Thursday, October 28, 2010

Pharmasset releases Phase 1 data on HCV nucleotide inhibitor PSI-938

Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C 
10/28/2010

PRINCETON, N.J., Oct. 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) reported positive preliminary results today from its phase I monotherapy trial of PSI-352938 ("PSI-938") for the treatment of chronic hepatitis C (HCV). PSI-938 is a guanosine nucleotide analog polymerase inhibitor in development for the treatment of chronic HCV infection.


PSI-938 Phase 1 Multiple Ascending Dose Study Overview
In August 2010, Pharmasset initiated a phase 1 multiple ascending dose study with PSI-938 administered once daily (QD) or twice daily (BID) for 7 days. The trial was conducted at two US centers as a blinded, randomized, and placebo-controlled study in 40 patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability, and pharmacokinetics of PSI-938 administered over 7 days. The secondary objective was to assess antiviral activity by measuring the change in HCV RNA. Patients were randomized within each cohort to receive either PSI-938 (8 patients per cohort) or placebo (2 patients per cohort). Four dose cohorts of PSI-938 (100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID) have been completed.
PSI-938 Antiviral Activity Summary
Preliminary Antiviral Response Observed Following PSI-938 Administered as Monotherapy for 7 Days
Dose
n
Median Change in
HCV RNA at Day 8
Range
Number of Subjects with
HCV RNA


(log10 IU/mL)
(log10 IU/mL)
100 mg QD
8
-4.31
-2.66 to -5.12
1
3
200 mg QD
8
-4.64
-3.49 to -5.35
5
7
300 mg QD
8
-3.94
-3.43 to -5.29
4
4
100 mg BID
8
-4.59
-3.94 to -5.08
2
3
Placebo
8
-0.05
+0.17 to -0.29
0
0
LOD = limit of detection (<15 IU/mL)
LOQ = limit of quantification (<43 IU/mL)

PSI-938 demonstrated potent antiviral activity with a mean HCV RNA change from baseline of 4.31 log10 IU/mL, 4.64 log10 IU/mL, 3.94 log10 IU/mL and 4.59 log10 IU/mL in patients receiving 100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID for seven days, respectively. HCV RNA declined consistently throughout the 7-day dosing period, with no viral breakthrough. For the 16 subjects who received PSI-938 200 mg QD or 300 mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).

PSI-938 Pharmacokinetic and Safety Summary
Pharmacokinetics parameters were similar between healthy subjects in the single ascending dose study and HCV infected patients in the seven-day multiple ascending dose study. PSI-938 at all doses provided good systemic exposure and continue to support once-daily administration.

PSI-938 was generally safe and well tolerated across all doses studied to date with no serious adverse events and no discontinuations. There were no dose-related trends in adverse events through the dose escalations, no grade 4 treatment emergent laboratory changes, and no trends in clinical laboratory abnormalities.

PSI-938 SAD and preclinical data
The Phase 1a single ascending dose study conducted earlier this year assessed single doses of PSI-938 ranging from 100 mg to 1600 mg or matching placebo in healthy male and female volunteers. No dose-limiting toxicity was identified. Safety and pharmacokinetic data supported progression of PSI-938 to the 7-day monotherapy trial. Full data from the SAD trial will be presented at the upcoming AASLD Annual Liver Meeting in Boston, MAOctober 29-November 3, 2010 (poster #1890).

Preclinically, both PSI-938 and Pharmasset's other guanosine analog, PSI-661, which is in late preclinical development, have demonstrated similar potency against wild-type HCV or HCV with the S282T mutation, which can be selected by RG7128 and PSI-7977 in vitro. Although the S282T has not been detected in treatment-naive individuals with HCV, nor selected in clinical trials with any of Pharmasset's nucleoside/tide analogs, the potential for interferon-sparing regimens may increase the focus on antivirals with complementary resistance profiles.

"We are very encouraged by the preliminary efficacy and safety data with PSI-938, our purine nucleotide analog for HCV," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "These data provide the first confirmatory evidence that a nucleoside/tide analog can exhibit substantial early antiviral activity in monotherapy as has been observed with compounds in other DAA classes. Unlike other classes of DAAs to date, our nucleotide analogs also provide a higher barrier to resistance and clinically-validated antiviral activity across a broad range of HCV genotypes, characteristics not yet demonstrated with other classes of DAA. We continue to believe that nucleoside/tide analogs will become the backbone of HCV therapy. In addition, similar to HIV, the combination of two complementary nucleoside/tide analogs could provide a differentiated therapy for HCV patients in the future."

