Gilead Announces Data for Investigational, All-Oral, Pan-Genotypic Three-Drug Regimen of Sofosbuvir, GS-5816 and GS-9857 for Chronic Hepatitis C

-- Data Support Ongoing Trials Evaluating Shortened Course of Therapy --

VIENNA, Austria--(BUSINESS WIRE)--Apr. 23, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced pre-clinical data and results from Phase 1 and Phase 2 studies supporting the development of an investigational all-oral, pan-genotypic regimen of Sovaldi^® (sofosbuvir 400 mg/SOF), the investigational NS5A inhibitor GS-5816 and GS-9857, an investigational NS3/4A protease inhibitor. These data will be presented at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria.

In pre-clinical studies, GS-9857 demonstrated similarly potent antiviral activity against HCV replicons of all tested genotypes (1-6), as well as an improved resistance profile compared to other HCV protease inhibitors (ePoster #P0899). In a healthy volunteer study, GS-9857 demonstrated a favorable pharmacokinetic profile (ePoster #P0861). Data from a three-day monotherapy study also demonstrated that GS-9857 was well-tolerated and achieved median HCV RNA reductions of more than 3 log10 IU/mL for HCV patients with genotypes 1, 2, 3 and 4 at the 100 mg dose (ePoster #P0901).

Presented as a late-breaker ePoster (ePoster #LP03), a Phase 2 study of triple-combination therapy with a fixed-dose combination of SOF/GS-5816 plus GS-9857 among genotype 1 patients demonstrated sustained virologic response (SVR12) rates following six weeks of treatment of 93 percent (n=14/15) among treatment-naïve, non-cirrhotic patients, 87 percent (n=13/15) among treatment-naïve, cirrhotic patients, and 67 percent (n=20/30) among those who had failed therapy with two or more direct-acting antiviral agents (DAAs). The four-week regimen resulted in a sub-optimal SVR12 rate of 27 percent (n=4/15).

“These data support the ongoing development of GS-9857 and the potential for an all-oral, triple combination therapy containing Sovaldi, GS-5816 and GS-9857 to attempt to further reduce treatment duration for hepatitis C patients,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “We are encouraged by the six-week SVR12 rates and other data presented at EASL demonstrating this regimen’s pan-genotypic potential, and have recently initiated additional Phase 2 studies to further evaluate the appropriate treatment duration of this regimen for all patients, regardless of genotype, including those who have failed prior therapy with directly acting antivirals and those with cirrhosis.”

SOF/GS-5816 plus GS-9857 was generally well tolerated. There were no Grade 3 or 4 adverse events nor serious adverse events. The most frequent adverse events were nausea (25 percent), headache (24 percent) and fatigue (16 percent). Transient, asymptomatic, elevated lipase (Grade 3 or 4) occurred in four patients (5 percent).

GS-5816 and GS-9857 are investigational products and their safety and efficacy have not been established. Additional information about these studies can be found at www.clinicaltrials.gov.

About Gilead

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may observe unfavorable results from additional clinical trials involving GS-9857, including in combination with Sovaldi and GS-5816. In addition, Gilead may make a strategic decision to discontinue development of GS-9857, including in combination with Sovaldi and GS-5816 if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. As a result, GS-9857 may never be successfully commercialized. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Sovaldi is available at www.gilead.com.

Sovaldi is a registered trademark of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Sung Lee, +1 650-524-7792 (Investors)
Nathan Kaiser, +1 650-522-1853 (Media)
Michele Rest, +1 650-577-6935 (Media)

Source

Idenix Announces Promising Clinical Data and Continued Progress in Nucleotide Prodrug Development Programs for the Treatment of Hepatitis C

• Idenix Reports Positive Proof-of-Concept Data for Lead Nucleotide Prodrug, IDX21437
• Idenix on Track to Initiate All-Oral Pan-Genotypic Phase II Combination Clinical Study of IDX21437 and Samatasvir in mid-2014
• Idenix Initiates Phase I Clinical Trial of Follow-on Nucleotide Prodrug, IDX21459
• Idenix to Host Conference Call / Webcast at 8:00 a.m. ET today

CAMBRIDGE, Mass., April 7, 2014 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced continued progress of the Company's program to develop nucleotide prodrug inhibitors for the treatment of hepatitis C virus (HCV) infection. Idenix is reporting potent antiviral activity of mean maximum 4.2-4.3 log₁₀ IU/mL reductions for patients infected with HCV genotype 1, 2 or 3 receiving 300 mg once daily of IDX21437 in the seven-day proof-of-concept portion of a phase I/II clinical trial. Based on this progress, the Company's goal is to initiate a combination clinical trial of IDX21437 and samatasvir, a pan-genotypic NS5A inhibitor, in mid-2014. In addition, Idenix has selected a follow-on uridine-based nucleotide prodrug, IDX21459, from its ongoing nucleotide discovery program and initiated enrollment for the healthy volunteer portion of a phase I clinical trial.

"As more all-oral regimens become available to treat hepatitis C, an increased number of patients will be diagnosed and treated. It will be important to have simple, short duration options for our patients. These early data for IDX21437 support its potential to be part of future treatment combinations." said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and a clinical investigator in the IDX21437 proof-of-concept study. "Nucleotide-based treatment combinations are favored because of safety, efficacy, high barrier to resistance and low drug-drug interaction potential and we look forward to seeing further results from studies with IDX21437."

"We are very pleased with these positive data for IDX21437 and we are excited to have two nucleotide prodrug candidates in the clinic," said Ron Renaud, Idenix's President and Chief Executive Officer.  "With the initiation of the phase II study of IDX21437 and samatasvir later this year, we will be one of a few companies with an all-oral, pan-genotypic, nucleotide-based combination approach in the clinic. We believe this regimen has the potential to play a significant role in advancing HCV care for the benefit of patients, physicians and payers."

IDX21437: Topline 7-Day Phase I/II Clinical Results

In January 2014, Idenix initiated the seven-day proof-of-concept portion of a phase I/II clinical trial for IDX21437. The trial completed enrollment of 44 treatment-naïve, genotype (GT) 1, 2 or 3 HCV-infected patients. Patients were randomized to receive once-daily doses of placebo, 50 mg, 150 mg, or 300 mg of IDX21437 for seven days. The topline clinical results include:

• IDX21437 was well-tolerated with no observed pattern of adverse events or laboratory abnormalities.
• Treatment with IDX21437 exhibited potent pan-genotypic activity in a dose-dependent manner:

• In GT 1 HCV-infected patients (n=8), the mean maximal viral load reduction was 4.2 log₁₀ IU/mL in the 300 mg arm.

• The mean maximal viral load reduction of 4.3 log₁₀ IU/mL was achieved in GT 2 and 3 HCV-infected patients in the 300 mg arm (n=10).

• More detailed findings are expected to be presented at a future scientific meeting.
• Based on these findings, the 300 mg dose of IDX21437 has been chosen for the anticipated phase II combination study with samatasvir.

