Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon–ribavirin...
Coverage@ Healio
SAPPHIRE II: Ritonavir-boosted triple regimen plus ribavirin achieved high SVR12 rates.
LONDON — Sustained virologic response rates at 12 weeks were more than 90% across several treatment groups in a cohort of patients who previously failed pegylated interferon and ribavirin therapy who received ritonavir-boosted ABT-450, ABT-267 and ABT-333 with ribavirin....
Coverage@NATAP
Slides
EASL: SAPPHIRE-II: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/r/ABT-267, ABT-333, AND RIBAVIRIN IN 394 TREATMENT-EXPERIENCED ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1
(04/10/14)
Cure Rate for Experimental Hepatitis C Drug Tops 95 Percent
April 10
HealthDay New
Researchers report that an experimental drug has cured more than 95 percent of patients infected with hepatitis C, including some who failed other treatments.
If it wins approval from the U.S. Food and Drug Administration, this new drug, called ABT-450, could potentially compete with another innovative hepatitis C medication that costs $1,000 a day.
Nearly 3 million Americans have hepatitis C, a disease that can cause liver cirrhosis and cancer.
These newer, advanced treatments are better-tolerated and easier to take than interferon, the traditional standard treatment for hepatitis C, researchers say.
"Interferon is no longer required to cure hepatitis C," said Dr. Stefan Zeuzem, a professor of medicine
at the J.W. Goethe University Hospital in Frankfurt, Germany, and lead researcher on the ABT-450 study. His research pairing ABT-450 with other interferon-free medications
showed "almost all patients with chronic hepatitis C can be cured even if previous treatments were unsuccessful," Zeuzem said. The report was published online April 10 in the New England Journal of Medicine, to coincide with presentation of the findings at the annual meeting of the European Association for the Study of the Liver in London. The drug trial was funded by the drug's maker, AbbVie.
"Hepatitis C is a big, bad problem," said Dr. William Carey, a liver specialist at the Cleveland Clinic in Ohio.
This new drug represents "one among many breakthroughs in our ability to deal with hepatitis C," Carey said.
An advantage to this treatment is that it is a pill, while interferon is given in weekly injections. Also, older treatments went on for a year, while this new therapy takes only three months to work, Carey said.
Interferon treatment also has severe side effects, including fatigue and flu-like symptoms.
"This is not the only drug combination that is interferon-free, but it's a very promising one," he said.
One drawback to the therapy is that some pills are taken once a day and some twice, which might make following the treatment tricky. Carey hopes that treatment eventually is simplified. "Wouldn't it be great if we could take one or two pills once a day and be done with it?" he said.
Since many people with hepatitis C remain symptom-free, the medical community has not agreed on whom to treat.
With these new cures, that question becomes easier to answer, Carey said. "When you have a treatment that is this simple, effective and free of side effects, there are fewer and fewer reasons to think about withholding treatment," he noted.
"The major barrier is cost," he added.
Whether the new drug will be priced like Sovaldi, the $1,000-a-day medication, is still unknown.
With Sovaldi, the necessary three-month course costs $90,000, plus any other drug expenses and medical care.
Carey said some insurance companies cover the cost of the drug, while others have denied it.
Cost is even more significant in light of the millions of Baby Boomers who are five times more likely to be infected with hepatitis C than other adults, according to the U.S. Centers for Disease Control and Prevention.
"It's going to get harder as time goes on for insurance companies not to cover the cost of these drugs," Carey said. "This is a curable disease."
According to a CBS News report, lawmakers and insurance companies complain that Gilead Sciences, the maker of Sovaldi, is trying to "milk desperate patients." Gilead says that, despite the high price, Sovaldi is cheaper because it "cures patients quickly and eliminates a long and expensive treatment using other drugs."
For this phase 3 trial of ABT-450 -- typically the last trial needed for FDA approval -- nearly 400 patients were randomly assigned to take a placebo or a combination of ABT-450 and these other pills: ombitasvir, ritonavir, dasabuvir or ribavirin. All patients had been treated before, but saw their diseases return or had a poor response or no response to treatment.
Taking the ABT-450 combination, 96.3 percent of the patients responded, the researchers said.
Previous research showed that patients who had never been treated also responded to this combination.
Dr. Marc Siegel, an associate professor of medicine at NYU Langone Medical Center, New York City, said the results look promising for the millions of people with hepatitis C.
"Hepatitis C is under-diagnosed," said Siegel.
These new treatments, with their high cure rates, make it important to diagnose and treat hepatitis C early to prevent cirrhosis and liver cancer, he said.
Hepatitis C can be spread by injectable drug use or sexual contact with an infected person. The U.S. Centers for Disease Control and Prevention recommends one-time screening for those born between 1945 and 1965 -- that's potentially millions of people who would qualify for treatment.
More information
For more information on hepatitis C, visit the U.S. National Library of Medicine.