PSI-938 and PSI-7977 Combination Study
In this quarter, Pharmasset plans to initiate a short-term study to assess the combination of PSI-938 and PSI-7977. The trial will be conducted in the US, as a blinded, randomized, placebo-controlled study in approximately 50 patients chronically infected with HCV genotype 1. The primary objective will be to assess the safety, tolerability, and pharmacokinetics of PSI-938 and PSI-7977 alone and in combination. Preliminary results are expected in the first half of 2011.

Conference Call and Webcast
Members of Pharmasset's management team will host a conference call today, October 28, 2010, at 8:00 a.m. ET to discuss the preliminary results of the multiple ascending dose trial with PSI-938. Investors may listen to the webcast of the conference call live on the "Events & Presentations" section of Pharmasset's website, www.pharmasset.com. Alternatively, investors may listen to the call by dialing 877-771-7028 from locations in the U.S. and 973-200-3092 from outside the U.S. The webcast replay will be available for at least 72 hours following the call.

About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in Phase 1. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.
Pegasys® and Copegus® are registered trademarks of Roche.

Biolex announces Locteron SVR12 & safety/tolerability advantages in SELECT-2 trial..

Market Wire - Oct. 28, 2010
PITTSBORO, NC -- (MARKET WIRE) -- 10/28/10 -- Biolex Therapeutics, Inc. announced positive efficacy, safety and tolerability results from its 72-week SELECT-2 Phase 2b dose-finding Phase 2b trial of Locteron®, the Company's lead product candidate for the treatment of hepatitis C. For each of the three Locteron doses tested in SELECT-2, the percentage of patients who maintained undetectable levels of virus at week 60 of the trial, 12 weeks after completion of 48 weeks of treatment (SVR12), were comparable with or exceeded the response rate for the PEG-Intron® control. As a result of its controlled-release mechanism, Locteron was dosed half as frequently as PEG-Intron. PEG-Intron is one of two currently marketed pegylated interferon products for the treatment of hepatitis C, a market that currently exceeds $2.5 billion in worldwide sales. 

Additional results from SELECT-2 demonstrated the substantial tolerability advantages of Locteron. Patients treated with each of the three Locteron doses in SELECT-2 reported a statistically significant reduction in flu-like adverse events (p < 0.001) compared to the PEG-Intron group. Accordingly, Locteron patients in all three dose groups used less concomitant medications (analgesics and antipyretics) than the PEG-Intron patients during the study period. Lastly, patients receiving the two lower doses of Locteron experienced lower rates of depression and discontinuations due to adverse events than patients receiving PEG-Intron.
Response rates and tolerability results for SELECT-2 are outlined in the table below:
                     
"The strong viral response of Locteron achieved with once-every-two-week dosing is an improvement over current interferons, and I am impressed by the consistency of the flu-like effect across trials and different reporting methodologies," said Nezam Afdhal, M.D., Chief of Hepatology at Beth Deaconess Medical Center, Harvard Medical School. "The reduction in symptoms of depression is quite promising and needs to be followed up in additional clinical evaluation. The Locteron safety and tolerability results are clearly important as recent clinical results demonstrate that interferon is likely to remain a core component of future treatment regimens that incorporate the new direct-acting anti-virals, highlighting the need for a more tolerable interferon to reduce the side-effect burden on patients from these multi-drug combinations and maximize their adherence to treatment." 

SELECT-2 Depression Results
In SELECT-2, depression was measured in both patient-reported and clinic-reported methods and showed an advantage for Locteron for the dose groups encompassing the expected commercial dose range, the 320 and 480 µg doses. Throughout the 48 weeks of treatment in SELECT-2, patients self-reported their status using the Beck's Depression Inventory (BDI), one of the most widely used instruments for measuring the severity of depression. Results demonstrated that fewer patients reported scores greater than 16 using the BDI (the threshold for mild depression) in the 320 and 480 µg Locteron dose groups compared to the PEG-Intron group.
These findings from SELECT-2 are of particular importance as a survey of hepatitis C patients published in the Journal of Viral Hepatitis in 2010, showed that depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. 

AASLD Presentation
Biolex also announced today that new tolerability data from two Phase 2b trials of Locteron have been accepted for a late-breaker presentation on November 1, 2010 at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston. These latest tolerability results include daily patient self-reporting of flu-like adverse events using an electronic patient reported outcome system (ePRO).
"We believe that the efficacy, safety and tolerability results from SELECT-2 support the profile of Locteron as the most combinable interferon for use with direct-acting anti-viral drugs in emerging combination regimens," said Mr. Jan Turek, Biolex's President and Chief Executive Officer. "We are pleased that the ePRO results, the newest data supporting the tolerability advantages of Locteron, have been accepted for presentation at the AASLD conference." 

Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency. 

About SELECT-2 Study
Biolex's SELECT-2 Phase 2b trial was designed to identify one or more doses of Locteron that demonstrated viral kinetics and response rates comparable to the PEG-Intron® control while also achieving at least a 50% reduction in flu-like adverse events. SELECT-2 is being conducted in the United States and Europe in 116 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients were treated for 48 weeks and are being followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. All patients in the trial have reached at least the 60-week time point of the study, or 12 weeks of follow-up after completion of the scheduled 48 weeks treatment.
In SELECT-2, all adverse events were recorded during weekly clinic visits by the clinical site personnel. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia. Under the statistical analysis plan for the trial, the reductions in flu-like adverse events were tested after four and 12 weeks of treatment and were statistically significant for all three Locteron doses (p < 0.001 at 12 weeks for each of the 320, 480 or 640 µg doses of Locteron). In addition to the weekly clinic reporting, flu-like adverse events were self reported daily by patients through an electronic patient reported outcome system (ePRO). The ePRO results will be reported at the upcoming AASLD meeting as detailed above. 

Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016. 

Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.

Sunday, October 24, 2010

Vertex Pharmaceuticals - Telaprevir oral and poster presentations at AASLD 2010

Vertex Oral Presentations
November 1, 2010 @
5:00 p.m. ET
#LB-2 “Telaprevir in Combination with Peginterferon Alfa2a and Ribavirin for 24 or 48 weeks in Treatment-Naïve Genotype 1 HCV Patients who Achieved an Extended Rapid Viral Response: Final Results of Phase 3 ILLUMINATE Study”
Hynes Auditorium
November 2, 2010 @
8:00 a.m. ET
#211 “Telaprevir in Combination with Peginterferon and Ribavirin in Genotype 1 HCV Treatment-Naïve Patients: Final Results of Phase 3 ADVANCE Study”
Hynes Auditorium
November 2, 2010 @
11:45 a.m. ET
#227 “Long-term Follow-up of Patients with Chronic Hepatitis C Treated with Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Interim Analysis of the EXTEND Study”
Hynes Room 304/306
Vertex Poster Presentations
October 31, 2010 @
8:00 a.m. ET
#805 “No Impact of Insulin Resistance on Antiviral Efficacy of Telaprevir-based Regimen in HCV Genotype 1 Treatment-Naïve Patients: Subanalysis of C208 Study”
Hynes Exhibit Hall C

#828 “Activity of Telaprevir Monotherapy or in Combination with Peginterferon-alfa-2a and Ribavirin in Treatment-naïve Genotype 4 Hepatitis-C Patients: Final Results of Study C210”
Hynes Exhibit Hall C

#1051 “Spontaneous Viral Clearance in a Patient With Chronic Hepatitis C who Relapsed After Telaprevir-based Treatment”
Hynes Exhibit Hall C

#899 “The Effect of Hepatitis C Treatment Response on Medical Costs: a 5-Year Longitudinal Analysis in a Managed Care Setting”
Hynes Exhibit Hall C
November 1, 2010 @
8:00 a.m. ET
#LB-11 “Clinical Virology Results from Telaprevir Phase 3 Study ADVANCE”
Hynes Exhibit Hall C

Thursday, October 21, 2010

Aethlon Medical starts patient enrollment of Hemopurifier in battle against HCV...

From the PharmaLive.com News Archive - Oct. 21, 2010
SAN DIEGO, Oct. 21 /PRNewswire-FirstCall/ -- Aethlon Medical, Inc. (OTC Bulletin Board: AEMD), the pioneer in developing therapeutic filtration devices to address infectious disease and cancer, announced today it has established primary clinical endpoints and clarified efficacy assessments related to a study that will evaluate the use of the Aethlon Hemopurifier® in combination with standard of care (SOC) HCV drug therapy.  As a result, Aethlon will now initiate the recruitment of candidate patients and begin exporting its Hemopurifier® for clinical purposes.  The study will be conducted at Medanta, The Medicity Institute (Medicity), which is a $360 million multi-specialty medical institute recently established on a 43-acre campus to be a premier center of medical tourism in India. The Aethlon Hemopurifier® is a first-in-class medical device that selectively targets the removal of infectious viruses and immunosuppressive proteins from the entire circulatory system.

