Early Access Program Research Articles

Sustained virological response with telaprevir in 1078 patients with advanced hepatitis C: The international telaprevir access program

There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24). 1078 patients with bridging fibrosis (n=552) or cirrhosis (n=526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/mm(3), Hb >12/13 g/dl) and liver function (Albumin >3.3g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label. Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR)=1.51, 95% CI 1.31-2.00, p=0.005), (B) subtype 1b (OR=1.63, 95% CI 1.18-2.24, p=0.0029), (C) alpha-fetoprotein <10 ng/ml (OR=2.50, 95% CI 1.87-3.36, p<0.0001) and (D) any prior response other than null (OR=3.29, 95% CI 2.40-4.52, p<0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail. Naïve and experienced patients with advanced fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver function, can effectively and safely be treated by TVR triple therapy. Baseline predictors of outcome have been identified to optimize pre-treatment counselling.

AB0494 Early Clinical Experiences with Belimumab in Polish Patients with Systemic Lupus Erythematosus

BackgroundBelimumab is a monoclonal antibody, inhibitor of soluble B-cell activating factor, that is used in the adjuvant treatment of adult patients with active seropositive systemic lupus erythematosus (SLE) [1]. Belimumab...

PIN40 - Cost Of Erythropoietin Use In The Early Access Program Of Telaprevir For The Treatment Of Metavir F3-F4 Patients With Genotype 1 Hcv In Brazil

To estimate the direct medical costs associated with the use of erythropoietin (EPO) in the treatment of anemia in patients with advanced fibrosis and cirrhosis (METAVIR F3-F4) receiving telaprevir in association with peg-interferon and ribavirin (TVR+PR) in the early access program in Brazil. Anemia events and EPO use during TVR therapy were gathered from published results of 97 patients in the early access program (EAP) of TVR in Brazil. Anemia treatment was assumed to be one vial of erythropoietin (EPO) 40.000U per week. Medication unit costs were gathered from a public (SUS) and private payer perspective in Brazil. Sensitivity analysis was carried out for anemia treatment duration and patients with EPO use. A sub-analysis was performed to estimate the cost of anemia treatment with boceprevir (BOC+PR) based on data from the phase 3 clinical trials. The cost of EPO during TVR+PR treatment in the EAP /anemic patient was R$ 10.190,04 from a private payer perspective compared to R$ 3.545,06 from a SUS perspective. The average cost of EPO was R$ 4.727,34 /patient from a private payer perspective and R$ 1.644,87 /patient from the SUS perspective. Considering the sensitivity analysis, the total cost of EPO treatment ranged between R$ 382.126,50-R$ 601.212,36 from a private payer perspective compared to R$ 132.960,00-R$ 209.190,40 from a SUS perspective for all patients. Considering EPO use for BOC+PRr, the average anemia treatment cost was R$ 7.851,34 /patient from a private payer perspective and R$ 2.731,86 /patient from a SUS perspective. In a real life setting, TVR+PR was associated with EPO use although few patients discontinued treatment. Compared to EPO use in clinical trials, TVR+PR was associated with less EPO costs than BOC+PR in a real life setting such as the Brazilian EAP.

Real-world Cabazitaxel Safety: The Italian Early-Access Program in Metastatic Castration-Resistant Prostate Cancer

Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death. Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.

Regional analysis of a cohort compassionate-use program (CUP) and early access program (EAP) with cabazitaxel (Cbz) plus prednisone (P; Cbz + P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D).

242 Background: Cbz is an established second-line treatment for pts with mCRPC, having demonstrated an overall survival benefit (with P) vs mitoxantrone with P in the Phase III TROPIC trial. The global CUP (CABAZ_C_05005) and EAP (NCT01254279) (both funded by Sanofi) aimed to provide access to Cbz + P before commercial availability and to document safety in a real-world population. We present a regional analysis of interim data from the CUP and EAP. Methods: Expected total enrolment is 1,450 pts. Pts received Cbz 25 mg/m2 IV Q3W + P 10 mg QD until disease progression (PD), death, unacceptable toxicity or physician/pt decision. Granulocyte colony-stimulating factor (G-CSF) was administered per ASCO guidelines. The cut-off date for this analysis was 30 May 2012. Results: Globally, 1,301 pts have been included from eight regions (Eastern Europe [EE], Western Europe [WE], Northern Europe [NE] and Southern Europe [SE]; Asia [As]; Canada [Ca]; Latin America [LA]; and Australia [Aus]). Key data by region are shown in the Table. Median age varied from 65 years (Ca) to 70 years (Aus, LA, SE). In pts who progressed after last D line, time from last D dose to last PD ranged from 2.3 months (EE, LA) to 6.6 months (Ca). G-CSF use (therapeutic or prophylactic) at Cycle 1 varied widely between regions, from 23% (WE) to 79% (As). Between 11% (LA) and 30% (NE) of patients received ≥10 cycles of Cbz. Conclusions: In this extensive, real-world CUP/EAP cohort of mCRPC pts, substantial regional variation was observed for baseline and on-treatment parameters, including time from last D dose to last PD and G-CSF use. The low proportion of patients receiving ≥10 cycles in LA, Ca and WE may result from a limit of 10 cycles of therapy in some centers. Clinical trial information: NCT01254279. [Table: see text]

