April 30, 2013

HIV-Infected Men at Increased Risk for Cancer

Jim Kling

Apr 30, 2013

BERLIN, Germany — HIV-infected men are at twice the risk for non-AIDS defining cancers as the general population, but highly active antiretroviral therapy has a protective benefit, according to a new study.

Little is known about how HIV infection affects the risk for non-AIDS defining cancers that don't have an infectious component. "HIV patients are living longer, and they live with chronic diseases that can compromise the immune system. People with impaired immunologic status are at increased risk for lung cancer," Laura Albini, PhD, professor of infectious diseases at the University of Brescia, Italy, told Medscape Medical News.

She presented the study results here at the 23rd European Congress of Clinical Microbiology and Infectious Diseases.

Dr. Albini and her team conducted a retrospective analysis of 5090 HIV-infected patients registered in the Local Health Authority of Brescia in Northern Italy. The researchers linked their own clinical database to the Local Health Authority general database and the Local Health Authority population-based cancer registry to diagnose nonvirus-related non-AIDS defining cancers.

They used Poisson regression to compare the risk for cancer in people infected with HIV and those in the general population living in the same geographic region.

There were 138 cancers diagnosed in 131 patients over the course of the study (42.6 per 10,000 person-years; median age at diagnosis, 49 years). The most common cancers were nonmelanoma skin (29.7%), lung (16.7%), and breast (7.3%).

More Lung Cancer

Males were at higher risk for cancer (standardized incidence ratio [SIR], 1.86; 95% confidence interval [CI], 1.55 - 2.26) than people in the general population. They also had an increased risk for lung cancer (SIR, 3.59; 95% CI, 2.36 - 5.45) and testis cancer (SIR, 3.11; 95% CI, 1.48 - 6.52).

There were no differences in prostate and breast cancers in HIV-positive men (SIR, 1.10; 95% CI, 0.53 - 2.32) and women (SIR, 0.91; 95% CI, 0.47 - 1.74).

Predictors of nonvirus-related non-AIDS defining cancers included older age (incidence rate ratio [IRR], 1.10; 95% CI, 1.08 - 1.12 for each additional year) and a shorter duration or lack of exposure to highly active antiretroviral therapy (IRR, 2.31; 95% CI, 1.38 - 3.89; P = .002). Severe immunodeficiency (CD4+ count below 50 cells/mm³) was associated with malignancies, but only in the univariate model (IRR, 1.40; 95% CI, 0.99 - 1.98; P = .057).

The increased risk for lung cancer is likely due, in part, to the fact that smoking is a common habit, but immunodeficiency also likely plays a role, according to Dr. Albini.

The results of this study are similar to those from other studies of cancer incidence in HIV-infected individuals, "although there are some differences. Other studies have shown increases in breast cancer, but this one does not," session moderator José Miró, MD, PhD, professor of medicine at the University of Barcelona in Spain, told Medscape Medical News.

The results underscore the importance of lung cancer screening in HIV patients, Dr. Miró added. "Lung cancer is really epidemic in the HIV population. Physicians should use appropriate diagnostic tools if there are any symptoms suggesting lung cancer."

Dr. Albini and Dr. Miró have disclosed no relevant financial relationships.

23rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID): Abstract O155. Presented April 27, 2013.

Source

Embolizing Vascular Shunts Relieves Hepatic Encephalopathy

Daniel M. Keller, PhD

Apr 30, 2013

AMSTERDAM, the Netherlands ― Embolizing large spontaneous portosystemic shunts can relieve hepatic encephalopathy and can keep many patients free of it for as long as they have sufficient functional liver reserve, a new study has shown.

In the 100 days after embolization, 60% of patients were free of hepatic encephalopathy. During the overall follow-up of more than 2 years, that was reduced to still a very impressive 49%. Compared with the 2-year period before embolization, both reductions were significant (P < .001), reports Wim Laleman, MD, PhD, from the Department of Liver and Biliopancreatic Disorders at University Hospitals Leuven and the Catholic University of Leuven in Belgium.

Dr. Laleman presented the study results here at the International Liver Congress 2013.

The retrospective study involved men and women from a European multicenter cohort with cirrhosis, refractory encephalopathy, and large spontaneous portosystemic shunts that were amenable to angiographic embolization. Patients were excluded if they had a surgical shunt or transjugular intrahepatic portosystemic shunt graft, portal vein thrombosis, or hepatocellular carcinoma.