IDX21459: Phase I Clinical Program

In April 2014, Idenix initiated enrollment for the healthy volunteer portion of a phase I clinical trial of IDX21459 in Europe. This portion of the study is expected to enroll approximately 50 healthy volunteers and will evaluate once-daily doses of IDX21459 ranging from 10 mg - 300 mg. The proof-of-concept portion of the study is expected to enroll a total of 40 treatment-naïve, genotype 1 HCV-infected patients who will receive once-daily doses of placebo, 50 - 300 mg of IDX21459 for seven days. IDX21459 has shown a favorable preclinical profile including potent, pan-genotypic activity and favorable safety with respect to cardiac, mitochondrial and genotoxicity assessments.

Additional Nucleotide Candidates

Idenix's primary efforts in nucleotide development will continue to focus on its lead candidate, IDX21437, and follow-on prodrug candidate, IDX21459, as well as earlier-stage nucleotide prodrugs. An important objective for the discovery program is to identify nucleotides offering distinct resistance profiles that can be combined with one of the Company's current nucleotide clinical candidates to treat HCV. Idenix also announced today that the Company has elected not to continue its clinical development program for HCV nucleotide prodrug, IDX20963, previously placed on clinical hold by the U.S. Food and Drug Administration (FDA).

CONFERENCE CALL AND WEBCAST INFORMATION

Idenix management will host a conference call at 8:00 a.m. ET today. To access the call, please dial (877) 640-9809 (U.S./Canada) or (914) 495-8528 (International) and enter passcode 26004979. A live webcast will be available through the Investor section of the Idenix website at www.idenix.com under "Events & Presentations". The archived webcast will be available for two weeks following the call on the Idenix website.

ABOUT IDX21437

IDX21437, Idenix's lead uridine-based nucleotide prodrug inhibitor, has completed the single-dose and seven-day proof-of-concept portions of a phase I/II clinical trial. Extensive preclinical testing for IDX21437 has demonstrated favorable antiviral activity across genotypes 1-6 and a safety profile which supported advancement into clinical trials. Based on this progress, the Company's goal is to initiate an Idenix-sponsored combination clinical trial of IDX21437 and samatasvir in mid-2014.

ABOUT SAMATASVIR

Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log₁₀ IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

Under a non-exclusive collaboration with Janssen Pharmaceuticals, Inc., Idenix is evaluating all-oral, direct-acting antiviral HCV combination regimens including samatasvir, simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, and TMC647055/r, a once-daily non-nucleoside polymerase inhibitor boosted with low-dose ritonavir being developed by Janssen. In this program, Idenix is conducting two ongoing phase II 12-week clinical trials, HELIX-1 and HELIX-2.

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 150 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of samatasvir, IDX21437, IDX21459 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; and the likelihood and success of any future clinical trials involving samatasvir, IDX21437, IDX21459 or our other drug candidates. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2013 as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contact:
Teri Dahlman (617) 995-9807

Source: Idenix Pharmaceuticals

Source

Biotron secures approval to carry out antiviral drug trial at more sites

Tuesday, March 11, 2014 by Proactive Investors

Biotron (ASX: BIT) has received ethics approval from Khon Kaen University for additional sites to carry out the ongoing phase 2 trial of its lead antiviral drug, BIT225, in patients co-infected with HIV and Hepatitis C virus (HCV).

The company now has approval to carry out the trial in Chiang Mai and an additional site in Bangkok.

These new sites in Chiang Mai and Bangkok are expected to initiate and then commence screening and enrolment over the next fortnight.

The study is a placebo controlled, double blind study of BIT225 in 60 patients infected with HCV genotypes 1 or 3.

Trial participants will receive 12 weeks of 200 mg BIT225 or placebo, dosed twice daily, in combination with current standard of care therapies - pegylated interferon alfa 2b (IFN) and ribavirin (RBV).

On completion of dosing with BIT225, they will remain on IFN/RBV for an additional 12 weeks (genotype 3) or 36 weeks (genotype 1).

The trial has been designed to generate safety and efficacy data on BIT225 over an extended treatment period.

Previous studies have shown BIT225 to be safe and well tolerated over a 28 day dosing period, with positive efficacy data in patients infected with HCV genotypes 1 and 3, as well as in HIV/HCV co-infected patients.

Source

BIT225 HIV/HCV Trial Patients Virus Free at Six Months

6 March 2014

The Manager Companies
ASX Limited
20 Bridge Street
Sydney NSW 2000

• Study evaluated BIT225 in patients co-infected with HIV and HCV
• All HCV genotype 3 patients completing treatment are virus-free at 24 weeks
• Preliminary data from subset of patients shows benefit extends out to 48 weeks

Sydney, Australia, 6 March 2014 – Australian drug development company Biotron Limited
(ASX:BIT) today announced additional interim positive data from a key phase 2 trial of its lead
antiviral drug, BIT225, in patients co-infected with HIV and Hepatitis C virus (HCV).

Analysis of blood samples from patients indicated that all of the HCV genotype 3 patients completing treatment are virus free at the 24 week (6 month) time point. This extends previous data
that showed patients had undetectable virus levels at 12 weeks.

Response to treatment at this time point is generally a good indication of final outcome at 48 weeks. Preliminary data from patients who have completed 48 weeks of treatment indicate that they remain virus free at this key time point.

Under the protocol of this open label pilot study, 12 patients received IFN/RBV for 7 days before
commencing treatment with BIT225. They then received 300 mg BIT225 twice daily plus IFN/RBV
for 28 days. After that time, patients continued to take IFN/RBV for 48 weeks.

Biotron Managing Director Dr Michelle Miller commented; "This 24 week data further validates the
efficacy of BIT225 as a potential new therapy for HCV and, in particular, for this difficult to treat
group of HIV/HCV co-infected patients who typically have more serious HCV infection and lower
response rates to treatment with existing standard therapies."

In vitro assays have shown that BIT225 has pan-genotypic activity. Previous clinical trials of
BIT225 have focused on patients infected with the genotype 1 variant of the virus, which is the most
common genotype in Western populations. This data further extends the Company's clinical data
portfolio to include genotype 3, which is endemic in south-east Asia.

In HCV, BIT225 targets the p7 protein which is responsible for virus assembly. BIT225 also
impacts on the assembly of the HIV virus and specifically targets the virus in reservoir cells. No
existing therapy works in this way.

Dr Miller further commented; "Both the HIV and HCV viruses present substantial challenges and there is global demand for novel therapeutics. We look forward to progressing commercialisation of this important compound as a valuable new therapy that is synergistic with current and future treatment strategies."

Enquiries

Dr Michelle Miller
Managing Director
Biotron Limited
+61-2 9805 0488 +61-(0)412313329

Rudi Michelson
Monsoon Communications 
+61-3 9620 3333

Source

Chronic hepatitis C: future treatment

Clin Pharmacol. 2014 Jan 8;6:1-17. eCollection 2014.

Wendt A, Adhoute X, Castellani P, Oules V, Ansaldi C, Benali S, Bourlière M.

