Hepatitis C patients petition for life-saving drug combination

by Wendy Rigby / KENS 5

Posted on June 28, 2012 at 3:26 PM Updated today at 3:59 PM

SAN ANTONIO -- South Texas patients with hepatitis C virus (HCV) have launched a petition to speed up development of some promising new drugs. They believe a pharmaceutical company is putting profits ahead of people.

Hepatitis C is a virus that attacks the liver. It’s the number one reason for liver transplants in the U.S. It kills more people than AIDS.

Margaret Dudley, 61, of San Antonio is a woman on a mission. More than a decade ago, she had permanent cosmetic tattooing. Last fall, she was tested for hepatitis C, a deadly disease she believes she contracted from the tattoos.

“You know, I had no idea,” Dudley said. “I had no reason to think it would come back positive, but it did.”

HCV hides out in the liver. Over the years, cysts form and scar tissue forms causing cirrhosis or hardening of the liver. Tumors can develop and the liver can fail.

Two promising pills from two different drug makers showed a 100 percent cure rate in early clinical trials when combined. GS-7977 is made by Gilead. Daclatasvir is from Bristol-Myers Squibb. But the companies have each invested millions and cannot agree on moving forward to get the winning combination to patients which could save their lives.

“So that’s basically what me and millions of others have been waiting for,” Dudley commented. “We started this petition asking Gilead Sciences to please go forward in these trials. We’re asking them to put best patient health before profits.”

Dudley has turned into a patient activist, using her voice to speak for four million Americans, mostly baby boomers, infected with this insidious disease.

She has 3,000 signatures on her online petition so far. She says public pressure may spark the pharmaceutical companies to keep going with clinical trials.

Dudley’s goal is to gather 100,000 signatures by July 28, 2012, which is World Hepatitis Day.

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Hepatitis B and Liver Cancer Among Asian Americans

By Jeffrey Norris on June 20, 2012

Liver cancer is expected to become more common in the United States in coming years. “It’s deadly and it’s preventable,” says UCSF physician and researcher Tung Nguyen, MD.

The cause of more than eight in 10 liver cancers in the United States is chronic infection with the hepatitis B or hepatitis C virus. Today the number of new hepatitis infections is declining. But just as there has been a lag between the decline in smoking and the drop in lung cancers, it may take many years before the trend toward fewer hepatitis cases and better hepatitis treatments leads to fewer liver cancers instead of more.

UCSF and Hepatitis

• Hepatitis — UCSF and San Francisco at Ground Zero
• Hepatitis C — Urgency to Fight Viral Foe Grows in the Suburbs and on the Streets
• Students Vaccinate Against Hepatitis B in Chinatown

Nguyen — who emigrated as a child from Vietnam — is fighting hepatitis in Bay Area Asian American communities. Through outreach and training of key community members and through campaigns in ethnic media, Nguyen and his collaborators aim to help reverse the US liver cancer trend as quickly as possible.

Hepatitis B Is Common

Why focus on Asian Americans? Hepatitis B is common in many parts of the globe, including Asia. Because of this, liver cancer is the third most common cause of cancer death worldwide. Immigrants from Asian countries are infected at high rates. So too are their children. For instance, in San Francisco, where according to the 2000 census nearly one in three people is Asian or of Asian ancestry, an estimated one in 10 Chinese is infected with hepatitis B.

Today in the United States, hepatitis C mainly is spread by IV drug users sharing needles. There is not yet a commercially available vaccine. On the other hand, there are vaccines to prevent hepatitis B infection. The vaccine strategy originated with pioneering research at UCSF. Children in the United States now are routinely vaccinated early.

But mothers can easily pass hepatitis B to their children in the womb. This is the major source of existing hepatitis infections in the U.S. Asian American community, Nguyen says. In addition, many children who immigrate to the United States miss school vaccinations and risk becoming infected later.

While most adults clear the hepatitis B virus without becoming chronically infected, most infants do not. Once infection becomes chronic, treatment can help control the virus, but chronic infection lasts a lifetime.

Only a minority infected with hepatitis go on to develop liver cancer. But because so many in Asian communities already are infected at birth, Nguyen explains, some are developing liver cancer in their 30s or even in their 20s. Increasing liver cancer screening among people who test positive for hepatitis is an important outreach goal, Nguyen notes.

Disease Is Often Symptomless

Hepatitis often has no symptoms. “Some people get vaccinated without getting tested first to see if they already have been infected,” Nguyen says. “They think they are protected, when in reality they already may be infected, and infecting others.”

In addition to serving on the President’s Advisory Commission on Asian Americans and Pacific Islanders, Nguyen is a partner in a San Francisco Department of Public Health program to combat hepatitis B. The aim of “San Francisco Hep B Free” is to screen, vaccinate and treat all Asians and Pacific Islanders who live in the city, in part by providing free or low-cost testing.

Nguyen also directs the Vietnamese Community Health Promotion Project through which he and his colleagues have targeted the community with messages via radio, television, print publications and online media. Vietnamese in the United States have the highest rate of liver cancer, about 11 times higher than the rate among whites.

