The results of AbbVie’s Aviator trial have company representatives flying high today. Their release at the 2013 International Liver Congress (ILC2013) has generated a great deal of excitement amongst the many attending physicians and researchers who work with hepatitis C (HCV) infected patients. The phase IIb trial examined the efficacy of the company’s triple direct-acting antiretroviral (DAA) regimen in both treatment naïve patients and patients who had previously failed treatment with the current standard of care — treatment with pegylated interferon and ribavirin (RBV).
Aviator was an astounding success. The triple-therapy combination, which included the protease inhibitor ABT-450/r, the polymerase inhibitor ABT-333, and the NS5A inhibitor ABT-267, in combination with RBV achieved a 24-week sustained viral response (SVR24) in over 90 percent of patients in both the treatment naïve and non-responder groups. Sustained viral response is the standard measurable outcome in HCV treatment studies, as it measures not just a temporary decrease in viral load but the ability of a drug to maintain an undetectable viral load for an extended period of time after the end of treatment.
However, the overall success of the Aviator trial was not the only important information about the study presented at ILC2013. Perhaps even more interesting to attending scientists were the details of the results of a number of sub-analyses. In particular, the Aviator trial presented strong evidence that, in both treatment groups, both twelve weeks and twenty-four weeks of therapy were similarly efficacious. This means that, going forward, scientists will be able to focus on the shorter duration therapy – potentially halving drug costs for patients and insurers as well as significantly decreasing the duration of any treatment-side effects.
Fortunately though, treatment side effects do not appear to be as serious a concern with the Aviator regimen as they have been with other HCV treatments. Fewer than two percent of study participants discontinued the study because of potentially drug-related adverse events. More common side effects, such as headache, fatigue, nausea, insomnia, and diarrhea, appeared to be reasonably well tolerated and did not result in anyone stopping their treatment. Furthermore, and more importantly, although a small number of patients had laboratory abnormalities in total bilirubin and alanine aminotransferase (ALT) over the course of the study, they all resolved without a need to alter the patients’ treatment regimen
The AbbVie triple-drug DAA regimen shows enormous promise as a treatment for HCV genotype 1 infection, both for treatment naïve patients and for patients who have previously failed treatment with current therapies. It may even usable without RBV, where appropriate. In treatment-naïve patients, SVR24 rates for triple-therapy alone (without RBV) reached 87 percent after 12 weeks of treatment.
All things considered, the results of the Aviator trial are great news for patients with HCV, who should also be particularly excited about the fact that the ABT-450/267/333 + RBV combination was similarly effective for individuals infected with a diverse set of risk factors. Strong results were seen for those infected with both genotype 1a and 1b viruses, as well for patients with both the CC and non-CC IL28B genotypes, which are known to affect treatment response. The treatment regimen also worked well in patients with varying degrees of liver fibrosis as well as a range of viral loads.
Barry Bernstein, divisional vice president of infectious disease development at AbbVie has said that, “AbbVie’s clinical development program aims to improve virologic cure rates, including in patients who have historically been harder to treat with current therapies, such as prior null responders.” These results suggest that the company is well on their way to achieving that goal. They have, unquestionably, engaged the enthusiasm of attendees at ILC2013, who are already looking forward to hearing about the results of the phase III trials that must be successful before this regimen can move into the realm of regular patient care.