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ICAAC 2014: AbbVie 3D Regimen Shows High Cure Rates for Genotype 1b HCV Patients

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AbbVie's interferon-free 3D regimen containing ABT-450, ombitasvir, and dasabuvir led to sustained virological response in nearly 100% of people with genotype 1b chronic hepatitis C regardless of unfavorable patient or viral characteristics, researchers reported at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy this week in Washington, DC.

Direct-acting antiviral agents that target different steps of the hepatitis C virus (HCV) lifecycle have brought about a revolution in treatment, especially with the advent of all-oral regimens that omit interferon and its difficult side effects.

David Bernstein from Hofstra North Shore-LIJ School of Medicine presented pooled findings from the multinational Phase 3 PEARL-II and PEARL-III trials, looking at how patient and viral factors affect treatment response.

Both trials evaluated an interferon-free regimen containing the HCV protease inhibitor ABT-450 (150 mg) boosted with ritonavir (100 mg), and the NS5A replication complex inhibitor ombitasvir (formerly ABT-267; 25 mg) -- all in a once-daily coformulation -- plus the non-nucleoside NS5B polymerase inhibitor dasabuvir (formerly ABT-333; 250 mg twice-daily). Participants were randomly assigned to take the 3D regimen either with or without weight-based ribavirin for 12 weeks.

These studies enrolled people with HCV genotype 1b, which is considered easier to treat than subtype 1a. People with liver cirrhosis -- another harder-to-treat group -- were excluded, as were those with HIV or hepatitis B coinfection.

The primary endpoint of the trials was sustained virological response, or continued undetectable HCV RNA at 12 weeks after finishing treatment (SVR12). The present analysis assessed the relationship between SVR12 rates and baseline characteristics previously linked to poorer response including demographics, prior treatment history, HCV viral load, and psychiatric conditions traditionally considered contraindications for interferon-based therapy.

This analysis included 605 participants. About half were men, most were white, and the mean age was about 50 years. Approximately 30% were treatment-experienced, about evenly divided between prior null responders, partial responders, and relapsers. Most (about 80%) had unfavorable IL28B non-CC gene variants and about 75% had high baseline viral load (HCV RNA >800,000 IU/mL). Approximately 10% had a history of depression or bipolar disorder.

Results

  • Overall combined SVR12 rates in the 2 trials combined were 98.7% for the 3D regimen plus ribavirin and 99.3% for the 3D regimen alone.
  • 1 person experienced viral breakthrough during treatment, but there were no post-treatment relapses.
  • SVR12 rates were high with both regimens regardless of baseline patient or viral characteristics:
  • 3D regimen + ribavirin:

o   Sex: 99% for men and 99% for women;

o   Age: 99% for age <55 years and 100% for age 55 or older;

o   Obesity: 99% for BMI <30 and 98% for BMI >30;

o   HCV viral load: 100% for <800,000 IU/mL and 98% for >800,000 IU/mL;

o   Depression/bipolar disorder: 97% for those with and 99% for those without;

o   Prior treatment: 99% for treatment-naive and 97% for treatment-experienced.

  • 3D regimen alone:

o   Sex: 99% for men and 100% for women;

o   Age: 98% for age <55 years and 100% for age 55 or older;

o   Obesity: 100% for BMI <30 and 97% for BMI >30;

o   HCV viral load: 100% for <800,000 IU/mL and 99% for >800,000 IU/mL;

o   Depression/bipolar disorder: 96% for those with and 99% for those without;

o   Prior treatment: 99% for treatment-naive and 100% for treatment-experienced.

  • The 3D regimen was generally safe and well-tolerated.
  • The most common side effects were fatigue, headache, nausea, itching, weakness, and insomnia, most of which were more common in the ribavirin arm.
  • Only 2 participants taking ribavirin, and none taking the 3D regimen alone, discontinued treatment due to adverse events. 
  • 6 people in each regimen group experienced severe adverse events, only 1 of which (arthritis) was considered possible related to the study drug.
  • 20 people in the ribavirin arm developed moderate (grade 2) and 1 person developed serious (grade 3) anemia; no one in the 3D-only arm developed anemia.

"99% oftreatment-naive and treatment-experienced HCV genotype 1b-infected patients without cirrhosis receiving the 3D regimen with or without ribavirin achieved SVR12," the researchers concluded. "No differences in SVR12 rates were observed regardless of baseline characteristics."

The 3D regimen is currently under regulatory review in the U.S. and Europe. The FDA has designated it as a "breakthrough therapy"and is expected to issue an approval decision by the end of the year.

9/7/14

Reference

D Bernstein, F Nevens, JV Enejosa, et al. High SVR12 Rates in HCV Genotype 1b-Infected Patients Receiving ABT-450/r/Ombitasvir and Dasabuvir With or Without Ribavirin Regardless of Baseline Characteristics. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014. Abstract V-672.