deleobuvir (BI 207127) / Boehringer Ingelheim - LARVOL DELTA

Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients (clinicaltrials.gov) - P1; N=72; Active, not recruiting; Sponsor: Boehringer Ingelheim; N=102 -> 72

Enrollment change • Biosimilar • Hepatitis C Virus • Immunology

Long-term follow-up analysis of RAVS in HCV NS3, NS5A, and NS5B in DAA therapy failure patients (ILC 2015) - Presentation time: Friday 24 April 2015, 13:00 - 13:30; Abstract #P0767; P=NA, N=12; "Variable rates of persistence of RAVs in patients with failure to NS3, NS5A and NS5B inhibitors have been observed. While generally RAVs to protease inhibitors tend to decline and RAVs to NS5A inhibitors persist in single patients, highly resistant variants have been observed up to 3 years after treatment failure."

Retrospective data • Hepatitis C Virus

[Late breaking abstract] Rapid and consistent virologic responses in a phase 2 trial of a new all-oral combination of faldaprevir, deleobuvir, and PPI-668, with and without ribavirin, in patients with HCV genotype-1a infection (AASLD 2013) - Presentation time: Mon, Nov 04, 2013; 8:00 AM - 5:30 PM; P2, N=36; NCT01859962; Sponsor: Presidio; "...oral combination regimen of faldaprevir + deleobuvir + PPI-668 +/- RBV has consistently produced rapid virologic responses, with 28/29 (97%) patients to date achieving HCV RNA <25 IU/mL...and with 13/13 (100%) patients exhibiting non-detectable HCV RNA...at end of treatment (week 12). SVR4 data will be available at the meeting."

P2 data • Hepatitis C Virus

Rapid and consistent virologic responses in a phase 2 trial of a new all-oral combination of faldaprevir, deleobuvir, and PPI-668 (HepDART 2013) - Abstract 100; P2a, N=36; NCT01859962; Sponsor: Presidio Pharmaceuticals; "Of 29 patients with at least 4 weeks of treatment, 28 achieved HCV RNA <25 IU/mL (<LLOQ). Two of these patients had potentially meaningful pre-existing NS5A resistance substitutions and 9 had NS5B Thumb 1 polymorphic substitution A421V....Adverse events were mild to moderate, with rashes and gastrointestinal side effects similar to previous faldaprevir and deleobuvir trials." 

P2 data • Hepatitis C Virus

High rate of sustained virologic response in patients with HCV genotype-1a infection: A phase 2 trial of faldaprevir, deleobuvir and PPI-668, with and without ribavirin (EASL 2014) - Presentation time: 11.04.2014, 16:00-18:00; Abstract #O65; P2, N=36; NCT01859962; Sponsor: Presidio; “27/28 (96%) patients had HCV RNA levels below lower limit of detection (< LLOD) at EOT. 19/20 (95%) patients who reached 4 weeks post-treatment have achieved SVR4 (1 relapse), and 12/12 (100%) have achieved SVR8…Rash and GI events are similar to previous FDV/DBV trials, with the RBV-free cohort showing fewer AEs.”

P2 data • Hepatitis C Virus

Presidio Pharmaceuticals teams up with Boehringer Ingelheim on hepatitis C drug combo (San Francisco Business Times) - "Presidio's drug PPI-668 will be combined in an oral treatment with Boehringer Ingelheim's two protease inhibitors BI201335 and BI207127...The two companies will test a combination...in a Phase IIa clinical trial over 12 weeks. The tests begin in the second quarter of 2013."

Anticipated new P2a trial • Hepatitis C Virus

Bioavailability of 3 different formulations of BI 207127 (clinicaltrials.gov) - P1, N=18; Recruiting -> Completed

Trial completion • Hepatitis C Virus

BI 207127 / faldaprevir combination therapy in hepatic impairment (Child-Pugh B) patients with genotype 1b chronic hepatitis C infection: HCVerso3 (clinicaltrials.gov) - P2, N=36 -> 35; Sponsor: Boehringer Ingelheim; Recruiting -> Active, not recruiting.

Enrollment closed • Hepatitis C Virus

This trial evaluates safety, pharmacokinetic profile and anti-viral response of BI 207127 and BI 201335 for patients with chronic hepatitis C (clinicaltrials.gov) - P2, N=25; Sponsor: Boehringer Ingelheim; Active, not recruiting -> Completed.

Trial completion • Hepatitis C Virus

Highly efficient infectious cell culture of three HCV genotype 2b strains and sensitivity to lead protease, NS5A, and polymerase inhibitors (Hepatology) - PMID: 23913364; "NS5B inhibitors Sofosbuvir, Mericitabine, and BI207127 had activity against 1a (strain TN), 2a...and the 2b strains, whereas VX-222 and Filibuvir only inhibited 1a. Genotype 2b strains were least sensitive to seven lead protease inhibitors, including MK-5172....NS5A inhibitor Daclatasvir was exceptionally potent, but efficacy was affected by the HCV strain."