Posted: April 2014
Press Release
Enanta Pharmaceuticals Announces Detailed Data from SAPPHIRE-I and SAPPHIRE-II Phase 3 Studies in Patients with Chronic Hepatitis C Virus Being Presented at EASL 2014
April 11, 2014
The SAPPHIRE-I and SAPPHIRE-II studies report results from AbbVie’s investigational three direct-acting antiviral regimen containing ABT-450, Enanta’s lead protease inhibitor developed through Enanta’s collaboration with AbbVie. The regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333.
In the SAPPHIRE-I (N=631) and SAPPHIRE-II (N=394) placebo-controlled studies, adult, non-cirrhotic patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection receiving the investigational three-direct-acting antiviral regimen with ribavirin (RBV) for 12 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR12) of 96.2 percent (n=455/473) and 96.3 percent (n=286/297), respectively.
In SAPPHIRE-II, treatment-experienced sub-populations randomized to the three direct-acting antiviral regimen with RBV in the study were prior null responders (49.2 percent), prior relapsers (29.0 percent) and prior partial responders (21.9 percent) to pegylated interferon and RBV.
SAPPHIRE-I and SAPPHIRE-II Results
|
||||||||||
| SAPPHIRE-I SVR12
(n=473)
|
SAPPHIRE-II SVR12
(n=297)
|
|||||||||
| All GT1 | 96.2% (n=455/473) | 96.3% (n=286/297)* | ||||||||
| GT1a | 95.3% (n=307/322) | 96.0% (n=166/173) | ||||||||
| GT1b | 98.0% (n=148/151) | 96.7% (n=119/123) | ||||||||
| Treatment-experienced (GT1a and GT1b) | ||||||||||
| Prior null responders | n/a | 95.2% (n=139/146) | ||||||||
| Prior relapsers | n/a | 95.3% (n=82/86) | ||||||||
| Prior partial responders | n/a | 100.0% (n=65/65) | ||||||||
In SAPPHIRE-I, high response rates were seen across patients with certain variable characteristics, including gender, race, body mass index, fibrosis stage and baseline HCV viral load, as some of these patients have historically had a reduced response to treatment.
Discontinuations due to adverse events were reported in 0.6 percent of patients in both arms in SAPPHIRE-I and in 1.0 percent of patients receiving the AbbVie regimen in SAPPHIRE-II and no patients receiving placebo. The most commonly reported treatment-emergent adverse events (>10 percent in either arm) for both SAPPHIRE-I and SAPPHIRE-II were fatigue, headache, nausea, asthenia, insomnia, pruritus and diarrhea. Additional common adverse events occurring in the studies were rash in SAPPHIRE-I and dyspnea, cough and myalgia in SAPPHIRE-II. In SAPPHIRE-I, the adverse events that occurred with a significantly greater frequency in the treatment arm compared to placebo were pruritus, insomnia, diarrhea, nausea and asthenia; in SAPPHIRE-II, only pruritus.
About Study M11-646 (SAPPHIRE-I)
SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected adult patients new to therapy.
The study population consisted of 631 patients: 473 were randomized to the three direct-acting antiviral regimen with RBV for 12 weeks, and 158 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the AbbVie regimen with RBV for 12 weeks.
Of the 473 patients randomized to the three direct-acting antiviral regimen with RBV, one case (0.2 percent) of on-treatment virologic failure occurred and seven patients (1.5 percent) experienced post-treatment relapse. In addition, three patients (0.6 percent) were lost to follow-up and seven patients (1.5 percent) discontinued the study prematurely. Patients lost to follow-up were considered treatment failures.
About Study M13-098 (SAPPHIRE-II)
SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and RBV.
The study population consisted of 394 patients: 297 were randomized to the three direct-acting antiviral regimen with RBV for 12 weeks, and 97 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the three direct-acting antiviral regimen with RBV for 12 weeks.
Of the 297 patients randomized to the three direct-acting antiviral regimen with RBV, there were no cases of on-treatment virologic failure and seven patients (2.4 percent) experienced post-treatment relapse. Of these patients, six were prior null responders and one was a prior relapser. Three patients (1.0 percent) prematurely discontinued therapy due to adverse events and one patient (0.3 percent) prematurely discontinued the study.
Additional information about AbbVie’s phase III studies can be found on www.clinicaltrials.gov.
About ABT-450
ABT-450 is an NS3 protease inhibitor discovered through Enanta’s collaboration with AbbVie. AbbVie and Enanta have an agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors. Protease inhibitors play an essential role in the viral life cycle of the hepatitis C virus (HCV). Inhibition of the protease prevents non-structural (NS) proteins from forming and thereby prevents replication and survival of the HCV virus. ABT-450 is part of AbbVie’s investigational regimen for HCV that consists of boosted protease inhibitor ABT-450/ritonavir (referred to as ABT-450/r), NS5A inhibitor ABT-267 and non-nucleoside polymerase inhibitor ABT-333.
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Sounds promising
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