Sunday, November 23, 2014

Locally grown GMO corn used in effort to produce hepatitis B vaccine

A local firm aims to make a hepatitis B vaccine but draws opposition from using genetically modified corn

John A. Howard of Cayucos has an ambitious, even noble goal — to produce an affordable and easy-to-administer vaccine for hepatitis B.

But there is one problem.

In order to produce this vaccine, Howard, 63, and his Cal Poly-based firm Applied Biotechnology Institute are experimenting with genetically engineered corn that he hopes will contain the traits for a hepatitis B vaccine.


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Thursday, November 13, 2014

Drug Combo Disappoints in Hepatitis B

BOSTON -- A drug combination cured only a small fraction of patients with chronic hepatitis B (HBV), a researcher said here.

After 48 weeks of treatment with tenofovir (Viread) and pegylated interferon, fewer than one patient in 10 lost the HBV surface antigen (HBsAg), the gold standard for cure of the virus, according to Joerg Petersen, MD, PhD, of the University of Hamburg in Germany.

But that was significantly better than either drug alone or a shorter combination of the two, Petersen reported at the American Association for the Study of Liver Diseases annual meeting.


Arrowhead's midstage hep B data shows promise for RNA-based 'functional cure'

RNA interference specialist Arrowhead ($ARWR) presented new data from an ongoing Phase IIa study of its hepatitis B treatment ARC-520, demonstrating a reduction of the disease's surface antigens in what the company says is a first for RNAi.

Arrowhead has been chugging along on its hepatitis B candidate, which makes use of the company's delivery system designed to overcome the vast challenges associated with RNAi. Last year, CEO Christopher Anzalone told FierceDrugDelivery that the polymer-based platform stands apart from other RNA platforms due to its ability to release the genetic material, what they term "endosomal escape." The company's Dynamic Polyconjugate approach allows for a "masking" and "unmasking" process that protects the RNA as it enters the cell, but also allows it to perform its interference duty once inside.

The new human data for ARC-520 showed significant reduction of the hepatitis B surface antigen (HbsAg), according to Arrowhead, as compared to placebo for up to 85 days, with the lowest point at about a month after dosing in the 54-patient study. Back in March, the company called its candidate a "functional cure" due to the presence of an "immunological flare" in primate studies.

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Wednesday, November 12, 2014

Tenofovir Plus Interferon Improves Antigen Clearance in Chronic Hepatitis B

Treatment with a combination of tenofovir and pegylated interferon yielded higher rates of hepatitis B surface antigen (HBsAg) loss than when either drug was used singly. Further, with longer therapy duration improved results. Jörg Petersen, MD, PhD, Director of the Liver Institute at IFI Institute for Interdisciplinary Medicine, University of Hamburg, presented findings from an international multicenter study of chronic hepatitis B (CHB) patients during The Liver Meeting 2014 in Boston, MA.

Speaking on November 10 to an overflow plenary session, Petersen noted that loss of HBsAg is associated with better outcomes and is considered the gold standard for successful CHB treatment. However, treatment either with nucleoside/nucleotide analogs (NAs) or pegylated interferon (PEG) yields low HBsAg loss rates, and previous studies of NA+PEG regimens have not been sufficiently powered to examine the HBsAg loss question.

Overall, Petersen noted, though HBsAg loss rates remained low, the study helped clarify that the well-tolerated combination of TDF + PEG for a full 48 weeks resulted in significantly higher rates of HBsAg loss than either monotherapy for this patient population. 16 weeks of TDF + PEG produced a lower HBsAg loss rate than the longer course of the combination, so both duration of treatment and combination treatment play into the increased rate of HBsAg loss.

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Tuesday, November 11, 2014

Hepatitis B Virus Testing Gets Short Shrift at VA

BOSTON -- Testing, treatment and surveillance of patients who are infected with hepatitis B virus (HBV) and are treated at the nation's Veterans Affairs Medical Centers appear to be "suboptimal," researchers reported here.

In reviewing the patient records of 21,828 patients at these facilities who tested positive for HBV infection, Marina Serper, MD, of the Philadelphia VA Medical Center/University of Pennsylvania, determined that:
  • 73% underwent liver function tests.
  • 56% received a diagnosis.
  • 31% were referred to a specialist.
  • 26% had DNA analyses performed.
  • 25% received antiviral treatment.
  • 13% were screened for hepatocellular cancer.

