November 3, 2013

Many Liver Transplant Patients Unable to Afford Meds

Medscape Medical News > Conference News

Miriam E. Tucker

November 03, 2013

WASHINGTON — One in 6 liver transplant recipients say they make trade-offs between buying food and their medication or they space out doses because they cannot afford them and try to make them last longer, a new study finds.

"Transplantations are not immune from these cost barriers," Marina Serper, MD, a transplant hepatology fellow at the University of Pennsylvania in Philadelphia, told Medscape Medical News. "Financial situations change. These things are important in the chronic disease population, and they're important in the transplant population as well."

Dr. Serper presented the results here at the Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD).

Session comoderator David Reich, MD, said, "When I started transplant surgery, I perceived the surgical hurdles, the immunosuppressive hurdles, and the organ shortage hurdles as the real challenges, but what you find is it's the simple things."

Dr. Reich, from Drexel University College of Medicine in Philadelphia, said during an interview that even relatively affluent patients can become financially challenged with the huge burden of medications and sometimes the inability to work. "Noncompliance is a big problem. It's not usually a problem of attitude; it's basically the realities of life."

“Patients are embarrassed to ask. They feel proud and don't want to display vulnerability. Dr. David Reich”

And although there are resources available ― including compassionate-use drug availability by most pharmaceutical companies ― people might not bring the issue up. "Patients are embarrassed to ask. They feel proud and don't want to display vulnerability," Dr. Reich explained. "It's definitely a problem."

Dr. Serper told Medscape Medical News, "I think we may want to check in once in a while and see how people are doing and if they're having issues. We need to give them more social support and to have our social workers get them help covering their meds. We're able to do that if we know about the problem," she pointed out. "We do a really good job of helping people cover medications, but sometimes if we don't ask, we don't know."

Previous studies have shown that the rate of nonadherence among patients with chronic conditions is about 50%. In the transplant world, approximately 30% of patients are nonadherent overall, with about 20% attributed to cost. About 50% of late transplant rejections and 15% to 35% of graft losses are due to nonadherence, Dr. Serper said.

In this new cross-sectional pilot study, a total of 105 liver transplant patients were interviewed at 2 US transplant centers, Northwestern in Chicago and Emory in Atlanta.

The mean age of the patients was 57.5 years; 41.8% were women, 80.6% were white, and 13.6% were black. A quarter did not complete high school, and 15.8% had annual household incomes of less than $20,000.

The interview included 4 questions about medication trade-offs that have been previously validated for the diabetes population:

  1. During the past 12 months, was there any time when you needed prescription meds but didn't get them because you couldn't afford it?

  2. Did you ever put off paying for meds so that you'd have money to buy food?

  3. Did you ever space out the frequency of taking your meds because you couldn't afford to buy more?

  4. Have you ever had to make a choice between buying medication and buying food?

Overall, 16.9% reported having made 1 or more medication trade-offs, with 9.7% answering yes to question 1, 4.9% to question 2, 5.8% to question 3, and 8.8% to question 4, Dr. Serper reported.

The patients reporting trade-offs did not differ by age, sex, or race compared with those without trade-offs. However, the trade-off group did have significantly lower household income (P = .001) and lower educational level (P = .06).

Patients with trade-offs were more than twice as likely to have limited literacy (34.9 vs 76.5%, P = .001). They also had more chronic comorbid conditions (1.1 vs. 1.9, P < .01), were taking more medications (10.0 vs. 12.6, P = .02), and had slightly higher readmission rates (0.8 vs. 1.0, P = .06).

When queried, nearly a quarter of the patients did not know what the majority of their medications were for, 26.9% were nonadherent by self-report, and 41.9% were unable to demonstrate proper dosing. In multivariate analysis, trade-offs were independently associated were inadequate knowledge, nonadherence by self-report, and readmission rate, Dr. Serper reported.

"We should think about multifaceted trials to look at interventions to improve adherence, additional patient and caregiver education, use of regimen monitoring and feedback, and improved coordination of care," she concluded in her presentation.

Dr. Serper told Medscape Medical News that one limitation of the study was that the questions did not ask all of the things that patients were trading for medications, nor did they assess whether it was antirejection medications, other chronic disease medications, or both that were being skipped.

