In the Journals

Ultrashort treatments may benefit some patients with HCV

Response-guided ultrashort therapy may work in some patients with hepatitis C, according to results published in The Lancet Gastroenterology & Hepatology.

“Our hypothesis was that the faster the viral load decline, the faster one can reduce the virus to a point — cure boundary — to allow the immunity to take over the job and eradicate the virus — sustained virological response,” George Lau, MD, of the division of Gastroenterology and Hepatology at Humanity and Health Medical Centre in Hong Kong, told Healio.com/Hepatology.

George Lau, MD
George Lau

“No one expected that even 4 weeks of treatment would be sufficient. All previous studies had failed,” Raymond F. Schinazi, PhD, DSc, the Frances Winship Walters Professor of Pediatrics at Emory University School of Medicine, Atlanta, Ga., told Healio.com/Hepatology. “To the best of our knowledge this is the first time anyone was able to get this outstanding result using such an ultrashort therapy. We will expand this proof of principle study to 300 HCV infected persons to confirm and extend these observations.”

In this open-label, phase 2a single center study, researchers studied 26 patients with chronic HCV genotype 1b infection without cirrhosis from China. They were placed into one of three groups:

Raymond F. Schinazi
Raymond F. Schinazi

Patients assigned sofosbuvir received 400 mg/day; ledipasvir dosage was 90 mg/day; daclatasvir dosage was 60 mg/per day; simeprevir dosage was 150 mg/day and dosage of asunaprevir was 100 mg twice a day.

All medications were taken until six patients in each group reached ultrarapid virological response (plasma HCV RNA < 500 IU/mL by day 2). Patients who reached this milestone went on to receive 3 weeks of therapy and were subsequently cured “with excellent tolerability”, researchers wrote.

Patients who failed to reach ultrarapid virological response received sofosbuvir/ledipasvir for either 8 weeks or 12 weeks and were not included in future studies.

Further analyses

Further research on “cured” patients who received sofosbuvir, ledipasvir and asunaprevir showed:

  • it took 4 days to achieve HCV RNA less than 25 IU/mL
  • liver stiffness from baseline to 12 weeks was 6.1 kPa vs. 4.9 kPa (P = .028).

Further research on “cured” patients who received sofosbuvir, daclatasvir and asunaprevir showed:

  • it took 14 days to achieve HCV RNA less than 25 IU/mL
  • liver stiffness from baseline to 12 weeks was 5.5 kPa vs. 5.4 kPa (P = .53).

Further research on “cured” patients who received sofosbuvir, daclatasvir and simeprevir showed:

  • liver stiffness from baseline to 12 weeks 5.8 kPa vs. 5.1 kPa (P = .046).

Financial benefits

“Less exposure of the drugs due to the ultrashort period of treatment, proper dosing and the savings of drug by close to 60% are all beneficial to the patient,” Schinazi told Healio.com/Hepatology. “Thus more patients can be treated for less money; while at the same time simplifying and shortening duration of treatment. This is a highly desirable goal for all viral diseases since there is less of an opportunity for drug resistant virus to emerge.”

“Our study may not be welcome by big pharma at the moment, but we believe the benefit to patient[s] should be our ultimate goal,” Lau told Healio.com/Hepatology.

Lau and colleagues’ success may not be replicated in all groups, Markus Cornberg, and Michael P. Manns, MD, professors of the department of gastroenterology, hepatology and endocrinology at the Hannover Medical School in Germany wrote in a related editorial. “Direct-acting antiviral combinations might have a different efficacy in patient cohorts with different genotypes or ethnicities,” they wrote. – by Janel Miller

Disclosure: Schinazi reports he is the founder, chairman and director of Cocrystal Pharma Inc., and previous founder and shareholder of Pharmasset Inc. Cornberg reports receiving lecture and advisory board fees from AbbVie, Bristol-Meyers-Squibb, Boehringer-Ingelheim, Biodec Idec, Falk, Gilead Sciences, Janssen-Cilag, MSD/Merck, Roche Diagnostics, Roche Pharma and Siemens. Manns reports receiving lecture and advisory board fees from AbbVie, Bristol-Meyers-Squibb, Boehringer-Ingelheim, Gilead Sciences, Janssen-Cilag, MSD/Merck, Novartis and Roche Pharma. All other researchers report no relevant financial disclosures.