Monday, November 10, 2014

Arrowhead Presents Data on ARC-520 and ARC-AAT at AASLD The Liver Meeting® 2014

       - ARC-520 shows statistically significant reduction in HBsAg through day 43 after a single injection (p < 0.05)
- Repeat dosing of ARC-AAT in primates shows reduction of approximately 90% of serum alpha 1 antitrypsin (AAT) with long duration of effect suggesting that monthly or less frequent dosing may be sufficient for sustained suppression of hepatic AAT production
- ARC-AAT abstract highlighted in the AASLD President’s Press Conference as a promising new treatment
- Arrowhead will host an investor event and presentation to discuss results that will be webcast at 8:00 p.m. EST

AASLD 2014

PASADENA, Calif.--()--Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that initial data from the ongoing Phase 2a study of ARC-520, its RNAi therapeutic candidate for the treatment of chronic hepatitis B (HBV) infection, was presented today in the late-breaking poster session at the 2014 American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Boston. Arrowhead also delivered a plenary presentation with new preclinical efficacy data on ARC-AAT, its RNAi therapeutic candidate for the treatment of liver disease associated with Alpha-1 antitrypsin deficiency.
“A hepatocyte-targeted RNAi-based treatment for liver disease associated with alpha-1 antitrypsin deficiency”
The Company will host an investor event and presentation to discuss these results that will be webcast tonight at 8:00 p.m. EST. Investors may access the webcast and presentation slides on the Events page of the Company’s website at An audio only version of the live webcast may also be accessed by calling 844-825-4406 toll-free from the U.S., or 315-625-3230 for international callers, using conference ID 31449966. An archive of the call will be available for seven days and may be accessed by calling 855-859-2056 or 404-537-3406. Copies of the AASLD poster and plenary presentation will also be available to view on the Events page of the Company’s website.

“We presented some important advancements today for both ARC-520 and ARC-AAT,” said Christopher Anzalone, Ph.D., Arrowhead’s President and Chief Executive Officer. “These programs and our expanding pipeline of RNAi therapeutics continue to generate exciting data that further validate the utility of the DPC delivery system. We have seen clear activity across multiple preclinical models and are now seeing activity in humans. We are still dose escalating in the ARC-520 Phase 2a, where dosing is complete in the 3 mg/kg cohort and screening has begun for 4 mg/kg. We believe that the initial data from the first two dose cohorts as well as safety data from the Phase 1 volunteer study are encouraging and support advancement of the program into multi-dose Phase 2b studies. We are currently preparing regulatory filings for the ARC-520 Phase 2b and the ARC-AAT Phase 1, both of which we expect to be filed this quarter. We intend to initiate those studies soon after receiving regulatory permission to begin.”

ARC-520 Data
In a Late-Breaking Poster titled, “Phase II, dose ranging study of ARC-520, a siRNA-based therapeutic, in patients with chronic hepatitis B virus infection,” interim data on ARC-520 was presented by Man-Fung Yuen, M.D., Ph.D., Chair of Gastroenterology and Hepatology, and Li Shu Fan Medical Foundation Professor in Medicine, The University of Hong Kong, and a principal investigator for the study. The poster included up-to-date safety data on ARC-520 from this study, an ongoing Phase 2a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study, as well as a recently completed Phase 1 normal volunteer study.

The nine dose group, Phase 1, normal volunteer trial was designed to characterize the safety profile of ARC-520 across a range of doses and evaluate pharmacokinetics. It was a single-center, randomized, double-blind, placebo-controlled, single dose-escalation, first-in-human study of ARC-520 administered intravenously to healthy adult volunteers for which partial data has been previously reported. All subjects received either placebo or ARC-520 in doses ranging from 0.01 mg/kg to 4.0 mg/kg. The study successfully enrolled all 54 subjects (36 received ARC-520, 18 placebo). The Phase 2a study has enrolled three dose cohorts including 24 patients, 18 receiving drug and 6 receiving placebo. Unblinded data is available for the first two cohorts. Cohort 3 data collection is ongoing and this cohort remains blinded. Full results for the first two dose cohorts at 1.0 mg/kg and 2.0 mg/kg and partial (blinded) safety results from the 3.0 mg/kg dose cohort were included in the poster.

In both studies, there have been no reports of serious AEs, no dose limiting toxicities, no discontinuations due to AEs, and a modest overall occurrence rate of AEs without a clear dose-related increase in frequency or severity. There has been a modest occurrence rate of non-clinically significant abnormal laboratory tests. There were no reported drug related or clinically significant differences for vital signs or ECGs between subjects receiving drug versus placebo. To date, ARC-520 when administered as a single dose up to 4.0 mg/kg to healthy volunteers and up to 3.0 mg/kg to patients with chronic HBV appears to be well tolerated.