But regardless, the solution lies in improved communication, the session's other comoderator, David Mulligan, MD, from Yale University and Yale–New Haven Transplantation Center in Connecticut, told Medscape Medical News.

"The message is always about better communication. We need to continue to educate patients of the need to let caregivers know if they're having financial difficulties. If they're running into problems, before they start cutting back on medications, they need to engage and get medications from other sources. There are a lot of sources out there to provide compassionate use of meds. If patients don't know about those resources and don't talk to their transplant providers, they won't have access."

Dr. Serper, Dr. Reich, and Dr. Mulligan report no relevant financial relationships.

The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD): Abstract 5. Presented November 3, 2013.

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November 02, 2013

Clinical trial studies an all-oral, 12-week regimen containing the investigational compounds faldaprevir, deleobuvir, and Presidio Pharmaceuticals’ PPI-668 with and without ribavirin in 36 difficult-to-treat genotype-1a HCV patients
All 13 patients who reached the 4-week post-treatment follow-up had undetectable hepatitis C virus (SVR 4)

For U.S. Media Only

Ridgefield, CT, November 2, 2013 Boehringer Ingelheim Pharmaceuticals, Inc. today announced interim data from its Phase 2a hepatitis C (HCV) clinical collaboration (NCT01859962) with Presidio Pharmaceuticals, Inc. that showed all patients (13/13) who reached the 4-week post-treatment follow-up had undetectable levels of hepatitis C virus (SVR4) with an investigational, 12-week, all-oral regimen of faldaprevir and deleobuvir, in combination with Presidio’s pan-genotypic NS5A inhibitor, PPI-668, with ribavirin. The primary efficacy endpoint of this ongoing trial is sustained virologic response 12 weeks after completion of treatment (SVR12).

An additional study arm evaluating the regimen without ribavirin, which was added per protocol following initial results in the ribavirin-containing arms, showed that after four weeks on treatment, 12/12 patients had hepatitis C virus levels below an amount that can be quantified (LLOQ).  

These data are being presented during the late-breaking poster session at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington, D.C.

“We continue to be encouraged by the preliminary results of this investigational triple combination of direct-acting antivirals in patients with genotype-1a HCV, and in particular that, at this stage, the ribavirin-free combination has yielded similar results to the ribavirin-containing arms of the trial,” said Jacob Lalezari, M.D., director of Quest Clinical Research in San Francisco, CA.

This ongoing Phase 2a study evaluates 36 treatment-naïve genotype-1a HCV patients. Two thirds of patients have the difficult-to-treat CT or TT IL28B genotype. Previous studies have shown that presence of the CT and TT IL28B genotypes led to a reduced likelihood of achieving viral cure. In addition, more than half the patients in the study (20/36) have pre-existing HCV mutations. These include the Q80K variant in 12 of these patients, all of which had virologic responses to the faldaprevir-based triple direct-acting antiviral (DAA) regimen. Also in this trial, 19% of patients are African American.

“These results add to the growing body of data for HCV regimens containing our investigational compound, faldaprevir,” said Peter Piliero, M.D., vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are looking forward to the final results of this trial, as well as our other studies evaluating all-oral regimens, as researchers strive to make an interferon-free future a reality for a broad range of HCV patients.”

This study contains three arms:

  • The first arm enrolled 12 patients and is evaluating faldaprevir 120 mg once-daily (QD), PPI-668 200mg once-daily (QD) and deleobuvir 600mg twice-daily (BID) with ribavirin
  • The second arm enrolled 12 patients and is evaluating faldaprevir 120 mg QD, PPI-668 200mg QD and deleobuvir 400mg BID with ribavirin
  • The third arm enrolled 12 patients and is evaluating faldaprevir 120 mg QD, PPI-668 200mg QD and deleobuvir 600mg BID without ribavirin

All patients in the study have received at least 4 weeks of treatment and 97% (35/36) achieved LLOQ. To date, one patient who had pre-existing NS5A and NS5B mutations failed treatment. This patient had a partial response to treatment but developed viral breakthrough and was discontinued.

