Abbott hepatitis C drugs bring high cure rates in trial
Ransdell Pierson Reuters
11:34 a.m.
CST, November
10, 2012
(Reuters) - A trio of oral medicines from Abbott
Laboratories Inc to treat hepatitis C produced unprecedented cure rates in
patients who had failed to benefit from standard treatment, as well as very high
cure rates for newly treated patients, Abbott said on Saturday.
Detailed
data from the mid-stage trial, called Aviator, were released Saturday at the
annual meeting of the American Association for the Study of Liver Disease
(AASLD) in Boston.
Investors and patients have very high hopes for the
Abbott drugs - a protease inhibitor called ABT-450, a polymerase inhibitor
ABT-333 and ABT-267 from a class known as NS5A inhibitors. They are used without
interferon, an injectable standard treatment that causes flu-like
symptoms.
Abbott said it plans to move ahead with large Phase III studies
of the three drugs, used either with or without the standard antiviral pill
ribavirin, based on favorable results seen in patients treated for eight weeks
or twelve weeks in the Aviator study. Patients in the study had the most common,
and hardest-to-treat, strain of hepatitis C known as Genotype 1.
Some 93
percent of patients who failed prior therapy had a sustained virologic response
(SVR), meaning they were considered cured, after 12 weeks of taking the trio of
new drugs, plus ribavirin.
"Nobody anywhere has broken the 50 percent
mark in (cure rates) for this population," Scott Brun, a senior Abbott research
executive said in an interview. "These are robust results."
Abbott said
it aims to be the first company to market an interferon-free regimen to patients
with Genotype 1 infections.
Four of 448 patients in the study
discontinued treatment due to adverse events, a dropout rate that Abbott said
suggested the medicines were very well tolerated.
About 97 percent of
previously untreated patients were considered cured after 12 weeks of treatment
with the three Abbott drugs, plus ribavirin. Moreover, similarly impressive cure
rates were seen among patients taking the three drugs, plus ribavirin, for 8
weeks.
Without ribavirin, 87 percent of previously untreated patients
were considered cured after 12 weeks on Abbott's three drugs, Abbott
said.
Rival drugmaker Gilead Sciences Inc stole a bit of Abbott's thunder
on Saturday by releasing data showing a 100 percent cure rate among previously
untreated genotype 1 patients who took only two of its oral treatments, plus
ribavirin, for 12 weeks.
A pair of new hepatitis C drugs approved last
year, Vertex Pharmaceuticals Inc's Incivek and Merck & Co's Victrelis,
significantly boosted cure rates and cut treatment duration to as low as 24
weeks for some patients. But the protease inhibitors must still be taken with
interferon, an injected drug that often causes severe flu-like symptoms that
lead many hepatitis patients to delay or discontinue treatment.
Gilead,
Bristol-Myers Squibb Co and Vertex are racing to develop interferon-free
treatment regimens. They are expected to become blockbuster products, if
approved, because of their far shorter treatment times and better cure rates,
compared with existing drug regimens.
Many analysts view Gilead as
current leader both on timing and perceived advantages of its experimental
hepatitis C program.
An estimated 3 million Americans are believed
infected with the virus, which quietly damages the liver over years or decades
and is the biggest reason for liver transplants in the United States. Abbott
said as many as 170 million people worldwide are infected.
(Reporting by
Ransdell Pierson; Editing by Vicki Allen and Jackie Frank)
Abbott Press Release
Abbott Presents Promising Phase 2b Interferon-free Hepatitis C Results at
2012 Liver Meeting®
- Investigational Triple-DAA Regimen plus Ribavirin Treatment for 12 Weeks
Demonstrated High SVR12 Rates in Intent-to-Treat Analysis
- Phase 3 Registrational Program Currently Enrolling
November 10, 2012
Abbott Park, Illinois (
NYSE: ABT) —
Results from Abbott’s phase 2b clinical trial, "Aviator," demonstrated high
sustained viral response rates at 12 weeks post-treatment (SVR
12) in
all 8- and 12-week arms, with combinations of direct acting antivirals (DAAs)
given with and without ribavirin (RBV). Results will be presented at the
President's Press Conference and the latebreaking clinical trials session at the
Liver Meeting, the Annual Meeting of the American Association for the Study of
Liver Disease (AASLD) in Boston.