Source

Idenix Announces Positive Clinical Data for HCV Drug Candidates IDX184 and IDX719

June 19, 2012

In an Interim Analysis From an Ongoing Phase IIb Clinical Trial of IDX184, an HCV Nucleotide Inhibitor, 89% of Patients Who Completed an Additional 12 Weeks of Pegylated Interferon Plus Ribavirin Treatment Achieved SVR4; 100% (4/4) in 100 mg Arm and 80% (4/5) in 50 mg Arm

IDX719, an HCV NS5A Inhibitor, Achieves Potent Pan-Genotypic Activity in Three-Day Proof-of-Concept Clinical Trial

CAMBRIDGE, Mass., June 19, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced results from an ongoing phase IIb study of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV). Of the first cohort of 31 patients enrolled in the study, those who achieved an eRVR (n=18), defined as having undetectable levels of virus at 4 weeks and 12 weeks, were randomized to stop treatment after either an additional 12 weeks (n=9) or 36 weeks (n=9) of PegIFN/RBV. Of the nine patients who completed their 12-week PegIFN/RBV extended treatment phase, 100% of patients (4/4) in the 100 mg arm and 80% of patients (4/5) in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment (SVR4). Patients who did not achieve an eRVR automatically entered the 36-week PegIFN/RBV extended treatment phase which is ongoing. To date, the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegIFN/RBV alone.

"We are encouraged by the initial SVR results from the phase IIb program, which have confirmed previous data showing that IDX184 is a potent nucleotide inhibitor with a profile supporting its potential role as a key component of all-oral direct-acting antiviral (DAA) combination regimens for HCV," stated Ron Renaud, President and Chief Executive Officer of Idenix. "We look forward to initiating interferon-free DAA combination studies in the near term."

IDX184 Phase IIb Study Design

In July 2011, the company initiated enrollment of treatment-naive genotype 1 HCV-infected patients into a randomized, double-blind, parallel group phase IIb clinical trial of IDX184. The study features two treatment arms, either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with PegIFN/RBV. Response-guided therapy was used to complete an additional 12 or 36 weeks of PegIFN/RBV treatment. Study objectives include safety and tolerability, and antiviral activity endpoints.

IDX719 Proof-of-Concept Clinical Trial Data and Study Design

Idenix also announced today positive data from a three-day proof-of-concept study evaluating IDX719, an NS5A inhibitor, in 64 treatment-naïve, genotype 1, 2, 3 or 4 HCV-infected patients. Genotype 1 patients were randomized to receive placebo, 25 mg QD (once-daily), 50 mg QD, 50 mg BID (twice-daily) or 100 mg QD for three days. Genotype 2, 3 or 4 patients were randomized to receive placebo, 50 mg BID or 100 mg QD for three days.

IDX719 was well tolerated with no serious adverse events reported. Treatment with IDX719 exhibited potent pan-genotypic activity across genotypes:

• In genotype 1 patients (n=28), mean maximal viral load reductions were 3.2 log₁₀ IU/mL in the 25 mg QD arm, 3.7 log₁₀ IU/mL in the 50 mg QD arm, 3.2 log₁₀ IU/mL in the 50 mg BID arm and 3.5 log₁₀ IU/mL in the 100 mg QD arm.
• In genotype 2 patients (n=8), the mean maximal viral load reduction was 2.0 log₁₀ IU/mL in both the 50 mg BID and 100 mg QD dose arms with a greater variability in responses among these patients (range: 0.3 — 4.1 log₁₀ IU/mL). The company is currently conducting pharmacokinetic and sequencing analyses to further characterize these results.
• In genotype 3 patients (n=8), mean maximal viral load reductions were 3.3 log₁₀ IU/mL in the 50 mg BID arm and 3.4 log₁₀ IU/mL in the 100 mg QD arm.
• In genotype 4 patients (n=7), mean maximal viral load reductions were 3.9 log₁₀ IU/mL in the 50 mg BID dose arm and 3.4 log₁₀ IU/mL in the 100 mg QD dose arm.

More detailed findings are expected to be presented at a scientific meeting in the second half of 2012.

"We are pleased to demonstrate the first clinical validation of IDX719 in patients in a multiple-dose study with robust activity across multiple HCV genotypes," commented Douglas Mayers, M.D., Chief Medical Officer of Idenix. "Given these promising findings, we look forward to initiating a phase II combination study of IDX719 with IDX184 by the end of this year."

ABOUT IDX184

IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. In the ongoing phase IIb clinical trial, IDX184 has been well tolerated with a side effect profile similar to that of PegIFN/RBV. In the first cohort of 31 patients, at 12 weeks in an intent-to-treat analysis, the complete early virologic response ( < 25 IU/mL at 12 weeks) was 93% for the 100 mg IDX184 arm (n=15) and 81% for the 50 mg IDX184 arm (n=16) of the study. The company completed enrollment of a second cohort of 36 additional patients in May 2012.

ABOUT IDX719

IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. In 36 healthy volunteers, IDX719 was safe and well tolerated at single doses of 5-100 mg as well as multiple doses of 100 mg for 7 days. Single doses of IDX719 demonstrated potent pan-genotypic antiviral activity in 18 genotype 1, 2 or 3 HCV-infected patients, with greater than 3 log₁₀ viral load reductions achieved in the 100 mg dose arm.

