Gilead Sciences' CEO Discusses Q4 2013 Results - Earnings Call Transcript

These are two very interesting excerpts from todays Earnings Conference Call. There was a lot of talk about Sovaldi as well other HCV drugs in trials. I have pulled 2 very interestiong quoted pieces from the call, the first concerning European pricing and the second concerning new Research and Development (R&D). I would encourage everyone to go to read the entire transcript which is available at Seeking Alpha. It is very informative as well as enlightening.

“I would like to talk a little bit about the rest of the pricing for Europe. We have now listed our price in the U.K. The price in the U.K. is almost UK35,000, so that’s about $57,000. And I think, as a benchmark for the majority of Europe, that would be a good price point for you going forward. So I’ll say that again. About UK35,000, this is the 12-week course of treatment, or about $57,000.

And I also mentioned the German pricing. The German pricing is almost EUR49,000, or $66,000. So Germany typically is a little bit higher. And my final comment on European pricing is just to say that these are significant differences to the telaprevir pricing. And the [unintelligible] that we’ve taken for Sovaldi, we believe, is very justified according to cost effectiveness data, and the premium is very comparable to the premium that we took on Sovaldi versus the original price of telaprevir in the United States.”

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“Thanks for asking an R&D question. I thought I was going to escape this call without having been asked one single question. So thank you very much. As you know, we have now succeeded with our ledipasvir/sofosbuvir fixed dose combination to actually incredibly shorten treatment duration to 8 weeks and 12 weeks and Sovaldi treatment experience with response rates that go up to 95% or higher.

But we’re not stopping there. This is, of course, for genotype 1. We have another fixed dose combination in development, 5816 combined with sofosbuvir. You will see some of those early data at EASL, and we’re still waiting for the treatment experienced cirrhotic genotype 3 cohort to make a decision or to feel really comfortable going into Phase III.

And then finally, as you know, we have efforts underway to shorten the treatment duration even further, to six weeks, by adding a third drug. So you know, all of those things are ongoing, and I think we will be competitive with our, you know, you can’t really do much more than having one single pill, once daily. Very safe, very well tolerated tablet, given for eight weeks and achieving response rates of 95%.”

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Read full transcript here …….

Alcohol-linked deaths a problem for the Americas

Elizabeth DeVita-Raebrun
Reuters
3:05 p.m. CST, February 4, 2014

NEW YORK (Reuters Health) - Liver disease and brain disorders due to alcohol abuse are important causes of premature death in the Americas, a new study concludes.

The toll of too much drinking is especially high among men and among middle-aged people, according to the report, whose authors say it's the first to tabulate deaths resulting solely from alcohol.

"This provides direct evidence of the impact of alcohol on the health of countries in the region," said one of the study's authors, Dr. Vilma Pinheiro Gawryszewski, an advisor on health information and analysis for the Pan American Health Organization(PAHO).

In the 16 North, Central, and South American countries studied, alcohol was the sole cause of 79,456 deaths a year, the researchers say. That represented 1.4 percent of deaths from all causes, and alcohol-related liver disease alone accounted for 0.6 percent of all-cause mortality.

The study was based on data collected between 2007 and 2009 for countries in the PAHO mortality database.

The researchers excluded deaths from vehicle accidents and other fatal situations where alcohol might have been involved but there could also have been other causes.

Looking just at deaths due directly to alcohol, they found 63 percent were from liver disease and 32 percent were from neurological and psychiatric conditions grouped under "degeneration of the brain and nervous system."

Other listed causes of death included alcohol poisoning, alcohol-linked heart and gastric problems and fetal alcohol syndrome.

The death toll is the "tip of the iceberg," meaning that there are probably many more alcohol-related deaths that the researchers were not able to identify, said another of the study's authors, Dr. Maristela Monteiro, regional advisor on alcohol and substance abuse at PAHO.

Monteiro said that raising the price of alcohol and increasing taxes would help to prevent some of these deaths. Many countries have found these steps effective in controlling tobacco use, but such measures have not been used to control alcohol consumption, she said.

Even the U.S., which was included in the study, has not done as much as it could, said David Jernigan, director of the Center on Alcohol Marketing and Youth at Johns Hopkins Bloomberg School of Public Health.

"The single most efficient thing you can do is to raise taxes," Jernigan told Reuters Health. "Many states haven't raised it in decades. That means the price doesn't go up with inflation, and alcohol gets cheaper every year."

And while the U.S. and other countries have limited tobacco advertising, alcohol advertising "is virtually everywhere," he said.

Mortality due to alcohol was highest in El Salvador, Guatemala and Nicaragua, with death rates of 27.4, 22.3 and 21.3 per 100,000 people, respectively. These were also the countries with the highest consumption of hard liquor, the authors noted.

