Boehringer Ingelheim (BI) announced that faldaprevir (BI201335) and BI207127 combined with Ribavirin showed up to 85% SVR in treatment naive Hep C patients and up to 69% SVR in G1a and 1b patients, including some with advanced liver disease.  According to BI, subtype, genome type, and gender proved to be significant predictors for success.  Results are being presented at the AASLD conference in Boston Nov, 2012.  BI will also begin Phase 3 trials that will include Cirrhotics soon.
Faldaprevir (BI201335) is a direct acting antiviral small molecule protease inhibitor.
Advocate1955
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

AASLD- BI 201335 and BI 207127: Interferon-Free Hepatitis C Treatment Show Viral Cure Achieved in Up to 85% Of Treatment-Naive

Phase 2b Data of Boehringer Ingelheim's Interferon-Free Hepatitis C Treatment Show Viral Cure Achieved in Up to 85% of Treatment-Naive Patients

Results to be presented at American Association for the Study of Liver Diseases (AASLD) Annual Meeting, Phase 3 IFN-free trial program now being initiated..

By Boehringer Ingelheim Pharmaceuticals, Inc.

Published: Saturday, Nov. 10, 2012 - 7:07 am
BOSTON and RIDGEFIELD, Conn., Nov. 10, 2012 -- /PRNewswire/ -- Final Phase 2b data from Boehringer Ingelheim's interferon (IFN)-free Phase 2b SOUND-C2 study showed that up to 85 percent of genotype 1b (GT1b) hepatitis C (HCV) patients achieved sustained virologic response (SVR or viral cure) 12 and 24 weeks after the end of treatment with the investigational treatment regimen of faldaprevir (BI 201335) and BI 207127, in combination with ribavirin (RBV). A viral cure was achieved for 69 percent of all patients included in the study (both GT1a and GT1b HCV infections), and includes patients with advanced liver disease that are more challenging to cure.
Pivotal Phase 3 trials evaluating an IFN-free regimen of faldaprevir, BI 207127 and ribavirin are now being initiated.

"Final results from this Phase 2b study show potential for an interferon-free HCV cure for patients with chronic HCV that historically have been among the most difficult to cure," said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Goethe University Hospital in Frankfurt, Germany, and lead investigator of the study. "The SOUND-C2 trial provides valuable information regarding the types of patients that are more likely to respond to treatment with faldaprevir and BI 207127, which may be useful for attaining optimal antiviral outcomes in the clinical setting."

Comprehensive results from SOUND-C2 will be presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in Boston, MA.
• An oral presentation of final results from the SOUND-C2 study, including an analysis of predictors of treatment response, will be presented on Tuesday, November 13 (ID# 232)
• An oral presentation of results from a sub-analysis of patients with compensated liver cirrhosis from the SOUND-C2 study will be presented on Sunday, November 11 (ID# 84)
• A poster presentation of a comparison of SVR4, SVR12 and SVR24 results from SOUND-C2 will be presented on Sunday, November 11 (ID# 778)

The SOUND-C2 study, which includes compounds each of which targets HCV in a different way (polymodal therapy*), is the largest Phase 2 IFN-free HCV trial to date, enrolling 362 HCV GT1 patients, the most difficult genotype to treat successfully and the most common genotype found in the US. Nine percent of patients in the SOUND-C2 study had compensated liver cirrhosis due to HCV (damaged or scarred liver tissue). As part of the study, investigators performed a detailed analysis of patient and virus characteristics to explore the likelihood of a patient's response to treatment with faldaprevir and BI 207127 in combination with RBV (regression analysis). HCV GT1 subtype, patient IL-28b genome type and patient gender were identified as significant predictors of treatment success.

*Polymodal therapy involves treatment that combines compounds that each work with different modes of action to inhibit viral replication, as seen with faldaprevir + BI 207127 + ribavirin.

"We are looking forward to continuing development of our HCVerso™ program and are now initiating Phase 3 clinical trials investigating interferon-free HCV treatment with faldaprevir and BI 207127," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Through HCVerso™ Boehringer Ingelheim is striving to deliver new solutions that consider real-world challenges faced by patients and clinicians."