Most of the cirrhosis was caused by alcohol abuse or hepatitis C. Child–Pugh score before embolization was 7.9, and model for end-stage liver disease (MELD) score was 13.2 (range, 5 - 28).

In 37 of 38 patients, embolization was achieved with a percutaneous, transhepatic, or femoral vein approach using coils, Amplatzer plugs, or matrix. The most common spontaneous shunt was splenorenal (n = 20); the rest were mesentericocaval, periumbilical, or mesentericorenal.

In addition to the reduction in hepatic encephalopathy, embolization was associated with a reduction in the number of hospitalizations, from 3.8 in the preprocedure period to 1.3 in the follow-up period (P < .001). Hospital days were reduced from 41.0 to 17.8 (P >.001).

Quality of Life

Dr. Laleman explained that quality of life is very important in the context of hepatic encephalopathy. Before embolization, almost 73% of patients had limited quality of life and were in need of help with daily activities. After embolization, only 25% of patients had limited quality of life. Autonomy increased from 21.6% of patients to 64.9%, but there was no change in complete disability (about 10% before and after embolization), he reported.

Near-term safety was excellent. There was no mortality and 8 procedure-related complications, only 1 of which was serious (hypovolemic shock after a transhepatic approach that resolved after surgical hemostasis).

Dr. Laleman put to rest concerns about possible long-term complications of worsening liver function, thrombosis, and portal hypertensive complications. "There was no increase in the presence of gastroesophageal varices and no increase in gastropathy (2 patients developed de novo varices, but this was not considered statistically significant). With regard to ascites, we saw a similar evolution, so there was no apparent increase in portal hypertensive complications," he said.

There was no change in liver function (MELD score) from before to after the procedure (13.2 vs 15.2; P = .26). Although 4 patients had thrombotic problems, this was not statistically significant.

Patient Selection

On multivariate analysis, adjusted for time between diagnosis of hepatic encephalopathy and embolization, serum albumin, International Normalized Ratio, the presence of ascites, and preprocedure Child score, the only independent predictors of recurrence of hepatic encephalopathy were sex (odds ratio [OR], 0.06; 95% confidence interval [CI], .005 - 0.971; P = .048) and pre-embolization MELD score (OR, 1.52; 95% CI, 1.073 - 2.180; P = .019).

"Embolization of these shunts is feasible, effective, and safe, provided that sufficient functional liver reserve is guaranteed," Dr. Laleman concluded. According to the investigators, patients should have a MELD score of 11 or lower to be considered for the procedure.

This is important work because it is a large study, session chair Isabelle Colle, MD, PhD, professor of hepatology and gastroenterology and head of the gastroenterology clinic at Gent University in Belgium, told Medscape Medical News.

She explained that embolization of large spontaneous portosystemic shunts is "a good treatment for patients who have really important hepatic encephalopathy and have large shunts, because they are often Child A patients.... It's clinically important that we can offer treatment to those patients without offering transplantation."

Dr. Laleman and Dr. Colle have disclosed no relevant financial relationships.

International Liver Congress 2013: 48th Annual Meeting of the European Association for the Study of the Liver (EASL). Abstract 77. Presented April 26, 2013.

Source

Also See: Shunt Correction Eases Hepatic Encephalopathy

(Ref: ViewPoints Desk)

April 30th, 2013

Once again, a combination of Gilead Sciences' sofosbuvir and Bristol-Myers Squibb's daclatasvir appears to offer the most efficacious way of treating patients with hepatitis C without the need for either interferon or ribavirin. However, Gilead has chosen not to pursue development of this combination – prompting speculation that off-label usage could prove a feasible alternative for physicians. Such an outcome is possible, say experts, although cost is likely to be a deciding – and ultimately limiting – factor.

Insight, Analysis & Opinion

Data unveiled last week showed that among a cohort of 41 patients treated with the sofosbuvir/daclatasvir combination, 40 patients were virus free (100 percent SVR) after 12 weeks of therapy. It is not the first time this combination has impressed; a year ago similarly robust data was released, providing a backdrop against which Gilead's decision to not pursue a combination therapy with Bristol-Myers Squibb was met with some consternation. See Spotlight On: Bristol-Myers Squibb and Gilead Sciences deliver stellar HCV results, decide to go separate ways?