Colombia, Argentina and Canada had the lowest death rates attributable to alcohol at 1.8, 4.0 and 5.7 per 100,000, respectively. The alcohol death rate in the United States was "intermediate," at 6.7 per 100,000, Monteiro said.

Men accounted for 84 percent of the deaths overall, but that proportion was not the same in all countries. The risk of a man dying from alcohol in El Salvador was nearly 30 times higher than that of a woman, but only about three times higher in Canada and the U.S.

People in the mid-to-late 50s and 60s age range were at the highest risk. This later in life risk, Jernigan said, points to the long-term impact of heavy drinking.

"Mostly in this country, we talk about alcohol and the risk for the young," in whom drunk driving, violence, and accidents are important causes of death, Jernigan said. "This really shows the impact over the life course."

Despite the grim statistics, Jernigan says studies like this one are a positive sign.

"On one hand, you could say, 'this is a huge problem, and not enough is being done.' On the other," he said, "you could say, 'we're getting better at documenting it and showing that, until we take meaningful action, it's not going to go away.'"

In poorer countries, other factors contributing to the deaths could include infectious diseases that hasten the course of liver disease, as well as poor nutrition and limited access to health services.

"In the U.S., people wouldn't wait until they were too sick for help to seek out services, because treatment is available," said Monteiro. That is not always the case, she said, in other countries.

Source: http://bit.ly/1enwJIT Addiction, online January 14, 2014.

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The Risk of Long-term Morbidity and Mortality in Patients With Chronic Hepatitis C

JAMA Internal Medicine

February 2014, Vol 174, No. 2

Original Investigation | February 2014

Results From an Analysis of Data From a Department of Veterans Affairs Clinical Registry

Jeffrey McCombs, PhD¹; Tara Matsuda, BA^1,2; Ivy Tonnu-Mihara, PharmD²; Sammy Saab, MD³; Patricia Hines, BA⁴; Gilbert L’Italien, PhD⁴; Timothy Juday, PhD⁴; Yong Yuan, PhD⁴

[+] Author Affiliations

JAMA Intern Med. 2014;174(2):204-212. doi:10.1001/jamainternmed.2013.12505.

Abstract

Importance The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV.

Objective To describe the natural history of HCV in real-world clinical practice.

Design, Setting, and Participants Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present.

Exposures Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load.

Main Outcomes and Measures The primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models.

Results A total of 28 769 of 360 857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients.

Conclusion and Relevance Achieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

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CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults

Can J Infect Dis Med Microbiol. 2013 Winter;24(4):217-38.

Hull M¹, Klein M², Shafran S³, Tseng A⁴, Giguère P⁵, Côté P⁶, Poliquin M⁶, Cooper C⁷.

Abstract

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.

OBJECTIVE: To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context.

METHODS: A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale.

RESULTS: All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients.

DISCUSSION: Recommendations may not supersede individual clinical judgement.

KEYWORDS: Antivirals, Direct-acting antivirals, HCV, HIV, Pharmacokinetics

PMID: 24489565 [PubMed]

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How heroin kills you

By Jen Christensen, CNN
updated 11:05 AM EST, Tue February 4, 2014

(CNN) -- The autopsy results aren't in yet, but police believe heroin played a role in the death of Academy Award winning actor Philip Seymour Hoffman -- if not the primary role.

Using heroin can kill you, but it may not be in the way you think. If Hoffman did die from using heroin, his death was atypical in some aspects. Here's how heroin kills.

The numbers

Drug overdose deaths in the United States have risen steadily since 1970. Painkillers actually kill more Americans than heroin and cocaine combined, according to the Centers for Disease Control, but heroin is still one of the No. 1 killers of illegal drug users. Only one in 10 heroin overdoses ends in death.

Overdose deaths from heroin have increased recently, and heroin use is also on the rise. In 2011, 4.2 million Americans over the age of 11 had tried heroin at least once, according to the National Institute on Drug Abuse.

An estimated 23% of them will become addicts. And it's addicts who die more frequently than new users, studies show.

How heroin works

Heroin is most often mixed with water and injected. Injecting it minimizes the lag time between when the drug is taken and effects are felt -- with injection, the effects are almost immediate.

It can also be smoked, snorted or eaten, but smoking or eating destroys some of the drug and mutes its effects.

When someone takes heroin there is an immediate rush. Then the body feels an extreme form of relaxation and a decreased sense of pain.

What's happening inside the body is the heroin is turning into morphine. Morphine has a chemical structure similar to endorphins -- the chemicals your brain makes when you feel stressed out or are in pain. Endorphins inhibit your neurons from firing, so they halt pain and create a good feeling.

