July 2, 2013

Preliminary results suggest safety, efficacy of tremelimumab as HCC, HCV therapy

Provided by Healio

Sangro B. J Hepatol. 2013;59:81-88.

July 2, 2013

Patients with hepatocellular carcinoma and chronic hepatitis C may experience antiviral and antitumoral benefits from treatment with tremelimumab, according to results of a recent pilot study.

In the phase 2, noncontrolled, multicenter, open-label trial, researchers administered 15 mg/kg tremelimumab intravenously daily to 21 adult patients with chronic HCV genotype 1b and hepatocellular carcinoma (HCC) for 90 days for a maximum of four cycles or until severe toxicity or tumor progression occurred. Toxicity was evaluable in 20 participants and tumor response was measurable in 17 cases.

Forty-six cycles were administered, with 13 patients receiving two or more cycles. Sixteen deaths occurred, with a median overall survival of 8.2 months and survival rates of 64% at 6 months and 43% at 1 year post-treatment.

Partial tumor response occurred in 17.6% of cases, while stable disease resulted in a 76.4% disease control rate. Forty-five percent of patients maintained disease stability for more than 6 months. The median time to tumor progression was 6.48 months.

Median HCV viral loads decreased significantly from baseline (3.78 x 105 IU/mL) to 3.02 x 104 IU/mL at 120 days among 11 participants (P=.011 for difference) and 1.69 x 103 IU/mL at 210 days among six patients (P=.017). Positive viral load was observed in the only patient with evaluable data at 230 days after treatment completion.

No treatment-related deaths occurred. The most common treatment-related adverse events included elevated AST (70%) and ALT levels (55%), skin rash (65%) and fatigue (55%).

“Immune stimulation with monoclonal antibodies that block key targets in the immune synapses, such as [cytotoxic T-lymphocyte-associated antigen 4], may induce objective tumor responses in patients with advanced hepatocellular carcinoma,” Bruno Sangro, MD, PhD, director of the Liver Unit at Clinica Universidad de Navarra in Pamplona, Spain, told Healio.com. “[Also,] that CTLA-4 blockade may exert a potent antiviral effect via immune stimulation warrants further investigation in other chronic infections that lack efficient therapies, including HIV.”

Disclosure: Researcher Ignacio Melero, MD, PhD, has served as a consultant for Pfizer, Bristol-Myers Squibb and AstraZeneca.


Health-related QOL poorer during early HCV treatment with addition of telaprevir

Provided by Healio

Vera-Llonch M. Aliment Pharmacol Ther. 2013;38:124-133.

July 1, 2013

Patients with chronic hepatitis C experienced a temporary decrease to health-related quality of life during interferon-based therapy that was more pronounced with the addition of telaprevir in a recent study.

Researchers evaluated the health-related quality of life (HRQOL) of 722 patients with chronic HCV genotype 1 enrolled in the multicenter, phase 3, placebo-controlled, double blind ADVANCE study. All patients were treatment-naive and received either 48 weeks of therapy with pegylated interferon alpha-2a and ribavirin (PR; n=359), or 12 weeks of telaprevir with either 24 (T12PR24; n=210) or 48 weeks (T12PR48; n=153) of PR.

Patients responded to the EQ-5D-3L questionnaire (EQ), which assessed pain and discomfort, mobility, self-care, performance of usual activities and symptoms of anxiety and/or depression, upon initiation and at 4, 12, 24, 36, 48 and 72 weeks. The index ranged from 0 to 1, with a higher score indicating better HRQOL.

The pooled mean EQ score, after adjustment for age and sex, was 0.91, which was higher than the norm for patients aged 45 to 54 years (0.87). Regardless of treatment, the mean EQ score decreased after 12 weeks (mean 0.8 among telaprevir groups and 0.83 for PR alone), then returned to baseline at 72 weeks in the PR-only and T12PR48 groups, with higher values than baseline in the T12PR24 group (mean 0.94).