Gilead claims that its decision to focus on internal developments, rather than partnering with Bristol-Myers Squibb has accelerated the development of its own efforts to bring a single tablet, interferon-sparing treatment to market. Gilead remains the leading player in this development race, albeit if its own impressive-looking combinations have yet to fully match the efficacy seen with sofosbuvir/daclastasvir, which are regarded as the best in class nucleotide NS5B inhibitor and NS5A inhibitor products, respectively.

With different assets in the HCV development space offering various mechanisms of action, mechanism diversity and potency, one suggestion is that once individual components become available, physicians will prescribe them together in an off-label capacity. In this respect, the HIV market – where combinations of best-in-class molecules are used despite different companies owning them – could prove to be a valid benchmark. Key opinion leaders (KOLs) suggest that such activity is likely to occur in the early period following the approval of new treatments, with off-label use also likely to be driven by independently-run clinical trials looking at cross-company regimens. See KOL Insight: Hepatitis C: the race for the first interferon-free regimen

Potential off-label use will have a direct impact on how companies price their own fixed-dose combinations, note KOLs, while the broader cost of treating an expanding HCV population will in turn limit the use of off-label prescribing, they add – particularly as Gilead, for example, has shown robust data for its own combination. One KOL told FirstWord that "there are just too many patients out there and the system could go bankrupt if screening and diagnosis rate of hepatitis C go up and everybody is just put on just a combination of the best drug classes. You may have people prescribing daclatasvir, simeprevir plus sofosbuvir, three drugs off label in a combination just because they feel that is really the best they can provide to their patients, but which from a healthcare perspective would be a disaster."

Source

Also See:

  1. HCV Combo Impresses, but Use Unlikely (April 30, 2013)
  2. Shunned Gilead/Bristol-Myers hep C combo may be too good for docs to ignore (April 28, 2013)
  3. Gilead-Bristol Hepatitis C Drug Combo Cures All in Study (April 28, 2013)
  4. Gilead-Bristol Hepatitis C Combo Cures 100% of Patients in Study (April 27, 2013)

FDA Rejects Two Gilead HIV Drugs as Standalone Products

Apr 29, 2013

By Toni Clarke

WASHINGTON (Reuters) Apr 29 - Gilead Sciences Inc said on Monday that U.S. health regulators rejected two of its HIV drugs as standalone therapies, citing deficiencies in documentation and validation of certain quality testing procedures.

The company is seeking approval for its integrase inhibitor elvitegravir for people with HIV who have already been treated with other products.

Gilead is also seeking approval of cobicistat, a drug that does not itself fight the virus but boosts the function of other HIV medicines.

Both drugs are already contained in Gilead's once-daily single-tablet HIV treatment Stribild, which combines four different medications and was approved in the United States last August.

Stribild contains elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate.

Gilead said it is working with the U.S. Food and Drug Administration to address the questions raised in the rejection letter in order to move the application forward.

Source

Benjamin Young, MD, PhD

Apr 30, 2013

Advances in antiretroviral medications have revolutionized the care and prognosis of people living with HIV around the world. Where individuals have access to trained care providers and medications, HIV-related morbidity and mortality have decreased; in many highly affected regions, new infection rates are beginning to decrease.

Yet, as impressive as these gains seem, recent studies show that only a minority of people living with HIV in the United States are successfully engaged in care and achieve viral suppression.[1,2] Central problems in HIV care are related to delays in testing, delays in care, and early dropout from medical care, and late access to HIV testing and treatment have been associated with increased immune system damage, risk for HIV transmission, and increased hospitalizations.[3]

Unfortunately, these seemingly obvious barriers to successful implementation of therapeutics have only recently drawn systematic attention. Improving engagement in HIV medical care is hobbled by a relative dearth of scientific literature on the vast subject. In appreciating such challenges, our group, the International Association of Providers in AIDS Care (IAPAC), convened an international expert panel to identify best practices and evidence for engagement and adherence to HIV care and treatment. These first-ever evidence-based recommendations on improving entry into and retention in HIV care and treatment adherence were published in 2012.[4]

In the current issue of JIAPAC, we describe a clinical management algorithm based on the evidence-based recommendations that charts simple operational interventions for engagement and care and treatment adherence. We believe that such tools can assist busy care programs in improving the delivery of important health interventions.