Morphine, acting like your endorphins, binds to molecules in your brain called opioid receptors. When those receptors are blocked, that creates a high.

Why you die

Most people die from heroin overdoses when their bodies forget to breathe.

"Heroin makes someone calm and a little bit sleepy, but if you take too much then you can fall asleep, and when you are asleep your respiratory drive shuts down," said Dr. Karen Drexler, director of the addiction psychiatry residency training program and an associate professor in Emory University's psychiatry and behavioral sciences department.

"Usually when you are sleeping, your body naturally remembers to breathe. In the case of a heroin overdose, you fall asleep and essentially your body forgets."

A heroin overdose can also cause your blood pressure to dip significantly and cause your heart to fail.

Studies show intravenous heroin users are 300 times more likely to die from infectious endocarditis, an infection of the surface of the heart.

Heroin use can also cause an arrhythmia -- a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart may not be able to pump enough blood to the body, and lack of blood flow affects your brain, heart and other organs.

Heroin use can also cause pulmonary edema. That's when the heart can't pump blood to the body well. The blood can back up into your veins, taking that blood through your lungs and to the left side of the heart.

As pressure in the blood vessels increases and fluid goes into the alveoli, the air spaces in the lungs, this reduces the normal flow of oxygen through your lungs, making it hard to breathe. This too can give you a heart attack or lead to kidney failure.

Heroin can also come with other toxic contaminants that can harm a user -- although deaths from such instances, while not unheard of, are thought to be rare.

Studies suggest instantaneous death -- like what may have happened in Hoffman's case -- is unusual. The actor was found dead on his bathroom floor with a needle sticking out of his left arm, authorities have said.

Such deaths, where a needle and syringe are still in place, would be considered instant by scientists. One study showed this accounts for only 14% of heroin-related deaths.

Heroin deaths increase when...

There are some common social characteristics in heroin deaths that would make Hoffman more of a typical case. Most fatalities involve men, particularly those who have struggled with other drugs or alcohol (he admitted to this in the past) and other drugs or alcohol are often present.

While many are single (Hoffman had a partner), most users die in their homes and/or in the company of another person.

An addict does have a much higher chance of dying if he or she leaves treatment. The risk of death is higher for newly clean heroin addicts. A number of fatalities appear to happen after periods of reduced use, one 2000 study showed.

In fact, long-term users who die from overdoses are likely to have heroin levels no higher than those who survive.

That may be in part because those who are newly clean don't know how much of the drug to give themselves any more, Drexler said. They won't need the same amount to get high as when they were using more regularly.

There are also some studies that show tolerance to the respiratory depressive effects of opiates increases at a slower rate than tolerance to the euphoric and analgesic effects. As your tolerance to the drug develops, you typically need more of it to produce the high you are used to getting. This may be why long-term users are potentially at greater risk of overdose than novices.

Statistics suggest that newer heroin users aren't the ones most likely to die. One study showed only 17% of the deaths studied were in new heroin users.

However, Drexler said newer users can overdose because they don't know how much drug to take, compared to experienced users. "I think it is misleading to say you would not die if you only use it once or twice," she said.

A person's chances of dying from heroin use increase dramatically after 20 years of use. Studies show that after 30 years of use, 16% of heroin users have died, compared with 6.5% of cocaine users and 1.5% of meth users.

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AbbVie hep. C combo wows in hard-to-treat

Provided by MM&M

KEVIN MCCAFFREY

FEBRUARY 03, 2014

AbbVie unveiled Phase-III trial results for its multi-drug hep. C regimen Friday, and the all-oral regimen looks impressive. Up to 99% of genotype-1b, treatment-naive patients taking the cocktail achieved SVR12 (sustained virologic response, or cure, at 12 weeks). And up to 96% of cirrhotic patients, or those with liver scarring and poor liver function, reached SVR after a three-month course of the regimen, which consists of ABT-450/r + -267 + -333.

Some specialists might find value in using a regimen like AbbVie's for their cirrhotic patients, but the question is how they compare against those offered up last December by Gilead for its HCV fixed-dose oral therapy. Gilead's two-drug all-oral regimen, which pairs recently approved antiviral Sovaldi with the experimental drug ledipasvir and ribavirin (RBV), saw 97% SVR12 in the treatment-naïve, while 94% of those in the same population got to SVR12 taking a RBV-free regimen.

Gilead has yet to break down how effective its regimen is in cirrhotic patients, but ISI Group analyst Mark Schoenebaum, in an investor note Friday, estimated the lower boundary to be around 95% SVR12 rate with and without ribavirin, based on other trial data.