A primary clinical goal of the study will be to demonstrate that the Aethlon Hemopurifier® improves the acceleration of viral load depletion when administered at the outset of SOC drug therapy. Clinical endpoints of the study will assess Early Viral Response (EVR) rates, Rapid Viral Response (RVR) rates, as well as Immediate Viral Response (IVR) rates, which are all highly predictive of a sustained viral response (SVR), which is defined as undetectable viral load six months after the completion of SOC drug therapy.  As the Hemopurifier® is designed to decrease the presence of circulating HCV virus, Aethlon will also seek to quantify the amount of HCV captured within the Hemopurifier® after the first application of the device in each enrolled patient. A lower body burden of HCV at the outset of SOC also correlates with improved treatment outcomes.

Early Viral Response (EVR)
As reported in the McHutchinson, et al 2009 study of 1,019 genotype I patients who initiated 48-week standard dose SOC PegIFN-a2b therapy, 39.9% of treated patients achieved an EVR.  Those patients who achieved an EVR, which represents undetectable viral load at day 90 of SOC treatment, achieved 99% SVR rates, representing an improved clinical benefit of greater than 200% as compared to patients that do not achieve an EVR.  A clinical goal of the Hemopurifier® study will be to increase the established likelihood that patients achieve an EVR.

Rapid Viral Response (RVR)
Also reported in the McHutchinson, et al 2009 study of 1,019 genotype I patients who initiated 48-week standard dose SOC PegIFN-a2b therapy, only 11.4% of treated patients achieved a RVR, which is defined as undetectable viral load at day 30.  However, those patients who achieved an RVR had SVR rates of approximately 90%, which represents a clinical benefit greater than 100% as compared to patients that do not achieve an RVR.  An additional clinical goal of the Hemopurifier® study will be to increase the likelihood that patients achieve an RVR.

Immediate Viral Response (IVR)
Aethlon will also seek to demonstrate that the addition of the Hemopurifier® to SOC drug therapy improves Immediate Viral Response (IVR) rates as compared to patients who receive SOC alone.  IVR, also known as first-phase kinetics, will be determined by measuring viral load at the end of day one (1), day two (2), day three (3), and day seven (7).  In this regard, an additional clinical goal will be to demonstrate the application of the Hemopurifier® in combination with SOC improves first-phase viral depletion kinetics in enrolled patients.
The principal investigator of the clinical study, which has been registered with the Clinical Trials Registry of India, will be Vijay Kher, M.D., Chairman of the Department of Nephrology at the Medanta Kidney & Urology Institute. Dr. Kher previously served as the principal investigator of Hemopurifier® human studies to treat HCV at the Apollo and Fortis hospitals in Delhi, India. The Apollo and Fortis studies demonstrated safety and the effectiveness of the Hemopurifier® to reduce viral load in the absence of drug therapy. Patients enrolled in the Medicity study will receive a maximum of six Hemopurifier® treatments within the first week of initiating SOC drug therapy.   The study will enroll up to 30 patients.

Upon the demonstration of improved clinical outcomes, Aethlon plans to advance commercialization through the Medicity and other regional treatment centers in India. The company has entered into an agreement with GVK Biosciences (GVK BIO) to expand the opportunity for Aethlon to commercialize its Hemopurifier® treatment technology at three to five new clinical centers in India.  GVK BIO is Asia's leading Discovery Research and Development organization. The HCV treatment opportunity for Aethlon is significant as it is estimated that 20 million of the 180 million people infected with HCV worldwide reside in India.  Based on patient feedback, Aethlon also believes that citizens of other nations that are infected with HCV may choose to travel to India to seek out new therapies that could help address their HCV infection. However, Medanta's Independent Ethics Committee (MIEC) has not yet approved the enrollment of treatment candidates who reside outside of India.

Intercell & Romark to start Phase II combination trial with HCV vaccine IC41 and nitazoxanide.

From the PharmaLive.com News Archive - Oct. 21, 2010
-- The companies are designing a treatment that combines Intercell's investigational Hepatitis C vaccine, IC41, with Romark's antiviral drug, nitazoxanide.

-- A combination Phase II trial is expected to start in H1/2011.

-- The trial will be sponsored by Romark. Intercell will provide the vaccine candidate IC41.

VIENNA, Oct. 21 /PRNewswire/ -- Intercell AG (VSE; "ICLL") and Romark Laboratories L.C. today announced plans to commence clinical trials of Intercell's investigational therapeutic Hepatitis C virus (HCV) vaccine, IC41, in combination with Romark's antiviral drug, nitazoxanide, during the first half of 2011.
Intercell's vaccine candidate has demonstrated a sustained reduction of viral load in chronic Hepatitis C (CHC) patients in a Phase II proof-of-concept trial. Nitazoxanide is an oral therapy that targets host cell factors involved in HCV replication and is not associated with viral mutations conferring resistance. Nitazoxanide has been shown to induce sustained virologic response as monotherapy in some patients chronically infected with HCV.