Abstract

The launch of first-generation protease inhibitors (PIs) is a major step forward in HCV treatment. However, the major advance is up to now restricted to genotype 1 (GT-1) patients. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants. NS5B inhibitors include nucleoside/nucleotide inhibitors (NIs) and non-nucleotide inhibitors (NNIs). NIs have high efficacy across all genotypes. Sofosbuvir has highly potent antiviral activity across all genotypes in association with pegylated interferon and ribavirin (PR), thus allowing shortened treatment duration. NS5A inhibitors (NS5A.I) have highly potent antiviral activity. It has recently been shown for the first time that NS5A.I in combination with protease inhibitors can cure GT-1b null responders in an interferon-free regimen. Besides, several studies demonstrate that interferon (IFN)-free regimens with direct-acting antiviral agent combinations are able to cure a large number of either naïve or treatment-experienced GT-1 patients. Moreover, quadruple regimen with PR is able to cure almost all GT-1 null responders. The development of pan-genotypic direct-acting antiviral agents (NIs or NS5A.I) allows new combinations with or without PR that increase the rate of sustained virological response for all patients, even for those with cirrhosis and independently of the genotype. Therefore, the near future of HCV treatment looks promising. The purpose of this article is to provide an overview of the clinical results recently reported for HCV treatment.

KEYWORDS: SVR, cirrhosis, direct antiviral agents, host-targeting agents, interferon-free regimen, pangenotypic activity

PMID: 24470777 [PubMed - as supplied by publisher]

Read full article here {Free} …..

A randomized, double-blind, multiple-dose study of the pan-genotypic NS5A inhibitor samatasvir in patients infected with hepatitis C virus genotype 1, 2, 3 or 4

Journal of Hepatology

Article in Press

Bradley Vince,John M. Hill,Eric J. Lawitz,William O’Riordan,Lynn R. Webster,Daniel M. Gruener,Ricky S. Mofsen,Abel Murillo,Eileen Donovan, Jie Chen,Joseph F. McCarville,John Z. Sullivan-Bólyai,Douglas Mayers,Xiao-Jian Zhou

Received 8 October 2013; received in revised form 29 December 2013; accepted 6 January 2014. published online 15 January 2014.

Abstract

Background & Aims

Samatasvir is a pan-genotypic inhibitor of the hepatitis C (HCV) nonstructural protein 5A (NS5A). This study evaluated the antiviral activity, pharmacokinetics and safety of samatasvir monotherapy in treatment-naïve subjects infected with HCV genotype 1-4.

Methods

Thirty-four genotype 1 and thirty genotype 2, 3 or 4 subjects were randomized to receive for 3 days placebo or samatasvir 25-100 mg per day. Plasma samples for HCV RNA, pharmacokinetics and sequencing were collected up to day 10.

Results

Samatasvir achieved potent antiviral activity across genotypes: mean maximum reductions from baseline were 3.2-3.6 (genotype 1a), 3.0-4.3 (genotype 1b), 3.2-3.4 (genotype 3) and 3.6-3.9 (genotype 4) log₁₀/mL respectively; no viral rebound was observed during the 3-day treatment period. For genotype 2 HCV, samatasvir was active in subjects with NS5A L31 polymorphism at baseline (individual range 2.5-4.1 log₁₀/mL), but showed minimal activity in those with baseline M31 polymorphism. Samatasvir exhibited a long plasma half-life of approximately 20 hours which supports once daily dosing. Samatasvir was well tolerated in all subjects with no safety-related discontinuations or serious adverse events. The most common adverse events included constipation, nausea and headache and occurred at similar frequency in active and placebo subjects. All events were mild or moderate in intensity. There were no patterns or dose dependence of adverse events, vital signs, laboratory parameters or electrocardiograms.

Conclusions

Samatasvir 25-100 mg monotherapy for 3 days was well tolerated and induced a rapid and profound reduction in plasma HCV RNA in subjects infected with HCV genotype 1-4. Samatasvir is being evaluated in combination with other direct-acting antiviral agents in subjects with HCV infection.

Abbreviations: HCV, hepatitis C virus, NS5A, nonstructural protein 5A, DAA, direct-acting antiviral agent, EC₅₀, 50% effective concentration, CYP, cytochrome P450, HBV, hepatitis B virus, HIV, human immunodeficiency virus, QD, once daily, BID, twice daily, AE,adverse event, BMI, body mass index, HCC, hepatocellular carcinoma, ECG, electrocardiogram, SAE, serious adverse event, PK,pharmacokinetic(s), AM, morning, PM, evening, C_max, maximum concentration, T_max, time to C_max, C_τ, predose trough concentration, AUC,area under curve, t_1/2, half-life, EC₉₀, 90% effective concentration

Keywords: Samatasvir, NS5A inhibitor, Hepatitis C virus, Pan-genotypic anti-HCV activity, IDX719, NS5A, Chronic hepatitis C, Pan-genotypic antiviral activity, Direct-acting antiviral agents, Pharmacokinetics

Source

Modeling viral kinetics and treatment outcome during alisporivir interferon-free treatment in HCV genotype 2/3 patients

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

Jeremie Guedj^1,2, Jing Yu³, Micha Levi⁴,  Bin Li³, Steven Kern⁵, Nikolai V. Naoumov⁵, Alan S. Perelson^2,*

DOI: 10.1002/hep.26989

Copyright © 2013 American Association for the Study of Liver Diseases

Publication History

Accepted manuscript online: 23 DEC 2013 03:36AM EST
Manuscript Accepted: 19 DEC 2013
Manuscript Revised: 18 OCT 2013
Manuscript Received: 13 JUL 2013

Abstract

Alisporivir (ALV) is a cyclophilin inhibitor with pan-genotypic activity against hepatitis C virus (HCV). Here we characterize the viral kinetics observed in 249 patients infected with HCV genotypes 2 or 3 and treated for six weeks with different doses of ALV with or without ribavirin (RBV). We use this model to predict the effects of treatment duration and different doses of ALV plus RBV on the sustained virologic response (SVR).

Continuous viral decline was observed in 214 (86%) patients that could be well described by the model. All doses led to a high level of antiviral effectiveness equal to 0.98, 0.96 and 0.90 in patients treated with 1000, 800 and 600 mg ALV once-daily, respectively. Patients that received RBV had a significantly faster rate of viral decline, which was attributed to an enhanced loss rate of infected cells, δ (mean δ=0.35 d^-1 vs 0.21 d^-1 in patients +/- RBV, respectively, P=0.0001). The remaining 35 patients (14%) had a suboptimal response with flat or increasing levels of HCV RNA after one week of treatment, which was associated with ALV monotherapy, high body weight and low RBV levels in patients that received ALV+RBV.

Assuming full compliance and the same proportion of suboptimal responders, the model predicted 71% and 79% SVR following ALV 400 mg with RBV 400 mg twice-daily for 24 and 36 weeks, respectively. The model predicted that response guided treatment could allow a reduction in the mean treatment duration to 25.3 weeks and attain a 78.6% SVR rate.