Response-guided ultrashort therapy may work in some patients with hepatitis C, according to results published in The Lancet Gastroenterology & Hepatology.

“Our hypothesis was that the faster the viral load decline, the faster one can reduce the virus to a point — cure boundary — to allow the immunity to take over the job and eradicate the virus — sustained virological response,” George Lau, MD, of the division of Gastroenterology and Hepatology at Humanity and Health Medical Centre in Hong Kong, told Healio.com/Hepatology.

George Lau, MD
George Lau

“No one expected that even 4 weeks of treatment would be sufficient. All previous studies had failed,” Raymond F. Schinazi, PhD, DSc, the Frances Winship Walters Professor of Pediatrics at Emory University School of Medicine, Atlanta, Ga., told Healio.com/Hepatology. “To the best of our knowledge this is the first time anyone was able to get this outstanding result using such an ultrashort therapy. We will expand this proof of principle study to 300 HCV infected persons to confirm and extend these observations.”

In this open-label, phase 2a single center study, researchers studied 26 patients with chronic HCV genotype 1b infection without cirrhosis from China. They were placed into one of three groups:

Raymond F. Schinazi
Raymond F. Schinazi

Patients assigned sofosbuvir received 400 mg/day; ledipasvir dosage was 90 mg/day; daclatasvir dosage was 60 mg/per day; simeprevir dosage was 150 mg/day and dosage of asunaprevir was 100 mg twice a day.

All medications were taken until six patients in each group reached ultrarapid virological response (plasma HCV RNA < 500 IU/mL by day 2). Patients who reached this milestone went on to receive 3 weeks of therapy and were subsequently cured “with excellent tolerability”, researchers wrote.

Patients who failed to reach ultrarapid virological response received sofosbuvir/ledipasvir for either 8 weeks or 12 weeks and were not included in future studies.

Further analyses

Further research on “cured” patients who received sofosbuvir, ledipasvir and asunaprevir showed:

  • it took 4 days to achieve HCV RNA less than 25 IU/mL
  • liver stiffness from baseline to 12 weeks was 6.1 kPa vs. 4.9 kPa (P = .028).

Further research on “cured” patients who received sofosbuvir, daclatasvir and asunaprevir showed:

  • it took 14 days to achieve HCV RNA less than 25 IU/mL
  • liver stiffness from baseline to 12 weeks was 5.5 kPa vs. 5.4 kPa (P = .53).

Further research on “cured” patients who received sofosbuvir, daclatasvir and simeprevir showed:

  • liver stiffness from baseline to 12 weeks 5.8 kPa vs. 5.1 kPa (P = .046).

Financial benefits

“Less exposure of the drugs due to the ultrashort period of treatment, proper dosing and the savings of drug by close to 60% are all beneficial to the patient,” Schinazi told Healio.com/Hepatology. “Thus more patients can be treated for less money; while at the same time simplifying and shortening duration of treatment. This is a highly desirable goal for all viral diseases since there is less of an opportunity for drug resistant virus to emerge.”

“Our study may not be welcome by big pharma at the moment, but we believe the benefit to patient[s] should be our ultimate goal,” Lau told Healio.com/Hepatology.

Lau and colleagues’ success may not be replicated in all groups, Markus Cornberg, and Michael P. Manns, MD, professors of the department of gastroenterology, hepatology and endocrinology at the Hannover Medical School in Germany wrote in a related editorial. “Direct-acting antiviral combinations might have a different efficacy in patient cohorts with different genotypes or ethnicities,” they wrote. – by Janel Miller

Disclosure: Schinazi reports he is the founder, chairman and director of Cocrystal Pharma Inc., and previous founder and shareholder of Pharmasset Inc. Cornberg reports receiving lecture and advisory board fees from AbbVie, Bristol-Meyers-Squibb, Boehringer-Ingelheim, Biodec Idec, Falk, Gilead Sciences, Janssen-Cilag, MSD/Merck, Roche Diagnostics, Roche Pharma and Siemens. Manns reports receiving lecture and advisory board fees from AbbVie, Bristol-Meyers-Squibb, Boehringer-Ingelheim, Gilead Sciences, Janssen-Cilag, MSD/Merck, Novartis and Roche Pharma. All other researchers report no relevant financial disclosures.