HCV Studies Performed on New Iranian DAA Drugs Shahin Merat, M.D. Professor of Medicine Digestive Disease Research Institute Tehran University of Medical Sciences

Studies Performed by DDRI Digestive Disease Research Institute (DDRI) of Tehran University of Medical Sciences (TUMS) SOF5 Sofosbuvir, pegylated interferon, ribavirin 5 patients, easiest to treat SD6 Sofosbuvir, daclatasvir (Sovodak) 6 patients, easiest to treat SD100 Sofosbuvir, daclatasvir (Sovodak), ribavirin 100 patients, most difficult to treat

The SOF5 Study Five easy-to-treat patients Treated for 12 weeks: Genotype 1a/1b Treatment naïve Non-cirrhotic Treated for 12 weeks: Weekly PEG-IFN (pegaferon), 180 micg SQ Ribavirin (1000mg/d for <75kg, 1200mg/d for>75kg) PO in two divided daily doses Sofosbuvir 400 mg daily PO

SOF5 Study Results Viral count at week 1 Viral count at week 4 All non-detectable Viral count at week 4 Viral count at week 12 (end of treatment) Viral count at week 24 (SVR)  Response rate: 100%

The SD6 Study Six easy-to-treat patients Treated for 12 weeks: Genotype 1a/1b Treatment naïve Non-cirrhotic Treated for 12 weeks: Sofosbuvir 400 mg/Daclatasvir 60 mg in a single caplet (Sovodak), once daily

SD6 Study Results Viral count at week 1 Viral count at week 4 All non-detectable Viral count at week 4 Viral count at week 12 (end of treatment) Viral count at week 24 (SVR) One lost to follow-up, other 5 non-detectable  Response rate (per-protocol): 100%

The SD100 Study 100 difficult-to-treat patients Treated for 12 weeks: Cirrhotics, including decompensated and Child’s C All genotypes, including genotype 3 (difficult to treat) Previous treatment failures HIV, post transplant, immune supressors… Treated for 12 weeks: Sofosbuvir 400 mg/Daclatasvir 60 mg in a single caplet (Sovodak), once daily Ribavirin (1000mg/d for <75kg, 1200mg/d for>75kg) in two divided daily doses

SD100 Study Subjects 100 patients included, all cirrhotic Age: mean 54.8 years Male/Female: 66/34 Genotype 55 genotype 1 42 genotype 3 1 genotype 4 2 unknown 2 HIV 4 post transplant 6 decompensated cirrhosis 1 AIH

Follow-up One patient developed increased creatinine level following severe diarrhea and gastroenteritis  Excluded Two patients died from unrelated reasons perforated duodenal ulcer sepsis following IV drug abuse in an HIV patient Five patients lost to follow-up 92 subjects finished the study.

Viral Counts During Treatment Viral count at week 1 available for 94 patients All non-detectable except for 1 (145 IU/ml) Viral count at week 4 available for 90 patients All non-detectable Viral count at week 12 available for 92 patients

Final Results Response rate: Per protocol: 97.8% Viral count at week 24 (SVR12) available for 92 patients 90 non-detectable, 2 recurrence One genotype 1 One genotype 3 Response rate: Per protocol: 97.8% Intention to treat: 90% Remember these are cirrhotics. The response rate for cirrhotics in the literature is around 80%