Cohort compassionate-use program (CUP) and early access program (EAP) with cabazitaxel (Cbz) plus prednisone (P; Cbz + P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D): Analysis by age group.

109 Background: Cbz + P demonstrated an overall survival benefit vs mitoxantrone + P in pts with mCRPC in the Phase III TROPIC trial. The CUP (CABAZ_C_05005) and EAP (NCT01254279) (both funded by Sanofi) were established to allow access to Cbz ahead of commercial availability. The programs are also evaluating Cbz safety in a real-world population. Data analyzed by age group (≤75 and &gt;75 years) are presented here. Methods: Expected enrolment across both programs is 1,450 pts from 236 centres worldwide. Pts received Cbz 25 mg/m2 IV Q3W + P 10 mg QD until disease progression, death, unacceptable toxicity or physician/pt decision. G-CSF is administered as per ASCO guidelines. Results: As of May 30, 2012, 1,301 pts have enrolled (≤75 years: 1,061 pts [81.6%]; &gt;75 years: 240 pts [18.4%]). Eastern Cooperative Oncology Group performance status and incidence of visceral metastases were generally balanced between treatment groups. The most frequent reasons for discontinuation were disease progression (46.8%) followed by adverse events (AEs; 24.4%) in pts ≤75 years, and AEs (36.4%) followed by disease progression (31.1%) in pts &gt;75 years. Time from initial diagnosis to inclusion was greater in pts &gt;75 years (median 79.66 months) than in pts ≤75 years (median 53.94 months), but time from mCRPC diagnosis to inclusion was approximately equivalent (&gt;75 years: median 22.6 months; ≤75 years: median 20.94 months). G-CSF use was more frequent in pts &gt;75 years (cycle 1: 62.9% of pts) compared with pts ≤75 years (cycle 1: 52.2% of pts). AEs of clinical concern were more frequent in the older age group (Grade ≥3 AEs: &gt;75 years 64.2%; ≤75 years 54.8%). Grade ≥3 neutropenia was observed in 25.8% of pts &gt;75 years and in 17.0% of pts ≤75 years. Conclusions: We observed several differences between age groups in baseline and on-treatment parameters, suggesting differences in the natural history of mCRPC (faster disease progression in pts ≤75 years than in pts &gt;75 years) and secondary to treatment (AEs more frequent in pts &gt;75 years compared with pts ≤75 years). Clinical trial information: NCT01254279.

Enzalutamide in men with prostate cancer resistant to docetaxel and abiraterone.

247 Background: Since FDA approval in 2011, abiraterone (Zytiga) has supplanted docetaxel as preferred first-line treatment for metastatic castrate-resistant prostate cancer. In August 2012 enzalutamide (Xtandi) was FDA-approved for the treatment of castrate-resistant prostate cancer after docetaxel (Taxotere). We performed a retrospective chart review at a large medical oncology clinic specializing in prostate cancer to determine the PSA response rates of enzalutamide administered to men who had previously progressed on both abiraterone and docetaxel. This report includes some patients who participated in the Astellas/Medivation-sponsored Early Access Program; however, it represents the author’s independent clinical experience. Methods: Enzalutamide was administered at a dose of 160 mg daily. Patients were subsequently followed with monthly physical examination, PSA and routine blood tests. No hepatotoxicity or seizures occurred. Men were considered evaluable for PSA response if they received enzalutamide for twelve weeks. A PSA decline of 30% from baseline after 12 weeks was defined as a response. A PSA increase of 30% from baseline within 12 weeks was defined as disease progression. Men with neither a 30% increase nor a 30% decline were classified as having stable disease. Results: 66 men were treated and 63 were evaluable for PSA response. Median age was 67. Median baseline PSA was 68.5. All participants had disease that had progressed on abiraterone. 55 men received previous docetaxel. 38 had received previous Provenge. Two men stopped before 12 weeks because of intolerable fatigue. One man died of progressive disease before 12 weeks. After a median follow up of 12.5 weeks, 18(29%) men met criteria for PSA response. 13(21%) men had stable disease and 32(51%) men had PSA progression. Conclusions: Enzalutamide has activity in a heavily pretreated population of men resistant to abiraterone and docetaxel.