Final Results from SOUND-C2 and Predictors of Response
SOUND-C2 was an open-label, randomized, Phase 2b study that enrolled 362 treatment-naive HCV GT1 patients into five different treatment arms evaluating polymodal, IFN-free HCV treatment with Boehringer Ingelheim's investigational compounds faldaprevir and BI 207127, with and without RBV, for up to 40 weeks.

SOUND-C2 Trial Design and Results – SVR12 and 24
SVR
Group
Faldaprevir BI 207127 RBV Duration (wks) All Patients GT1a GT1b
A
N=81 120 mg QD 600 mg TID Y 16 48 (59%) 13/34 (38%) 35/47 (75%)
B
N=80 120 mg QD 600 mg TID Y 28 47 (59%) 14/32 (44%) 33/48 (69%)
C
N=77 120 mg QD 600 mg TID Y 40 40 (52%) 16/34 (47%) 24/43 (56%)
D
N=78 120 mg QD 600 mg BID Y 28 54 (69%) 13/30 (43%) 41/48 (85%)
E
N=46 120 mg QD 600 mg TID N 28 18 (39%) 2/18 (11%) 16/28 (57%)

In SOUND-C2, regression analysis identified HCV GT1 subtype, patient IL-28b genome type and gender as significant predictors of treatment response. Patients with GT1b were shown to be six times more likely to achieve SVR as compared to patients with HCV GT1a (95 percent CI; p<0.0001). Patients with the CC subtype of the IL-28b genome were more than four times as likely to achieve SVR compared to the CT and TT subtype of the genome.

The most common adverse events (AEs) in SOUND-C2 were skin changes (photosensitivity, rash), gastrointestinal (GI) disorders (vomiting, diarrhea), and jaundice due to transient benign bilirubin elevation (unconjugated hyperbilirubinemia). Treatment discontinuation due to AEs correlated with increased treatment duration, with discontinuations ranging from 4.9 percent in Arm A (16 weeks) to 24.7 percent in Arm C (40 weeks), which was the longest treatment duration evaluation in the study.

Results from SOUND-C2 Sub-analysis of Patients with Compensated Liver Cirrhosis due to HCV

Data from the SOUND-C2 study are the first data for an IFN-free regimen in HCV patients with compensated liver cirrhosis. This sub-analysis included 33 patients (nine percent of the study population) with compensated liver cirrhosis, as confirmed by either biopsy or Fibroscan. Investigators noted that data from this analysis support the continued development of this investigational IFN-free treatment regimen in Phase 3 trials for patients with compensated liver cirrhosis.

SOUND-C2 Sub-Analysis in Patients with Compensated Liver Cirrhosis
1335QD/7127TID/RBV
16, 28 or 40 weeks
Pooled (n=21) 1335QD/7127BID/RBV
28 weeks (n=9) 1335QD/7127TID 28 weeks (n=3)
GT1a
(n=7) GT1b
(n=14) GT1a
(n=4) GT1b
(n=5) GT1a
(n=0) GT1b
(n=3)
SVR12 / 24, n (%) 3 (43%) 8 (57%) 2 (50%) 4 (80%) N/A 1 (33%)
DCs due to AEs, n (%) 6* (29%) 1 (11%) 0
DCs due to rash, n (%) 3* (14%) 0 0
DCs due to photosensitivity, n (%) 2 (10%) 0 0
DCs due to vomiting, n (%) 1 (5%) 0 0
*No cases of erythema multiforme, Stevens-Johnson Syndrome (SJS), toxic epidermal necrosis, or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Comparison of SVR4, SVR12 and SVR24 Results from SOUND-C2

A comparison of results from the SOUND-C2 study shows that almost all patients (98 percent) in the study who achieved SVR4 continued to maintain undetectable virus levels and achieve SVR24. All of the patients who achieved SVR12 in the SOUND-C2 study maintained their undetectable virus levels and achieved SVR24.

Of the patients with undetectable hepatitis C virus levels at the end of treatment (EOT), and who received the treatment per the pre-specified protocol, 15 experienced documented relapse (7 percent). Relapse occurred within 12 weeks post-treatment for 14/15 patients. One patient in the 16 week study arm relapsed between 24-48 weeks post-treatment.

It should be noted that rare late relapses have been observed following both IFN-based and IFN-free treatment. It is unclear why these patients relapsed so late in the follow up period. These results emphasize the importance of monitoring patients for at least one year following the end of treatment regardless of whether they were treated with an IFN-based or IFN-free regimen.