Conclusion: Alisporivir plus ribavirin may represent an effective interferon-free treatment that is predicted to achieve high SVR rates in patients with HCV genotype 2 or 3 infection. (Hepatology 2013;)

Source

Biotron Limited: Study extends use of Hepatitis C virus treatment across more genotypes

Wednesday, November 27, 2013 by Proactive Investors

An independent study has found that Biotron's BIT225 drug candidate is effective against more genotypes of the Hepatitis C virus than previously demonstrated.

Biotron Limited's (ASX: BIT) shares are set to trade higher after receiving independent evidence that its BIT225 drug candidate for the treatment of the Hepatitis C virus is effective against more genotypes than previously demonstrated.

A new scientific paper published in the peer-reviewed journal Antiviral Research demonstrated that BIT225 is active against HCV genotypes 1, 2, 4, 5 and 6 using an in vitro cell culture assay.

This adds to the company’s studies, which demonstrated that it is active against genotypes 1 and 3, and indicates that its compound has pan-genotype activity.

Biotron’s BIT225 compound is the first in a new class of direct acting antiviral drugs for Hepatitis C. It specifically targets the p7 protein, which is involved in virus assembly.

It has recently received ethics approval to conduct a three month Phase 2 dosing study of its BIT225 drug candidate for the treatment of the Hepatitis C virus in Thailand.

The Hepatitis C global market is currently estimated at US$3.3 billion, but is expected to expand to over US$15 billion as safe, effective therapies enter the market.

Proactive Investors Australia is the market leader in producing news, articles and research reports on ASX “Small and Mid-cap” stocks with distribution in Australia, UK, North America and Hong Kong / China.

Source

Dr. Graham Foster to Present a Poster on Spring Bank Pharmaceuticals' HCV Drug SB 9200 at the AASLD

MILFORD, Mass., Oct. 7, 2013 /PRNewswire/ -- Dr. Graham R. Foster and his team from Queen Mary, University of London, London, United Kingdom, will be presenting a poster titled "Pangenotypic anti-HCV activity of SB 9200 assessed in the 'Capture-fusion' replication assay" (Abstract No. 473) at the 64^th Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), November 1-5, 2013, Washington, DC.  Details can now be viewed at the AASLD website at www.aasld.org.

The Poster is scheduled for presentation on Saturday, November 2, 2013, 2:00 pm –7:30 pm EDT.

About Spring Bank Pharmaceuticals   
Spring Bank Pharmaceuticals is engaged in the discovery and development of an entirely new class of pharmaceuticals based on the Company's proprietary SMNH, "Small Molecule Nucleic Hybrid" technology program. The company's lead compound, SB 9200, a potential breakthrough drug for the treatment of HCV and HBV, is currently in Ph. 1 clinical studies for HCV. In addition, the Company has preclinical programs for Respiratory Syncytial Virus (RSV) infections, a Broad-Spectrum Antiviral agent, and COPD. For more information, please visit our website: www.springbankpharm.com

Contact: Douglas Jensen (508) 473-5993 Ext.105

SOURCE Spring Bank Pharmaceuticals, Inc.

RELATED LINKS
http://www.springbankpharm.com

Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial of Miravirsen

Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial of Miravirsen In Null Responders to Pegylated Interferon and Ribavirin for the Treatment of the Hepatitis C Virus

-- Enrollment also begins in study investigating miravirsen in combination with telaprevir and ribavirin in null responders to pegylated interferon and ribavirin --

Hørsholm, Denmark/San Diego, California, August 27, 2013 — Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies, today announced the completion of enrollment of its Phase 2 miravirsen 12-week monotherapy study of miravirsen, a host-targeted, pan-HCV genotype antiviral agent, in subjects who were "null responders" to pegylated interferon alpha and ribavirin (peg-IFNα/RBV). The company also announced the enrollment of the first patient into another Phase 2 study of miravirsen in combination with telaprevir and ribavirin, also in null responders to peg-IFNα/RBV.

"The current standard of treatment for HCV is a combination of a direct acting-antiviral agent protease inhibitor with pegylated-interferon plus ribavirin. However, there remains a pressing need for therapeutic regimens that can attain high sustained virologic responses without peg-IFNα/RBV, which is poorly tolerated, and without drug-drug interactions. Miravirsen’s unique mode-of-action has shown potential in providing antiviral activity in patients who have failed previous treatment regimens for the hepatitis C virus," said Maribel Rodriguez-Torres, M.D., president of Fundacion de Investigacion and the study’s Principal Investigator. "We are excited to have completed enrollment and look forward to following the enrolled patients and reporting the data from this study. So far, the emerging viral load data suggest that miravirsen might be a unique treatment option, in combination with other antivirals, for the treatment of this type of difficult to treat patients."

The Phase 2, open-label study assesses the safety, antiviral activity and pharmacokinetics of miravirsen monotherapy over a total of 12 weeks of treatment. Patients enrolled in the study were chronically infected with HCV genotype 1 and had previously failed treatment with peg-IFNα/RBV therapy. Miravirsen was given as a total of five doses over five weeks, followed by a further four doses once every other week over seven weeks.

Developed using Santaris Pharma A/S proprietary Locked Nucleic Acid (LNA) Drug Platform, miravirsen is an inhibitor of miR-122, a liver specific microRNA that the hepatitis C virus requires for replication. Miravirsen is designed to recognize and sequester miR-122, making it unavailable to the hepatitis C virus. As a result, the replication of the virus is effectively inhibited and the levels of HCV RNA are profoundly reduced.

Santaris Pharma A/S has also enrolled its first patient into another Phase 2 clinical trial that will assess the safety, tolerability and antiviral activity of miravirsen given for 12 weeks in combination with telaprevir (TVR) and ribavirin (RBV) in patients with HCV infection who are non-responders to peg-IFNα/RBV.

"We are pleased to report on the progress in the miravirsen clinical program," said Michael R. Hodges, MD, Vice President and Chief Medical Officer at Santaris Pharma A/S. "We hope that data from these two 12-week studies in the hard to treat patients will confirm the earlier promising efficacy and safety data from the four-week monotherapy study in treatment naïve patients that was recently published in the New England Journal of Medicine. We continue to believe that miravirsen given in combination with direct acting-antiviral agent(s) has the potential to cure chronic HCV infection in hard-to-treat patients."