Efficacy and safety of Telaprevir in patients with hepatitis C genotype 1 infection: The German Telaprevir early access program

Efficacy and safety of Telaprevir in patients with hepatitis C genotype 1 infection: The German Telaprevir early access program

Treatment of hepatitis C genotype 1 patients with severe fibrosis or compensated cirrhosis: the telaprevir early access program in patients from Romania

Methods Patients were treated with telaprevir in combination with peginterferon alfa and ribavirin (PR) for 12 weeks, followed by PR for 12 or 36 weeks. Severe fibrosis/cirrhosis was defined by liver biopsy (Metavir F3-4 or Ishak 3-6) or noninvasive tests. Platelet count >90,000/cmm was required at entry. HCV RNA was evaluated at baseline and Weeks 4 and 12 of treatment. Virological response was defined as serum HCV RNA not detected, for the Intent to Treat (ITT) population.

Management and outcomes of side effects with focus on anaemia in patients with hepatitis C genotype 1 infection: the telaprevir early access program in patients from Romania

Management and outcomes of side effects with focus on anaemia in patients with hepatitis C genotype 1 infection: the telaprevir early access program in patients from Romania Adrian Streinu-Cercel, Anca Victorița Trifan, Florin Alexandru Caruntu, Ioan Sporea, Liliana Simona Gheorghe, Manuela Curescu, Mihai Mircea Diculescu, Mihai Voiculescu, Oliviu Pascu, Isabelle Lonjon-Domanec, Andrew Martin Hill, Sorin Rugina

Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C

Background and aimSevere adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme...

P105 Treatment options in patients with metastatic castrate-resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen: A single UK cancer centre's experience using patients within the early access programme and cancer drugs fund

P105 Treatment options in patients with metastatic castrate-resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen: A single UK cancer centre's experience using patients within the early access programme and cancer drugs fund

PIN54 - Impact of Treatment Failure on the Total Cost of Triple Therapy Including Boceprevir or Telaprevir Based on the French Early Access Program (ANRS CO20-CUPIC) Study

PIN54 - Impact of Treatment Failure on the Total Cost of Triple Therapy Including Boceprevir or Telaprevir Based on the French Early Access Program (ANRS CO20-CUPIC) Study

158-P: NGSengine EARLY ACCESS PROGRAM: FINDINGS IN A MULTICENTER EVALUATION

NGS technology is developing fast and has come to a point where it can be applied routinely. Many HLA typing laboratories are considering introducing NGS technologies in their diagnostics routines. To facilitate HLA typing by NGS, we developed NGS-go®, a generic HLA gene amplification strategy, and NGSengine®, a software package to perform HLA typing based on NGS data. An NGS Early Access Program (EAP) was set up to determine if our NGS solutions fulfill the needs and requirements of users within the HLA field. This EAP gives laboratories the chance to evaluate both NGS-go® and NGSengine® with their NGS instrument of choice, and even more important, it gives laboratories influence on the design of the software package.In the NGS EAP over 20 laboratories from various geographical regions participated. All labs were given access to NGS-go® reagents and NGSengine® software and were stimulated to provide feedback on the performance. Based on their feedback, NGSengine® was adjusted and significantly improved. During the EAP new updates of NGSengine® are monthly released. Based on feedback received, the profiles of the participating labs were determined. Here, we present the NGS experience feedback received from the participating labs. We will also present statistics on the equipment used in the participating labs and show the laboratory profiles of the labs using NGS. 5 different platforms were evaluated by more than 20 participating labs located world-wide Participating labs had very variable levels of NGS experience Participating labs possess different favorite NGS platforms Many of the participating labs are in the early days of HLA testing with NGS and have not yet established a workflow Valuable feedback was obtained from participants for furtherimprovement of NGSengine®. Penning: GenDx: Employee. Kooter: GenDx: Employee. Ruzius: GenDx: Employee. Mulder: GenDx: Employee; Stockholder. Rozemuller: GenDx: Employee; Stockholder.

