May 14, 2014

Eradication of hepatitis C on the horizon

Originally published in the The Washington Times

By Lenny Bernstein May 12 at 7:00 am

gilead

Darryl Kato, research scientist for Gilead Sciences Inc., works on the synthesis of a potential hepatitis C virus drug candidate at the company’s lab in Foster City, California in 2012. (David Paul Morris/Bloomberg)

It’s an easy and reliable applause line for budget cutters to find some basic medical research and complain that it’s a complete waste of money, especially if those dollars are put up by taxpayers, as they often are. And let’s face it, those who feel otherwise don’t always do the best job of arguing the opposite position.

One exception I recently read is an article by two physicians, Raymond T. Chung and Thomas F. Baumert, with the lofty title: “Curing Chronic Hepatitis C — The Arc of a Medical Triumph.” Their analysis in an April issue of the New England Journal of Medicine shows exactly how valuable such research and a cooperative government can be.

For those who are not aware, the piece points out that 130 million to 170 million people — three percent of the world’s population —  are infected with the virus that causes hepatitis C. In the United States, Chung and Baumert note, chronic hepatitis C is the leading cause of death from liver disease and the top reason for liver transplants. It also recently passed HIV infection as a cause of death. According to the Centers for Disease Control and Prevention, for every 100 people in the United States infected by the hepatitis C virus, one to five will die from cirrhosis of the liver or liver cancer.

Unfortunately,  70 percent to 80 percent of people with the virus have no symptoms and many have no idea they are infected. Most at risk are injection drug users, dialysis patients, people who get tattoos or body piercings with non-sterile instruments, some health-care workers, people with HIV and children born to mothers with hepatitis C, according to the CDC.

But the good news is that today the development of anti-viral drugs “has revolutionized [hepatitis C] treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans,” according to the the authors, who are affiliated with Harvard Medical School and Massachusetts General Hospital. “This success can be traced to important scientific, clinical, and regulatory developments.”

At the risk of oversimplifying the piece, the authors note that the virus was discovered 25 years ago using new scientific approaches, and further research led to the discovery that the virus “requires continuous replication for its existence — an observation that would be leveraged for the design of strategies to permanently clear” it. Then, guided by the experience of developing the drugs used against HIV, researchers developed therapies that use more than one anti-viral agent.

The Food and Drug Administration then agreed to an unusual design of clinical trials that fast-tracked the testing of the drugs, which proved successful more than 90 percent of the time.

The result, Chung and Baumert say, is that “it may now be possible to imagine the global eradication of [hepatitis C]” if issues of cost, early detection and re-infection can be overcome — a potential landmark in public health progress, brought about by the system created to accomplish just that.

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To curb hepatitis C, test and treat inmates

PUBLIC RELEASE DATE: 14-May-2014 Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University

PROVIDENCE, R.I. [Brown University] — Problematic as it is for society, the high incarceration rate in the United States presents an important public health opportunity, according to a new "Perspective" article in the New England Journal of Medicine. It could make staving off the worst of the oncoming hepatitis C epidemic considerably easier.

Nearly 4 million Americans may be infected with the hepatitis C virus (HCV). Many of them don't know they carry HCV, which can take decades to make them ill with cirrhosis, cancer, or liver failure. About a million people could die because of HCV by 2060, the authors wrote, and many who are saved will have required critical and costly treatments, including liver transplants.

"We know this is going to come crashing down on us," said lead author Dr. Josiah D. Rich, professor of medicine and epidemiology at Brown University and director of the Center for Prisoner Health and Human Rights at The Miriam Hospital. "It's already starting to come crashing down. The next 10 to 20 years are going to be ugly."

The single best setting for fighting the epidemic is U.S. prisons and jails, where more than 10 million people cycle through each year. In part because a major means of HCV transmission is through injection drug use, a large portion of the nation's infected population passes through the criminal justice system. In the journal, for example, Rich and his coauthors estimate that one in six inmates is infected and one in three infected Americans ends up locked up for at least a little time in their lives.

"We can head off a lot of disease and expense if we invest now," Rich said. "How do we do that most efficiently and effectively? What we're arguing in the paper is that we do it using the criminal justice system infrastructure."

Worth the considerable cost

The key barrier, Rich readily acknowledges, is the very high cost of hepatitis C drugs. A 12-week course of Sovaldi, made by Gilead Sciences, costs $84,000 a person. Treating all current inmates with HCV would therefore cost $33 billion, the authors estimate. Treating just half the people who cycle through prisons and jails in a given year would cost $77 billion.

But drug costs don't have to be nearly so high if state prison systems can negotiate reasonable discounts with drug makers, as the federal government does for its prisoners.

And while prisons have a clear disincentive to spend money to treat people who may well be released before they become sick, the money cannot and need not come solely from their budgets.

"The criminal justice system cannot be expected to shoulder the prohibitive costs of hepatitis C treatments alone," said co-author Dr. Brie A. Williams, associate professor of Medicine at the University of California–San Francisco. "Recognizing that infectious disease epidemics cannot be contained behind prison walls, we must develop a national strategy for responding to them that includes financial support and an infrastructure to test and treat prisoners, both within prisons and jails and after they return to our communities."

U.S. society as a whole will pay the costs of an inadequately addressed HCV epidemic, the authors said. Helping prisons to provide this treatment will also curb the need for litigation by prisoner advocates to a community standard of HCV care for prisoners, said co-author Dr. Scott A. Allen, professor of medicine at the University of California–Riverside.

"Even with the high cost, the drugs appear to be cost-effective," Allen said. "Private insurers in the community appear to be covering it. That establishes a clear community standard, and prisons will be held to that standard by the courts. The public policy question isn't whether or not we pay for hepatitis C care but how we pay for it."