Pivotal Phase 3 Program Now Beginning

Based on the results of SOUND-C2, Boehringer Ingelheim is now initiating a pivotal Phase 3 program. Three clinical trials will enroll approximately 1,200 treatment-naive HCV patients, including patients with compensated cirrhosis and those who are ineligible for IFN treatment.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

Merck announced that 96% of trial patients achieved SVR12 with it's protease inhibitor (MK-5172) combined with Interferon and Ribavirin.  Merck plans to begin other Phase 2 studies soon.
Advocate1955
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

AASLD-Merck MK-5172 Hepatitis C Drug Shows Promise in Study
Merck Hepatitis C Drug Shows Promise in Study

Published:  November 10, 2012
Dow Jones Newswires

A regimen containing an experimental Merck & Co. (MRK) drug suppressed the hepatitis C virus in most patients in a new clinical trial, and appears to be more potent than the company's Victrelis treatment.

The mid-stage study included the injectable drug interferon that Merck and its rivals hope to drop from future regimens. Merck now plans to conduct new studies of its drug, MK-5172, as part of a potential all-oral hepatitis C regimen that eliminates interferon, which can be difficult for patients to tolerate.

Merck is among a pack of drug companies--including Gilead Sciences Inc. (GILD) and Abbott Laboratories (ABT)--racing to tap what's expected to be a multibillion-dollar market for all-oral regimens. Current standard therapies, including Merck's Victrelis, are typically given with interferon.

Hepatitis C is a viral disease that attacks the liver, and is believed to afflict about 180 million people world-wide, with more than four million in the U.S., according to the National Institute of Allergy and Infectious Diseases. At-risk groups include people who had blood transfusions before 1992, when a screening test for the virus was developed.

Merck is presenting clinical data for MK-5172 at the annual meeting of the American Association for the Study of Liver Diseases in Boston, which began Friday.

MK-5172 is a so-called protease inhibitor, the same class of drug as Victrelis, which went on sale last year and generated $387 million in sales for the first nine months of 2012. But MK-5172 is designed to be more potent and to carry a higher barrier to treatment resistance than Victrelis, said Eliav Barr, vice president of infectious diseases with Merck's research arm.

In a phase 2, or mid-stage, clinical trial of about 330 patients with hepatitis C, patients were given various dose levels of MK-5172 in combination with the drugs ribavirin and interferon for 12 weeks. One group of patients received Victrelis plus ribavirin and interferon--which is now a standard treatment.

The study found that 96% of patients who received the 100-milligram dose of MK-5172 had sustained virologic response 12 weeks after treatment ended, the highest response rate of the various treatment groups. Sustained virologic response is roughly equivalent to being virus-free or having nearly undetectable viral levels.

Higher doses of MK-5172 were associated with liver toxicities, said Dr. Barr.
Because the study contained interferon, additional studies are needed to test whether MK-5172 is efficacious without interferon.

Merck plans to conduct phase 2 studies of MK-5172 in combination with another experimental oral drug, MK-8742, plus ribavirin, which is also an oral drug. If testing goes well, Merck may consider removing ribavirin from the regimen and pursuing a combination of MK-5172 and MK-8742, he said. Ideally, they could be combined in a once-daily tablet.

"We're looking for something highly efficacious, short duration, well-tolerated and all-oral," he said.
Dr. Barr declined to provide a timeline for when Merck might be in a position to submit a new hepatitis C regimen for regulatory approval.

This has already been posted by Orphaned Hawk on the Hep C forum, but I thought it might be a good idea to post in my journals as well.  100% of treatment naive Hep C, G1 patients achieved SVR4 with Gilead's Sofosbuvir (GS-7977), combined with GS-5885 and Ribavirin, according to GS's announcement at the AASLD conference in Boston Nov, 2012.
Advocate1955
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

AASLD-100 Percent Sustained Virologic Response Rate (SVR4) Interferon-Free Regimen of Sofosbuvir (GS-7977), GS-5885 and Ribavirin in Treatment-Na ïve Geno 1 Hepatitis C Infected Patients
Gilead Announces 100 Percent Sustained Virologic Response Rate (SVR4) for an Interferon-Free Regimen of Sofosbuvir (GS-7977), GS-5885 and Ribavirin in Treatment-Na ïve Genotype 1 Hepatitis C Infected Patients