Interim safety analysis of a compassionate-use program (CUP) and early-access program (EAP) providing cabazitaxel (Cbz) plus prednisone (P) to patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel.

5055 Background: Cbz + P provides a significant survival benefit vs mitoxantrone + P in pts with mCRPC (Phase III TROPIC study [NCT00417079]; hazard ratio 0.70; p &lt; 0.0001). These findings supported the initiation of ongoing Sanofi-funded CUP and EAP (NCT01254279) to provide access to Cbz prior to commercialization and to collect real-life safety data. Methods: Expected enrollment is ~1600 pts with mCRPC from 250 centers worldwide. Pts receive Cbz (25 mg/m2 Q3W) + P (10 mg oral QD) until progressive disease (PD), death, unacceptable toxicity, physician/pt decision or Cbz commercial availability. Pts are followed until 30 days after last dose. Granulocyte colony-stimulating factor (G-CSF) use is recommended as per ASCO guidance. Results: Interim baseline and safety data from the first 1301 pts treated in 37 countries are now available. Mean age was 68 yrs (22% were ≥ 75 yrs). All pts had an ECOG performance status ≤ 2. Median time from initial prostate cancer diagnosis was 57.6 months and 60% of pts had ≥ 2 metastatic sites; the most common were bone (91%) and lymph nodes (regional 30%, distant 27%). In total, 17% had PD whilst on docetaxel. The median number of Cbz cycles was 6 (range 1–22); median relative dose intensity was 99%. Overall, 837 pts (64%) received G-CSF (n = 123 curative [C], n = 765 prophylactic [P] and n = 99 [C + P]). Of 1142 pts (88%) who discontinued Cbz + P, the most common reasons were PD (44%), adverse event (AE; 27%), physician decision (13%) and commercial availability of Cbz (7%). Grade 3–4 AEs possibly related to Cbz + P occurred in 43% of pts; the most frequent were clinical neutropenia (18%), febrile neutropenia (FN; 7%) and diarrhea (4%). Of 80 pts (6%) with AEs leading to death, the AE was related to Cbz + P in 39 pts (3%). Conclusions: These results provide valuable data on Cbz + P treatment in routine clinical practice, confirming the safety results of clinical trials and showing that treatment with Cbz + P is associated with a manageable safety profile. The incidence of FN seems slightly lower than in TROPIC, owing to more frequent use of G-CSF prophylaxis in the CUP and EAP. Clinical trial information: NCT01254279.

Quality of life (QoL) of patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel.

e16088 Background: The effects of cabazitaxel on QoL, pain response and preference/utility data have not been well studied in men with CRPC treated post-docetaxel. As part of a single-arm multicenter Sanofi-funded Early Access Program (EAP) for cabazitaxel, QoL data were collected on Canadian patients. Methods: Between May 2011 and February 2012, 61 patients (pts) were enrolled at 9 centers. QoL was assessed at the start of each cycle using the FACT-P and its subscales, and the EQ 5D-3L. EQ 5D-3L health state index (HIS) data were converted into utility values (Canadian tariff, Bansback 2011). Present pain intensity (PPI) and analgesic scores were assessed using the McGill-Melzack questionnaire. Results: QoL data were evaluable in 55 pts. Baseline pt characteristics were: median age 65 years (range, 42-79), 92.7% of pts were ECOG PS 0 or 1, 87% had bone metastases, and 56% (31/55) received at least 6 cycles of cabazitaxel. Statistically significant changes from baseline in mean QoL scores were observed on FACT-P total score at cycle 2, and prostate cancer specific subscale (PCS) at cycles 1 to 4. As a measure of QoL response, increases were observed and maintained for &gt; 2 consecutive cycles in 9% (&gt;16 points) and 25% (≥10) of pts for FACT-P total score. Improvements to the level of Minimal Important Differences (MID) (Cella 2009) maintained for &gt; 2 consecutive cycles were observed in 36% of pts for FACT-P total score (MID=6), 49% for PCS subscale (MID=2), and 26% for PCS-Pain subscale (MID=2), respectively. The percentage of pts reporting "no problem" in the EQ-5D pain/discomfort domain were above baseline levels at every cycle and improved from baseline to end of treatment from 19% to 29% (p &lt; 0.05). Other EQ-5D dimensions (anxiety/depression, mobility, self-care and usual activities) remained stable over the course of treatment. Improvement from baseline in utility value (HIS) was observed at cycle 4 with a utility value of 0.769 (vs 0.713 at baseline). PPI scores improved despite stable analgesic use and were significantly different from baseline at cycles 2, 4 and 9. Conclusions: Data from this EAP suggest improvements in QoL, pain and prostate cancer specific symptoms with second-line cabazitaxel treatment. Clinical trial information: NCT01254279.