ABOUT HEPATITIS C

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

ABOUT IDENIX

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

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX184 or IDX719 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; the likelihood and success of any future clinical trials involving our drug candidates; and expectations with respect to future milestone or royalty payments, funding of operations and future cash balances. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the Company's dependence on its collaboration with Novartis; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2011 and quarterly report on Form 10-Q for the quarter ended March 31, 2012, each as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

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

Source: Idenix Pharmaceuticals

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Flamel Technologies Medusa(R)-Formulated Interferon-Alpha Demonstrates Favorable Antiviral Activity and Safety in a Phase 2 Clinical Study

PRESS RELEASE

June 25, 2012, 8:31 a.m. EDT

Completion of Enrollment Reached in Its On-Going Phase 2 Clinical Study

LYON, FRANCE, Jun 25, 2012 (MARKETWIRE via COMTEX) -- Flamel Technologies today announced that its Medusa-formulated interferon-alpha ("IFN a-2b XL") was featured in a lecture and an oral presentation on June 25 at the 14th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD) held June 22-25, 2012 in Shanghai, China. The abstracts are entitled "Aggregate report on safety and efficacy of a new sustained release IFN (IFN XL) as compared to standard of care" and "Medusa formulated Interferon-alpha-2b Shows a Favorable Efficacy / Tolerability Profile vs. PEGylated IFN-alpha-2b in Hepatitis C Patients in the Phase 2 Study ANRS HC23 COAT-IFN." The abstracts presented by Professor Christian Trepo of Hopital de la Croix Rousse, Lyon, France, and Roger Kravtzoff, Preclinical and Clinical Director at Flamel Technologies, demonstrated a favorable antiviral activity and safety profile as compared with ViraferonPeg(TM) (marketed in the U.S. as PegIntron(TM)).

The abstracts presented the background, rationale and design of the on-going studies which are evaluating the therapeutic potential and safety of Flamel's Medusa-formulated IFN a-2b XL, a long acting, unmodified (in contrast to PEGylated interferons), fully active interferon injected once weekly in patients with chronic hepatitis C virus ("HCV") infection. The full presentation is available on Flamel's website at http://www.flamel.com/technology-platforms/medusa/ .

In addition, Flamel Technologies announced that it has reached its enrollment objective of 84 patients in its ongoing Phase 2 clinical study: ANRS HC23 COAT-IFN.

The principal investigator of the study, Professor Christian Trepo, remarked, "Preliminary results of this Phase 2 study are very consistent with those of Phase 1 and support the proof of concept of an improved tolerance without loss of efficacy of IFN XL. We believe this fulfills one of the most awaited needs for a future combination therapy."

Mike Anderson, Flamel's chief executive officer, stated, "Within the next five years, the number of HBV/HCV patients treated is expected to grow. In this context, the development of a new interferon formulation with good efficacy and better tolerance will be an important factor in hepatitis C treatment. Our formulation of Interferon-Alpha XL, a long acting formulation of Interferon-Alpha, is one of our more important development programs and is an example of the potential of the Medusa platform to improve the safety and efficacy of therapeutic proteins. In addition to seeing positive clinical data with our Medusa-formulated product candidate, we are grateful for the commitment of our clinical investigators to this important work and we look forward to their on-going participation in the trial."

Phase 2 Study Design 84 HCV patients have been treated in the on-going Phase 2 clinical study, randomized, three parallel-arm, comparative, open-label, multi-center study and were allocated to either IFN-a-2b XL, or PegIntron 1.5 ug/Kg, both in combination with weight based Ribavirin. Patients were each injected over a twelve-week period to compare the therapeutic potential and safety of IFN-a2b XL versus PegIntron in patients with chronic hepatitis C virus (HCV) infection (genotypes 1 and 4). This study was conducted on both naive and non-responder patients.

This Phase 2 clinical study is sponsored by Inserm-ANRS (French National Institute of Health and Medical Research -- French National Agency for Research on AIDS and Viral Hepatitis).

Summary of Results In the Phase 2 clinical study, the Medusa-formulated IFNa-2bXL at 27MIU has demonstrated a remarkably consistent safety profile across all available data. Improved tolerability of IFNa-2bXL was obtained in addition to good efficacy since the antiviral activity of IFNa-2bXL appears at least similar to that of reference Peg-IFNa-2b in a 3-month course of combined therapy.

Safety and Tolerability The available study data confirms the results obtained from previous clinical studies, indicating an improved tolerability of Medusa-formulated IFNa-2bXL at 27MIU compared to PegIntron. No serious adverse events were reported as definitely or probably attributable to Medusa-formulated IFN a-2b XL.

About IFN-alpha-2b XL IFN-alpha-2b XL is a new formulation of recombinant Interferon alpha-2b based on Flamel's proprietary Medusa hydrogel delivery system. Medusa is a versatile biodegradable carrier for the development of a wide range of novel and second-generation long-acting protein and peptide products. IFN-alpha-2b XL is designed to provide patients with a longer acting and more tolerable approach to interferon therapy compared with approved interferon regimens.

About Hepatitis C Hepatitis C virus is a blood-borne pathogen that causes inflammation of the liver. According to the U.S. Centers for Disease Control and Prevention (CDC), more than 75 percent of people infected with HCV will develop chronic infections, and 60 to 70 percent of these people will subsequently develop chronic hepatitis. HCV infection is the most common blood-borne viral infection in the United States. Approximately 4 million people in the United States are infected with HCV and the World Health Organization estimates that 170 million people worldwide -- 3 percent of the world's population -- are infected with HCV.