The planned European Phase II trial will include about 60 treatment-naïve patients chronically infected with HCV genotype-1 in three treatment arms: (1) IC41 plus nitazoxanide, (2) IC41 plus nitazoxanide and Pegasys® (peginterferon alfa-2a) and (3) Pegasys and Copegus® (ribavirin), the current standard of care, as an active control. The primary endpoint will be sustained virologic response (no detectable HCV RNA 24 weeks after end-of-treatment).

The companies involved in the combination study will retain commercial rights for their respective products.
"We are very pleased about this important next step in the development of our vaccine candidate against Hepatitis C. The distinctly different mode-of-action and the outstanding tolerability of both treatments create a joint approach in a field that will continue to have high unmet medical need over the next decades," stated Gerd Zettlmeissl, CEO of Intercell.

"We are excited about this novel therapeutic approach for chronic Hepatitis C," said Jean-Francois Rossignol, M.D., Ph.D., Chairman and Chief Science Officer of Romark. "There is an important need for novel therapies that offer improvements in safety and efficacy compared to current standard therapy. Our development program for nitazoxanide in combination with peginterferon addresses this need and promises to change paradigms for therapy of chronic Hepatitis C. The planned study of nitazoxanide in combination with Intercell's therapeutic vaccine further underscores our commitment to being a leader in the development of next-generation therapies."

Intercell's investigational therapeutic vaccine has been designed to restore an effective immune response against HCV, which ultimately is deemed necessary for sustained clearance of the virus. In a successful proof-of-concept trial involving around 50 treatment-naïve genotype-1 CHC patients, an optimized schedule of therapeutic vaccination achieved viral load reductions of more than 75% (0.6 log) in patients with high baseline RNA levels. Importantly, this reduction was sustained for at least six months following the end of treatment. As in previous trials with the vaccine from Intercell, vaccination was safe and well tolerated with minimal side effects.

Nitazoxanide, the first of a new class of broad-spectrum antiviral drugs called the thiazolides,(1,2,3) is an investigational new drug for CHC. It is a potent inhibitor of HCV in replicon studies,(2) and laboratory studies indicate that it does not induce viral mutations that confer drug resistance.(3,4) Nitazoxanide is synergistic with interferon and direct acting antivirals in replicon studies.(2,5) In a clinical trial of nitazoxanide monotherapy in patients with genotype 4 CHC, 17% (4 of 23) patients achieved sustained virologic response (undetectable serum HCV RNA 24 weeks after end of therapy), with all responders having low baseline serum HCV RNA levels (<400,000 IU/mL).(6) In other clinical trials, the addition of nitazoxanide to peginterferon or peginterferon plus ribavirin was associated with improvement in sustained virologic response rates without increasing the toxicities associated with peginterferon and ribavirin.(7,8) Romark is preparing to initiate Phase III clinical trials of nitazoxanide plus peginterferon for treatment of CHC.

Monday, October 18, 2010

Rash scare & potential crowded marketplace keeps ANA598 partnerless...

BioWorld Today - Oct. 18, 2010
Financings Roundup
Having yet to sign a partnership for hepatitis C drug ANA598, Anadys Pharmaceuticals Inc. is pulling in $25 million in a public offering to support an upcoming Phase IIb study of the non-nucleoside polymerase inhibitor.
The San Diego-based firm priced the offering of about 13.9 million shares at $1.80 apiece, marking a 13.5 percent discount to Thursday's closing price.
That discount, plus the added dilution to the company's stock, sent shares (NASDAQ:ANDS) tumbling 33 cents, or 15.9 percent, to close Friday at $1.75.
In May, Anadys raised $12.5 million in a registered direct offering and hired Lazard Freres & Co. LLC to help pursue strategic alternatives such as sale of the company or out-licensing assets.
That includes ANA598, which, despite promising early efficacy data, has been dinged by reports of rash in a Phase Ib trial, followed by a higher-than-expected placebo effect that diminished 12-week virological response data in a Phase II study. (See BioWorld Today, April 24, 2009, and Feb. 26, 2010.)
Add to that the increasing competition in the HCV space, and it's no surprise that prospective partners might be skeptical.
Leerink Swann analyst Howard Liang noted last month that recent Phase III data on HCV protease inhibitors, especially Vertex Pharmaceuticals Inc.'s telaprevir "set a high efficacy bar" while early data for NS5A inhibitor BMS-790052 from Bristol-Myers Squibb Co. and nucleoside polymerase inhibitors for Roche AG (RG7128) and Pharmasset Inc. (PSI-7977) also have been impressive.