While AbbVie's regimen showed strong efficacy, and demonstrated it in what has been the largest Phase-III program of an all-oral, interferon-free therapy for HCV GT1 patients to date, Schoenebaum—in another investor note from Friday—shared concerns that it may fall short when compared to Gilead's fixed-dose combo and that AbbVie's results were “right in-line with Street expectations.”

“Gilead's regimen continues to have potential commercial advantages on multiple points,” he wrote. Of those competitive advantages, Schoenebaum cited the Gilead regimen's lower pill burden (one pill daily vs. AbbVie's expected four to six), a potential for shorter duration (8 weeks vs. 12 weeks) and a possibly larger population to cater to that includes GT1-naïve patients, as well as a lack of ribavirin, which can lead to anemia.

Gilead's combo also stands to hit pharmacy shelves before the competition. The Foster City, CA, drugmaker said it will file within the first quarter of this year. AbbVie confirmed, along with Friday's data, that it won't file its regimen with regulators until the early part of the second quarter of this year.

Source

Also See: Abbvie completes largest phase III program of an all-oral, interferon-free therapy for the treatment of hepatitis C genotype 1

Video: Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection

Published on Jan 15, 2014

Dr. Gregory T. Everson discusses his manuscript "Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection." To view abstract http://bit.ly/1astcIL.

Also See: Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection – Full Text

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BPA Exposure in Womb Linked with Liver Tumors

Provided by Nature World News

By Staff Reporter Feb 03, 2014 06:13 AM EST

mice exposed to BPA have high risk of liver tumors. (not pictured) (Photo : REUTERS/Asmaa Waguih)

University of Michigan School of Public Health researchers found liver tumors in mice whose mothers were exposed to the chemical BPA.

Bisphenol A or BPA is a chemical used in plastics and epoxy resins. The chemical is found in many products including water bottles, cups and impact resistant material. Compact discs Epoxy resin is used to coat metal products such as food cans, bottles and cup.

Previous research has shown that BPA can affect fertility in animals. A related study on mice had linked the chemical with prostate cancer in the rodents.

The study shows a direct link between BPA and cancer. The mice in the study were exposed to the chemical during gestation and nursing.

For the study, researchers fed female mice with food containing BPA. These mice were then allowed to mate and were given one of three chemical doses (50 µg, or 50 mg of BPA per kg diet) during gestation and nursing.

The scientists then followed one male and female mouse from each litter and tracked their growth for ten months.

They found that mice whose mothers were exposed to 50 mg of BPA per kg diet had seven times higher risk of developing liver tumor than other non-exposed mice.

"We found that 27 percent of the mice exposed to one of three different doses of BPA through their mother's diet developed liver tumors and some precancerous lesions. The higher the dosage, the more likely they were to present with tumors," said Caren Weinhouse, U-M doctoral student in the School of Public Health's Department of Environmental Health Sciences and first author of the paper, according to a news release.

Also, researchers found that BPA didn't discriminate between male and female. "In general, females are at lower risk of spontaneous development of liver cancer," she said in a news release. "That distinction was erased in this study, with both males and females showing tumors."

The study is published in the journal Environmental Health Perspectives.

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Liver disease and diabetes: Association, pathophysiology, and management

Diabetes Res Clin Pract. 2014 Jan 14. pii: S0168-8227(14)00005-9. doi: 10.1016/j.diabres.2014.01.003. [Epub ahead of print]

Ahmadieh H¹, Azar ST².

Abstract

Diabetes is associated with a spectrum of liver diseases including nonalcoholic liver disease, steatohepatitis, and liver cirrhosis with their increased complications and mortality. Hepatitis C virus (HCV) and its associated liver cirrhosis has been associated with diabetes through insulin resistance. Cryptogenic diabetes occurs as a consequence of liver cirrhosis with the pathophysiology being complex, but mostly attributed to the increased insulin resistance in muscle, liver, and adipose tissue. As for the management of diabetes in patients with liver disease, lifestyle modification plays an important role. Oral diabetic medications are contraindicated in patients with advanced liver diseases with associated cirrhosis, ascites, or encephalopathy. As for stable liver disease, metformin and thiazolenediones have shown mixed results, with some showing them to be effective in improving liver transaminases in addition to histological improvement in steatosis and inflammation. α-glucosidase inhibitors may be helpful in decreasing hepatic encephalopathy. Upregulation of Dipeptidyl peptidase-4 (DPP-4) has been suggested as a possible pathogenetic mechanism for HCV-related insulin resistance, and treatment with DPP-4 inhibitors could improve insulin sensitivity in diabetic patients with liver disease. Patients with impaired liver function with associated insulin resistance may need increased insulin requirements. On the other hand patients with altered liver metabolism might need decreased insulin requirements.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS: Diabetes mellitus, liver disease, liver transaminases, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis

PMID: 24485856 [PubMed - as supplied by publisher]

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