About Flamel Technologies Flamel Technologies SA /quotes/zigman/60259/quotes/nls/flml FLML -3.52% is a leading drug delivery company focused on the goal of developing safer, more efficacious formulations of drugs that address unmet medical needs. Its product development pipeline includes biological and chemical drugs formulated with the Medusa(R) and Micropump(R) proprietary platforms. Several Medusa-based products are at various clinical stages of development; Medusa's lead internal product candidate IFN-alpha XL (long-acting interferon alpha-2b) is being evaluated a Phase 2a trial in HCV patients. The Company has developed approved products and manufactures Micropump-based microparticles under FDA-audited GMP guidelines. Flamel Technologies has collaborations with a number of leading pharmaceutical and biotechnology companies, including GlaxoSmithKline (Coreg CR(R), carvedilol phosphate) and Merck Serono (long-acting interferon beta-1a). Flamel recently acquired Eclat Pharmaceuticals, a St. Louis, Missouri-based specialty pharmaceutical company focused on developing and commercializing niche brands and generic products. Additional information can be found at www.flamel.com

This document contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including certain plans, expectations, goals and projections regarding financial results, product developments and technology platforms. All statements that are not clearly historical in nature are forward-looking, and the words "anticipate," "assume," "believe," "expect," "estimate," "plan," "will," and similar expressions are generally intended to identify forward-looking statements. All forward-looking statements involve risks, uncertainties and contingencies, many of which are beyond our control that could cause actual results to differ materially from those contemplated in such forward-looking statements. These risks include risks that the acquisition of Eclat Pharmaceuticals will not be successful, the expected timing of the filing of our first New Drug Application (NDA) with the FDA may be delayed, the identified opportunities will not result in shorter-term, high value results, clinical trial results will not be positive or that our partners may decide not to move forward, management transition to a new chief executive officer may be disruptive or not succeed as planned, products in the development stage may not achieve scientific objectives or milestones or meet stringent regulatory requirements, products in development may not achieve market acceptance, competitive products and pricing may hinder our commercial opportunities we may not be successful in identifying and pursuing opportunities to develop our own product portfolio using Flamel's technology, and the risks associated with our reliance on outside parties and key strategic alliances. These and other risks are described more fully in Flamel's Annual Report on Form 20-F for the year ended December 31, 2011 that has been filed with the Securities and Exchange Commission (SEC). All forward-looking statements included in this release are based on information available at the time of the release. We undertake no obligation to update or alter our forward-looking statements as a result of new information, future events or otherwise.

SOURCE: Flamel Technologies

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New National Hepatitis C Referral Resource Maps

A new online resource for users all over the country to quickly pinpoint geo-mapped locations that provide the support and services most commonly sought by case managers, counselors, educators, and persons affected by hepatitis C.

Fort Lauderdale, FL, June 26, 2012 --(PR.com)-- HealthPro Solutions is pleased to announce the launch of “Interactive Referral Resource Maps,” a novel nation-wide resource helping patients and providers locate important hepatitis C services. Visit www.healthpro-solutions.org/maps.

Andi Thomas, HealthPro’s founder developed this new tool because “People affected by hepatitis C, along with frontline workers, public health and medical providers need easier access to comprehensive referral information.”

Ms. Thomas acknowledges that while useful information is available online, different portals share different types of information. Her concept of combining and visually mapping publically available data from reputable sources such as HRSA Bureau of Primary Care, SAMHSA, CDC, American College of Gastroenterology, and CMS was tested in a five-state pilot project in late 2011 with very positive results.

By clicking on one of the state flags on the main map page, users can to see the map for their home state in a familiar and fully featured Google Maps display. All of the resource icons appear on the map initially but can then be filtered by resource type.
· Health clinic
· Physician
· Support group
· Drug treatment
· Viral hepatitis coordinator

Each state map allows users to zoom in to find the closest resource location for their needs. When a user clicks on a map icon, a pop up box displays the name of the establishment or practice, the address, county, phone, and notes including scope of services.

HealthPro Solutions is a 501(c)3 nonprofit with a mission to assist people, and organizations that serve them, in promoting health and reducing the burden of chronic disease. HealthPro is a successor organization to Hep-C ALERT (1997 -2011), formed to continue and expand the reach of its strongest programs.

Contact Information

HealthPro Solutions
Jess Bardisa
954-324-8927
Contact
www.healthpro-solutions.org
Andi Thomas
954-692-0450

Source

FDA Hepatitis Update - Incivek (telaprevir) product labeling revised

(Received via email)

You are receiving this message as a subscriber to the FDA hepatitis electronic list serve. The purpose of the list serve is to relay important information about viral hepatitis-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.

Please do not reply to this message.

The Incivek (telaprevir) product labeling was recently revised to include the following changes:

1. Update the clinical comment for neuroleptic drug pimozide in Section 4 Contraindications to state: "Potential for serious and/or life-threatening adverse reactions such as cardiac arrhythmias"

2. Update Section 5 Warnings and Precautions subsection 5.4 Anemia to state: "Hemoglobin should be monitored prior to and at least at weeks 2, 4, 8 and 12 during INCIVEK combination treatment and as clinically appropriate."

3. Update Section 5 Warnings and Precautions subsection 5.6 Laboratory Tests to state the following: Use of a sensitive real-time RT-PCR assay for monitoring HCV-RNA levels during treatment is recommended. The assay should have a lower limit of HCV-RNA quantification equal to or less than 25 IU per mL and a limit of HCV-RNA detection of approximately 10-15 IU per mL.