Arrowhead also reported initial results for depth and duration of hepatitis B surface antigen (HBsAg) reduction in the Phase 2a study. In cohort 1 (1.0 mg/kg), the mean nadir of HBsAg was -39% (range -22 to -57) with a mean change on day 85 of -31% (range -14 to -39). In cohort 2 (2.0 mg/kg), the mean nadir of HBsAg was -51% (range -46 to -59) with a mean change on day 85 of -22% (range -7 to -40). For cohort 2, the percent reduction in HBsAg was statistically significant versus placebo (p < 0.05) for days 3 through 43 post-dose. For cohort 2, the mean day of HBsAg nadir was day 33 with a range of day 8 to day 57.

Arrowhead believes that this is the first time that a reduction in HBsAg mediated through RNA interference has been demonstrated in patients with chronic HBV infection. This study is ongoing with follow up continuing on Cohort 3 (3.0 mg/kg) and recruitment underway for a fourth cohort of patients at 4.0 mg/kg.

Preparations are underway to initiate a series of multi-dose Phase 2b studies of ARC-520, for which the Company plans to file with regulatory authorities in the fourth quarter of 2014. These studies are planned to have clinical sites in the US, Western Europe, Asia, and potentially other countries and/or regions. Several studies are currently contemplated, including ARC-520 in combination with entecavir or tenofovir as well as combination studies that add an immunostimulatory agent.

Arrowhead also presented data on ARC-AAT, its clinical candidate for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. These patients synthesize a mutant form of AAT (Z-AAT) in the liver which is poorly secreted and accumulates, resulting in liver injury. The goal of treatment with ARC-AAT is to silence production of Z-AAT thereby preventing further accumulation of Z-AAT in the liver and potentially reversing pre-existing liver injury and fibrosis.

The presentation in the prestigious Plenary Session titled, “A hepatocyte-targeted RNAi-based treatment for liver disease associated with alpha-1 antitrypsin deficiency,” was presented by Christine Wooddell, Ph.D., Group Leader, Arrowhead Research. AASLD President Dr. Adrian Di Bisceglie, MD, FACP also highlighted the presentation, along with just ten others, in the President’s Press Conference as a program that holds great promise for patients.

In preclinical studies with PiZ mice, which are genetically modified to produce the mutant human AAT (Z-AAT), ARC-AAT induced a greater than 95 percent reduction in circulating AAT after a single dose with a long duration of effect. Area covered by Z-AAT globules and globule size within the liver were significantly reduced after a single dose of ARC-AAT at day 15 post-dose (p < 0.005) and day 29 post-dose (p < 0.01). Multi-dose studies in PiZ mice showed that ARC-AAT was effective at reducing and preventing Z-AAT aggregates in the liver. At week 13 of the study, after 4 biweekly doses, the ARC-AAT treated group show 99% less soluble (monomer) Z-AAT and 79% less insoluble (polymer) Z-AAT, normalized to a saline control group. Thus, injection of ARC-AAT in transgenic mice expressing human Z-AAT resulted in prevention and reduction of Z-AAT globules and, importantly, liver inflammation.

In primate studies, a 90% reduction of AAT in serum was observed after a single injection, which persisted for over ten weeks with greater than 80 percent knockdown observed at the six-week time point. Multi-dose studies in primates showed a sustained reduction of AAT with once every six weeks dosing, suggesting that once monthly or less frequent dosing may be sufficient to maintain approximately 80-90% knockdown in humans. The treated animals showed no changes in clinical chemistry (ALT, AST, BUN, Creatinine), indicating that ARC-AAT appeared to be well tolerated at these optimal therapeutic dose levels.

About ARC-520
Arrowhead’s RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. The siRNAs in ARC-520 intervene at the mRNA level, upstream of where nucleotide and nucleoside analogues act. In transient and transgenic mouse models of HBV infection, a single co-injection of Arrowhead’s Dynamic Polyconjugate (DPC) delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. Arrowhead has completed enrollment in a Phase 1 single ascending dose study in normal volunteers. The company is conducting a single dose Phase 2a study in chronic HBV patients, and expects to follow with multi-dose, multi-national Phase 2b studies. Approximately 350 million people worldwide are chronically infected with the hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally.

Arrowhead has developed ARC-AAT for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. ARC-AAT employs a novel unlocked nucleobase analog (UNA) containing RNAi trigger molecule designed for systemic delivery using the Dynamic Polyconjugate delivery system. ARC-AAT is highly effective at knocking down the Alpha-1 antitrypsin (AAT) gene transcript and reducing the hepatic production of the mutant AAT (Z-AAT) protein. Reduction of liver production of the inflammatory Z-AAT protein, which has been clearly defined as the cause of progressive liver disease in AATD patients, is important as it is expected to halt the progression of liver disease and potentially allow fibrotic tissue repair. The Company plans to file with regulatory authorities in the fourth quarter of 2014 and commence clinical studies shortly after receiving permission to begin.