- Phase 3 Study with a Fixed-Dose Combination Tablet of Sofosbuvir and GS-5885 Now Underway

BOSTON--(BUSINESS WIRE)--Nov. 10, 2012
Gilead Sciences (Nasdaq: GILD) today announced interim data from the ongoing Phase 2 ELECTRON study examining a 12-week course of therapy with the investigational nucleotide sofosbuvir (formerly referred to as GS-7977), the NS5A inhibitor GS-5885 and ribavirin in patients with genotype 1 chronic hepatitis C virus (HCV) infection. Among treatment-naïve patients receiving this combination, 100 percent (n=25/25) remained HCV RNA undetectable four weeks after completing therapy (SVR4). These data will be presented on Tuesday, November 13th at the 63rd annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2012) in Boston.
  
“These results indicate that adding GS-5885 to sofosbuvir-based regimens may enhance SVR rates, potentially offering HCV genotype 1 infected patients a convenient 12-week course of oral therapy,” said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON study. “Along with other data from the ELECTRON study, these results add to the growing body of evidence supporting the potential for effective sofosbuvir-based all-oral regimens.”
  
Gilead recently initiated the first Phase 3 trial (ION-I) evaluating a fixed-dose combination of sofosbuvir and GS-5885 in treatment-naïve genotype 1 patients. This four-arm study is evaluating the fixed-dose combination with and without ribavirin for 12-and 24-week durations in 800 patients, 20 percent of whom have evidence of cirrhosis.
  
Data from five additional arms of the ELECTRON study examining sofosbuvir-based therapy in various patient populations also will be presented:
  

Treatment Population Results
Sofosbuvir + ribavirin for 12 weeks GT 1 treatment-naïve 84% (21/25) SVR12
GT 1 null responders 10% (1/10) SVR12
GT 2/3 treatment-experienced 68% (17/25) SVR12
Sofosbuvir + ribavirin for 8 weeks GT 2/3 treatment-naïve 64% (16/25) SVR12
Sofosbuvir + ribavirin (800 mg) for 12 weeks GT 2/3 treatment-naïve 60% (6/10) SVR8


Preliminary data from a subset of an ongoing cohort in the ELECTRON study in which nine genotype 1 previous null responders were treated with sofosbuvir, GS-5885 and ribavirin for 12 weeks also will be presented on Tuesday. Thus far, three of the nine patients have reached the four-week post-treatment time point and all three remain HCV negative.
  
Both sofosbuvir in combination with ribavirin and sofosbuvir in combination with GS-5885 and ribavirin were well tolerated in the ELECTRON study. In the sofosbuvir combined with GS-5885 and ribavirin groups, there was one discontinuation due to an adverse event unrelated to study drugs. Despite stopping therapy at week 8, this patient also achieved SVR4.
  
The most common adverse events were headache, fatigue, upper respiratory tract infection and nausea. The most common clinically significant grade 3/4 laboratory abnormality was a hemoglobin reduction.
  
Additional Safety Data for GS-5885
In a poster presentation at The Liver Meeting on Sunday, November 11th, investigators will report combined safety data for more than 1,000 patients who have received at least one dose of GS-5885, in combination with other HCV medicines, in six ongoing Phase 2 clinical trials. In this analysis, 616 patients received a 30 mg dose and 423 patients received the 90 mg dose of GS-5885, which is being assessed in Phase 3 research. More than 700 patients completed at least 12 weeks of treatment with GS-5885. Approximately 70 percent of patients were treatment-naïve and 70 percent had HCV genotype 1a infection.
  
Researchers concluded that GS-5885 is safe and well tolerated. No laboratory abnormalities or other safety signal of concern has been observed in the GS-5885 development program.
Sofosbuvir and GS-5885 are investigational products and their 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 possibility that the proportion of patients who maintain a sustained virologic response 12 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release, the possibility that results from the arm of the ELECTRON study evaluating the efficacy and safety of sofosbuvir, GS-5885 and ribavirin in genotype 1 previous null responder patients will not be favorable once four and 12 week post-treatment data from all nine patients are available and the possibility of unfavorable results from additional arms of the ELECTRON study and subsequent clinical trials involving sofosbuvir and GS-5885 with and without ribavirin. As a result, sofosbuvir and GS-5885 as single agents or as a fixed-dose combination may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of the compounds or the fixed-dose combination regimen if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. 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 quarter ended September 30, 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.
Patrick O’Brien, 650-522-1936
Investors
or
Cara Miller, 650-522-1616
Media