4. Update Section 7 Drug Interactions to remove desipramine from Table 5: Established and Other Potentially Significant Interactions. Also added to Section 7 was a statement that no dose adjustment is needed for Incivek when given with either raltegravir or buprenorphine. The corresponding results from the drug-drug interaction trial with raltegravir and buprenorphine are included in Section 12 Pharmacokinetics.

5. Update Section 14 Clinical Studies to include revisions to the definition of sustained virologic response (SVR) and to correct the SVR rates for African American and Cirrhotic subpopulations as follows:

SVR was defined as HCV RNA less than 25 IU per mL at last observation within the SVR visit window (i.e., weeks 32-78 for patients assigned to 24 weeks of treatment and weeks 56-78 for patients assigned to 48 weeks of treatment).

Trial 108 (ADVANCE)

• Twenty-six subjects were Black/African Americans. The overall SVR among Black/African American subjects was 62% (16/26). Among these subjects, 35% (9/26) were assigned to 24 weeks of treatment and of those 89% (8/9)achieved SVR.
• Twenty-one subjects had cirrhosis at baseline and the overall SVR in these subjects was 71% (15/21). Among subjects with cirrhosis, 43% (9/21)were assigned to 24 weeks of treatment and of those 78% (7/9)achieved SVR.

Trial 111 (ILLUMINATE)

• Sixty-one (11%) of subjects had cirrhosis at baseline. Among subjects with cirrhosis, 30 (49%) achieved an eRVR: 18 were randomized to T12/PR24 and 12 to T12/PR48. The SVR rates were 61% (11/18) for the T12/PR24 group and 92% (11/12) for the T12/PR48 group.
• Blacks/African Americans comprised 14% (73/540) of trial subjects. Thirty-four (47%) Black/African American subjects achieved an eRVR and were randomized to T12/PR24 or T12/PR48. The respective SVR rates were 88% (15/17) and 88% (15/17), compared to 92% (244/266) for Caucasians among randomized subjects.

Trial C216

• Twenty-six percent (139/530) of INCIVEK-treated subjects had cirrhosis at baseline. SVR rates among cirrhotic subjects who received INCIVEK combination treatment compared to Pbo/PR48 were: 84% (48/57) compared to 7% (1/15) for prior relapsers, 34% (11/32) compared to 20% (1/5) for prior partial responders, and 14% (7/50) compared to 10% (1/10) for prior null responders.
• Four percent (19/530) of treatment experienced subjects who received INCIVEK combination treatment were Black/African Americans; the SVR rate for these subjects was 63% (12/19) compared to 66% (328/498) for Caucasians.

The complete revised label can be viewed on the FDA web site at Drugs@FDA.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

Presidio Pharmaceuticals Successfully Completes Phase 1 Proof-of-Concept for PPI-668, its Potent HCV NS5A Inhibitor, in Hepatitis C Patients with Genotype-1 Infection

June 26, 2012 06:03 AM Eastern Daylight Time

SAN FRANCISCO--(EON: Enhanced Online News)--Presidio Pharmaceuticals, Inc. announced today successful completion of Phase 1b clinical testing of its lead HCV NS5A inhibitor in patients with HCV genotype-1 infection, with positive efficacy and safety observations supporting advancement of PPI-668 to Phase 2 combination studies.

The randomized, blinded Phase 1b trial of PPI-668 involved sequential cohorts of treatment-naïve HCV genotype-1 patients who received oral doses of PPI-668 of 40, 80, 160 or 240 mg, once daily for three consecutive days. Within each 10-patient cohort, patients were randomized 8:2 to PPI-668 or placebo.

In all of the Phase 1b dose cohorts, PPI-668 was well tolerated with no serious or severe adverse events, no premature treatment discontinuations and no apparent pattern of treatment-related clinical side effects or laboratory abnormalities.

The Phase 1 clinical results indicate that PPI-668 had a favorable pharmacokinetic (PK) profile that included rapid achievement of high (micromolar) plasma levels, prolonged maintenance of potentially effective levels between doses, and achievement of steady-state pharmacokinetics after the first dose.

The Phase 1b efficacy observations indicated consistently rapid, marked reductions in patients’ serum viral load (HCV RNA levels), that were dose-related. Patients’ HCV RNA reductions typically exceeded 3 log10 IU/ml (99.9%) by Day 2. During the 3-day treatment period, mean maximal HCV RNA reductions for the 4 dosing groups were:

• 3.2 log₁₀ IU/mL in the 40 mg dose group
• 3.5 log₁₀ IU/mL in the 80 mg dose group
• 3.5 log₁₀ IU/mL in the 160 mg dose group
• 3.7 log₁₀ IU/mL in the 240 mg dose group

There was only one minimal-responder in the trial. A patient in the 240 mg dose group was found to be fully resistant at baseline with 100% of this patient’s pre-treatment HCV RNA containing 3 genetically linked NS5A resistance mutations. This patient was excluded from the efficacy analysis of the 240 mg cohort, since he was pre-resistant and could not contribute to dose-response inferences.

Five other patients with detectable resistance mutations at baseline, including those harboring the relatively common L31M variant, responded well to PPI-668 treatment, with multi-log HCV RNA reductions.

A protocol amendment has been completed to explore the pan-genotypic clinical efficacy of PPI-668 in HCV genotype-2a/3a patients. Recruitment is currently underway for this added cohort.