To date, there has been one treatment discontinuation due to adverse events. The patient self-discontinued at week 9 on treatment due to gastrointestinal side effects. This patient had undetectable levels of HCV RNA by day 10 of treatment. Overall, adverse events have been mild to moderate, with the incidence and severity of skin rashes and gastrointestinal side effects similar to those observed in previous trials studying faldaprevir and deleobuvir. Benign bilirubin elevation (unconjugated hyperbilirubinemia) has been common in the trial and has occurred in 88% of patients in ribavirin-containing arms, and 46% of patients in the ribavirin-free arm. In the ribavirin-free treatment arm, most adverse events (83%) have been characterized as mild. In the ribavirin-containing arms, adverse events have been mild to moderate.

In March 2013, Boehringer Ingelheim and Presidio Pharmaceuticals entered into a non-exclusive collaboration to evaluate the three DAAs in combination regimens. Both companies will retain all rights to their respective compounds. Presidio has operational responsibility for this collaborative trial, with oversight by an intercompany project team. Final results are expected in Q2 2014.

Additional Boehringer Ingelheim Interferon-Free Data
Also at AASLD, data from Boehringer Ingelheim’s interferon-free Phase 2 clinical trial, SOUND-C3 (NCT01132313), are being presented. This study evaluated the investigational compounds, faldaprevir and deleobuvir, with ribavirin in treatment-naïve patients with genotype-1b HCV. The results of this study showed that 95% of patients achieved SVR12 after 16 weeks of treatment.

The SOUND-C3 trial was one of Boehringer Ingelheim’s first studies evaluating investigational faldaprevir without interferon, in combination with investigational deleobuvir and ribavirin. This study informed the company’s current interferon-free development program, including the ongoing clinical collaboration with Presidio Pharmaceuticals.

As part of Boehringer Ingelheim’s long-term commitment to an interferon-free future for patients with HCV, the company recently completed patient enrollment for its Phase 3 clinical trials, HCVerso®1 and 2 (NCT01732796, NCT01728324), which investigate the efficacy and safety of the investigational compounds, faldaprevir and deleobuvir, in combination with ribavirin. These trials evaluate genotype-1b HCV patients, including difficult-to-treat populations such as those who are ineligible for interferon and those with liver disease including cirrhosis. 

Faldaprevir, deleobuvir, and PPI-668 are investigational compounds and not approved. Their safety and efficacy have not been fully established.

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat. Our pivotal HCV clinical trials for faldaprevir and deleobuvir are comprised of two multi-trial programs, STARTVerso™ (NCT01343888, NCT01297270, NCT01358864, NCT01399619) and HCVerso®.

Faldaprevir (BI 201335) is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. Boehringer Ingelheim is developing faldaprevir as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. STARTVerso is a multi-study Phase 3 trial program that evaluates faldaprevir combined with PegIFN/RBV. The four trials that make up this program study the combination in treatment-naïve, treatment-experienced and HIV/HCV coinfected patients with chronic genotype-1 HCV. Deleobuvir (BI 207127) is an investigational NS5B non-nucleoside polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined in a regimen with faldaprevir and RBV. Phase 2 trials of this interferon-free regimen have been completed and Phase 3 HCVerso® trials investigating this regimen are now underway. As part of our long-term commitment to HCV, the company is exploring other combinations of investigational HCV compounds that work in complementary ways. The recent collaboration of Boehringer Ingelheim with Presidio Pharmaceuticals, Inc. for a Phase 2a clinical study investigating an interferon- and ribavirin-free, all-oral combination is part of the company’s continued commitment to discover and develop innovative options for the treatment of HCV.

STARTVerso and HCVerso® are registered service marks of Boehringer Ingelheim International GmbH.

Hepatitis C is a blood-borne infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, approximately 3.2-5.2 million people have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, which accounts for 10,000 -12,000 deaths in the United States per year.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim’s culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information please visit www.us.boehringer-ingelheim.com.