"In comparison, ANA598's early data do not look compelling," Liang wrote in a Sept. 27 research report.
Anadys is hoping that further Phase II data and results from the Phase IIb study slated to start early next year might prove tempting enough to snag a partner to help with the costly Phase III program.

The ongoing Phase II study is testing ANA598 in combination with the standard-of-care regimen pegylated interferon and ribavirin in treatment-naive HCV patients with genotype 1 disease.

Anadys has data for three of the six patients in the 200-mg twice-daily group, treated for 24 weeks and then had HCV levels measured 24 weeks after all treatment stopped. All three of those patients achieved sustained viral response.

The planned 48-week Phase IIb trial will test ANA598, again in combination with pegylated interferon and ribavirin, in about 200 patients, including both treatment-naive and treatment-experienced subjects.
Anadys is working to finalize the design with the FDA.
Elsewhere in its pipeline, the company has ANA773, an HCV drug designed to induce endogenous interferon that acts via the Toll-like receptor 7 pathway.
Work on that program was suspended in 2009 to concentrate resources on ANA598, but data from a monotherapy trial, plus recent developments suggesting that interferon-based treatment might continue to have a place in the HCV landscape, prompted the firm to restart ANA773. A 28-day combination study of the drug plus ribavirin is expected to begin dosing in the second quarter of 2011 . (See BioWorld Today, June 5, 2009.)
Proceeds from the latest financing, which will add to the $22. 1 million Anadys had in the bank as of June 30, also will be used for general corporate purposes, including working capital.

The firm could pull in an additional $3.7 million if underwriter Lazard Capital Markets LLC exercises its full overallotment option of about 2. 1 million shares.

Prior to the offering, Anadys had about 46.2 million shares outstanding.

Thursday, October 14, 2010

DGAT-1: A New STAT-C Target?

BioWorld Today - Oct. 14, 2010

Scientists have identified a potential new target in the fight against hepatitis C: diacylglycerol acyl transferase 1, or DGAT-1, an enzyme that is involved in fat droplet synthesis in the liver.

In their studies, the authors showed that DGAT1 anchors a key viral protein to the fat droplets, which serve as a sort of staging ground for the assembly of new viral particles in the cell. Inhibiting the enzyme essentially keeps hepatitis C from getting its parts together into new virus particles after the virus has copied its genome.
Other studies had shown that inhibiting fat droplet synthesis prevents hepatitis C virus from assembling. But the inhibition of one specific enzyme "is a very tailored intervention," senior author Melanie Ott told BioWorld Today. "We don't touch . . . the ability of the cell to produce these very important fat droplets . . . we are excited about that." Ott is an investigator at the University of California, San Francisco's Gladstone Institute of Virology and Immunology.

Estimates of just how many people are infected with hepatitis C globally vary widely, from 160 million to almost twice that. But what is clear is that it is a large public health problem. The infection turns chronic in about 80 percent of those who contract it, and can lead to consequences including cirrhosis and liver cancer. And hepatitis C is one of the biggest headaches for HIV-infected individuals, particularly intravenous drug users who often contract both viruses at the same time.

To top it off, roughly half of treated patients respond to the standard treatment and doctors currently have no advance way to tell responders from nonresponders to the harsh regimen. Together, it translates into a need for better therapies.

Ott said her team's work, which was published in the Oct. 10, 2010, online edition of Nature Medicine, was enabled by advances in two separate areas. One is an increasing realization that fat droplets "are an important organelle," not just a cellular storage closet for triglycerides and cholesterol. Fat droplets "used to be thought of as completely uninteresting," she said.

The other is recent advances in the ability to work with the hepatitis C virus itself. "Until 2005, we couldn't really study the virus very well," because it replicated neither in cell culture nor in mice, meaning that studies had to be done in primates.
In their paper, senior author Ott and her team used a DGAT1 inhibitor to treat hepatitis-infected liver cells. They found that such cells did not have any fewer fat droplets than untreated counterparts, but that hepatitis C was able to check into such cells, but not check back out after viral replication.