Preclinical • Hepatitis C Virus

Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients (clinicaltrials.gov) - P1; N=72; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting -> Completed ; Trial primary completion date: Dec 2013 ->Oct 2014

Trial completion • Trial primary completion date • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

New Boehringer Ingelheim hepatitis C data to be presented at AASLD (Businesswire) - BI will present new HCV data at scientific sessions of 62nd AASLD; Key data presented will include a week 12 interim analysis of SOUND-C2, a P2b study evaluating an interferon-free combination of its protease inhibitor BI 201335 & its polymerase inhibitor BI 207127 – with and without ribavirin in treatment-naïve HCV infected pts; In addition, SILEN-C1 & SILEN-C3 data will further assess efficacy & safety of BI 201335 in treatment-naïve HCV-infected pts, in combination PegIFN/RBV

Anticipated data presentation • Hepatitis C Virus

Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study. - Eur J Gastroenterol Hepatol - "In this small study, the interferon-free regimen of faldaprevir, deleobuvir and ribavirin resulted in high rates of virological breakthrough and low rates of SVR12 in IL28B non-CC genotype patients infected with genotype-1a HCV."

Journal • Biosimilar • Hepatitis C Virus • Immunology

Safety, tolerability and pharmacokinetics of different multiple doses of BI 207127 BID and multiple doses of BI 207127combined with faldaprevir in healthy male and female subjects (clinicaltrials.gov) - P1, N=32; Sponsor: Boehringer Ingelheim; Recruiting -> Active, not recruiting.

Enrollment closed • Hepatitis C Virus

Pivotal phase 3 data from Boehringer Ingelheim hepatitis C portfolio to be presented at 64th Annual AASLD Meeting (PRNewswire) - "New data...accepted for presentation at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)....Presentations will include data...faldaprevir, including final results from the STARTVerso™ 1, 2 and 3 pivotal trial programs...in treatment-naive and treatment-experienced patients."

Anticipated clinical data • Anticipated conference • Hepatitis C Virus

Interferon-free treatment with faldaprevir, deleobuvir and ribavirin for patients with HCV genotype-1b infection: Pooled data from the SOUND-C2 and SOUND-C3 studies (APASL 2014) - Abstract #684;  P2, N=110; SOUND-C2; SOUND-C3 (NCT01132313); Sponsor: Boehringer Ingelheim; "The interferon-free regimen of faldaprevir, deleobuvir BID, and ribavirin achieved SVR12 rates of 88% in GT-1b patients across the SOUND-C2 and -C3 studies. The removal of the deleobuvir induction dose and shortening treatment duration to 16 weeks in SOUND-C3 did not impact on efficacy." 

P2 data • Hepatitis C Virus

An analysis of response rates by fibrosis stage in patients treated with faldaprevir, BI 207127 and ribavirin in the Sound-C2 study (DDW 2013) - Presentation time: Saturday, 8:00AM - 5:00PM; Abstract #Sa1029; P2, N=360; SOUND-C2 (NCT01132313); Sponsor: Boehringer Ingelheim; “Patients treated with the interferon-free combination of faldaprevir, BI 207127 and ribavirin achieved high SVR rates whether they had no/mild/moderate liver fibrosis or advanced liver fibrosis/cirrhosis.”

P2 data • Hepatitis C Virus

HCVerso1: A phase III study of faldaprevir (FDV) plus deleobuvir (DBV) and ribavirin (RBV) for chronic HCV genotype (GT)-1b infection in treatment-naïve patients (AASLD 2014) - Presentation time: Tuesday, November 11, 2014; 8:00 AM - 12:00 PM; Abstract #1959; P3, N=470; HCVerso1 (NCT01732796); Sponsor: Boehringer Ingelheim; “Adjusted response rates were 81% after 24w (95%CI 77–86, p<0.0001 vs historical control) and 72% after 16w of treatment (95%CI 66–77, p=0.3989 vs historical control)….Overall, AEs were similar for Arms 1 and 2. Discontinuation of all medications due to AEs occurred in 8% of patients across all arms. Grade 3/4 bilirubin elevations (mostly unconjugated) occurred in 52% of all patients.” 