About Presidio in Hepatitis C Virus (HCV)
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company focused on the discovery and development of oral pan-genotypic therapeutics for HCV patients.  Efforts are currently focused on novel inhibitors of both the HCV NS5A and NS5B genes. PPI-668 is an investigational, pan-genotypic, once daily, NS5A inhibitor. In earlier clinical studies in healthy volunteers and HCV-infected patients, PPI-668 has been well-tolerated to date with no serious or severe adverse events and no apparent pattern of treatment-related clinical side effects or laboratory abnormalities. PPI-668 achieves plasma concentrations high enough to inhibit most pre-existing resistant variants and achieves steady-state levels after a single dose.  In a clinical study of PPI-668 monotherapy in GT1 HCV-infected patients, viral load reductions of 3.5 to 3.7 log10 HCV were achieved in 1-2 days. Activity was also noted in GT3a HCV-infected patients.

Presidio’s NS5B inhibitor, PPI-383, is a novel pan-genotypic non-nucleoside inhibitor with potential to inhibit all of the major HCV genotypes. This compound is currently in Phase 1 studies in healthy subjects.  For more information, please visit www.presidiopharma.com.

Source

Also See: Boehringer Ingelheim's interferon-free hepatitis C treatment portfolio strengthened by promising Phase II data

November 02, 2013

Multiple studies presented at The Liver Meeting® investigating faldaprevir include difficult-to-cure patient populations, such as those with HIV/HCV coinfection and advanced liver disease

For U.S. Media Only

Ridgefield, CT, November 2, 2013 Boehringer Ingelheim Pharmaceuticals, Inc. today announced new data from its Phase 3 clinical trial program, STARTVerso™, which evaluates the investigational protease inhibitor, faldaprevir, in combination with pegylated interferon and ribavirin (PegIFN/RBV). The Phase 3 clinical program includes trials in treatment-naïve (STARTVerso™1&2 - NCT01343888, NCT01297270), treatment-experienced (STARTVerso™3 - NCT01358864), and HIV/HCV coinfected (STARTVerso™4 - NCT01399619)  patients with genotype-1 (GT1) hepatitis C (HCV).  The primary efficacy endpoint of all trials is viral cure 12 weeks after the conclusion of treatment (SVR12).

In a pooled analysis of treatment-naive, gentotype 1 patients (STARTVerso™1&2), 73% (382/521) and 72% (378/524) of all patients treated with 120mg or 240mg of faldaprevir once-daily, both in combination with PegIFN/RBV, respectively, achieved SVR12. In comparison, 50% (131/264) of patients treated with PegIFN/RBV alone achieved SVR12. Also in the pooled analysis, 84% (436/521) of patients who received a regimen including 120mg of faldaprevir once-daily were eligible for an overall shortened time on treatment of 12 weeks on faldaprevir and 24 weeks on PegIFN/RBV. Of these patients, 83% (362/436) achieved SVR12.

In treatment-experienced patients (STARTVerso™3), 12 weeks of faldaprevir-based treatment (240mg once-daily), in combination with PegIFN/RBV,demonstrated SVR12 of 70% (69/99) in patients who relapsed on previous HCV treatment, compared to 14% (7/49) of patients taking PegIFN/RBV alone. In patients who partially responded to previous treatment, 58% (33/57) achieved SVR12, compared to 3% (1/29) of patients taking PegIFN/RBV alone. In patients who showed no response to previous treatment, 33% (48/145) achieved SVR12.

Additionally, early sustained viral response rates in patients coinfected with HIV/HCV (STARTVerso™4) showed that 74% (229/308) of patients treated with a faldaprevir-based regimen (120mg or 240mg once-daily), in combination with PegIFN/RBV, had undetectable HCV at four weeks following treatment completion (SVR4). The study includes patients coinfected with HCV and HIV who were treatment-naïve or had relapsed after previous HCV therapy with PegIFN/RBV, and were either HIV treatment-naïve or being treated with ART.
The results from these and additional studies will be presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting®, taking place November 1-5 in Washington, D.C.

“HCV patients have various treatment needs, and this data studying an interferon-based regimen may be particularly encouraging for those with advanced liver disease, including cirrhosis, who may need treatment urgently,” said Douglas Dieterich, M.D., professor of medicine in the Division of Liver Diseases, Mount Sinai School of Medicine.