The algorithm recommends:

  • Systematic monitoring of successful entry into and retention in HIV care; multiple data sources may need to be integrated to best achieve this monitoring goal. Intensive outreach is recommended for recently diagnosed individuals who do not enter care within 6 months of diagnosis. Peers or paraprofessionals may be considered to provide the needed human resources to achieve these goals.
  • The use of once-daily treatment for persons initiating therapy. Among regimens of equal efficacy and safety, fixed-dose combinations should be used to decrease pill burden.
  • Monitoring of adherence to treatment by routine self-reported adherence and pharmacy refill data. Reminder devices and the use of communications technologies with an interactive component and adherence-related educations and counseling are recommended.
  • Education and counseling through one-on-one and group education; multidisciplinary education and counseling are recommended.
  • It is important to note that although normative guidance is a necessary step in charting a pathway for improving care, recommendations frequently are not translated into operational improvements. Indeed, it is critical that agencies that author such documents take into consideration the operational and educational needs of implementation.

As a member-oriented organization, IAPAC strives to provide practical tools to assist front-line care providers in achieving the highest possible level of care in people living with HIV. In the past, efforts have focused primarily on the use of HIV treatment guidelines from the US Department of Health and Human Services and the World Health Organization. In constructing and publishing this algorithm, we extend this effort to improving engagement in care and treatment adherence.

References

Source

April 30, 2013

Treatment-naive patients with chronic hepatitis C experienced high rates of sustained virologic response from a combination of three direct-acting antivirals in a study presented at the International Liver Congress in Amsterdam.

In an open-label phase 2 study, researchers randomly assigned 32 treatment-naive patients with chronic HCV genotype 1 to 60 mg NS5A inhibitor daclatasvir (DCV) once daily, 200 mg protease inhibitor asunaprevir (ASV) twice daily and 75 mg non-nucleoside NS5B inhibitor BMS-791325 twice a day for 24 or 12 weeks (n=16 each). A second cohort was later assigned DCV, ASV and 150 mg BMS-791325 (Bristol-Myers Squibb) for 24 (n=16) or 12 weeks (n=18).

Nearly all patients had HCV RNA levels below 25 IU/mL after 4 weeks, excluding two participants from the 12-week, 150-mg group. No significant differences in virologic response were observed, with 92% of all evaluable patients experiencing SVR at 4 weeks. SVR12 and SVR24 were achieved by 94% of the first two groups, and all evaluable patients in this cohort experienced either or both SVR24 and SVR36, according to a press release.

In the second cohort, three treatment failures occurred, including virologic breakthroughs in the 12- and 24-week groups and one relapse in the 12-week group.

The most commonly reported adverse event was headache (27.3% of cases). Single cases of renal calculus and cerebral vasoconstriction unrelated to the study were considered serious adverse events, but no patients died or discontinued therapy because of treatment-related effects.

“The diversity of the hepatitis C patient population requires multiple treatment options that can enable a personalized approach,” Brian Daniels, MD, senior vice president of Global Development and Medical Affairs for Bristol-Myers Squibb, said in the release. “These data, which demonstrate comparable efficacy among the 12- and 24-week triple-DAA treatment groups, support the rapid phase 3 development of this investigational triple-DAA regimen and provide further data on daclatasvir as an important component of DAA-based therapy.”

For more information:

Everson GT. #1423: Interim Analysis of an Interferon (IFN)- and Ribavirin (RBV)-Free Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 in Treatment-Naive, Hepatitis C Virus Genotype 1-Infected Patients. Presented at: The International Liver Congress 2013; April 24-28, Amsterdam.

Source

April 30, 2013

Heavy alcohol consumption and obesity increase the risk for liver-related morbidity and death, while metabolic risk factors also elevate the risk for hepatocellular carcinoma, according to data presented at the International Liver Congress in Amsterdam.

In a study of 107,742 women (median age 60 years) stratified according to BMI (less than 25 kg/m2 vs. 25 kg/m2 or more) and alcohol intake (15 units or fewer consumed weekly vs. more than 15), researchers observed 90 incidents of morbidity or mortality related to liver disease. Patients with high BMI and alcohol intake were at significantly increased risk (HR=7.2; 95% CI, 3.4-15.5) compared with those with low BMI and low alcohol consumption, while the association also neared statistical significance among those with low BMI and high alcohol intake (HR=2.9; 95% CI 1.0-8.4).