Evaluable patients who achieved SVR across all three groups had higher EQ values than those who did not (0.9 vs. 0.86). Multivariate analysis indicated significant associations between improvement to EQ score and SVR at 72 weeks (P<.0001).

“To the best of our knowledge, this is the first report from a large clinical trial on the estimated HRQOL impact of [direct-acting antiviral] combination therapy in adult genotype 1 treatment-naive chronic hepatitis C patients,” the researchers wrote. “Our results are consistent with published data on the HRQOL impacts of IFN-based regimens … and supportive of the value of shorter treatment duration (when clinically appropriate) and highly effective HCV therapies from a patient-reported outcomes perspective.”

Disclosure: See the study for a full list of relevant disclosures.


Hepatitis C News Team Launch New Online Hep C TV Channel


The team behind HepatitisCNews.com, an online community for those living with hepatitis C, has launched Hep C TV, a weekly online news channel.

(PRWEB) July 01, 2013

The team behind HepatitisCNews.com, an online community for those living with hepatitis C, has launched Hep C TV, a weekly online news channel.

Hep C TV from HepatitisCNews.com will feature news, views and updates on hep C from around the world. Also on offer is a regular Ask the Expert slot fronted by Dr Matthew Foxton, consultant hepatologist with London’s Chelsea & Westminster Hospital, as well as regular interviews with key figures from leading patient organisations and support groups, real-life stories from those living with hep C and updates on treatment advancements.

Hepatitis C is a liver disease that affects around 150 million people worldwide. Often referred to as a silent disease, as in most cases it does not result in any symptoms, hepatitis C is most commonly transmitted through contact with an infected person’s blood. The hepatitis C virus can cause serious damage to the liver and, if left untreated, can result in scarring of the liver, liver disease or even death.

Launched in December 2012, HepatitisCNews.com offers those living with hepatitis C the opportunity to share their real-life experiences and tips with each other.

For further information, visit http://www.hepatitiscnews.com or http://www.youtube.com/hepatitiscnewsteam.

Contact Tudor Reilly Health
Christine Lydon, Tel: + 44 (0) 207 034 3200


Hepatocellular Carcinoma infographic

EASL Virtual Press Office

London, 28 June 2013

EASL has developed an infographic on hepatocellular carcinoma (HCC) in collaboration with ELPA, the European Liver Patient’s Association. The infographic is designed to provide a visual snapshot of prevalence and risk factors associated with HCC as well as an overview of management of the cancer.

Click to enlarge infographic



WHO issues new HIV recommendations calling for earlier treatment


Earlier, safer and simpler antiretroviral therapy can push the HIV epidemic into irreversible decline

News release

30 June 2013 | Geneva - New HIV treatment guidelines by WHO recommend offering antiretroviral therapy (ART) earlier. Recent evidence indicates that earlier ART will help people with HIV to live longer, healthier lives, and substantially reduce the risk of transmitting HIV to others. The move could avert an additional 3 million deaths and prevent 3.5 million more new HIV infections between now and 2025.

The new recommendations are presented in WHO’s "Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection", as new data reveal a total of 9.7 million people were taking these lifesaving drugs at the end of 2012.

“These guidelines represent another leap ahead in a trend of ever-higher goals and ever-greater achievements,” says WHO Director-General Dr Margaret Chan. “With nearly 10 million people now on antiretroviral therapy, we see that such prospects – unthinkable just a few years ago – can now fuel the momentum needed to push the HIV epidemic into irreversible decline.”

Call to initiate treatment at 500 CD4 cells/mm³ or less

The new recommendations encourage all countries to initiate treatment in adults living with HIV when their CD4 cell count falls to 500 cells/mm³ or less – when their immune systems are still strong. The previous WHO recommendation, set in 2010, was to offer treatment at 350 CD4 cells/mm³ or less. 90% of all countries have adopted the 2010 recommendation. A few, such as Algeria, Argentina and Brazil, are already offering treatment at 500 cells/mm3.