Based on promising results from Aviator, Abbott has selected triple-DAA
regimens, with and without ribavirin, to move forward into phase 3 clinical
trials. Topline intent-to-treat results for the 12-week, triple-DAA regimen with
ribavirin are as follows:
SVR
12 in treatment-naïve genotype 1 (GT1) patients was 97.5
percent (77 of 79), and 93.3 percent (42 of 45) in GT1 null responder
patients
In GT1a patients, SVR
12 was achieved in 96 percent (52 of 54) of
treatment naïve patients and 89 percent (25 of 28) of null responder
patients
In GT1b patients, SVR
12 was achieved in 100 percent of treatment
naïve (25 of 25) and null responder patients (17 of 17)
In addition, results from the 12-week triple-DAA regimen without RBV in
treatment naïve patients showed:
SVR
12 was achieved in 87.3 percent (69 of 79) of GT1
patients
SVR
12 in GT1a patients was 83 percent (43 of 52)
SVR
12 in GT1b patients was 96 percent (24 of 25)
"Based on the high SVR
12 results with Abbott’s triple-direct
acting antiviral regimen in GT1 patients, it appears we are moving closer to
potential oral treatment regimens that do not require interferon to treat HCV,"
said Kris Kowdley, M.D., director of the Liver Center of Excellence in the
Digestive Disease Institute at Virginia Mason Medical Center, and Clinical
Professor of Medicine at the University of Washington in Seattle. "This is
encouraging news for the many patients who are unable or unwilling to take
interferon."
About Study M11-652 (Aviator)
This phase 2b study assesses the safety, and efficacy of ABT-450/r (dosed
100/100mg to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin
in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin
null responders for 8, 12 or 24 weeks. Enrollment was open to GT1-infected
patients regardless of IL28B host genotype and ribavirin dosing was
weight-based. Results from the treatment groups are summarized in the chart
below.
| |
Treatment-Naïve |
Null Responders |
| Duration |
8 weeks |
12 weeks |
12 weeks |
| Regimen |
ABT-450/r
ABT-267
ABT-333
RBV |
ABT-450/r
ABT-333
RBV |
ABT-450/r
ABT-267
RBV |
ABT-450/r
ABT-267
ABT-333 |
ABT-450/r
ABT-267
ABT-333
RBV |
ABT-450/r
ABT-267
RBV |
ABT-450/r
ABT-267
ABT-333
RBV |
| Number dosed |
80 |
41 |
79 |
79 |
79 |
45 |
45 |
| Relapses |
9 |
4 |
5 |
5 |
1 |
5 |
0 |
| Breakthroughs |
0 |
1 |
1 |
1 |
0 |
0 |
3 |
| Lost to Follow up (LTFU) or withdrew consent |
1 |
1 |
2 |
4 |
1 |
0 |
0 |
| SVR12 (ITT)1 |
87.5%
(70/80) |
85.4% (35/41) |
89.9% (71/79) |
87.3% (69/79) |
97.5% (77/79) |
88.9% (40/45) |
93.3% (42/45) |
| SVR12 (OD)2 |
88.6% (70/79) |
87.5% (35/40) |
92.2% (71/77) |
92% (69/75) |
98.7% (77/78) |
88.9% (40/45) |
93.3% (42/45) |
| SVR12 (ITT) GT1a |
84%
(47/56) |
79%
(23/29) |
85%
(44/52) |
83%
(43/52) |
96%
(52/54) |
81%
(21/26) |
89%
(25/28) |
| SVR12 (ITT) GT1b |
96%
(23/24) |
100%
(12/12) |
100%
(27/27) |
96%
(24/25) |
100%
(25/25) |
100%
(18/18) |
100%
(17/17) |
ITT (Intent-to-treat) population: includes all patients who received at
least one dose of study drug
OD (Observed data): Excludes patients with values missing for reasons other
than virologic failure or discontinuation due to AEs
"The 93.3 percent SVR
12 seen with triple-DAA therapy with
ribavirin in previous null responder patients in Aviator is noteworthy given the
limited treatment options with interferon-based therapies for this patient
population," said Scott Brun, M.D., divisional vice president, Infectious
Disease Development, Abbott. "As the data from the Aviator study have matured,
we are encouraged that we have continued to see high SVR
12 rates.