The first series of non-clinical and clinical studies demonstrated the following key attributes for miravirsen:

• Miravirsen has a novel mechanism of action, inhibits a well conserved hepatic host target thus has an high barrier to resistance with predicted activity against all HCV genotypes, is not metabolized by cytochrome P450 enzymes therefore drug interactions are unlikely
• In in vitro studies, miravirsen was active against all six HCV genotypes, additive activity to direct acting antiviral agents (DAAs), active against DAA resistant virus and a showed a high barrier to resistance
• In clinical trials with four weeks of monotherapy, miravirsen was well tolerated, showed dose dependent antiviral activity that can be maintained weeks after the end of therapy
• In two separate drug-drug interaction clinical trials, miravirsen showed no interactions with peg-IFNα/RBV or with telaprevir

About Hepatitis C

Hepatitis C infection is a viral disease caused by the hepatitis C virus that leads to inflammation of the liver. The World Health Organization estimates that approximately 3 percent of the world’s population have been infected with HCV and that some 170 million have chronic hepatitis C and are at risk of developing liver cirrhosis and/or liver canceri. Approximately 3-4 million Americans are chronically infected with an estimated 40,000 new infections per yearii. In Europe, there are about 4 million carriersi. The current standard of care treatment for genotype 1 is a protease inhibitor given with pegylated-interferon α and ribavirin. This triple combination is effective in about 70-80% of those treatedii. Even though in Europe and the United States genotype 1 is the most prevalent, there are 50-70 million people worldwide that are infected with a non-genotype 1 virus. In these patients, the combination of pegylated-interferon α and ribavirin remains the currently approved standard of care treatmentiii. Patients that are not effectively treated have an increased risk for the progression of liver disease. By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion^iv.

About microRNAs

MicroRNAs have emerged as an important class of small RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression. Recent studies have demonstrated that microRNAs are associated with many disease processes. Because they are single molecular entities that dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets for controlling many biologic and disease processes.

About Locked Nucleic Acid (LNA) Drug Platform

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA is also sometimes referred to as BNA (Bicyclic or Bridged Nucleic Acid). LNA-based drugs are a promising new class of therapeutics that enable scientists to develop drugs that work through previously inaccessible clinical pathways. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favorable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles.

About Santaris Pharma A/S

Santaris Pharma A/S is a privately held, clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The company’s research and development activities focus on infectious diseases and cardiometabolic disorders, while partnerships with major pharmaceutical companies address a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The company has strategic partnerships with RaNA Therapeutics, Bristol-Myers Squibb, miRagen Therapeutics, Shire, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the company holds exclusive worldwide rights to manufacture and sell products that comprise LNA as active ingredient for studies performed with a view to obtaining marketing approval. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit www.santaris.com for more information.

Santaris Pharma A/S® is a registered trademark of Santaris Pharma A/S. Santaris^TM, Santaris Pharma^TM, Cureon^TM and LNA-antimiR™ are trademarks of Santaris Pharma A/S.

Media Contacts: Liz Narrillos Roux, Edelman (liz.narrillosroux@edelman.com) - Office: (323)202-1074

Source

Idenix Pharmaceuticals Announces Samatasvir (IDX719) Poster Presentations at the Asian Pacific Association for the Study of the Liver (APASL) Conference

CAMBRIDGE, Mass., June 6, 2013 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced three poster presentations featuring clinical and preclinical data for samatasvir (IDX719), Idenix's once-daily pan-genotypic NS5A inhibitor for the treatment of hepatitis C virus (HCV) infection, at the Asian Pacific Association for the Study of the Liver (APASL) Liver Week 2013, taking place in Singapore, June 6-10, 2013. Idenix recently initiated a phase II clinical trial (HELIX-1) evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of samatasvir and simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB.

The following abstracts will be presented in poster sessions during APASL Liver Week 2013 in the Conference Exhibition Hall on Friday, June 7, 2013, 8:30am - 5:30pm SGT:

• Abstract No. 2110: "Pharmacokinetics and Pharmacodynamics of IDX719, a Pan-Genotypic HCV NS5A Inhibitor, in Genotype 1, 2, 3 or 4 HCV-Infected Subjects."
  
• Abstract No. 2121: "Hepatitis C Virus NS5A Inhibitor IDX719 Demonstrates Potent, Pan-genotypic Activity in Preclinical and Clinical Studies."
  
• Abstract No. 2127: "IDX719, a Pan-genotypic HCV NS5A Replication Complex Inhibitor, Is a Promising Candidate for HCV Combination DAA Treatment."

ABOUT SAMATASVIR (IDX719)

Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers for up to 14 days' duration and up to 100 mg in HCV-infected patients up to 3 days' duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log₁₀ IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

The HELIX-1 trial is a 12-week, randomized, double-blind, parallel group study evaluating the safety and tolerability of samatasvir and simeprevir in addition to antiviral activity endpoints, with a target enrollment of 90 treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients. The HELIX-1 trial is the first study in HCV-infected patients to commence under a non-exclusive collaboration agreement signed with Janssen in January 2013. A second trial (HELIX-2) of samatasvir, simeprevir and TMC647055, a once-daily non-nucleoside polymerase inhibitor boosted with low-dose ritonavir being developed by Janssen, is expected to initiate in the second half of 2013.

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases.  Idenix's current focus is on the treatment of patients with hepatitis C virus (HCV) infection. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance.  For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements.  Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX719 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; the likelihood and success of any future clinical trials involving IDX719 or our other drug candidates; and expectations with respect to funding of operations and future cash balances.  Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries.  Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements.  These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q for the quarter ended March 31, 2013 as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release.  While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contact:
         Teri Dahlman, (617) 995-9807

Idenix Pharmaceuticals

Source

Achillion Nominates ACH-3422 as Nucleotide for the Treatment of Chronic HCV

May 30, 2013

— Advancement of ACH-3422 Complements Achillion's Portfolio of 2^nd Generation Protease and NS5A Inhibitors Providing the Opportunity to Optimize Treatment Duration and Outcomes for All HCV Patients —

— Conference Call and Webcast to be Hosted Today at 12:00pm EDT —

NEW HAVEN, Conn., May 30, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced the nomination of the preclinical compound, ACH-3422, a novel small molecule nucleotide prodrug of a uridine analog designed to inhibit HCV NS5B polymerase. This compound will be advanced as a development candidate for the treatment of chronic hepatitis C (HCV) viral infection. Achillion plans to complete regulatory submissions during the first quarter of 2014, with first-in-human studies anticipated in the first half of 2014, followed by combination development in the second half of 2014.

"Our research and discovery team has always maintained the highest standards for developing proprietary best-in-class compounds, and this has led to the nomination of ACH-3422, which we are now advancing toward the clinic," commented Milind Deshpande, Ph.D., President and Chief Executive Officer. "The addition of ACH-3422 gives Achillion a portfolio of assets that also includes a 2^nd generation protease inhibitor, sovaprevir, and a 2^nd generation NS5A inhibitor, ACH-3102, which together provide Achillion the opportunity to potentially optimize treatment outcomes and duration of therapy across all HCV patients."

Dr. Deshpande further commented, "Along with the nomination of this candidate, we continue our efforts to accelerate the development time-lines for our all-oral, interferon-free combination of sovaprevir and ACH-3102, our protease and NS5A inhibitors, as a regimen for the treatment of HCV. Beginning in the third quarter of 2013, we expect to begin to report interim results from the ongoing -007 clinical trial of these agents for the treatment of HCV genotype 1 treatment-naïve patients."