“These findings will have a significant impact on how we can help millions of people across the world at risk of developing liver disease,” Daniele Prati, MD, EASL Scientific Committee Member, said in a press release. “More research is required to determine the exact thresholds for each risk factor that independently and in combination increase the risk of chronic liver disease, but this is an important first step in the right direction.”

In another study presented at the congress, investigators evaluated 100 liver transplant recipients with alcoholic cirrhosis, including 24 with steatosis, 24 with metabolic risk factors such as obesity and/or diabetes (MRF), 20 with both and 32 with neither steatosis nor MRF.

Hepatocellular carcinoma (HCC) was present in 28 patients, who were significantly more likely to be overweight (54% of cases vs. 14%; P<.001) and have diabetes (43% vs. 22%; P<.04) than those without HCC. Half of participants with both steatosis and MRF had HCC, compared with 6% of those with neither. Significantly more patients in either the MRF/steatosis combined or MRF alone groups had HCC than those with neither or steatosis alone (48% vs. 13%; P=.0001). Adjustment for factors including age, sex and alcohol consumption did not eliminate the associations between HCC and obesity (P<.01) or diabetes (P<.04).

“Fatty liver and alcohol have long been known as risk factors for HCC, but this study tested their combined effect in patients with alcoholic cirrhosis,” Prati said in the release. “The results will be useful to improve the management of patients with cirrhosis, and to identify cancer at early stages.”

For more information:

Trembling PM. #115: Influence of BMI and Alcohol on Liver-Related Morbidity and Mortality in a Cohort of 108,000 Women From the General Population From UKCTOCS. Presented at: The International Liver Congress 2013; April 24-28, Amsterdam.

Pais R. #118: Metabolic Fatty-Liver Disease Increases the Risk of Hepatocellular Carcinoma in Patients With Alcoholic Cirrhosis Listed for Liver Transplantation. Presented at: The International Liver Congress 2013; April 24-28, Amsterdam.

Source

HCV Combo Impresses, but Use Unlikely

By Michael Smith, North American Correspondent, MedPage Today

Published: April 30, 2013

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • This phase II trial demonstrated a nearly 100% sustained virologic response rate with the use of daclatasvir and sofosbuvir in patients with hepatitis C virus infection refractory to standard therapy.
  • Unfortunately, the two drugs are made by different companies and will not be marketed together, making phase III trials difficult.

AMSTERDAM -- Researchers and clinicians got another look here at a combination of investigational oral hepatitis C virus (HCV) drugs that delivered impressive results but will likely never be marketed together.

In a small phase II cohort of very difficult-to-treat patients, the combination of sofosbuvir and daclatasvir led to viral cures in 40 of 41 patients 12 weeks after the end of therapy, according to Mark Sulkowski, MD, of Johns Hopkins University.

The 41st patient did not appear to be tested at week 12 and so was counted as a treatment failure, but was tested 24 weeks after the end of therapy and found to have unquantifiable levels of HCV RNA, Sulkowski reported at the meeting of the European Association for the Study of the Liver.

He added that of the 21 patients who have completed 24 weeks of follow-up after treatment, all have undetectable virus – the so-called 24-week sustained virologic response (SVR24).

In addition, the combination was well-tolerated with few adverse events, and no patient has yet relapsed, he said.

In other words, the all-oral, once-daily combination "looks exceedingly useful," commented Geoffrey Dusheiko, MD, of Royal Free Hospital in London, who was not involved with the study but who moderated the session at which it was presented.

But the combination is running afoul of diverging corporate interests, he noted. Daclatasvir, an NS5A replication complex inhibitor, is owned by Bristol-Myers Squibb, while sofosbuvir, a nucleotide analogue NS5B polymerase inhibitor, is being developed by Gilead Sciences.

The companies have stopped collaborating on the drugs, with each firm preferring to develop its own version of the other's medication.

The result, Dusheiko said, is that "we don't have a large body of phase III data and that may restrict physicians from prescribing this particular combination."

"Unless there's a change in the thinking," he said, it's unlikely the companies will get back together, adding that for clinicians, "It's a conundrum."

Sulkowski reported on 41 patients with the hard-to-treat genotype 1 of the virus who had failed treatment with the current standard of care: a protease inhibitor -- either telaprevir (Incivek) or boceprevir (Victrelis) -- combined with pegylated interferon and ribavirin.