Treatment of Genotype 1 Hepatitis C patients with severe fibrosis or compensated cirrhosis: the telaprevir early access program in patients from Austria and Switzerland

Background: HEP3002 is an ongoing, open-label, early access program of telaprevir in 16 countries, for adult patients with genotype 1 chronic hepatitis C with severe fibrosis or compensated cirrhosis.

Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

In phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme. 674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16. A high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic decompensation) (6.4%), and a difficult management of anaemia (erythropoietin and transfusion use in 50.7% and 12.1%) were observed. Independent predictors of anaemia < 8 g/dl or blood transfusion were: female gender (OR 2.19, 95% CI 1.11-4.33, p=0.024), no lead-in phase (OR 2.25, 95% CI 1.15-4.39, p=0.018), age ≥ 65 years (OR 3.04, 95% CI 1.54-6.02, p=0.0014), haemoglobin level (≤ 12 g/dl for females, ≤ 13 g/dl for males) (OR 5.30, 95% CI 2.49-11.5, p=0.0001). Death or severe complications were related to platelets count ≤ 100,000/mm(3) (OR 3.11, 95% CI 1.30-7.41, p=0.0105) and albumin <35 g/dl (OR 6.33, 95% CI 2.66-15.07, p=0.0001), with a risk of 44.1% in patients with both. However, the on-treatment virological response was high. The safety profile was poor and patients with platelet count ≤ 100,000/mm(3) and serum albumin <35 g/L should not be treated with the triple therapy.

Cabazitaxel for the Second-Line Treatment of Metastatic Hormone-Refractory Prostate Cancer: A NICE Single Technology Appraisal

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cabazitaxel (Jevtana®, sanofi-aventis, UK) to submit evidence of its clinical and cost effectiveness for the second-line treatment of metastatic hormone-refractory prostate cancer (mHRPC). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. Clinical evidence was derived from a multinational randomized open-label phase III trial of cabazitaxel plus prednisone or prednisolone in men with mHRPC that had progressed during or following treatment with docetaxel. The comparator was mitoxantrone plus prednisone or prednisolone. Use of cabazitaxel was associated with a statistically significant improvement in overall survival, median progression-free survival and time to tumour progression. However, it was also associated with an increased incidence of adverse events such as neutropenia. Utility data were based on interim results from the early access programme for cabazitaxel. Data were only available for a small number of patients with stable disease, resulting in great uncertainty as to the effect of cabazitaxel on quality of life. For their economic evaluation, the manufacturer estimated that the use of cabazitaxel was associated with an incremental cost of £74,908 per QALY gained. However, the ERG disagreed with the manufacturer over two key methodological points. The first concerned modelling and extrapolating survival; the second point was concerned with the choice of patient population. The ERG altered the manufacturer's evaluation to take into account these two points of disagreement. The resulting cost per QALY gained was £82,950. The NICE Appraisal Committee believed the analysis presented by the ERG to be more plausible, and likely to be an underestimate of the cost per QALY. They concluded that whilst the clinical effectiveness of cabazitaxel had been proven, it was not likely to represent a cost-effective use of NHS resources and so its use could not be recommended.

1185 GENERATION OF SELECTIVE HIGH AFFINITY LIGANDS TO BLOCK CD81-LARGE EXTRACELLULAR LOOP: HEPATITIS C VIRUS–E2 GLYCOPROTEIN INTERACTION

Background and Aims: HCV infects around 3.3% of the world population. The standard of care HCV treatment (Peginterferon/Ribavirin) leads to serious side effects and SVR is <50% in genotype-1 patients. The newly FDA approved protease inhibitors (Telaprevir/Boceprevir) were found to be effective when each is combined with PR giving higher SVR rates in GT-1. However the poor safety profile of TVR and BOC reported in the Week 16 analysis of the French Early Access Program suggest there is still a need for better HCV drugs. Many companies have active programs developing HCV protease and polymerase inhibitors. We are developing drugs to block an earlier step in HCV infection, CD81 mediated invasion. In this study we are developing Selective High Affinity Ligands (SHALs) to target the E2 binding site on CD81 and block their interaction.