Preclinical profile of ACH-3422

ACH-3422 is a small-molecule, nucleotide prodrug inhibitor of HCV NS5B polymerase. In vitro, ACH-3422 has demonstrated excellent potency, with activity demonstrated across all genotypes of HCV and an EC₅₀ of approximately 50 to 65 nanomolar against genotype 1 HCV. To date, Achillion has completed 14-day safety studies in animals, where no significant findings were noted at the highest dose tested. ACH-3422 appears to have high oral bioavailability, rapid uptake and conversion of the prodrug into the monophosphate within the liver, and a pharmacokinetic profile supportive of once-daily dosing. Manufacturing and IND-enabling studies have been initiated, with the expectation of submitting an IND to the FDA in the first quarter of 2014.

Conference Call

The Company will host a conference call and simultaneous webcast on Thursday, May 30, 2013 at 12:00 p.m. Eastern time. To participate in the conference call, please dial (877) 266-0482 begin_of_the_skype_highlighting (877) 266-0482 end_of_the_skype_highlighting in the U.S. or (631) 291-4567 for international callers. A live audio webcast of the call will be accessible at www.achillion.com, under the News Center section of the website. Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

A replay of the webcast will be available on www.achillion.com. Alternatively, a replay of the conference call will be available starting at 9:00 p.m. Eastern time on May 28, 2013, through 11:59 p.m. Eastern time on June 5, 2013 by dialing (855) 859-2056 or (404) 537-3406. The replay passcode is 87685598.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, making HCV more than twice as widespread as HIV. Three-fourths of the global HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

For additional information on Achillion's ongoing clinical trial please visit: http://clinicaltrials.gov

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000 begin_of_the_skype_highlighting 1-203-624-7000 end_of_the_skype_highlighting.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the expected potency, bioavailability, pharmacokinetic and other characteristics of development candidate ACH-3422; Achillion's expectations regarding timing for the commencement, completion and reporting of results of its clinical trials of ACH-3422, ACH-3102 in combination with ribavirin and sovaprevir in combination with ACH-3102. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," " estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: successfully advance ACH-3422 into clinical trials; replicate in later clinical trials positive results found in preclinical and earlier stage clinical trials of sovaprevir, ACH-3102, ACH-3422 and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

Source

Spring Bank Pharmaceuticals Initiates a Phase I Clinical Trial for SB 9200 in HCV-infected Patients

MILFORD, Mass., May 23, 2013 /PRNewswire/ -- Spring Bank Pharmaceuticals, Inc., a biopharmaceutical company developing innovative medicines for the treatment of viral infections, today announced that it has initiated dosing in a Phase I study of SB 9200, its investigational, once daily, oral therapy for the treatment of HCV infection. This study will be conducted in healthy, HCV-infected patients and is designed to assess both the safety and antiviral efficacy of SB 9200. SB 9200 is a first-in-class drug for the treatment of chronic HCV infections and is based on the Company's proprietary Small Molecule Nucleic Acid Hybrid (SMNH) technology platform. It has a unique mechanism of antiviral action involving the selective activation of the host-immune response in HCV-infected cells.

"The initiation of this clinical trial is an important milestone for our Company," said Doug Jensen , Spring Bank 's CEO. "This trial should not only give us proof of concept in HCV, but also will facilitate the advancement of our technology in other viral diseases such as HBV and RSV." SB 9200 is the first of a potentially important new class of drug based on Spring Bank 's proprietary "SMNH" technology platform. The Phase I clinical trial has been designed to provide a significant amount of data related not only to safety of SB 9200 but also the antiviral activity against multiple HCV genotypes.

"Unlike other classes of drugs for HCV infection that act directly on the virus, SB 9200 targets host cytosolic sensor proteins, RIG-I and NOD2," states Dr. Kris Iyer , CSO and Co-founder of Spring Bank . "This leads to the selective activation of the host immune response in the presence of viral infection." By way of its novel mechanism of action, SB 9200 is ideally suited for combination with other classes of HCV antivirals, including direct-acting antiviral agents (DAA) currently in clinical development. In preclinical studies, SB 9200 has shown synergistic antiviral activity when combined with other anti-HCV compounds and has demonstrated an excellent safety profile. In in vitro studies, the compound has demonstrated potent antiviral activity against multiple HCV genotypes 1a, 1b and 3. Thus, this novel mechanism of action is suggestive of pan-genotypic activity and potentially a high barrier to resistance. Moreover, this novel mechanism of action suggests it could have pan-genotypic activity and potentially a high barrier to resistance. These attributes could lead to the use of SB 9200 as part of an Interferon-free, all-oral regimen for HCV therapy.

The Phase I trial is currently being conducted in Australia with plans to expand into clinical sites in New Zealand. The trial is being conducted in two parts. Part A is a single ascending dose of SB 9200 to evaluate the safety and tolerability of a single oral dose of SB 9200, with 8 treatment naive Genotype 1 patients being enrolled into four sequential cohorts of 2 patients each with increasing doses ranging from 100-800mg. Part B of the study is a randomized, double blind, placebo-controlled multiple ascending dose escalation of once daily doses of SB 9200 once a day for 7-14 days. Part B will enroll approximately 40 HCV patients with 5 dosing cohorts, randomized 6:2 active versus placebo. The final dosing cohort will be in Genotype 2/3 patients to demonstrate pan-genotypic activity. The primary endpoint for both parts of the trial is safety. Secondary objectives include an analysis of dose versus viral load reduction, liver function, safety labs, host immune expression, as well as characterization of plasma and urine pharmacokinetics and assessment of pharmacodynamic activity.

About Spring Bank Pharmaceuticals

Spring Bank Pharmaceuticals is engaged in the discovery and development of an entirely new class of pharmaceuticals based on the Company's proprietary SMNH, "Small Molecule Nucleic Hybrid" technology program. The company's lead compound, SB 9200, is a potential breakthrough drug for the treatment of HCV and HBV. The Company also has preclinical programs for the development of immune-modulating therapies against Respiratory Syncytial Virus (RSV) infections, a Broad-Spectrum Antiviral, and a SMNH based therapy to treat Chronic Obstructive Pulmonary Disease (COPD). For more information please visit our website: www.springbankpharm.com

Contact: Douglas Jensen (508) 473-5993 Ext.105

SOURCE Spring Bank Pharmaceuticals, Inc.

RELATED LINKS
http://www.springbankpharm.com

Source

HCV Treatment — No More Room for Interferonologists?

EDITORIAL

Joost P.H. Drenth, M.D., Ph.D.

April 23, 2013DOI: 10.1056/NEJMe1303818

The landscape of therapy for hepatitis C virus (HCV) infection is changing rapidly. Until recently, the standard of care for HCV infection was a combination of peginterferon and ribavirin. Our increased understanding of the basic biology of HCV led to the identification of specific proteins involved in the replication of the virus. These proteins can be targeted by protease and polymerase inhibitors.