Such patients have no treatment options, Sulkowski said. He and colleagues randomly assigned the 41 volunteers to take sofosbuvir and daclatasvir alone or with ribavirin for 24 weeks. The primary endpoint of the analysis was unquantifiable HCV RNA 12 weeks after the end of therapy – the so-called SVR12.

All patients but one had unfavorable variants of the IL28B gene, which predicts response to interferon treatment, and 33 of 41 had HCV genotype 1a, which is regarded as more difficult to treat than 1b.

Nevertheless, Sulkowski reported, high response rates were seen early in treatment and by the end of therapy all 41 patients had unquantifiable virus, a state that persisted (with the one technical exception) through 12 weeks post-treatment.

There were no serious adverse events in patients taking the combination alone, no discontinuations owing to adverse events, and no grade 3 or 4 adverse events.

In the other arm, the combination plus ribavirin was nearly as well-tolerated with one serious adverse event – a single patient with hypokalemia.

Adverse events reported by at least 10% of patients included fatigue, headache, hair loss, muscle aches, constipation, and diarrhea, Sulkowski said, but all were mild or moderate.

The study had support from Gilead and Bristol-Myers Squibb. Sulkowski reported financial links with the company, as well as with Novartis, BMS, Gilead, Janssen, Vertex, BIPI, Abbott, Merck, Roche/Genentech, BIPI, and Pfizer.

Dusheiko reported financial links with Gilead, GSK, BMS, and Boehringer Ingelheim.

Primary source: European Association for the Study of the Liver
Source reference:
Sulkowski MS, et al "Sustained virologic response with daclatasvir plus sofosbuvir ± ribavirin (RBV) in chronic HCV genotype (GT) 1-infected patients who previously failed telaprevir (TVR) or boceprevir (BOC)" EASL 2013; Abstract 1417.

Source

Also See:

  1. Shunned Gilead/Bristol-Myers hep C combo may be too good for docs to ignore (April 28, 2013)
  2. Gilead-Bristol Hepatitis C Drug Combo Cures All in Study (April 28, 2013)
  3. Gilead-Bristol Hepatitis C Combo Cures 100% of Patients in Study (April 27, 2013)

PRESS RELEASE

* Reuters is not responsible for the content in this press release.

Tue Apr 30, 2013 11:45am EDT

GENFIT: GFT505 AT THE HEART OF POTENTIAL THERAPIES DURING THE ANNUAL EASL CONGRESS

Lille (France), Boston (Massachusetts, United States), April 30, 2013 - GENFIT (Alternext: ALGFT; ISIN: FR0004163111), a biopharmaceutical company at the forefront of drug discovery and development, focusing on the early diagnosis and preventive treatment of cardiometabolic and associated disorders, today announces that NASH was a prominent theme at the international liver congress of EASL held in Amsterdam, and that GFT505 is indisputably recognized as one of the most promising drug candidates in this indication.

NAFLD and NASH is a major preoccupation of experts in hepatology. As such, these liver disorders associated with conditions such as obesity and type 2 diabetes mellitus, were the subject of over 50 scientific communications during the EASL congress, underlining in particular the morbidities and increasing prevalence, not only in industrialized but also emerging countries. During a state-of-the-art session entitled "NAFLD 2013: a clinical update", Pr. Christopher Day clearly provided the latest results on epidemiology, pathophysiological processes, and natural history of the disease, which pointedly put forward the urgent need for new therapies. In this context, Pr. Day considered the mechanism of action of GFT505 as a promising approach presently in clinical evaluation for NASH.

In addition to the conference of Pr. Day, other communications were presented on GFT505 as an excellent drug candidate for the treatment of NASH. Notedly, in his presentation entitled « An overview of lipotoxicity by nuclear receptors », Pr. Bart Staels detailed the roles of nuclear receptors PPARa and PPARd, targets of GFT505, in the mechanisms associated with NASH. Based on these known mechanisms, Pr. Staels presented the latest preclinical and clinical results demonstrating the efficacy of GFT505, and indicated that these new findings have been accepted for publication in major international peer reviewed scientific journals (Hepatology and Diabetes Care). Their official publications will be announced in the coming weeks.

The important satellite meeting organized by GENFIT, which gathered together over 90 clinical investigators and key opinion leaders from different countries implicated in the GFT505-212-7 study, provided confirmation of the acute interest which the scientific community has on GFT505 as a treatment of NASH. The investigators noted in particular the exceptional efficiency of patient recruitment in the study, which demonstrates the hope and anticipation incited by GFT505 in NASH patients who today are without any therapeutic solution.

