, as well as over the larger wave of interferon-free regimens that
should arrive a bit further down the line. Franciscus acknowledges this but also
hopes that the hubbub doesn’t distract physicians from the hep C patients who
have urgent therapeutic needs.
“What really scares me is that people with
HCV and their medical providers are waiting for the interferon-free drug
approval, but there are definitely some people who should be treated now—it
could be dangerous to wait,” he says. “There is never a guarantee that the
interferon-free drugs will work for
everyone.”
Search: Hepatitis C virus, HCV, hep C, priority review, fast track, breakthrough therapy, U.S. Food and Drug Administration, FDA, AbbVie, Gilead Sciences, Bristol-Myers Squibb, sofosbuvir, daclatasvir, ABT-450/r, ABT-267, ABT-333, ribavirin, interferon, Incivek, telaprevir, Victrelis, boceprevir, simeprevir, Alan Franciscus, Daniel Fierer.
The FDA Makes Hepatitis C a Priority
by Benjamin Ryan
Recognizing that investigational
drugs from three pharmaceutical companies show advantages over existing
hepatitis C therapies, the FDA has sped up its development and review process
for the therapies.
With pharmaceutical companies clamoring to bring to market second-generation direct
acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV), the U.S.
Food and Drug Administration (FDA) has recently given a trio of companies a
significant leg up. Two promising investigational agents—Gilead Sciences’
nucleotide analogue inhibitor sofosbuvir and Janssen’s protease inhibitor
simeprevir—each received what is known as a priority review status from the FDA
over the past few weeks. And in early May, the FDA tapped AbbVie’s
interferon-free combination therapy, ABT-450/r, ABT-267 and ABT-333 (which has
been studied both with and
without ribavirin) as a “breakthrough therapy,” qualifying those drugs for an
expedited development and review process in preparation for FDA approval.
The FDA grants priority review to drugs in development that appear to
offer significant advantages over available therapies. As of now, there are two
FDA-approved DAAs to treat hep C: Incivek (telaprevir) and Victrelis
(boceprevir), each of which cures about 50 to 75 percent of those who undergo
therapy lasting between 24 and 48 weeks. Both must be taken with ribavirin and
also interferon, an injectable drug that often causes difficult, flu-like side
effects. So at this stage, the FDA’s imprimatur for the investigational
therapies, while not necessarily a promise of the final stamp of approval, marks
an official recognition that the research indicates these new drugs will likely
improve on the current crop of therapeutic options on various fronts.
Simeprevir, for one, has shown in clinical trials to have
somewhat higher cure rates than today’s DAAs, but its major advancements are in
its once-a-day dosing, its reduction of side effects and its shorter duration of
therapy. Sofosbuvir, meanwhile, has been a champion of sorts throughout the
clinical trials process, consistently boasting high cure rates when used in
combination with other drugs in development: either Bristol-Myers Squibb’s daclatasvir or Gilead’s
own ledipasvir (the company
has longer-range plans to develop sofosbuvir and ledipasvir as a fixed-dose
pill).
For practical purposes, the priority review is intended to cut
down the FDA’s review process, which begins 60 days after a new drug application
(NDA) is filed, from the standard 10 months to six. Companies that receive
priority review also get additional guidance from the FDA to expedite the
development and approval process. On March 28, Janssen filed its NDA for
simeprevir, to be taken with ribavirin and interferon for treatment of those
with genotype 1 of hep C; as such, the company expects an answer from the FDA in
late November. Gilead is just a couple
weeks behind in the same process; it’s seeking approval for sofosbuvir to be
administered as an all-oral therapy with ribavirin among those with genotype 2
or 3, and in combination with ribavirin and interferon for genotypes 1, 4, 5 and
6.
By comparison, Incivek and Victrelis each received priority review
designation in January 2011 and were approved in May that same year.
Achieving breakthrough therapy status, on the other hand, promises a more
dynamic range of benefits to AbbVie, which is the first company developing an
HCV therapy that has received the designation. Intended to expedite the
development and review of investigational drugs when clinical trial data shows
they promise at least one significant improvement over currently available
treatments, the designation means AbbVie receives, for starters, fast track
designation. This allows a pharmaceutical company to submit elements of its
marketing application before submitting its complete application for the drug.
Among other benefits, the breakthrough therapy designation also grants AbbVie
more FDA involvement in the combo therapy development—for example, by providing
increased access to the agency’s senior management, as well as giving practical
advice and helping design clinical trials that are as efficient as
possible.
Alan Franciscus, executive director of the Hepatitis C Support
Project in San Francisco, said that AbbVie’s breakthrough status was awarded
“clearly because of the less frequent dosing and pill burden, lower side effects
and high cure rates” when compared with Incivek and Victrelis.
“I
believe that this will greatly accelerate the approval process, especially if
the FDA has stated that they will provide guidance during the development and
approval process,” Franciscus says.
But even with all this extra help,
AbbVie’s combo is still running behind its competitors, not having submitted an
NDA. Furthermore, sofosbuvir and simeprevir have been researched as an interferon-free combination
therapy with one another: Taken with or without ribavirin, they were found in a
recent study to boast high cure rates among those with genotype 1 of hep C. If
both drugs receive FDA approval, clinicians are free to prescribe them together
off-label, providing yet another option outside the FDA-sanctioned uses for
people with hep C.
Daniel Fierer, MD, an assistant professor of medicine
in infectious diseases at Mount Sinai School of Medicine in New York City,
projects that “since simeprevir and sofosbuvir were already expected to hit the
market soonest, probably at the same time, the only thing I can see is that
maybe AbbVie moves up its timeline a little. But if it doesn’t move it up to
being out before [Janssen’s simeprevir and Gilead’s sofosbuvir] come to the
table, they will start eating without AbbVie, and then it’ll be leftovers for
lunch.”
Indeed, there is much excitement over these drugs in the
pipeline, as well as over the larger wave of interferon-free regimens that
should arrive a bit further down the line. Franciscus acknowledges this but also
hopes that the hubbub doesn’t distract physicians from the hep C patients who
have urgent therapeutic needs.
“What really scares me is that people with
HCV and their medical providers are waiting for the interferon-free drug
approval, but there are definitely some people who should be treated now—it
could be dangerous to wait,” he says. “There is never a guarantee that the
interferon-free drugs will work for
everyone.”
Search: Hepatitis C virus, HCV, hep C, priority review, fast track, breakthrough therapy, U.S. Food and Drug Administration, FDA, AbbVie, Gilead Sciences, Bristol-Myers Squibb, sofosbuvir, daclatasvir, ABT-450/r, ABT-267, ABT-333, ribavirin, interferon, Incivek, telaprevir, Victrelis, boceprevir, simeprevir, Alan Franciscus, Daniel Fierer.
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