Two years ago, the advent of protease inhibitors, such as telaprevir and boceprevir, profoundly affected the field.1,2 These agents improved the likelihood of cure but came with a number of inherent limitations. Protease inhibitors do not have antiviral activity in HCV genotypes other than the predominant genotype 1, which leaves at least five other HCV genotypes without coverage. Moreover, protease inhibitors can promote viral resistance, which usually signals therapeutic failure, and have multiple pharmacokinetic interactions with other drugs. Finally, protease inhibitors need to be administered with peginterferon and ribavirin, two drugs with extensive and well-established side-effect profiles that are aggravated by the addition of telaprevir or boceprevir.

Clinicians who treat patients with HCV infection have learned to accept and treat adverse effects as an integral part of patient care, but the inclusion of protease inhibitors in the therapeutic arsenal has added a layer of complexity. Indeed, the major challenge of contemporary interferon therapy is adequate management of side effects. Physicians and patients are ready for less toxic therapeutic options.

Two groups of investigators (Jacobson et al.3 and Lawitz et al.4) now suggest in the Journal that change is about to happen. They describe the use of sofosbuvir, a novel polymerase inhibitor, in a series of four experimental studies targeting patients with HCV infection. In three randomized trials — FISSION, POSITRON, and FUSION — investigators focused on patients with HCV genotype 2 or 3, as seen in everyday clinical practice, including patients who had received no previous treatment, those who were unwilling to take interferon or had unacceptable side effects, and those who did not have a response to previous therapy. All the studies had a similar end point: a sustained virologic response at 12 weeks after the end of therapy. In addition, in the single-group, open-label NEUTRINO study, investigators studied the use of a sofosbuvir-based regimen in patients with genotype 1, 4, 5, or 6 infection.

The FISSION study examined the efficacy of 12 weeks of sofosbuvir plus ribavirin, as compared with the standard of care, peginterferon alfa-2a plus ribavirin, administered for 24 weeks. Standard therapy was successful in 78% of patients with genotype 2 infection and 63% of those with genotype 3 infection, as compared with rates of 97% and 56%, respectively, with the sofosbuvir-based regimen.

The POSITRON study evaluated a population that was not deemed to be eligible for interferon-based therapy and compared 12 weeks of sofosbuvir plus ribavirin with placebo. The primary reasons for ineligibility were a preexisting psychiatric disorder (57%) or autoimmune disorder (19%). None of the patients in the placebo group achieved the end point, but 93% of those with genotype 2 infection and 61% of those with genotype 3 infection had a sustained virologic response with sofosbuvir plus ribavirin.

The FUSION study, which targeted patients without a sustained response to interferon-based therapy, compared a 12-week regimen of sofosbuvir–ribavirin with a 16-week regimen. Four additional weeks of treatment made a difference, with an increase in the rate of sustained virologic response from 86% to 94% in patients with genotype 2 infection and from 30% to 62% in those with genotype 3 infection.

Finally, the investigators captured some evidence for the pangenotypic anti-HCV properties of sofosbuvir. In the NEUTRINO study, patients with genotype 1 infection (89%), genotype 4 infection (9%), or genotype 5 or 6 infection (2%) who received 12 weeks of treatment with a combination of sofosbuvir, peginterferon, and ribavirin had a collective rate of sustained virologic response of 90%.

The speed of development of drugs to treat HCV infection is unprecedented. The publication of clinical data with respect to sofosbuvir comes only 3 years after the publication of the chemical discovery of the compound.5 Although the data from the four trials discussed here are encouraging, the design of the trials may have suffered from the intense competition that drug companies face in this market. In the tower of evidence-based medicine, randomized clinical trials are superior to open-label studies. However, of the four studies that are discussed here, only three were randomized, and only one was placebo-controlled. In addition, the results for sofosbuvir in these studies falls short of the findings reported for the drug in an earlier study by Gane et al.,6 in which the rate of sustained virologic response was 100%. One of the reasons for the difference may be that the design of the study by Gane et al. was less rigorous than the designs of the studies discussed here. Also of note, the end point that was used in the four studies differed from that used in the study by Gane et al. The Food and Drug Administration only recently approved an end point of a sustained virologic response at 12 weeks (rather than the previously approved 24 weeks) as acceptable for HCV trials.7

Our current therapy for HCV infection revolves around side-effect management in patients receiving interferon, who require intense monitoring. Current therapies are typically offered in dedicated centers by physicians (aptly termed interferonologists) who are well versed in dealing with the toxic effects of interferon. Without alternatives to interferon therapy, we are pushing the envelope in the acceptance of risks to certain patients (e.g., those with a psychiatric history). The data from the sofosbuvir trials suggest that a radical change in clinical practice is imminent. But it may be premature to start dismantling the dedicated centers now that interferon is in retreat, since ribavirin is still part of the most successful interferon-free regimens. Data from the study by Gane et al. suggest that excluding ribavirin compromises the efficacy of sofosbuvir. The use of ribavirin has been associated with hemolytic anemia, a condition that requires close attention, especially in patients with the most pressing need for treatment, such as those with cirrhosis. Even so, the studies by Jacobson et al. and Lawitz et al. suggest an acceptable safety profile for sofosbuvir plus ribavirin, with low rates of anemia and leukopenia among patients receiving this regimen, as compared with standard-of-care therapy. On the other hand, a note of caution is appropriate, since long-term data in larger populations are lacking, and rare but irreversible adverse events still may emerge with wider use of sofosbuvir.

What are we to conclude from these studies? The low incidence of side effects, the relatively short duration of treatment, and the pangenotypic properties of the drugs are strong selling points of a sofosbuvir–ribavirin regimen and will probably lower the threshold for HCV treatment for both patients and physicians. The likely next step is to combine sofosbuvir with other direct-acting antivirals to enhance its potency. Is the interferonologist down and out? I do not think so, but it is surely time for reeducation.

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

This article was published on April 23, 2013, at NEJM.org.

Source Information

From the Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

References

Source

Idenix Reports Favorable Resistance Profile for IDX719, a Potent, Pan-Genotypic HCV NS5A Inhibitor, at EASL Meeting

CAMBRIDGE, Mass., April 24, 2013 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today reported detailed resistance data from in vitro studies and from a three-day monotherapy clinical trial of IDX719, the Company's once-daily, potent, pan-genotypic NS5A inhibitor for the treatment of hepatitis C virus (HCV) infection. These data are being presented on Saturday, April 27, in a poster session at the 48^th Annual Meeting of the European Association for the Study of the Liver (EASL), which is being held April 24 - 28, 2013 in Amsterdam, The Netherlands.

Data from the three-day proof-of-concept study demonstrated that IDX719 was well-tolerated at daily doses up to 100 mg and showed potent antiviral activity across HCV genotypes 1-4, with mean maximal viral load reductions up to approximately 4.0 log₁₀ IU/mL. These data were supported by earlier in vitro findings. Clinical plasma samples at baseline, at end of treatment and at one week post-treatment were sequenced for mutations in NS5A at known IDX719 resistance-associated locations.