Further experiments showed that DGAT1 inhibition appears to work by interfering with the hepatitis C virus core protein, which is required for assembling viral particles after replication. That assembly, it turns out, has to happen on the surface of the fat droplets that DGAT1 helps synthesize; without DGAT1 activity, the fat droplets still form, but the viral protein cannot bind to them. The fat droplets "serve as assembly platforms in the cell," Ott said.
DGAT1 has several advantages that could make it a good candidate for therapeutic inhibition.
For one thing, though it appears to be critical for viral assembly, it is not irreplaceable for synthesis of the fat droplets themselves, which have important roles in cellular life. Another enzyme, DGAT2, takes over their synthesis of the fat droplets when DGAT1 is inhibited.
For another, DGAT1 inhibitors are already being tested in the arena of metabolic disorders. Pfizer Inc. completed several Phase I studies of a DGAT1 inhibitor it is developing for the treatment of diabetes earlier this year, and at least one additional trial is ongoing. Other companies also are working on inhibitors, which could obviously also be tested against hepatitis.
Ott's team is also interested in learning more about the biological function of DGAT1. DGAT1 and DGAT2 are "structurally very different, but biochemically very similar," Ott said. Taken together, the available data "point to DGAT1 as something very unique" â?? and from first biological principles, the enzyme's main function is surely not to enable the hepatitis C virus to ravage its owner's livers.

Monday, October 11, 2010

The American Association for the Study of Liver Diseases (AASLD) and the Trust for America's Health (TFAH) issue sobering report on HBV & HCV in America

Washington, DC -- September 27, 2010 -- The American Association for the Study of Liver Diseases (AASLD) and the Trust for America's Health (TFAH) issued a new report today calling for action to be taken to transform how the country deals with viral hepatitis -- to help identify millions of Americans who know they are living with chronic forms of hepatitis B and C and to assure access to treatment for all who need it, to prevent even more Americans from becoming infected.

Main Findings:
An estimated 65 to 75 percent of the five million Americans currently infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) do not even know they have the virus;

The Institute of Medicine (IOM) estimates that 150,000 Americans could die from liver cancer or end-stage liver disease associated with HBV or HCV in the next decade;

The death rate from HCV is expected to triple in the next 10 to 20 years;

An independent analysis found total medical costs for HCV patients could more than double over the next 20 years -- from $30 to $80 billion per year;

Liver cancer treatment can be more than $62,000 for the first year cost and the first-year cost of a liver transplant can be more than $267,000;

Two-thirds of HCV cases are Baby Boomers -- and if they are left untreated, it could lead to a major increase in upcoming Medicare spending;

One in 10 Asian and Pacific Islander Americans are estimated to have a chronic HBV infection;

An estimated 540,000 to 858,000 African Americans are estimated to have a chronic HCV infection;

Approximately 800 to 1,000 infants in the United States are infected with HBV at birth each year;

At least 100,000 patients have been notified about potential exposure to HBV, HCV, and/or HIV while receiving health care since 1998.

Some highlight recommendations from AASLD and TFAH in the report include:
HBV and HCV screening and HBV vaccination should be the standard of care in the reformed health system. All Americans should be screened for HBV and HCV and all Americans should be vaccinated for HBV;

All pregnant women should be screened for HBV and appropriate health measures should be taken to prevent perinatal transmission from infected mothers to their newborns. All newborns should receive their initial (birthdose) of hepatitis vaccine within twelve hours of birth;

Every person diagnosed with HBV or HCV should have access to and receive a minimum standardized level of care and receive support services;

Strong public education campaigns and improved surveillance must be put in place to help prevent new infections;

Policies must be established to ensure that health care associated hepatitis infections are treated as a "never event";

The investment in hepatitis-related biomedical and behavior must be significantly increased -- and should be more proportionate to the public health threat associated with hepatitis.


Download the full AASLD /Trust For America's Health report HBV & HCV America's Hidden Epidemicshere

Thursday, October 7, 2010

InterMune spins of Danoprevir development and commercialization rights to Roche...

Roche Pays InterMune $175M for Rights to Danoprevir

BioWorld Today - Oct. 07, 2010
$530M Deal Axed
InterMune Inc. reported late Wednesday that it sold worldwide development and commercialization rights to danoprevir (RG7227 or ITMN-191) to partner Hoffman-La Roche Inc. and F. Hoffman-La Roche Ltd., of Basel, Switzerland, for $175 million in cash.
In connection with the transaction, the collaboration agreement that Brisbane, Calif.-based InterMune and Roche entered into in October 2006, valued at a potential $530 million, has been terminated. In addition, the companies are actively exploring ways to continue their ongoing work together on other hepatitis C virus research programs. (See BioWorld Today, Oct. 18, 2006.)
With the net proceeds from the transaction, InterMune expects to have a cash balance of about $290 million at the end of 2010.
InterMune's Dan Welch, chairman, CEO and president, said the cash infusion will allow his company to "aggressively pursue" the registration and commercialization of pirfenidone, a drug that failed to win FDA approval as a treatment for idiopathic pulmonary fibrosis despite the strong backing of an agency panel of experts. (See BioWorld Today, May 5, 2010.)
The company's stock (NASDAQ:ITMN) lost 32 cents, to close at $13.45 Wednesday, but following the late-breaking news, was up as much as 9 percent in after-hours trading.