P3 data • Hepatitis C Virus

HCVerso2: A phase III study of faldaprevir (FDV) plus deleobuvir (DBV) and ribavirin (RBV) for chronic HCV genotype (GT)-1b infection in treatment-naïve patients including those ineligible for pegylated interferon (PegIFN) (AASLD 2014) - Presentation time: Tuesday, November 11, 2014; 8:00 AM - 12:00 PM; Abstract #1966; P3, N=496; HCVerso2 (NCT01728324); Sponsor: Boehringer Ingelheim; “In treatment-naïve, non-cirrhotic patients with HCV GT-1b infection, FDV+DBV+RBV for 16 or 24w resulted in comparable SVR12 rates (76% vs 82%), with similar tolerability profiles. Patients with cirrhosis achieved SVR12 of 74% (24w). The adjusted SVR12 rates for 16 or 24w in patients with or without cirrhosis were significantly higher than historical control.” 

P3 data • Hepatitis C Virus

Interferon-free treatment of chronic hepatitis C with faldaprevir, deleobuvir, and ribavirin: SOUND-C3, a Phase 2b study (Liver Int) - P2, N=32; SOUND-C3 (NCT01132313); Sponsor: Boehringer Ingelheim; "Sustained virologic response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b, respectively....The most frequently reported adverse events of at least moderate intensity were anemia (16%), nausea, vomiting, and fatigue (9% each)."

P2b data • Hepatitis C Virus

The efficacy and safety of the interferon-free combination of BI201335 and BI207127 in genotype 1 HCV patients with cirrhosis - Interim analysis from SOUND-C2 (EASL 2012) - Presentation time: 19.04.2012, 09:00-18:00; P2b, N=37; SOUND-C2; Interferon-free combination therapy with BI201335, BI207127 and ribavirin achieved up to 60% SVR12 in GT-1a and up to 83% in GT1b patients with compensated liver cirrhosis

P2 interim data • Hepatitis C Virus

An analysis of response rates by fibrosis stage in patients treated with faldaprevir, BI 207127 and ribavirin in the SOUND-C2 study (EASL 2013) - Presentation time: 27.04.2013, 09:00-18:00; Abstract 1227; P2, N=252; SOUND-C2 (NCT01132313); Sponsor: Boehringer Ingelheim; “Patients treated with the interferon-free combination of faldaprevir, BI 207127 and ribavirin achieved high SVR rates whether they had no/mild/moderate liver fibrosis or advanced liver fibrosis/cirrhosis”

P2 data • Hepatitis C Virus

Pharmacokinetic modeling of the relationship between SVR and plasma concentrations of faldaprevir or BI207127 in HCV GT1-infected patients in SOUND-C2 (IWCPHT 2013) - Abstract: O_12_PK; P2, N=487; SOUND-C2 (NCT01132313); Sponsor: Boehringer Ingelheim; "Patients with GT1b (any IL28B genotype) had flat or shallow relationships between trough concentrations of FDV and BI207127 and predicted SVR12....For both drugs there was a significantly greater effect of trough concentration on SVR12 in GT1a-CC patients compared with GT1b patients; GT1a-CC patients had predicted SVR12 >70% only at higher concentrations."

P2 data • Hepatitis C Virus

Interferon-free treatment with faldaprevir, deleobuvir (BI 207127) and ribavirin in SOUND-C3: 95% SVR12 in HCV-GT1b (AASLD 2013) - Presentation time: Sun, Nov 03, 2013; 8:00 AM - 5:30 PM; Abstract #1102; P2, N=32; Sponsor: Boehringer Ingelheim; SOUND-C3 (NCT01132313); “In SOUND-C3, optimizing treatment for GT1b-infected patients improved efficacy compared with SOUND-C2: 95% of patients with GT1b (including patients with compensated cirrhosis) achieved SVR12 with 16 weeks treatment”

P2 data • Hepatitis C Virus

Boehringer Ingelheim announces phase 3 SVR12 results in HCV/HIV co-infected patients treated with faldaprevir (Boehringer Ingelheim Press Release) - P3, N=308; STARTVerso4 (NCT01399619); Sponsor: Boehringer Ingelheim; "In each faldaprevir dose group, 71% (120mg) and 72% (240mg) of patients achieved SVR12. SVR12 results were consistent across patients regardless of HCV genotype-1 subtype (GT1a or GT1b), presence of compensated cirrhosis, dose and duration of faldaprevir, and duration of PegIFN/RBV....Serious adverse events (AEs) were reported in 32 patients (10%)....If authorized by the European Commission, faldaprevir could be available for marketing in the EU in the second half of 2014. Following an assessment of the blinded Phase 3 trial data from HCVerso® 1 and 2 for the combination of deleobuvir, faldaprevir and ribavirin, Boehringer Ingelheim has decided to halt further development of deleobuvir-containing HCV regimens." 

Anticipated launch Europe • Discontinued • P3 data • Hepatitis C Virus