“The rapid 3.5 to 3.7 log₁₀ HCV RNA reductions observed with PPI-668 at the three higher dose levels and the encouraging safety profile support advancement of PPI-668 to Phase 2 combination studies with other promising HCV antiviral agents,” said Nathaniel A. Brown, M.D., Presidio’s Chief Medical Officer. “The PK profile of PPI-668 appears to be a major factor in its efficacy profile, with rapid achievement of potentially effective plasma levels and with inter-dose plasma concentrations exceeding those needed to inhibit both wild-type HCV and many naturally-occurring HCV variants.”

Detailed results of the completed trial are expected to be presented at a scientific meeting in the fall of 2012.

About Hepatitis C

Chronic hepatitis C is a progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Approximately 170 to 200 million persons have chronic HCV infection worldwide, resulting in more than 350,000 deaths annually.

The current standard treatment for patients with hepatitis C genotype-1 infection in the United States and several other countries is combined administration of pegylated-interferon-alfa, ribavirin, and an HCV protease inhibitor. This treatment is characterized by incomplete efficacy and severe side effects in some patients.

There is a continuing need for all oral, more consistently effective and better tolerated antiviral combinations for HCV infection, regardless of HCV genotype, patient genetic factors, or disease stage.

About Presidio

Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company focused on the discovery and development of novel oral antiviral therapeutics. For more information, please visit our website at: www.presidiopharma.com

Contacts

Presidio Pharmaceuticals, Inc.
H. Daniel Perez, M.D., 415-655-7560
dperez@presidiopharma.com

Source

Clinical Trial Results, When Overlapped With Health Technology Assessments, Provides More Complete Outlook for Reimbursement Decisions

PRESS RELEASE

June 27, 2012, 8:45 a.m. EDT

Clinical Trial Results Alone do Not Determine Reimbursement

PHILADELPHIA, Jun 27, 2012 (GlobeNewswire via COMTEX) -- A recent global comparison between clinical outcomes and Health Technology Assessments (HTAs) -- which are often influential in decision making for approving and/or providing reimbursement for pharmaceuticals and other medical technology -- for Hepatitis C drugs found that while clinical trial outcomes were generally broader in scope, and their results often overlapped, they do not always account for measures found in HTAs that had a direct impact on reimbursement decisions. The analysis was presented today at DIA's 2012 international conference.

"While clinical trial data certainly provides the broadest range of outcomes to pharmaceutical companies, the outcomes that drive regulatory approval are not always inclusive of those that drive reimbursement," said Yin Ho, MD, MBA, CEO of New York-based Context Matters, and co-author of the study. "HTAs often weigh patient-reported measures, which clinical trial outcomes do to a lesser extent. When we evaluate the copious amounts of data available for both approval and reimbursement, it is instructive to recognize the trends of which measures were influential in making both regulatory and reimbursement decisions, in order to best predict future outcomes for Hepatitis C and other treatment areas."

The study examined clinical outcomes for Hepatitis C drugs from 42 technology assessments across seven agencies, as well as 41 current Phase 3 clinical trials from 2006-2012. While the most common outcome in both HTAs and clinical trials was sustained virological response at 24 weeks post-treatment, clinical trial outcomes trended toward virological response at different time frames and other quantitative measures, including relapse rates (time), treatment failure, drug resistance and others. Comparatively, HTAs were more likely to also include qualitative measures, including liver quality (1.5 times as often) and quality of life (twice as often).

The study was sponsored and performed by Context Matters, Inc.

Context Matters, Inc. is the next generation of healthcare data analytics, focusing on risk assessment metrics for pharmaceutical and biotechnology products. Its data-driven /evidence-based approach begins with our proprietary software database platform of intelligently culled, curated, and relevant business information and data to answer strategic business questions and provide actionable analysis. Its platform and approach result in more informed decision-making by allowing users to access and understand complex data that has never before been quantified or aggregated through a tailored, needs-based approach.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Context Matters

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High-tech way to explore, share about AIDS quilt

SARAH PARNASS, Associated Press

Updated 05:31 a.m., Thursday, June 28, 2012

WASHINGTON (AP) — For tourists struck by the summer heat in the nation's capital, a quilt might be the farthest thing from their minds. But thanks to the NAMES Project Foundation, one quilt in particular is stealing the show at the national Mall.

To mark its 25th anniversary, the AIDS Memorial Quilt has returned to Washington as part of the Smithsonian Folklife Festival. It's the quilt's first appearance on the Mall since 1996. Each of the 8,000 panels of the quilt on display for the festival memorializes a man or woman who died battling HIV/AIDS.

When the quilt was here 16 years ago, the entire thing stretched across the Mall. At 1.3 million square feet, organizers say today's quilt is too large to be displayed in full.

Most of the panels sent in come from friends, family or loved ones of those who died of HIV/AIDS. At the onset of the project in 1987, organizers believed the disease would be cured and the squares would be taken apart and sent back within five years, said Julie Rhoad, NAMES Project Foundation executive director.

Rhoad said the foundation has made a lot of progress in 25 years towards educating the public, but there still is not a cure.

"I think that we've come a long way," Rhoad said, "but the question is: 'Do we settle on where we are right now?'"

Almost 35,000 people were diagnosed with AIDS in 2009, according to the Centers for Disease Control and Prevention. Though medication exists to slow HIV from becoming AIDS, the agency says these treatments must be taken daily for the rest of the patient's life.

