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.

Inhibitex completes phase 1a trial of nucleotide polymerase inhibitor INX-189

Proof-of-Concept Trial in Patients with Chronic Hepatitis C Planned for Q4 2010

ATLANTA--(BUSINESS WIRE)--Sep 1, 2010 - Inhibitex, Inc. (Nasdaq: INHX), announced today that it has successfully completed a Phase1a, first-in-man, single ascending dose trial of INX-189, its nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C (HCV) infections. In this trial, 42 healthy volunteers received either a single oral dose of INX-189, ranging from 3 mg to 100 mg, or placebo. The Company plans to present detailed results from this trial during a future scientific meeting. Preliminary data from the trial are as follows:

• INX-189 was generally well tolerated at all dose levels;
• No drug-related serious adverse events;
• No dose-related trends in frequency or type of adverse events; adverse events occurring in more than one subject were headache and nasal congestion;
• No grade II or higher laboratory abnormality adverse events or clinically significant changes in ECGs; and
• Pharmacokinetic data supports INX-189's potential for once daily (QD) dosing.

“We are encouraged with the initial safety and pharmacokinetic profile of INX-189 in this first-in-man trial,” stated Dr. Joseph Patti, Senior Vice President and Chief Scientific Officer of Inhibitex, Inc. “Based upon the pharmacokinetics observed in this study, we continue to believe that INX-189 has the potential to demonstrate antiviral activity with a low once-daily dose, and we look forward to assessing its ability to reduce HCV RNA viral loads in patients with chronic hepatitis C in a Phase 1b multiple ascending dose trial we plan to start in the fourth quarter.”

About Inhibitex

Inhibitex, Inc., headquartered in Alpharetta, Georgia, is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company's pipeline includes FV-100, which is in Phase II clinical development for the treatment of shingles, and INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections. The Company also has additional HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM^® protein platform to Pfizer for the development of staphylococcal vaccines. For additional information about the Company, please visit www.inhibitex.com.

Pharmasset Announces Submission of Abstracts to AASLD Liver Meeting Including an Interim Analysis of Roche's Phase 2b PROPEL Trial of RG7128

PRINCETON, N.J., June 9, /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that the interim results from the PROPEL study conducted by its partner Roche demonstrate that RG7128 triple combination therapy was safe and well tolerated. In that study, the safety profile of RG7128 (1000mg BID or 500mg BID), when administered for 8 or 12 weeks with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin), the standard of care (SOC), was similar to the safety profile of SOC alone. An interim analysis of the study included all safety data from all 408 patients who had completed the first 12 weeks of the study.  The most common adverse events were no different than those frequently noted with SOC alone. There were no findings related to rash, anemia, bone marrow suppression, or nephrotoxicity across any of the arms. 

The PROPEL study is evaluating the dose and duration of treatment of RG7128 in combination with SOC in patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 4 who have not been treated previously. The interim analysis also included on-treatment efficacy data demonstrating that >80% of patients had undetectable HCV RNA in all cohorts receiving the 12-week triple regimen compared to <50% for the placebo/SOC cohort. The safety and efficacy results from the interim analysis of the PROPEL Phase 2b study of RG7128 have been submitted by Roche as an abstract to AASLD for the Annual Liver Meeting (October 29 to November 2, 2010). The title of the abstract is:

"High rates of early viral response, promising safety profile and lack of resistance-related breakthrough in HCV GT 1/4 patients treated with RG7128 plus PegIFN alfa-2a (40KD)/RBV: Planned Week 12 interim analysis from the PROPEL study" 

"We are encouraged by the reported efficacy, safety, and resistance data from this interim analysis of the PROPEL study," said M. Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "We believe safety, absence of resistance, as well as antiviral potency will all be important considerations as HCV treatment incorporates direct acting antivirals in combination with interferon, and in potential interferon-free antiviral combination regimens."

No viral rebounds or resistance-related breakthroughs were noted during the first 8 or 12 weeks of triple combination therapy, consistent with the demonstrated high barrier to resistance in earlier RG7128 clinical studies.  In clinical reports to date, the S282T mutation associated with RG7128 resistance in vitro has not been detected at baseline in HCV-infected patients enrolling in clinical trials. A separate abstract has been submitted by Roche including details of the resistance analyses that have been conducted during this study, including sequencing of the HCV RNA from all patients at baseline. The abstract is entitled:

"No evidence of drug resistance or baseline S282T resistance mutation among GT1 and GT4 HCV infected patients on nucleoside polymerase inhibitor RG7128 and Peg-IFN/RBV combination treatment for up to 12 weeks: interim analysis from the PROPEL study."

About the Phase 2b PROPEL Study

The Phase 2b study enrolled 408 patients with HCV genotypes 1 or 4, cirrhotic and non-cirrhotic, who have not been treated previously. The primary efficacy endpoint of the study is the proportion of patients who achieve an SVR, defined as HCV below the limit of detection (<15 IU/mL as measured by Roche TaqMan assay) 24 weeks after completion of all treatment. The study is being conducted in North America, Europe, and Australia. Patients were enrolled into one of 5 arms:

• 24 weeks of total treatment;  RG7128 500mg BID in combination with SOC for 12 weeks, followed by 12 weeks of SOC ("12+12", RVR guided)
• 24 weeks of total treatment; RG7128 1000mg BID in combination with SOC for 12 weeks, followed by 12 weeks of SOC ("12+12", RVR guided)
• 24 weeks of total treatment; RG7128 1000mg BID in combination with SOC for 8 weeks, followed by a further 16 weeks of SOC ("8+16", RVR guided)
• 48 weeks of total treatment; RG7128 1000mg BID in combination with SOC for 12 weeks, followed by a further 36 weeks of SOC ("12+36", non-RVR guided")
• A control arm with SOC for 48 weeks.

Patients in the 24-week arms will discontinue all treatment at week 24 if they have achieved RVR, defined as HCV RNA below the limit of detection (<15 IU/mL) at week 4 and maintain these low levels of HCV RNA until week 22, a strategy known as "RVR-guided" treatment. Patients who do not meet these criteria will continue on the standard of care until week 48. 

RG7128 is also currently being evaluated in a Phase 2b study in which RG7128 and SOC are given for a total of 24 weeks each ("24+0", RVR guided). The regimen will be assessed in treatment-naive HCV-infected patients with genotypes 1 or 4.  Enrollment in this study was completed in early May.  In addition, Roche anticipates the initiation of another Phase 2 study in HCV-infected patients with genotypes 2 or 3 by the end of 2010.