WHO has based its recommendation on evidence that treating people with HIV earlier, with safe, affordable, and easier-to-manage medicines can both keep them healthy and lower the amount of virus in the blood, which reduces the risk of passing it to someone else. If countries can integrate these changes within their national HIV policies, and back them up with the necessary resources, they will see significant health benefits at the public health and individual level, the report notes.

Further recommendations

The new recommendations also include providing antiretroviral therapy - irrespective of their CD4 count - to all children with HIV under 5 years of age, all pregnant and breastfeeding women with HIV, and to all HIV-positive partners where one partner in the relationship is uninfected. The Organization continues to recommend that all people with HIV with active tuberculosis or with hepatitis B disease receive antiretroviral therapy.

Another new recommendation is to offer all adults starting to take ART the same daily single fixed-dose combination pill. This combination is easier to take and safer than alternative combinations previously recommended and can be used in adults, pregnant women, adolescents and older children.

“Advances like these allow children and pregnant women to access treatment earlier and more safely, and move us closer to our goal of an AIDS-free generation,” said UNICEF Executive Director, Anthony Lake. “Now, we must accelerate our efforts, investing in innovations that allow us to test new born babies faster and giving them the appropriate treatment so that they enjoy the best possible start in life.”

The Organization is further encouraging countries to enhance the ways they deliver HIV services, for example by linking them more closely with other health services, such as those for tuberculosis, maternal and child health, sexual and reproductive health, and treatment for drug dependence.

“The new WHO guidelines are very timely in view of the rapid progress we have made in expanding programmes for prevention and treatment,” says Dr Mark Dybul, Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. “This is an example of how the Global Fund and the WHO work together to support countries as we move towards removing HIV as a threat to public health." Since its creation in 2002, the Global Fund has supported more than 1,000 programmes in 151 countries, providing HIV treatment for 4.2 million people.

Challenges remain

Challenges still remain. Alongside the new treatment guidelines, a treatment progress update by WHO, UNAIDS, UNICEF identified areas in need of attention.

While the number of all eligible children on ART has increased by 10% between 2011 and 2012, this is still too slow compared to the 20% increase in adults. A further complication is that many key populations such as people who inject drugs, men who have sex with men, transgender people and sex workers, continue to face legal and cultural barriers that prevent them getting treatment that otherwise would be more easily available. Another factor that needs to be addressed is the significant proportion of people who, for many reasons, ‘drop out’ of treatment.

Data reinforces feasibility of recommendations

Despite this, the Global update on HIV treatment: results, impact and opportunities contains encouraging data that reinforces the feasibility of the new WHO recommendation on earlier ART, which would expand the global number of people eligible for antiretroviral therapy to 26 million.

Between 2011 and 2012, the largest acceleration ever of people enrolled on ART was achieved, with an extra 1.6 million people benefitting from antiretroviral therapy, increasing the total to 9.7 million people. Furthermore, increased coverage of treatment occurred in every region of the world, with Africa leading. Four out of 5 people who started treatment in 2012 were living in sub-Saharan Africa.

“Today nearly 10 million people have access to lifesaving treatment. This is a true development triumph,” says Michel Sidibé, Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS). “But we now have a new challenge - ensuring that all 26 million people eligible for treatment have access - not one person less. Any new HIV infection or AIDS-related death due to lack of access to antiretroviral therapy is unacceptable.”

Today’s recommendations were released by WHO on the opening day of the International AIDS Society 2013 conference in Kuala Lumpur. Among those endorsing the recommendations at the launch were representatives from countries, where such earlier ART intervention is already national policy, along with development agencies who are providing technical and financial support.

The International AIDS Society conference is held every two years and attracts leading scientists, clinicians, public health experts and community leaders to examine the latest developments in HIV-related research, and to explore how scientific advances can inform the global response to HIV/AIDS.

Note to editors:

The recommended treatment is now a combination of three antiretroviral drugs: tenofovir and lamivudine (or emtricitabine) and efavirenz, as a single pill, given once daily.

