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‘Real-world’ Experience Confirms Effectiveness Of Sofosbuvir/velpatasvir/voxilaprevir In People With Chronic Hepatitis C (HCV) Infection Failing Direct-acting Antivirals (DAAs)

ILC 2019: ‘Real-world’ studies in Germany and the USA confirm high rates of sustained virological response with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in individuals with chronic HCV infection failing DAAs

10 April 2019, Vienna, Austria

EASL (EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER)

‘Real-world’ studies conducted in Germany and the USA have confirmed the effectiveness and tolerability of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) when used to treat individuals with chronic hepatitis C (HCV) infection who had previously failed direct-acting antivirals (DAAs). The two studies presented today at The International Liver Congress™ 2019 in Vienna, Austria, reported sustained virological response rates (SVR) of 93–100%, confirming the effectiveness of this treatment in clinical practice.

DAAs have transformed HCV therapy and made virological cure possible in most patients.1 Combination regimens of DAAs achieve SVR rates in excess of 90%, regardless of HCV genotype (GT), disease stage, or treatment history.2 While DAAs rarely fail to achieve viral clearance, up to 10% of patients will experience virological relapse/failure,3 with HCV RNA reappearing a few weeks after completing therapy. In the past, treatment options for these patients were limited.4,5 The once-daily, all-oral combination tablet containing SOF/VEL/VOX, was approved in Europe in July 20176 for patients infected with any genotype who have previously failed therapy with DAAs.1

In the first study presented today, a German research group evaluated all consecutive patients enrolled into the German Hepatitis C Registry (DHC-R) who were retreated with SOF/VEL/VOX ± ribavirin (RBV) due to virological failure up to February 2019 (N=110; HCV GT1 [71%], GT3 [34%], and GT4 [5%]; median age 54 years; 86% male; 27% with cirrhosis). Prior DAA regimens included paritaprevir/ritonavir/ombitasvir ± dasabuvir ± RBV (PrO ± D ± RBV [n=30]), ledipasvir/sofosbuvir ± RBV (LDV/SOF ± RBV [n=35]), SOF/velpatasvir ± RBV (SOF/VEL ± RBV [n=18]), daclatasvir + SOF ± RBV (DCV + SOF ± RBV [n=13]), elbasvir/grazoprevir (EBR/GZR [n=8]), SOF + RBV (n=2), and simeprevir + SOF + RBV (n=1). Four patients had received SOF/VEL/VOX + RBV (HCV GT1b [n=2], GT3a [n=2]).

According to investigator Dr Johannes Vermehren from the Goethe University Hospital in Frankfurt, Germany, with SVR data available from 74 patients as of February 2019, sustained virologic response was 100%. SOF/VEL/VOX was well tolerated, with fatigue (14%) and headaches (10%) the most frequently reported adverse events (AEs). No severe AEs were attributed to SOF/VEL/VOX treatment.

In the USA, data from 196 patients treated with SOF/VEL/VOX between July 2017 and April 2018 were collected from a health management program provider (Trio Health) and analysed. Duration of treatment was 12 weeks for all but one patient, who received treatment for >12 weeks. Seven patients (4%) also received RBV off-label. Most patients were treatment experienced (173/196; 88%) while 21 patients (11%) were treatment naïve. Treatment status for two patients was unavailable. The most frequently-used prior therapies were: LDV/SOF ± RBV (n=92), SOF/VEL ± RBV (n=20), EBR/GZR ± RBV (n=19), other SOF-based regimens (n=17), and PrOD (n=11). The SVR rates at 12 weeks after therapy in the per-protocol and intent-to-treat groups were reported to be 98% (183/186) and 93% (183/196), respectively. Of the 3 patients that did not achieve SVR12 in the per-protocol group, 2/3 were white males, cirrhotic (F4), and had prior regimens of SOF/VEL and LDV/SOF ± RBV while 1/3 was a black female with moderate fibrosis (F2); her prior regimen was not specified. One patient had a baseline viral load between 800K-6MM and the other 2 patients had baseline viral loads >6MM. The insurance types were: 1 (commercial), 1 (Medicare), and 1 (not specified); all 3 patients were GT1.

‘We are now seeing real-world evidence that SOF/VEL/VOX is highly effective when used in clinical practice to treat patients who have failed previous DAA therapy,’ concluded Dr Bruce Bacon from Saint Louis University School of Medicine, St Louis, USA.

‘This important real-world experience from Germany and the USA showed that almost all patients with chronic hepatitis C – Including DAA treatment failures – can finally be cured,” said Professor Markus Cornberg from Hannover Medical School in Germany, a member of EASL’s governing board.

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About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2019 will take place from 10­–14 April 2019 at the Reed Messe Wien Congress and Exhibition Center, Vienna, Austria.

About The European Association for the Study of the Liver (EASL)

Since its foundation in 1966, this not-for-profit organization has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact

For more information, please contact the ILC Press Office at:

Onsite location references

Session title: Viral hepatitis C: Therapy and resistance (Posters)

Time, date and location of session: 09:00–19:00, 11 April 2019, Poster area

Presenter: Johannes Vermehren, Germany

Abstract: Retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C virus infection and prior DAA failure: An analysis from the German hepatitis C registry (DHC-R) (THU-188)

Session title: Viral hepatitis C: Therapy and resistance (Posters)

Time, date and location of session: 09:00–19:00, 11 April 2019, Poster area

Presenter: Bruce Bacon, USA

Abstract: Effectiveness of the salvage therapy sofosbuvir-velpatasvir-voxilaprevir (SOF-VEL-VOX) in chronic hepatitis C: Clinical practice experience from the TRIO Network (THU-116)

Author disclosures

Johannes Vermehren has received speaking fees from AbbVie, Gilead, Intercept, and Merck/MSD.

Bruce Bacon consults for, is on the speakers’ bureau for, and received grants from Merck. He advises for, is on the speakers’ bureau for, and received grants from AbbVie and Gilead. He advises for and is on the speakers’ bureau for Janssen. He advises for and received grants from Bristol-Myers Squibb. He is on the speakers’ bureau for Valeant.

References

  1. Vermehren J, et al. Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection. J Hepatol. 2018;69(5):1178–87.
  2. Naggie S, Muir Oral combination therapies for hepatitis C virus infection: successes, challenges, and unmet needs. Annu Rev Med. 2017;68:345–58
  3. Benítez-Gutiérrez L, et al. Prevention and management of treatment failure to new oral hepatitis C drugs. Expert Opin Pharmacother. 2016;17(9):1215–23.
  4. Bourlière M, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV -infection. N Engl J Med. 2017;376(22):2134–46.
  5. Chhatwal J, et al. Hepatitis C virus re-treatment in the era of direct-acting antivirals: projections in the USA. Aliment Pharmacol Ther. 2018;47(7):1023–31.
  6. European Medicines Agency. European Public Assessment Report (EPAR) for the Public: Vosevi. Available from: https://www.ema.europa.eu/documents/overview/vosevi-epar-summary-public_en.pdf. Last accessed February 2019.