Related-UPDATE2: Abbott, Gilead impress with upbeat results for oral hep C drugs

Gilead posts positive results in mid-stage Hepatitis C study

(Reuters) - Gilead Sciences Inc on Saturday reported a 100 percent cure rate using a combination of drugs in a small number of patients with the most common and hardest to treat form of hepatitis C.
Rival Abbott Laboratories Inc, meanwhile, said a trio of its oral medicines to treat hepatitis C produced unprecedented cure rates in a larger number of patients who had failed to benefit from standard treatment, as well as very high cure rates for newly treated patients.

Data from both companies' mid-stage trials were released Saturday at the annual meeting of the American Association for the Study of Liver Disease in Boston.

Gilead's study, dubbed Electron, examined 25 patients with genotype 1 chronic hepatitis C virus (HCV) infection who were treated for 12 weeks with a combination of three drugs: sofosbuvir, ribavirin and GS-5885.

GS-5885 is from a promising new class of drugs known as NS5A inhibitors, which prevent the hepatitis C virus from replicating.

The infection was undetectable four weeks after completing therapy in all of the patients who had never received this combination of drugs before, Gilead said.

The drugs generally were well tolerated in the study, Gilead said.

In the sofosbuvir combined with GS-5885 and ribavirin patient groups, one patient dropped out because of an adverse side effect that the company said was unrelated to the drugs.
Sofosbuvir and GS-5885 are still being studied for their safety and efficacy.

The biopharmaceutical company will present the data on Tuesday at the annual meeting of the American Association for the Study of Liver Diseases in Boston.

Mark Schoenebaum, a biotech analyst with ISI Group, said in a research note that he expects Gilead shares to rise on Monday based on these "best case" results.

UBS analyst Matthew Roden said "these data strongly support Gilead's leadership position" in the hepatitis C virus space.

Gilead recently started the first Phase 3 trial evaluating a fixed-dose combination of sofosbuvir and GS-5885 in patients with genotype 1 chronic hepatitis C virus infection who had not received these drugs before.

This study is evaluating the fixed-dose combination with and without ribavirin for 12- and 24-weeks in 800 patients, 20 percent of whom have evidence of cirrhosis, or liver scarring.

Vertex presented information at the AASLD conference in Boston in Nov., 2012.  According to this article Vertex's VX-135, an oral nucleotide, demonstrated a median 4.54 log 10 reduction in HCV RNA after dosing once daily for seven days in treatment naive patients both w/ and w/o Ribavirin.  Vertex will be conducting Phase 2 trials pf VX-135 combined with simeprevir (TMC435).
Advocate1955
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

AASLD- ALS-2200 (VX-135), Vertex's Oral Nucleotide Analogue in Development for Hepatitis C
Data from Viral Kinetic Study Showed Rapid Reduction of HCV RNA with ALS-2200 (VX-135), Vertex's Oral Nucleotide Analogue in Development for the Treatment of Hepatitis C

BOSTON --(Business Wire)—Nov. 10, 2012
Vertex (News - Alert) Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that data on ALS-2200 (VX-135), an oral medicine Vertex is developing for the treatment of hepatitis C, are being presented for the first time at The Liver Meeting®, the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

There was a median 4.54 log10 reduction (range -3.81, -5.08) in hepatitis C virus (HCV) RNA after seven days of dosing with ALS-2200 (200 mg) once daily in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Similar reductions in HCV RNA were seen in a seven-day viral kinetic study of once daily ALS-2200 (200 mg) in combination with ribavirin (n=8). ALS-2200 was well-tolerated in this study, with no serious adverse events and no discontinuations due to adverse events.

Based on these data, and to further characterize the medicine's safety and efficacy profile, Vertex plans to begin multiple Phase 2 studies of 12-week all-oral regimens in people with genotype 1 hepatitis C in early 2013, pending discussions with regulatory authorities. These studies will include combinations of VX-135 with GSK2336805 and separately with simeprevir (TMC435). Upon the start of Phase 2 studies, ALS-2200 will be known as VX-135. Screening in the first study, which will evaluate VX-135 in combination with ribavirin, is expected to begin in the coming weeks.