For more information please contact:

Mr Glenn Thomas
Communications Officer, WHO
Telephone: +41 22 791 3983
Mobile: +41 79 509 0677
E-mail: thomasg@who.int


Safety of ribavirin-containing regimens of ABT-450/r, ABT-333 and ABT-267 for the treatment of HCV genotype 1 infection and efficacy in subjects with ribavirin dose reductions

IAS 2013: 7th IAS Conference on HIV
Pathogenesis Treatment and Prevention
June 30 - July 3 2013
Kuala Lumpur, Malaysia

TUAB0103 - Oral Abstract Session
Safety of ribavirin-containing regimens of ABT-450/r, ABT-333 and ABT-267 for the treatment of HCV genotype 1 infection and efficacy in subjects with ribavirin dose reductions
Presented by Barry Bernstein (United States).
D. Cohen, W. Xie, L. Larsen, C. Marincic, M. Knauss-Townsend, A. Khatri, T. Podsadecki, B. Bernstein
AbbVie Inc., North Chicago, United States

Background: Sustained virologic response (SVR12) rates of 93-99% have been reported for HCV genotype 1 (GT1)-infected subjects treated with a peginterferon (pegIFN)-free, 3 direct-acting antiviral (DAA) regimen of ABT-450/r (HCV protease inhibitor dosed with ritonavir 100 mg, identified as a lead compound by AbbVie and Enanta), ABT-267 (NS5A inhibitor), and ABT-333 (non-nucleoside NS5B inhibitor) plus ribavirin (RBV). When used with pegIFN, RBV has been associated with adverse events (AEs) including anemia, necessitating frequent RBV dose reductions. Rate of RBV dose reduction was approximately 30% in HCV GT1-infected subjects treated with pegIFN/RBV in the IDEAL study. We examined the safety of a RBV-containing, 3-DAA, pegIFN-free regimen and the impact of RBV dose reduction on treatment response.

Methods: 571 non-cirrhotic treatment-naïve and previous pegIFN/RBV null responding patients with chronic HCV GT1 infection were enrolled in Study M11-652. We analyzed the subset receiving ABT-450/r (100/100-150/100 mg QD), ABT-267 (25 mg QD), and ABT-333 (400 mg BID) plus weight-based RBV for 12 or 24 weeks. SVR12 rates (percent of patients with HCV RNA < 25 IU/mL at post-treatment week 12) were analyzed (ITT).

Results: 247 patients (159 treatment-naïve and 88 previous null responders) received a 12- or 24-week regimen of 3 DAAs + RBV. Four patients (1.6%) discontinued due to study drug-related AEs, and 1 patient (0.4%) had a serious AE (arthralgia) considered possibly related to study drug. Hemoglobin values < 10 g/dL and < 8.5 g/dL occurred in 16 (6.5%) and 1 (0.4%) subjects during treatment, respectively. RBV dose was reduced in 27 subjects (10.9%) due to toxicity. Sixteen of the 27 reductions were due to anemia AEs. Other AEs, including diarrhea, fatigue, increased blood creatinine, and dizziness, led to RBV dose reductions less frequently. The table shows SVR12 rates.

  Treatment-naive subjects Previous null responders
RBV dose reduced 21/21 (100) 6/6 (100)
RBV dose not reduced 129/138 (93.5) 76/82 (92.7)
[ITT SVR12 Rates by RBV Dose Reduction Status]

Conclusions: RBV dose reductions were required less frequently with this pegIFN-free regimen than in previously reported studies of subjects receiving pegIFN-containing regimens. High SVR12 rates (100%) were achieved among subjects requiring RBV dose reduction.