Results from Aviator have allowed Abbott to confidently move into larger,
confirmatory Phase 3 trials with the goal of being the first company to bring an
interferon-free treatment regimen to genotype 1 patients."
Aviator Safety Results
Four of 448 patients (one percent) in the 8- and 12-week arms discontinued
due to adverse events. Of five serious AEs (1 percent), one (arthralgia or joint
pain) was possibly study drug-related. In the trial, the most common adverse
events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for
treatment naïve and null responders respectively.
About the Hepatitis C Virus
Hepatitis C is a liver disease affecting as many as 170 million people
worldwide. The virus is primarily spread through direct contact with the blood
of an infected person. HCV increases a person's risk of developing chronic liver
disease, cirrhosis, liver cancer and death; and liver disease associated with
HCV infection is growing rapidly.
Of the six main genotypes of hepatitis C, genotypes 1, 2 and 3 are the most
widespread. Genotype 1 is the most common genotype in the U.S. and the most
difficult to treat with interferon based therapies. Patients with genotypes 2
and 3 are more likely than individuals with genotype 1 to respond to therapy
with peg-interferon or the combination of peg-interferon and ribavirin.
About Abbott's HCV Development Programs
Abbott's HCV portfolio includes investigational medicines with three
different mechanisms of action, including protease (ABT-450/r), polymerase
(ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical
trials. ABT-450 is being developed with low dose ritonavir which enhances the
pharmacokinetic properties of ABT-450. The use of ritonavir 100mg with ABT-450
for the treatment of HCV is investigational.
ABT-450 was discovered during the course of a collaboration between Abbott
and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include
protease inhibitors. ABT-450 is being developed by Abbott for use in combination
with Abbott's other investigational medicines for the treatment of HCV. Abbott
is well-positioned to explore combinations and co-formulations of these
medicines.
On Monday, November 12 at 5:30 p.m. EST, Abbott will host an investor webcast
to discuss the phase 2b Aviator data, as well as our recently initiated phase 3
registrational program. The webcast can be accessed on Abbott’s investor
relations website at
abbottinvestor.com.
Ritonavir Use in Treatment of HIV
Ritonavir is in a class of medicines called the HIV protease inhibitors.
Ritonavir is used in combination with other anti-HIV medicines to treat people
with human immunodeficiency virus (HIV) infection. Ritonavir is for adults and
for children greater than 1 month in age and older.
Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of
passing HIV to others. People taking ritonavir may still get opportunistic
infections or other conditions that happen with HIV infection. Some of these
conditions are pneumonia, herpes virus infections, and Mycobacterium avium
complex (MAC) infections.
Ritonavir Safety in Treatment of HIV
Patients should not take ritonavir with certain medicines, as these can cause
serious or life-threatening problems such as irregular heartbeat, breathing
difficulties, or excessive sleepiness. Patients should not take ritonavir if
they have had a serious allergic reaction to any of its ingredients. Some
patients taking ritonavir may develop liver and pancreas problems, which can
cause death.
Patients may develop large increases in triglycerides and cholesterol,
diabetes, high blood sugar, changes in body fat, increased bleeding in people
with hemophilia, allergic reactions, and/or changes in heart rhythm. Patients
may develop signs and symptoms of infections that they already have after
starting anti-HIV medicines.
For more information, please see
Important Safety
Information and
Full
Prescribing Information.
About Abbott
Abbott (
NYSE: ABT)
is a global, broad-based health care company devoted to the discovery,
development, manufacturing and marketing of pharmaceuticals and medical
products, including nutritionals, devices and diagnostics. The company employs
approximately 91,000 people and markets its products in more than 130
countries.
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