More than 2,200 patients have been studied in the STARTVerso™ trial program, including a large proportion of patients with difficult-to-cure types of HCV:

  • Over 300 patients in the STARTVerso™ program have HIV/HCV coinfection (STARTVerso™4); these patients are known to have lower response rates to treatment and are therefore considered difficult to cure. In this trial, 14% of patients are African American
  • 677 patients in the STARTVerso™ program (STARTVerso™3) are treatment-experienced, meaning they had attempted previous HCV treatment but did not achieve viral cure
  • 40% of patients in STARTVerso™3 (treatment-experienced patients) have advanced liver disease (≥F3 fibrosis)
  • 59% of patients in STARTVerso™1&2 (treatment-naïve patients) have a non-CC IL28B genotype; in previous studies, these patients have been less likely to achieve viral cure

“These pivotal data from STARTVerso™ are important for Boehringer Ingelheim’s HCV portfolio as they support the filing of a New Drug Application for faldaprevir with the Food and Drug Administration,” said Peter Piliero, M.D., vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “These results take us a step closer towards our goal of making faldaprevir available for patients who urgently need HCV treatment.”

In the STARTVerso™ clinical trial program, adverse events (AEs) most commonly included nausea, fatigue, diarrhea, headache, anemia, weakness, rash and jaundice due to transient bilirubin elevation (unconjugated hyperbilirubinemia). In STARTVerso™1&2, anemia occurred in 14%, 13%, and 14% of patients taking 120mg and 240mg faldaprevir regimens or PegIFN/RBV alone, respectively. Hyperbilirubinemia occurred in 12% (120mg), 46% (240mg) and less than 1% (PegIFN/RBV) of patients, and was transient. ALT elevations in the faldaprevir arms were similar to placebo, and occurred in 2% (120mg), 2% (240mg) and 3% (PegIFN/RBV) of patients. Gastrointestinal side effects occurred in 11% (120mg), 18% (240mg) and 7% (PegIFN/RBV) of patients. Rash occurred in 7% (120mg), 10% (240mg) and 4% (PegIFN/RBV) of patients. There was no occurrence of photosensitivity in the faldaprevir 120mg arm, and a 1% occurrence in the 240mg arm. Bilirubin associated AEs occurred in 3% (120mg), 9% (240mg) and 1% (PegIFN/RBV) of patients. Further, AEs leading to the discontinuation of faldaprevir occurred in 1% (120mg) and 3% (240mg) of patients.

In STARTVerso™3, AEs of at least moderate intensity in the 12- and 24-week faldaprevir arms included gastrointestinal side effects, which occurred in 20% (12-week), 17% (24-week) and 6% (PegIFN/RBV alone) of patients. Anemia occurred in 10% of patients in both faldaprevir arms (12- and 24-week) and 5% of patients taking (PegIFN/RBV alone). Rash, photosensitivity, and jaundice occurred in ≤ 5% of faldaprevir patients (12- or 24-week arms). Further, AEs leading to the discontinuation of faldaprevir occurred in 7% (12-week) and 8% (24-week) of patients. In STARTVerso™4 to date, nausea has occurred in 28% and 44% of patients taking 120mg and 240mg faldaprevir regimens, respectively. Additionally, fatigue has occurred in 32% (120mg) and 35% (240mg) of patients, diarrhea has occurred in 25% (120mg) and 28% (240mg) of patients, headache has occurred in 24% (120mg) and 25% (240mg) of patients, asthenia has occurred in 26% (120mg) and 21% (240mg) of patients, and decreased appetite has occurred in 24% (120mg) and 20% (240mg) of patients. Thus far, discontinuation of faldaprevir due to AEs leading to the discontinuation of faldaprevir has occurred in 1% (120mg and 240mg) of patients. Serious AEs occurred in 14% (120mg) and 8% (240mg) of patients, resulting in one death from Stevens-Johnson syndrome (SJS) with onset 145 days after discontinuing treatment while on systematic antibiotics.

Additional Boehringer Ingelheim Data at the Meeting
Additional late breaking data from Boehringer Ingelheim’scollaborative interferon-free trial with Presidio Pharmaceuticals will be presented on Monday, November 4. This ongoing Phase 2a study evaluates a 12-week, all-oral regimen of Boehringer Ingelheim’s investigational compounds, faldaprevir and deleobuvir, in combination with Presidio’s investigational pan-genotypic NS5A inhibitor, PPI-668, with and without ribavirin.