"We're working quickly to evaluate multiple all-oral treatment regimens with VX-135 and expect to have a significant amount of data from several Phase 2 studies by the end of 2013," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "Our goal is to proceed to pivotal development with one or more regimens that have the greatest potential to offer doctors and the people they treat a more tolerable, short-duration therapy with high viral cure rates for hepatitis C."

Seven-day viral kinetic data showed that when once-daily ALS-2200 (200 mg) was dosed in combination with ribavirin, there was a median 4.18 log10 reduction (range -3.6, -5.2) in HCV RNA in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Five patients achieved HCV RNA levels below the limit of quantification (< LOQ = < 25 IU/mL), and two of these five achieved HCV RNA levels below the limit of detection (Roche COBAS Taqman HCV test, Version 2) after seven days of dosing. Similar to the data from the monotherapy cohort, ALS-2200 in combination with ribavirin was well-tolerated, no patients discontinued due to adverse events and there were no serious adverse events.

"The early antiviral activity and tolerability of this nucleotide analogue are very promising as we seek to develop new interferon-free treatment regimens," said Patrick Marcellin, M.D., Ph.D., Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "The data suggest VX-135 could be a core component of all-oral regimens for the treatment of hepatitis C."

"Preclinical characterization of ALS-2200, a potent nucleotide polymerase inhibitor for the treatment of chronic hepatitis C."
Poster presentation #1882
November 13, 2012, 8:00 a.m. - 12:00 p.m. EST
Preclinical data on ALS-2200 will be presented at AASLD that support the Phase 1 viral kinetic study and further clinical development plans. In preclinical studies, ALS-2200 was shown to be a potent, selective, specific, and pan-genotypic nucleotide analogue that inhibits the HCV NS5B polymerase. Specifically, there was no in vitro inhibition of non-HCV viruses, human DNA (ß or ?) or RNA (II) polymerases, or mitochondrial protein synthesis. The studies also showed that ALS-2200 retains potency in vitro against a panel of HCV variants resistant to NS3/4A, NS5A and non-nucleoside NS5B inhibitors.

"Analysis of ALS-2200, a novel potent nucleotide analog, combination drug interactions in the hepatitis C virus (HCV) subgenomic replicon system."
Poster presentation #1887
November 13, 2012, 8:00 a.m. - 12:00 p.m. EST
Combination studies with ALS-2200 were performed in vitro to determine whether interactions with other drugs were additive, synergistic or antagonistic. Combination of ALS-2200 with either telaprevir or VX-222 demonstrated a synergistic effect, and combination with ribavirin resulted in an additive response. No significant cytotoxicity or antagonism were observed at any concentration of the combinations tested. Combinations of ALS-2200 and 18 other compounds were also tested, including simeprevir, which showed significant synergy with ALS-2200.
"We're pleased with the strength of our collaboration with Vertex and how it may lead to advances in the treatment of hepatitis C," said Lawrence M. Blatt, Ph.D., Founder, President and Chief Executive Officer of Alios BioPharma. "We're looking forward to seeing the results of several studies evaluating various all-oral combinations including VX-135."

VX-135 Phase 2 Trials
Vertex recently announced that it has entered into two non-exclusive agreements to conduct Phase 2 proof-of-concept studies of VX-135 in combination with simeprevir (TMC435), a protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB, and with GSK2336805, an NS5A inhibitor in development by GlaxoSmithKline (GSK). The studies with GSK2336805 and simeprevir are expected to begin in early 2013, pending discussions with regulatory authorities. Screening is expected to begin in the coming weeks for a Phase 2 study of VX-135 and ribavirin. Vertex also plans to begin a study of VX-135 and telaprevir, the company's approved protease inhibitor marketed as INCIVEK®(telaprevir) tablets for people with chronic genotype 1 hepatitis C, in early 2013, pending discussions with regulatory authorities. All of these Phase 2 studies will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment) using 12-week combination regimens.

About VX-135 (ALS-2200)
VX-135 (ALS-2200) is a uridine nucleotide analogue pro-drug that appears to have a high barrier to drug resistance based on in vitro studies. It is designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In vitro studies of the compound showed antiviral activity across all genotype, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.