"The least among us don't have access to quality care," Rhoad said.

At the opening ceremony for the festival held Wednesday, Rep. John Lewis, D-Ga., said the AIDS Memorial Quilt symbolizes a need for people "to learn to live together."

"The AIDS Quilt is saying we all live in the same house, the American house, the world house," Lewis said. "We can never, ever leave this house, so together we must build a world community that is free from disease and is finally at peace with itself."

For those unable to get to the Mall to see the quilt in person, researchers from the University of Southern California created a website for the Names Project Foundation that launched at the festival Wednesday.

Organized alphabetically by first name, it allows users to see blocks dedicated to specific people, their name, city, date of birth and date of death if that information is available, and the block's location among those laid out on the mall. Users can also post stories and comments alongside squares of the quilt displayed online. Those at the event can use it to locate specific panels laid out on the mall.

The standard size of a panel is 6 feet-by-3 feet. Eight panels make up one block, and on the Mall, four blocks were cable-tied together to form what they refer to as a patch, with an area of about 576 square feet, bigger than some D.C. studio apartments.

Many of the panels on the Mall indicate birth and death dates of the people they memorialize.

Festival visitor Nancy Bard of Seaford, Del., was surprised to see that she was born in the same year as many of those who had passed away.

Since the first cases of AIDS appeared in the United States more than 600,000 people diagnosed with the disease have died, according to the CDC.

"I think people have put their heart and soul into this," Bard said, "and I'm surprised. As I see them, you know it hits home how many people have and are dying from AIDS."

Kelly Rivera Hart, a volunteer for the NAMES Project Foundation from San Francisco, contributed a panel this year in honor of his friend, Rick Flener, who succumbed to AIDS in 2002.

The panel for Flener is a blue rectangle with a disco ball in the left-hand corner made from shiny fabric Hart found in the Haight-Ashbury district. Clear letters written on the panel spell out one of Flener's favorite jokes and qualities that friends and family remember about him: "his sweet smile," ''his warm friendship" and "silliness."

Hart became involved with HIV/AIDS activism when he received his diagnosis in 1992. He said finding out he had HIV woke him up.

"I thought, you know, I need to be doing something with my life," Hart said.

After his diagnosis, Hart began taking medication to treat the disease, which he said gave him nerve damage, forcing him to give up running and going out dancing four nights a week.

But Hart remains optimistic.

"Things slow me down," Hart said, "I'm not letting them stop me."

The Folklife Festival also contains an exhibit called "Citified" that displays art from southeast Washington D.C. and one called "Campus and Community," celebrating colleges established by land grants in 1862. Those exhibits and the AIDS Memorial Quilt exhibit will run from June 27 to July 1 and July 4-8.

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New biomarker for liver cancer diagnosis

DKK1 was more accurate than the most
commonly tested marker

Hugo Wilcken

A newly tested serum protein marker for hepatocellular carcinoma (HCC) could improve early diagnosis and better distinguish HCC from non-malignant chronic liver diseases, say Chinese researchers.

Dickkopf-1 (DKK1) – a secretory antagonist of the WNT pathway – was more diagnostically accurate across a range of scenarios than the most widely tested biomarker for HCC, alpha-Fetoprotein (AFP), a retrospective study involving nearly 1,300 participants found.

DKK1 maintained diagnostic accuracy for patients with early-stage HCC as well as for AFP-negative disease, which was important since 30-40% of all HCC patients were AFP-negative, the investigators said.

Reporting in The Lancet Oncology, the authors wrote that raised concentrations of DKK1 in serum could differentiate HCC from both chronic hepatitis B virus (HBV) infection and liver cirrhosis, which AFP was unable to do. In all scenarios, DKK1 alone or together with AFP was better than AFP alone.

“Our results indicate that serum DKK1 could potentially be used to diagnose HCC, especially early-stage disease, and will help to resolve the deficiencies of AFP-negative patients, and can be used to make differential diagnoses,” the authors concluded.

However in an accompanying editorial, two Spanish experts said although DKK1 showed promise, there was still a long way to go before it could be used as a diagnostic tool.

They noted the specificity of DKK1 was 85-90% whereas almost 100% was needed in oncology – although it might be acceptable for surveillance where high sensitivity was preferred to high specificity to avoid excessive false-negative rates.

Until further data were available, “practice guidelines should continue to state that tumour markers cannot be recommended for surveillance or diagnosis of liver cancer,” the researchers cautioned.

The Lancet Oncology 2012; doi: 10.1016/S1470-2045(12)70233-4; 10.1016/S1470-2045(12)70271-1

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Surgeons Seek Repeal of Transplant Ban Between HIV-Positive People

As many as 1,000 lives might be saved each year in U.S., experts say

June 27, 2012

By Randy Dotinga
HealthDay Reporter

WEDNESDAY, June 27 (HealthDay News) -- Transplant surgeons plan to meet with U.S. Congressional staff members Wednesday to push for the repeal of a law that forbids HIV-positive patients from getting organ transplants from other HIV-positive people.

If the law is changed, patients infected with the AIDS-causing virus will have more organs available to them for transplantation, advocates say.

"We want to save lives of people with HIV who may otherwise die on the waiting list for organs," said Kimberly Crump, policy officer of the HIV Medical Association, a group of AIDS doctors and researchers.

Crump said the advocates hope to encourage lawmakers to sponsor a bill calling for the law's repeal.

