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No Surprises in Real-World Data for Interferon-Free HCV Therapy
Real-world data on new hepatitis C virus (HCV) treatments have gradually become available following their recent entry into the market. These data are critical for evaluating the new treatments in practice and recommending future HCV management guidelines. Real-world clinical findings about interferon (IFN)-free, all-oral, direct-acting antiviral (DAA) regimens for chronic HCV infection were the focus of presentations at the Viral Hepatitis Congress from September 10 to 12, 2015, and they demonstrated high efficacy and good tolerability for these drugs in clinical practice.
Overall, consultant GlobalData notes, observations from North America and Europe showed that efficacy, safety, and tolerability in the real world have been very similar to those in clinical trials, reinforcing the value of these new treatments. Experts explained that the close similarity between real-world and clinical trial data in these cases differs from that of IFN-based treatment. This is probably because these new drugs are more effective; easier to take in terms of pill burden, dosing frequency, and duration of therapy; and better tolerated compared with IFN-based regimens. As a result, adherence rates for all-oral regimens have not fallen off dramatically from those seen in clinical trials.
The real-world observations also echoed the clinical trial results in demonstrating that several conditions can predict suboptimal rates of sustained virological response (SVR). These factors include having HCV genotypes three (GT3) and 1a (GT1a); being treatment-experienced or having previous treatment failure; having late-stage liver fibrosis or cirrhosis; and having decompensated liver diseases.
The negative effects of genotype, treatment experience, and liver disease appear to be additive. For example, data from HCV-TARGET, an international collaboration that is conducting a longitudinal observational study on DAA HCV agents in North America and Europe, showed that among GT3 patients treated with sofosbuvir plus ribavirin (RBV), non-cirrhotic patients achieved better SVR rates than cirrhotic patients, and treatment-naïve patients achieved better SVR rates than treatment-experienced patients, while GT3 treatment-experienced patients with cirrhosis achieved the lowest SVR rate at around 43%. In addition, the relapse rate was also higher in populations with more factors predicting negative outcomes, and was the highest, again, in GT3 treatment-experienced patients with cirrhosis.
The HCV-TARGET study also provided data on patients with decompensated liver cirrhosis, considered difficult to treat. Overall, GT1 patients with decompensated cirrhosis achieved a lower SVR rate in week 12 post-treatment (SVR12) with sofosbuvir-based regimens (74% without RBV and 66% with RBV) than the overall GT1 population (81% to 89% with various sofosbuvir-based regimens). The differences in SVR12 rates between treatment-naïve and experienced groups — and between GT1a and GT1b groups — were marginal and inconsistent, possibly due to the low patient numbers recorded so far. GT1a patients also had a higher relapse rate, at 26%.
AbbVie announced interim results in GT1 HCV patients with severe liver disease from the phase III AMBER study, which is investigating the efficacy and safety of ombitasvir/ paritaprevir/ritonavir and dasabuvir, with or without RBV, in real-life settings. The majority of study participants had late-stage (F4) fibrosis (61%) or had failed previous treatment with pegylated IFN (PEG-IFN) or RBV (80%). The interim analysis demonstrated rapid viral suppression in these patients with or without RBV. A total of 98% of patients achieved undetectable HCV RNA at the end of therapy. The treatment was well tolerated, with adverse events (AEs) mostly related to RBV.
Bristol-Myers Squibb (BMS) and Gilead Sciences also presented their latest findings in patients with severe liver disease in the European compassionate-use program and the SOLAR 2 trial, respectively. Both studies are in more stringent clinical trial settings. The results showed excellent efficacy and tolerability of respective treatments in these difficult-to-treat patients.
Patients with renal impairments have also been considered difficult to treat. Data on a small number of these patients from the HCV-TARGET program showed 100% SVR12 with sofosbuvir plus PEG IFN and RBV, sofosbuvir plus RBV, and sofosbuvir plus simeprevir and RBV, and 80% SVR12 with sofosbuvir plus simeprevir. In addition, cirrhotic patients with renal impairment only achieved an overall 67% RSV12. The treatments were generally well tolerated. These data were in line with those from clinical trials.
Real-world data confirmed that eight-week treatment can be as effective as 12-week treatment for most patients. The addition of RBV was beneficial in some but not all populations. The differences in SVR rates among drug combinations varied and were small in most cases; there was no clear trend across different populations. For example, real-world data presented at the congress from access programs in Europe comparing ledipasvir/sofosbuvir with sofosbuvir plus daclatasvir seemed to show the latter had some advantage in GT3 patients with decompensated cirrhosis, while the ledipasvir/sofosbuvir performed better in the equivalent GT1 patients. In addition, RBV showed small beneficial effects with either treatment in both GT1 and GT3 patients with decompensated cirrhosis, while this effect is not commonly seen in non-cirrhotic patients. Experts at the congress appeared to agree that for patients with risk factors for low SVR rates, longer treatment, more effective drug components, and the addition of RBV and even IFN (if tolerated) should be considered to improve clinical outcomes.
Overall, real-world data presented at the congress demonstrated excellent efficacy and good tolerability of the IFN-free, all-oral DAA regimens in most patients with chronic HCV infection. Patients who have been considered difficult to treat now stand a decent chance to achieve a SVR to HCV. But the data also demonstrated room for improvement in specific populations, especially patients who have GT3 infections, who are treatment-experienced, and who have late- to end-stage liver disease. The differences among various therapeutic combinations in different populations require detailed analysis to guide treatment choices.
GlobalData anticipates intense competition in the chronic HCV market will fuel further improvement in efficacy, especially for difficult-to-treat patients.
Source: GlobalData; September, 2015.