About Arrowhead Research Corporation
Arrowhead Research Corporation is a biopharmaceutical company developing targeted RNAi therapeutics. The company is leveraging its proprietary Dynamic Polyconjugate delivery platform to develop targeted drugs based on the RNA interference mechanism that efficiently silences disease-causing genes. Arrowhead’s pipeline includes ARC-520 for chronic hepatitis B virus, ARC-AAT for liver disease associated with Alpha-1 antitrypsin deficiency, and partner-based programs in obesity and oncology.

For more information please visit, or follow us on Twitter @ArrowRes. To be added to the Company's email list and receive news directly, please visit
Source: Arrowhead Research Corporation


Arrowhead Research Corporation
Vince Anzalone, CFA
Investor Relations:
The Trout Group
Lauren Glaser
Russo Partners
Martina Schwarzkopf, Ph.D.

Press Release Source:

Novira Therapeutics Announces Presentation of Phase 1a Safety and Pharmacokinetic Data for NVR 3-778

Phase 1b Clinical Studies Ongoing in Patients with Chronic HBV Infection

DOYLESTOWN, Pa., Nov. 10, 2014 /PRNewswire/ -- Novira Therapeutics, Inc., a privately held biopharmaceutical company developing novel therapies for curative treatment of chronic hepatitis B virus (HBV) infection, today announced the presentation of Phase 1a safety and pharmacokinetic data for its lead HBV antiviral candidate, NVR 3-778 (also known as NVR-1221), in a late-breaking poster presentation at the 2014 annual meeting of the American Association for the Study of Liver Diseases in Boston. Dr. Edward J. Gane, Chief Hepatologist and Deputy Director of the New Zealand Liver Transplant Unit at Auckland City Hospital in Auckland, New Zealand is the lead author on the poster and the principal clinical investigator for the study.

The randomized, placebo-controlled Phase 1a trial enrolled 40 healthy adult volunteers to assess the safety and tolerability of NVR 3-778 after single oral doses of 50 to 800 mg/day, followed by an assessment of 200 mg once-daily dosing for 14 days. The study results indicated that NVR 3-778 was well-tolerated at all doses. There was no pattern of treatment-related or dose-related clinical adverse events (AEs), and no serious or severe AEs. All AEs were of common types, and most were not attributed to study drug treatment. The AEs were all transient and mild (grade 1) in severity except for two grade 2 AEs not attributed to study treatment (sprain and tooth pain). The pharmacokinetic profile of NVR 3-778 indicated substantial dose-related plasma levels that were consistent across the subjects within each dosing cohort. At doses of 200 mg or more, plasma concentrations of NVR 3-778 remained above in vitro HBV-inhibitory concentrations for more than 24 hours, supporting evaluation of once-daily dosing in HBV patients.

"These encouraging Phase 1a results indicate that NVR 3-778 was well-tolerated at all dose levels in human volunteers, and once-daily doses of 200 mg or more provided systemic levels of NVR 3-778 high enough to potentially be associated with antiviral efficacy in hepatitis B patients," said Nathaniel Brown MD, Novira's Chief Medical Officer. "The Phase 1a results support advancement to Phase 1b testing in patients with chronic HBV infection, which is now underway. The Phase 1b clinical study is designed to evaluate the safety and antiviral efficacy of NVR 3-778 in HBV patients as both a single agent and in combination with current HBV therapies after a four week dosing period."

About NVR 3-778
NVR 3-778 is a small molecule, direct acting antiviral, for oral administration in patients with Chronic Hepatitis B (CHB) that inhibits the HBV core or capsid protein. HBV core is a novel and promising drug target with multiple activities required for viral replication and persistence. Inhibition of HBV core protein function by NVR 3-778 offers the potential for more efficient suppression of the virus leading to improved durable viral suppression and functional cure rates.

About Novira Therapeutics
Novira Therapeutics, Inc., is a privately held biopharmaceutical company focused on discovery and development of first-in-class antiviral drugs for the treatment of chronic HBV infection (CHB), a global disease with a high level of unmet medical need. The company is employing innovative chemistry and biology technologies to discover small molecule inhibitors of the HBV core or capsid protein as well as other drugs with novel mode of action. The company's novel antivirals will offer the potential to address the limitations of current CHB therapies when used either as mono-therapy or in combination with existing standards of care.

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SOURCE Novira Therapeutics, Inc.

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