Achillion Provides Update on Sovaprevir Development Program


July 1, 2013

Following Phase 1 drug-drug interaction study with ritonavir-boosted atazanavir showing elevated liver enzymes, sovaprevir placed on clinical hold by FDA

Ongoing enrollment and treatment of patients remains unaffected in Phase 2 -007 combination trial evaluating 12-weeks of sovaprevir and ACH-3102 for treatment-naive genotype 1 patients

Conference call and webcast to be hosted today at 4:15 p.m. EDT

NEW HAVEN, Conn., July 1, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that the Company has received notice from the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on sovaprevir after elevations in liver enzymes associated with significantly higher than anticipated exposures to atazanivir and sovaprevir were noted in a Phase 1 healthy subject drug-drug interaction (DDI) study evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. The FDA has allowed continued enrollment and treatment of patients in the Phase 2 -007 clinical trial evaluating 12-weeks of sovaprevir in combination with ACH-3102 and ribavirin for patients with treatment-naive genotype 1 hepatitis C viral infection (HCV).

In a Phase 1 drug-drug interaction study, Achillion was evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. While conducting this study, Achillion detected unanticipated elevations in ALT liver enzymes (grade 3 or 4) in multiple subjects, although none of these met the criteria for a serious adverse event (SAE). Achillion voluntarily stopped further dosing in the DDI study and promptly notified the FDA of these findings. Preliminary pharmacokinetic results indicate a metabolic interaction whereby plasma concentrations of both atazanavir and sovaprevir were substantially increased upon co-administration. Such ALT elevations have not been seen in the 12-week combination -007 trial, the 12-week combination -005 trial with ACH-3102 and ribavirin, or in any other drug-drug interaction studies completed with sovaprevir to date.

With the preliminary draft data on hand at the time of notification, the FDA placed sovaprevir on clinical hold. In order to resolve the clinical hold, the FDA has asked for study reports from two drug-drug interaction studies and an integrated safety analysis of on-going sovaprevir trials, each of which Achillion expects to provide to the FDA within approximately six weeks.

With respect to the ongoing -007 Phase 2 clinical trial, Achillion is treating patients in the first segment of the study and plans to release interim clinical trial results, including rapid virologic response (RVR) during the third quarter and sustained viral response (SVR) during the fourth quarter, as previously anticipated. To date, patients enrolled in the trial have received up to six weeks of combination treatment with no safety issues noted.

Conference Call

The Company will host a conference call and simultaneous webcast on Monday, July 1, 2013 at 4:15 p.m. Eastern time. To participate in the conference call, please dial (877) 266-0482 in the U.S. or (631) 291-4567 for international callers. A live audio webcast of the call will be accessible at http://www.achillion.com or http://ir.achillion.com. Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

A replay of the webcast will be available on www.achillion.com. Alternatively, a replay of the conference call will be available starting at 7:15 p.m. Eastern time on July 1, 2013, through 11:59 p.m. Eastern time on July 7, 2013 by dialing (855) 859-2056 or (404) 537-3406. The replay passcode is 14259844.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potential causative factors for the unexpected results in Achillion's Phase 1 drug-drug interaction study of sovaprevir and ritonavir; Achillion's expectations regarding timing for the completion and reporting of results of its clinical trial of ACH-3102 in combination with sovaprevir and ribavirin; and Achillion's expectations regarding timelines for submitting additional data to FDA in response to the clinical hold. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," " estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: satisfactorily respond to regulatory actions with regard to its clinical development programs, including the FDA's request for further information and data regarding the Phase 1 drug-drug interaction study; successfully resolve the partial clinical hold with regard to sovaprevir; continue to advance sovaprevir in clinical trials; replicate in later clinical trials positive results found in preclinical and earlier stage clinical trials of sovaprevir, ACH-3102, and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2013 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

CONTACT: Company Contact:

Glenn Schulman

Achillion Pharmaceuticals, Inc.

Tel. (203) 624-7000



Sally Barton Ogilvy

PR Tel. (212)880-5240



Kay Fenton

Achillion Pharmaceuticals, Inc.

Tel. (203) 624-7000



Seth Lewis The Trout Group, LLC

Tel. (646) 378-2952