*About NAFLD/NASH:
NAFLD (non-alcoholic fatty liver disease) and in particular NASH (non-alcoholic steatohepatitis) are serious liver diseases that can lead to cirrhosis and liver cancer. The development of NAFLD/NASH is associated with the pathophysiological process of insulin resistance in patients that are overweight and/or diabetic. NAFLD is believed to affect 70-80% of diabetic patients, and progresses to chronic liver disease (NASH) in 20-50% of cases. Mortality due to liver disease is thus 2-3-fold higher in the diabetic population than in the overall population. The NASH market was estimated at 615 $M in 2010 and should reach 2,008 $M in 2018.

About GENFIT:

GENFIT is a biopharmaceutical company focused on the Discovery and Development of drug candidates in therapeutic fields linked to cardiometabolic disorders (prediabetes/diabetes, atherosclerosis, dyslipidemia, inflammatory diseases.). GENFIT uses a multi-pronged approach based on early diagnosis, preventive solutions, and therapeutic treatments and advances therapeutic research programs, either independently or in partnership with leading pharmaceutical companies, including Sanofi, to address these major public health concerns and their unmet medical needs.
GENFIT's research programs have resulted in the creation of a rich and diversified pipeline of drug candidates at different stages of development, including GENFIT's lead proprietary compound, GFT505, that is currently in Phase IIb.
With facilities in Lille, France, and Cambridge, MA (USA), the Company has approximately 80 employees. GENFIT is a public company listed on the Alternext trading market by Euronext(TM) Paris (Alternext: ALGFT; ISIN: FR0004163111). www.genfit.com

Contacts:

GENFIT
Jean-François Mouney - CEO & Chairman of the Management Board
Ph. +333 2016 4000

Milestones - Press Relations
Bruno Arabian
Ph. +331 7544 8740 / +336 8788 4726 - barabian@milestones.fr

2013.04.30 PR GENFIT EASL

Source

PR-Logo-GlobeNewswire

PRESS RELEASE

April 30, 2013, 8:02 a.m. EDT

 

Data Support Unmet Therapeutic Need in Primary Biliary Cirrhosis and Strong Statistical Correlation of POISE Phase 3 Primary Endpoint With Clinical Outcomes

NEW YORK, April 30, Apr 30, 2013 (GLOBE NEWSWIRE via COMTEX) -- Intercept Pharmaceuticals, Inc. /quotes/zigman/12230574/quotes/nls/icpt ICPT -0.09% , a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic liver diseases, today announced additional details relating to the analysis presented by the Global Primary Biliary Cirrhosis Study Group (Study Group) at the annual meeting of the European Association for the Study of the Liver (EASL) held in Amsterdam on April 24-28, 2013. The Study Group presented an analysis of data from over 2,100 primary biliary cirrhosis (PBC) patients, among whom 981 patients met Intercept's ongoing Phase 3 POISE trial entry criteria at the time they initiated ursodiol therapy of having an alkaline phosphatase (ALP) level exceeding 1.67 times upper limit normal (ULN) and/or an abnormal bilirubin level. The analysis of this cohort of patients from the Study Group further substantiates the primary endpoint used in POISE as being strongly predictive of adverse clinical outcomes such as liver transplant and death in PBC patients.

"This independent analysis from the Study Group further validates the use of a surrogate endpoint in PBC trials to predict long-term outcomes," said Mark Pruzanski, M.D., Chief Executive Officer and President of Intercept. "Our selection of the POISE trial endpoint was based on a recent emerging consensus of leading PBC opinion leaders and we are glad to see that the Study Group data analyzed to date support its clinical utility."

The data show that after one year of ursodiol therapy 58.7% of the patient cohort (n=576/981) had an inadequate therapeutic response as determined by failure to meet the POISE trial primary endpoint, which is defined as the achievement of both an ALP level of less than 1.67 times ULN (with a minimum 15% reduction from baseline) together with a normal bilirubin level. In the non-responder group, 30.0% of patients went on to require a liver transplant or die (n=173/576) as compared to 12.6% of patients in the responder group (n=51/405), reflecting a 2.4-fold higher event rate for the non-responders (p=4.5x10E-10).

