Novel Drug Combo Succeeds Against Multiple HCV Genotypes
by
Contributing Writer, MedPage Today
No cases of virologic failure observed with ABT-493 plus ABT-530
SAN DIEGO -- An investigative combination of two drugs helped patients infected with hepatitis C virus (HCV) across genotypes 1, 2, 3.4, 5 and 6 achieve sustained virologic responses, researchers reported here.
No cases of virologic failure were observed in the 8-week courses of ABT-493 plus ABT-530 in non-cirrhotic patients infected with genotypes 1, 2 and 3, and no virologic failures were observed among patients with genotypes 4, 5 and 6 who were treated in a 12-week course, according to Tarek Hassanein, MD, of the Southern California GI and Liver Centers/UC San Diego Health System, David Wyles, MD, of the University of California San Diego, and colleagues.
In multiple presentations at the annual Digestive Disease Week (DDW), they described preliminary studies using the pangenotypic agents against the 6 different genotypes of HCV.
The only patients across the studies who failed to achieve a sustained virologic response at 12 weeks (SVR12) -- the standard defined as a function cure of the disease -- were three individuals who failed to complete their regimens. All of them, however, had no quantitative level of circulating virus at the time they left the study, the researchers reported.
During a DDW press conference, Kimberly Brown, MD, of Henry Ford Hospital in Detroit, noted that ABT-493 plus ABT-450 were "able to achieve very similar outcomes with the 8-week regimen as compared with 12 weeks of therapy. And in a third study, they were able to treat more difficult genotypes 4, 5 and 6 with their 12-week therapy with excellent outcomes."
The studies "highlight the advances in safety and tolerability as well as the cure rates for these therapies," she said.
ABT-493 is a pangenotypic NS3/4A protease inhibitor which was paired with ABT-530, a pangenotypic NS5a inhibitor. The regimens did not contain either ribavirin or interferon, which up to 5 years ago were considered mainstays of HCV treatment, but have taken a bit of a backseat to more effective, better tolerated treatments.
For genotypes 1 and 2, the researchers enrolled non-cirrhotic treatment-naïve patients or pegylated interferon/ribavirin treatment-experienced non-responders who received once-daily ABT-493 at a dose of 300 mg plus ABT-530 at a dose of 120 mg for 8 weeks.
For genotype 3, the researchers enrolled treatment-naïve patients without cirrhosis and treated them with a once-daily ABT-493 dose of 300 mg plus ABT-530 at a dose of 120 mg for 8 weeks.
For genotypes 4, 5 and 6, the researchers enrolled treatment-naïve or pegylated interferon/ribavirin treatment-experienced patients who were treated with once-daily ABT-493 at a dose of 300 mg plus ABT-530 at a dose of 120 mg for 12 weeks.
Hassanein reported that in 34 patients diagnosed with genotype 1, 33 patients achieved an SVR12 after 8 weeks of treated with the investigative agents. In the modified intention-to-treat protocol, 33 of 33 patients achieved SVR12.
Also, in 54 patients diagnosed with genotype 2, 53 patients achieved an SVR12 after 8 weeks of treatment with the once-daily regimen, and in the modified intention-to-treat protocol, all achieved SVR12.
Wyles reported that in 29 patients diagnosed with genotype 3, 28 patients achieved an SVR12 after 8 weeks of treatment, and in the modified intention-to-treat protocol, all patients achieved SVR12.
In 11 patients diagnosed with genotype 4, all patients achieved an SVR12 after a 12-week treatment regimen, Hassanein stated.
One patient diagnosed with genotype 5 achieved an SVR12 after the 12-week regimen, and in 22 patients diagnosed with genotype 6, all achieved an SVR12 after the 12-week regimen, he said.
"Based on these findings, and those in patients with hepatitis C virus genotype 1, 2 and 3 infection, phase III studies are evaluating ABT-493 and ABT-530 in patient with and without cirrhosis across all 6 major hepatitis C virus genotypes, including 8-week duration treatments," Hassanein said.
Wyles and Hassanein reported few adverse events in the patients, with none discontinuing the trials due to adverse drug reactions. One patient left the study because he found blood draws intolerable. One patient was removed from the study due to advanced adenocarcinoma, not related to the drugs, Hassanein said. One person was lost to follow-up after 6 weeks of treatment.
"Over the past 10 years, we have made huge strides in the area of hepatitis C, a disease which really impacts...3.5 million people in this country," Brown stated. "With this research, there is greater understanding of the genome and several proteins in the virus and that has led to several developments, which now means we have the opportunity to cure more than 95% of these patients."
"In particular, researchers have been looking at direct-acting agents, which target specific proteins within the virus, disrupting viral replication," she added. "With these advances, investigators are now looking to see if we can shorten therapies. We have gone from treatment periods that have lasted nearly a year for patients with fairly significant side effects to...the majority of treatment paradigms [lasting] 12 weeks with very minimal side effects."
The studies were supported and funded by AbbVie. The company participated in the interpretation of data, review, and approval of the content.
Hassanein disclosed relevant relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Eisai, Gilead Sciences, Ikaria, Janssen, La Jolla Pharmaceuticals, Merck, Mochida, NGM BioPharmaceuticals, Obalon, Roche, Ocera, Sundise, Salix, Taigen, Takeda, Tobria, Vertex, Vital Therapies, and Baxter.
Wyles disclosed relevant relationships with AbbVie, BMS, Gilead, Merck, Tacere Therapeutics, and Janssen.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
Primary Source
Digestive Disease WeekSource Reference: Poordad F, et al "High SVR rates with the combination of ABT-493 + ABT-530 for 8 weeks in non-cirrhotic patients with HCV genotype 1 or 2 infection" DDW 2016; Abstract 752.
Secondary Source
Digestive Disease WeekSource Reference: Gane E, et al "SURVEYOR-1: 100% Svr12 and favorable safety of Abt-493 + Abt-530 administered for 12 weeks in non-cirrhotic patients with genotypes 4, 5, or 6 infection (Surveyor-I)" DDW 2016; Abstract 755.
Additional Source
Digestive Disease WeekSource Reference: Muir A, et al "High SVR Rates with ABT-493 + ABT-530 co-administered for 8 weeks in non-cirrhotic patients with HCV genotype 3 infection" DDW 2016; Abstract 753.
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