Tuesday, October 5, 2010

Bye, Bye Zalbin...

From the PharmaLive.com News Archive - Oct. 05, 2010
ROCKVILLE, Md.--(BUSINESS WIRE)--Oct 5, 2010 - Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that, as expected, it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the Company's Biologics License Application (BLA) for 900-mcg ZALBIN™ (albinterferon alfa-2b, known in Europe as JOULFERON®) dosed every two weeks for the treatment of chronic hepatitis C. HGS and Novartis have decided not to develop ZALBIN further.
HGS, Human Genome Sciences and ZALBIN are trademarks of Human Genome Sciences, Inc. Other trademarks referenced are the property of their respective owners.

Monday, October 4, 2010

Medivir Announces Publication of Five TMC435 Abstracts for Presentation at the 61st AASLD Meeting

Cision (English) - Oct. 01, 2010
Medivir Announces Publication of Five TMC435 Abstracts for Presentation at the 61st AASLD Meeting
 Including a Late-breaking Oral Presentation of 24-Week interim data of the TMC435 phase 2b PILLAR study Ë

Medivir AB (OMX: MVIR), a research-based speciality pharmaceutical company focused on infectious diseases, today announces that five abstracts related to its hepatitis C drug in development, TMC435, have been accepted for presentation at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place from 29 October â?? 2 November 2010 in Boston, USA. The abstracts have been published today and can be accessed on the AASLD website http://www.aasld.org  The accepted titles only are provided below. TMC435, a hepatitis C protease inhibitor, is being jointly developed by Medivir and Tibotec Pharmaceuticals.

At the meeting, in a late-breaking oral presentation, the results from a pre-planned Week 24 interim analysis of the ongoing Phase 2b PILLAR study of TMC435 will be presented. In this study, patients were dosed once-daily with TMC435 in combination with peg interferon a-2a (PegIFN) and ribavirin (RBV) in treatment naive patients infected with HCV genotype 1 (G1). 24-Week interim analysis data will be reported including rapid virologic response (RVR), complete early viral response (cEVR), sustained viral response rates after four weeks (SVR4), and twelve weeks (SVR12) respectively. Secondary endpoints, including the assessment of antiviral activity, viral breakthrough, safety and tolerability, and response rates in IL-28B genotypes, will also be presented.

Additionally, there will be four poster presentations shown at the meeting. Two poster presentations will describe the antiviral activity, safety, tolerability, and pharmacokinetics from a phase 2a open-label, proof-of-concept study of TMC435 in patients infected with HCV genotype 2 to 6.

The other two poster presentations will describe the virologic analysis of G1 infected patients following treatment with once-daily TMC435 in the phase 2a (OPERA-1) study and in vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters.

Accepted titles for Abstracts to be presented at the 2010 AASLD meeting are as follows:
Late Breaker Oral Presentation for presentation at Monday 1 Nov. 17:45 (EST): LB-5. Efficacy and safety of TMC435 in combination with peginterferon a-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study.

Poster Presentations: 278. In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters. To be presented: Saturday 30 Oct, 14:00 (EST). 812. Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study.â?? To be presented: Sunday 31 Oct, 08:00 (EST). 895. A Phase 2a, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2a.  To be presented: Sunday 31 Oct, 08:00 (EST). 1873. Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6. To be presented: Tuesday 2 Nov, 07:00 (EST).

Friday, October 1, 2010

Achillion Pharmaceuticals kicks off Phase II trial for ACH-1625 for HCV....

EquityBites - Oct. 01, 2010
Pharmaceutical company Achillion Pharmaceuticals Inc (Nasdaq:ACHN) revealed on Thursday that the company has initiated patient dosing in a Phase II clinical trial of ACH-1625 for the treatment of hepatitis C virus (HCV) infection.
The company added that ACH-1625 is a potent small molecule inhibitor of HCV protease, an enzyme necessary for viral replication.
This Phase IIa, randomised, double-blind, placebo-controlled trial will evaluate the safety, tolerability and antiviral activity of oral ACH-1625 in combination with pegylated interferon alfa-2a and ribavirin after 28 days of dosing and after 12 weeks of dosing in subjects with chronic hepatitis C virus genotype 1.
Additionally, the company stated that the trial will take place in the US and Europe and the data is anticipated in the first and fourth quarters of 2011, respectively.