In order to censor out deaths due to causes other than PBC-associated liver failure, the Study Group, among other things, analyzed a younger subgroup of patients who were under 60 years old (n=666) at the time they initiated ursodiol therapy. In this subgroup, 61.3% of patients (n=408/666) failed to meet the POISE endpoint after one year of ursodiol therapy and 26.2% of these patients went on to require a liver transplant or die (n=107/408), as compared to 7.4% of patients in the responder group (n=19/258), reflecting a 3.6-fold higher event rate for the non-responders (p=1x10E-7).

The event rate among the responders in this subgroup was 41.3% lower than the event rate of the responder group in the overall patient cohort that included older patients. We believe that this difference is likely due to the greater exclusion of mortality unrelated to PBC in the younger patient subgroups, resulting in even greater differentiation of the responder and non-responder groups.

About The Global Primary Biliary Cirrhosis Study Group

The Global Primary Biliary Cirrhosis Study Group is currently comprised of a group of 15 academic medical centers from eight countries that are pooling their data to investigate the relationship between biochemical assessments of liver function and adverse clinical outcomes in primary biliary cirrhosis. Intercept is sponsoring this independent academic research program but is not involved in the data collection and analysis, which are being conducted by Dr. Henk van Buuren and Dr. Bettina Hansen of Erasmus University Medical Centre in Rotterdam, The Netherlands. The data demonstrate that the primary endpoint being used in Intercept's Phase 3 POISE trial is highly statistically predictive of liver transplant-free survival in primary biliary cirrhosis patients. Intercept anticipates final data from at least 4,000 patients will be collected and analyzed as part of the study.

About Obeticholic Acid (OCA) and the POISE Trial

Intercept's lead product candidate, obeticholic acid, is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR). OCA is initially being developed for the second line treatment of primary biliary cirrhosis in patients with an inadequate response to, or who are unable to tolerate, ursodiol (ursodeoxycholic acid), the only approved therapy for this indication. Primary biliary cirrhosis is a chronic autoimmune liver disease that may progress to cirrhosis and liver failure, and it is currently the fifth leading indication for liver transplant in the United States. Intercept is currently conducting a Phase 3 clinical trial of OCA in primary biliary cirrhosis, called the POISE trial, which is anticipated to serve as the basis for seeking regulatory approval in the United States and Europe. Intercept completed enrollment of 217 patients in the POISE trial in December 2012 and expects results to be available in the second quarter of 2014. OCA has orphan drug designation in both the United States and Europe for the treatment of PBC. Intercept owns worldwide rights to OCA outside of Japan and China, where it has out-licensed the product candidate to Dainippon Sumitomo Pharma.

About Intercept

Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat orphan and more prevalent liver diseases utilizing its expertise in bile acid chemistry. For more information about Intercept, please visit the Company's website at www.interceptpharma.com.

Safe Harbor Statement

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the relationship between ALP and bilirubin and adverse clinical outcomes, the clinical utility of the POISE trial selected endpoints and any potential consensus relating thereto, the acceptance by regulatory authorities of the POISE trial endpoint or results, clinical, preclinical and regulatory developments for our product candidates, the anticipated results of our clinical and preclinical trials and other development activities, and our strategic directives under the caption "About Intercept." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the initiation, cost, timing, progress and results of Intercept's development activities, preclinical studies and clinical trials; the timing of and Intercept's ability to obtain and maintain regulatory approval of OCA and any other product candidates it may develop, and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; Intercept's plans to research, develop and commercialize future product candidates; the election by Intercept's collaborators to pursue research, development and commercialization activities; Intercept's ability to attract collaborators with development, regulatory and commercialization expertise; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; Intercept's ability to successfully commercialize its product candidates; the size and growth of the markets for Intercept's product candidates and its ability to serve those markets; the rate and degree of market acceptance of any future products; the success of competing drugs that are or become available; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; Intercept's ability to obtain additional financing; Intercept's use of the proceeds from its recently completed initial public offering; the accuracy of Intercept's estimates regarding expenses, future revenues, capital requirements and the need for additional financing; the loss of key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in Intercept's annual report on Form 10-K for the year ended 2012 filed with the Securities and Exchange Commission on April 1, 2013, as well as any updates to these risk factors filed from time to time in Intercept's other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intercept undertakes no duty to update this information unless required by law.

For more information about Intercept, please contact Mark Pruzanski, M.D., or Barbara Duncan, both of Intercept Pharmaceuticals, at 1-646-747-1000.

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