Further, data from other Boehringer Ingelheim studies will be presented at AASLD. The aim of these studies is to better understand faldaprevir’s drug-drug interaction profile in patients who are taking birth control and common anti-addiction medications. Additionally, a study evaluating faldaprevir in patients who have renal impairment will also be presented. Studies have shown that there is a higher prevalence of chronic kidney disease, also known as renal impairment, in patients with HCV making it important to understand the activity of HCV treatments in this population.  

Faldaprevir and deleobuvir are investigational compounds and not approved by the FDA. Their safety and efficacy have not been established.

Abstracts from The Liver Meeting® can be accessed on the AASLD website at www.aasld.org.

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to cure. Our pivotal HCV clinical trials for faldaprevir and deleobuvir are comprised of two multi-trial programs, STARTVerso™ and HCVerso®.

Faldaprevir is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. Boehringer Ingelheim is developing faldaprevir as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. STARTVerso is a multi-study Phase 3 trial program that evaluates faldaprevir combined with PegIFN/RBV. The four trials that make up this program study the combination in treatment-naïve, treatment-experienced and HIV/HCV coinfected patients with chronic genotype-1 HCV. Deleobuvir is an investigational NS5B non-nucleoside polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined in a regimen with faldaprevir and RBV. Phase 2 trials of this interferon-free regimen have been completed and Phase 3 HCVerso® trials investigating this regimen are now underway. As part of our long-term commitment to HCV, the company is exploring other combinations of investigational HCV compounds that work in complementary ways. The recent collaboration of Boehringer Ingelheim with Presidio Pharmaceuticals, Inc. for a Phase 2a clinical study investigating an interferon- and ribavirin-free, all-oral combination is part of the company’s continued commitment to discover and develop innovative options for the treatment of HCV.

STARTVerso and HCVerso® are registered service marks of Boehringer Ingelheim International GmbH.

The Liver Meeting® is a registered trademark of the American Association for the Study of Liver Diseases (AASLD).

Hepatitis C is a blood-borne infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, approximately 3.2-5.2 million people have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, which accounts for 10,000 -12,000 deaths in the United States per year.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim’s culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information please visit www.us.boehringer-ingelheim.com.

Source

Also See: Phase III data show Boehringer Ingelheim's faldaprevir* was highly effective in a broad range of patients with genotype-1 hepatitis C

WebsEdgeHealth

Published on Nov 3, 2013

AASLD President-Elect Adrian Di Bisceglie, MD gives AASLD TV an overview of this exciting plenary at The Liver Meeting 2013.

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Presented: November 4, 2013 -- Walter E. Washington Convention Center, Washington, DC

WASHINGTON, Nov. 3, 2013 /PRNewswire/ -- Although very rare, the use of oral contraceptive can lead to benign tumors in the liver. The tumors, known as hepatocellular adenomas, can become malignant. It is, however, difficult for physicians to assess the risk of these tumors becoming malignant.

The study's researchers examined and classified data from 250 patients with hepatocellular adenomas. They examined classical adenomas (223), borderline lesions between adenomas and carcinomas (18), and carcinomas (9). The data was examined using whole exome sequencing, CGH-SNP analyses, and methylome analyses.

Researchers were able to identify the genetic determinants of malignant transformation as well as the key factors at stages of the transformation. "Our work reported for the first time a molecular mechanism of malignant transformation of hepatocellular adenomas to carcinomas," lead researcher, Camilla Pilati, PhD, said, "Surprisingly, we were able to identify the chronology of the genetic defects that accumulate in hepatocytes to promote their malignant transformation. In this line, we identified genetic alteration that acts at early and late steps of the malignant transformation process, in the accumulation of early genetic alteration at the origin of the malignant transformation of the hepatocytes."

Two genes with somatic mutations -- one in the early stages and one in the later stages -- were identified in the malignant transformation. Mutations of beta-catenin are associated with many forms of cancer, and beta-catenin activation and TERT promoter mutations in the early and later stages, respectively, were identified in the malignancy process. In addition, the researchers were able to identify factors that determined adenomas that were not at a high risk of becoming carcinoma.