• The most common treatment-emergent resistant mutations were detected at NS5A positions 28, 31 and 93. The profile of these mutations varied among genotypes.
• The only resistance mutation present at baseline found to negatively affect IDX719 response was M31 in GT2-infected patients. In contrast, all GT4-infected patients had virus with M31 at baseline and responded favorably to IDX719 treatment.
• A GT1b-infected patient with a baseline Y93H mutation, which confers in vitro resistance to IDX719, achieved a 2.79 log₁₀ IU/mL viral load reduction after three days of once-daily 25 mg IDX719, indicating that IDX719 can retain activity against virus with known resistance mutations.

The poster presentation is titled, "Treatment-Emergent Variants Following 3 Days of Monotherapy with IDX719, a Potent, Pan-Genotypic NS5A Inhibitor, in Subjects Infected with HCV Genotypes 1-4" (Abstract No. 1209).

"These additional resistance data support the promising profile of IDX719 as a potent, pan-genotypic component of future HCV combination treatment regimens," commented Douglas Mayers, M.D., Chief Medical Officer of Idenix. "We look forward to evaluating IDX719 as part of all-oral combination therapies through our collaboration with Janssen, beginning with the initiation of a phase II clinical trial of IDX719 and simeprevir in the first half of this year."

ABOUT IDX719

IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, IDX719 has been safe and well tolerated after single and multiple doses of up to 100 mg in healthy volunteers (n=36; up to 7 days duration) and HCV-infected patients (n=69; up to 3 days duration). There have been no treatment-emergent serious adverse events reported in the program. IDX719 has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log₁₀ IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with HCV. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are any expressed or implied statements with respect to: the Company's plans to continue to developing nucleotide polymerase inhibitors for HCV; its clinical development plans for its uridine nucleotide analog drug candidate and IDX719; its plans to advance other preclinical nucleotides; and statements regarding the efficacy and safety of its clinical compounds. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization due to numerous risks inherent in pharmaceutical research and development; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, preclinical and clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; competition; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2012, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contact:

Teri Dahlman (617) 218-7987

Source

Data from Phase 3 Studies of Gilead’s Sofosbuvir for Hepatitis C To Be Presented at 48th Annual EASL Meeting; Findings Published Online Today in The New England Journal of Medicine

AMSTERDAM--(BUSINESS WIRE)--Apr. 23, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that detailed results from four Phase 3 clinical trials (NEUTRINO, FISSION, POSITRON and FUSION) evaluating sofosbuvir, the company’s investigational once-daily nucleotide NS5B inhibitor for the treatment of chronic hepatitis C virus (HCV) infection, will be presented this week in oral sessions at the 48th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2013) in Amsterdam, The Netherlands. In addition, detailed results from the four clinical studies have also been published online in two papers, ahead of print, in The New England Journal of Medicine (NEJM).

In the four trials, sofosbuvir was administered to nearly 1,000 patients with chronic HCV infection as part of an all-oral 12-week or 16-week treatment regimen in combination with ribavirin (RBV) in genotypes 2 and 3, or with RBV and pegylated interferon (peg-IFN) for 12 weeks in genotypes 1, 4, 5 and 6. Overall SVR12 rates (sustained viral response 12 weeks after completing therapy) from 50 to 90 percent were observed. Patients who achieve SVR12 are considered cured of their HCV infection.

A description of the four Phase 3 studies and SVR12 results are summarized in the table below. Detailed results from the Phase 3 studies of sofosbuvir are available at www.nejm.org/online-first.

Sofosbuvir Phase 3 Studies
Study		Population		Treatment groups		SVR12 Rates
NEUTRINO		Genotype 1/4/5/6 treatment-naïve		Sofosbuvir + RBV + Peg-IFN for 12 weeks		90% (295/327)
FISSION		Genotype 2/3 treatment-naïve		Sofosbuvir + RBV for 12 weeks or		67% (107/253)
				Peg-IFN + RBV for 24 weeks		67% (162/243)
POSITRON		Genotype 2/3, IFN intolerant, ineligible or unwilling		Sofosbuvir + RBV for 12 weeks or		78% (161/207)
				Placebo for 12 weeks		0% (0/71)
FUSION		Genotype 2/3 treatment-experienced		Sofosbuvir + RBV for 12 weeks or		50% (50/100)
				Sofosbuvir + RBV for 16 weeks		73% (69/95)

“There remains an urgent unmet medical need for individuals diagnosed with chronic hepatitis C infection,” commented Ira Jacobson, MD, Chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, The Joan Sanford I. Weill Medical College of Cornell University, Attending Physician, New York-Presbyterian Hospital Cornell Campus. “The breadth of data from the Phase 3 program evaluating sofosbuvir will help physicians understand how to treat the disease in the future across various HCV genotypes and patient populations.”

“In these particular studies, sofosbuvir-based HCV therapy demonstrated high efficacy rates and a favorable safety profile while reducing the need for interferon injections to 12 weeks, or eliminating interferon completely from the regimen,” said Eric Lawitz, MD, President and Medical Director, The Texas Liver Institute, University of Texas Health Science Center, San Antonio. “Based on these findings, sofosbuvir, once approved, has the potential to play an important role in addressing the global hepatitis C epidemic.”

The NS5b region of the HCV viral genome for all patients who relapsed was sequenced and no S282T mutations were observed by population or deep sequencing (1 percent cutoff). There was no change in susceptibility to sofosbuvir or RBV observed by phenotypic analyses.

With the exception of one patient in FISSION who was non-compliant, relapse accounted for all virologic failures. Adverse events were generally mild and included fatigue, nausea, headache, insomnia, pruritis, anemia and dizziness. Less than 2 percent of patients in the sofosbuvir treatment groups discontinued due to adverse events.

On April 8, Gilead submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sofosbuvir for the treatment of HCV infection. The data submitted in the NDA support the use of sofosbuvir and RBV as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and peg-IFN for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

Gilead plans to file for regulatory approval of sofosbuvir in other geographies, including the European Union, in the second quarter of 2013. The European Medicines Agency (EMA) has accepted Gilead’s request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Accelerated assessment could shorten the EMA’s review time of sofosbuvir by two months. Granting of accelerated assessment does not guarantee a positive opinion from the CHMP or approval by the European Commission.

About Sofosbuvir

Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B protein, which plays an essential role in HCV replication. Sofosbuvir is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Sofosbuvir is intended to become a cornerstone of interferon-free, all-oral treatment regimens for HCV that achieve higher cure rates more rapidly and with fewer side effects than current therapeutic options. Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that FDA and other regulatory agencies may not approve sofosbuvir, and that any marketing approvals, if granted, may have significant limitations on its use. Additional clinical studies of sofosbuvir, including in combination with other compounds, may not produce favorable results. As a result, Gilead may not be able to successfully commercialize sofosbuvir, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2012, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at

1-800-GILEAD-5 or 1-650-574-3000 .

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Investors
Patrick O’Brien, +1 650-522-1936
Media (U.S.)
Cara Miller, +1 650-522-1616 Media (EU)
Nick Francis, +44 (208) 587-2412

Source

Also See: Rapid, Sustained Response With Sofosbuvir in Hepatitis C