However, hurdles exist. For instance, questions remain about the health risks of transplanting organs between HIV-positive patients, and research is needed to make sure such transplants are safe, experts say. And some transplant surgeons refuse to perform transplants on HIV-positive patients.

Specialists, including Dr. Dorry Segev, director of clinical transplant research at Johns Hopkins School of Medicine, will discuss the special transplant needs of HIV-positive patients at the lunchtime meeting.

HIV-positive patients are vulnerable to a variety of diseases that can threaten their organs if their immune systems weaken. For example, they're susceptible to hepatitis B, which worsens faster in HIV-infected people than others and can lead to liver disease and the need for a liver transplant, explained Dr. Margaret Ragni, a professor of medicine at the University of Pittsburgh Medical Center.

HIV-positive patients are also susceptible to developing kidney problems that require kidney transplants.

HIV-positive patients can receive organ transplants from people who aren't infected with HIV, but federal law banned transplants between HIV-positive patients in the 1980s during the AIDS crisis.

Ragni said medical officials have had a variety of concerns, including fears that the recipients may receive a stronger viral strain from a donor and get sicker, that HIV-related infections could be transmitted during the transplant, or that an organ from an HIV-positive donor may accidentally get transplanted into a patient who doesn't have the virus.

A coalition of medical associations and advocates for AIDS patients, including amfAR, the Foundation for AIDS Research and Human Rights Campaign, maintain that the law is outdated and denies HIV-positive patients access to more opportunities for organ transplants.

Researchers estimate that changing the law could pave the way to saving the lives of 1,000 HIV-positive patients each year in the United States.

Advocates also say a law change will mean that patients who aren't infected with HIV will have quicker access to organs because HIV-positive patients will have a wider array of options.

But even if the law changes, some issues would still need to be resolved, said Dr. Lynda Frassetto, an internist and kidney specialist at the University of California, San Francisco.

Transplants between HIV-positive patients are still experimental, although promising research has been conducted in South Africa, Frassetto said.

Also, some transplant surgeons prefer not to treat HIV-positive patients, Frassetto said. "The transplant surgeons I work with say that some transplant groups don't want to transplant HIV patients," she said. "They don't want to be exposed to the blood and don't have the infrastructure in place to handle the complicated problems they get."

Recently, a panel of U.S. Department of Health and Human Services experts voted to uphold a decades-old ban on gay men donating blood, while advocating for more research on the controversial issue. Advocates say that improved screening techniques make the ban unnecessary.

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Supreme Court Upholds Entire Affordable Care Act

From Medscape Medical News

Robert Lowes

Posted: 06/28/2012

June 28, 2012 — The Supreme Court today declared in a 5-4 vote that the Affordable Care Act (ACA) — the most significant healthcare legislation since the creation of Medicare — is also a constitutional act.

The ruling comes as a shock to many observers, who predicted the court would strike down the individual mandate to obtain insurance coverage, if not the entire law, after its 5-member conservative wing voiced misgivings about the controversial provision during oral arguments in March. The court decision also represents an early Christmas present for President Barack Obama, who seeks reelection this fall against a Republican opponent committed to rolling back "Obamacare."

The individual mandate was at the core of a lawsuit filed against the ACA by officials from 26 states, all but 1 of whom were Republican, as well as a business association. Similar to their Republican allies in Congress, the plaintiffs claimed that the mandate violated the Constitution's Commerce clause, which empowers Congress to regulate interstate commerce. They argued that although healthcare is a form of interstate commerce, Congress cannot compel "inactive" individuals to engage in commerce; that is, to buy or sell something. To allow the mandate to stand, they said, would open the door to further encroachments on personal liberty.

A federal district court in Florida and a federal appeals court in Georgia sided with the plaintiffs and invalidated the individual mandate. However, the Supreme Court had other precedents to follow.

The majority of lower federal courts that ruled on similar challenges to the ACA gave the mandate a clean bill of health, agreeing with the Obama administration's argument that contrary to the law's critics, individuals foregoing insurance coverage actively participate in the healthcare marketplace because they will eventually require medical attention. Their decision not to get coverage is bad for everyone else because the cost of their free or subsidized care is passed on to others in the form of higher provider costs and higher premiums, according to the administration. In addition, the decision by healthy Americans to go uninsured leaves the existing risk pool of insured Americans smaller and sicker, driving up premiums even more.

The mandate helps cure all these problems, the administration contended, by forcing "free riders" to finance their healthcare now as opposed to later, if at all.

During the oral arguments in March, several conservative Supreme Court justices did not appear to buy into the administration's point of view.

"Here the government is saying that the federal government has a duty to tell the individual citizen that it must act," said Justice Anthony Kennedy, "and that is different from what we have in previous cases, and that changes the relationship of the federal government to the individual in a very fundamental way."

The court's ruling on the ACA addressed more than the mandate. The justices also upheld the constitutionality of the law's dramatic expansion of the Medicaid program, which the plaintiffs had portrayed as a usurpation of states' rights. The court also declared that a penalty levied on individuals who fail to obtain health insurance coverage beginning in 2014 does not bar consideration of the case beforehand. At issue was a law called the Anti-Injunction Act (AIA), which prohibits anyone from challenging a tax in court until it has been paid. A federal district judge in Richmond, Virginia, last year ruled that the ACA penalty amounted to a tax, and thus triggered the AIA.

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