"This work provided new insights about the major genetic determinants of malignant transformation and their timeframe accumulation during the adenoma-carcinoma sequence. At the clinical level, we believe that these results open new avenues for personalized medicine in hepatocellular adenomas," said Dr. Pilati.

"The aim of this classification is the identification of new biomarkers useful for a more precise diagnosis and that could be used as therapeutic targets. This is clearly an important step to develop a more personalized medicine with, for example, the selection of patients with high risk of malignant transformation that require a specific follow-up and more radical treatment," Dr. Pilati concluded. "Identification of CTNNB1 and TERT promoter mutation as key genetic determinants of malignant transformation in HCA will be useful to propose tailored treatment in these subtypes of patients.

Abstract title:

Integrative genomic profiling of hepatocellular adenomas identify mutational processes involved in malignant transformation.

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Washington, November 2-5, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 1 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.

Press releases and all abstracts are available online at www.aasld.org.

Media Contact: Gregory Bologna
703/299-9766  
gbologna@aasld.org
Press Room: November 1 – 5, 2013
Walter E. Washington Convention Center, Washington, DC
Telephone: 202-249-4092

Researcher: Camilla Pilati, PhD
Email: campilati@gmail.com
Phone: 0033 1 53725193

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

SOURCE American Association for the Study of Liver Diseases (AASLD)

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SVR12 Rates of 95% in HCV Treatment Naïve Patients and 90% in Prior Null Responders Reported in PEARL-I Study

WATERTOWN, Mass.--(BUSINESS WIRE)--Nov. 3, 2013-- Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA) a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that additional data from AbbVie’s M13-393 study, referred to as PEARL-I, will be presented in an oral presentation at 5:15 p.m. ET today at The Liver Meeting, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C.

In PEARL-I, SVR12 rates of 95% (40/42) in hepatitis C (HCV) GT-1b treatment-naïve patients and 90% (36/40) among prior null responders will be presented in this intent-to-treat analysis. Two patients in the treatment-naive arm did not achieve SVR12 due to loss to follow up. In the null responder arm, one patient experienced breakthrough and three patients relapsed.

PEARL-I is a phase-2b, interferon-free, 320 patient study being conducted by AbbVie to evaluate the once-daily, two-DAA regimen consisting of ABT-450/r (protease inhibitor plus ritonavir) + ABT-267 (AbbVie’s NS5A inhibitor) in HCV treatment-naïve patients and treatment-experience patients. GT-1b treatment arms are ribavirin-free and also include cirrhotic patients while GT-4 arms explore treatment with and without ribavirin.

“We are very encouraged by the strong SVR12 rates from this simplified 2-DAA, once-daily regimen that includes our lead HCV protease inhibitor, ABT-450,” commented Jay R. Luly, Ph.D., President and Chief Executive Officer. “We look forward to data from Phase 3 studies of three-DAA regimens containing ABT-450 being reported in the coming months.”

Protease Inhibitor Collaboration with AbbVie (formerly the research-based pharmaceutical business of Abbott Laboratories)

In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. ABT-450 is a protease inhibitor identified as a lead compound through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450. Enanta received $57 million in connection with signing the collaboration agreement, has received $55 million in subsequent clinical milestone payments, and is eligible to receive an additional $195 million in payments for regulatory milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration’s protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the U.S. portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of U.S. development costs and U.S. commercialization efforts (sales and promotion costs) for the additional protease inhibitor in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval instead of receiving payments for U.S. commercial regulatory approval milestones and royalties on U.S. sales of that protease inhibitor.

About Enanta

Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field. Enanta is discovering and developing novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a host-targeted antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Forward Looking Statements Disclaimer

This press release contains forward-looking statements, including with respect to clinical data, plans for announcing additional data, and the planned clinical development of ABT-450. Statements that are not historical facts are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include final results of ongoing clinical trials, the development and marketing efforts of AbbVie (our collaborator on ABT-450), regulatory actions affecting clinical development of ABT-450 and clinical development of competitive product candidates. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law.

Source: Enanta Pharmaceuticals, Inc.

Investor Contact
Enanta Pharmaceuticals, Inc.
Carol Miceli, 617-607-0710
cmiceli@enanta.com
or
Media Contact
MacDougall Biomedical Communications
Kari Watson, 781-235-3060
kwatson@macbiocom.com

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