A potential model already exists in the Ryan White Care Act, the three authors note. Congress could consider replicating that achievement of funding widespread HIV services and treatment for people who couldn't obtain them otherwise them. An HCV version could include programs and grants for prisons and jails, as well as programs to prevent reinfection of inmates after they are released.

"Seizing this opportunity for timely care will require leaders to consider the criminal justice system as part of the fabric of U.S. health care," the authors concluded. "This step will help to change the perception of the HCV epidemic in the criminal justice system, transforming it from a legal liability to a critical opportunity to change the course of HCV in the United States."

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The research for the article required no direct funding, but Rich disclosed an honorarium he received from Gilead for speaking at a meeting in 2012.

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Video: Interferon-free regimens for HCV patients highlighted

Provided by Healio

May 13, 2014

CHICAGO — Bruce R. Bacon, MD, James F. King, MD, Endowed Chair in Gastroenterology, St. Louis University School of Medicine, discusses the advances in hepatitis C demonstrated by studies presented at Digestive Disease Week, and the results from the SAPPHIRE-II and ION studies that showed high cure rates across many patient groups.

“One of the most exciting concepts that’s going around at this meeting and a few weeks ago at the EASL meeting is the tremendous advances in treatment of viral hepatitis with the new interferon-free regimens,” Bacon told Healio.com. “These medicines were very well tolerated without any significant side effects, short duration of treatment and high efficacy.”

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AbbVie Eyes Hepatitis C Cure with New Regimen

Provided by Drug Discovery & Development

Wed, 05/14/2014 - 1:47pm

Christina Jakubowski, News Editor

AbbVie is tossing its metaphorical hat into the quickly growing and highly competitive hepatitis C treatment ring with an experimental, all-oral, interferon-free regimen – one that is boasting sustained viral response rates 12 weeks post treatment (SVR12 rates) that range from 90 to 100%.

While the research-based biopharmaceutical company, which split from parent company Abbott Laboratories in early 2013, may be a relative newcomer, the folks behind the pipeline are no strangers to virology.

“AbbVie has a longstanding history of development work in virology dating back to the early 90s. We introduced one of the first protease inhibitors for HIV in 1996 and followed that with Kaletra in 2000,” says Barry Bernstein, MD, AbbVie’s vice president of infectious disease development. “Early in the last decade, we then turned our attention to start work on hepatitis C, using much of what we’d learned from the HIV development activities. Our work was expanded through a collaboration with Enanta, which was formed in 2006. Since then, we’ve advanced a number of different compounds into the clinic.”

The culmination of that hard work came in mid-April of this year, when AbbVie submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the use of its experimental regimen in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV). That was quickly followed by the submission of multiple marketing authorization applications (MAAs) for the same regimen, and the same use, to the European Union (EU) in early May.

Both submissions are backed by a breakthrough Phase 3 clinical trial program. The pivotal TURQUOSE-II trial showed viral response rates of 91.8% and 95.9% after 12 and 24 weeks of treatment, respectively. These rates are in patients considered to be a “difficult-to-treat” population: those who have GT1 HCV and compensated liver cirrhosis.

“The Phase 3 program involved six different clinical trials which were targeted to different populations. They ranged from patients who had not received prior treatment, they had no evidence of cirrhosis, to patients who had advanced disease with compensated cirrhosis and who had failed prior therapy with interferon- and ribavirin-based regimens. So, it was a broad spectrum of patients, which we think reflects the population currently infected with the hepatitis C virus,” says Bernstein. “The studies enrolled rapidly, I think reflecting, in part, a great deal of excitement about the potential for these interferon-free therapies to really transform the face of HCV treatment.”

Bernstein was “pleased” with these overall response rates. “We felt that they reflected the new regimen’s potential to [help] a vast majority of patients with HCV infection,” he says.

He added: “We had previously performed a Phase 2b trial, the AVIATOR study, and in that study we achieved SVR rates as high as 99% in some populations. This Phase 3 program expanded on that, to additional populations including cirrhosis, and overall we saw similar response rates confirming the Phase 2b data. So, response rates in the various arms of the study ranged from 90 to 100%.”

While awaiting approval in both the United States and EU, AbbVie will continue to make strides in other areas of its hepatitis C program. According to Bernstein, the company currently has a Phase 3 program in Japan, and is looking to initiate work in China soon. Perhaps most promising is AbbVie’s recently presented data out of Egypt, where genotype 4 HCV is endemic.

“[In Egypt], we enrolled both treatment-na├»ve and treatment-experienced genotype-4-infected patients,” Bernstein says. “There, we saw SVR rates as high as 100%, so we are very encouraged by those results.”

Abbvie’s regimen, which consists of the fixed-dose combination of ABT-450 and ritonavir, co-formulated with ABT-267 (ombitasvir), dosed once daily, and ABT-333 (dasabuvir) – with or without ribavirin – dosed twice daily, faces tough competition if approved. Gilead’s Sovaldi (which carries a controversial price tag) was approved by the FDA in December 2013 and by the European Medicines Agency (EMA) in January. In the pipeline at Bristol-Myer Squibb is a dual regimen of daclatasvir and asunaprevir, which has received Breakthrough Therapy Designation from the FDA. An NDA for the BMS treatment is also pending.

So what sets AbbVie’s treatment apart?

“We feel the most important characteristic of a regimen is its ability to cure patients. This is a devastating disease and it has a tremendous impact on patients’ quality of life as well as morbidity and mortality. So, the ability to cure is by far the most important characteristic of the regimen,” Bernstein says. “We’ve focused our development program on maximizing the SVR (or cure) rates that we can achieve with our therapy. So, we have targeted different populations with slightly different regimens to meet that objective and we feel that with the SVR rates that we are seeing in Phase 3, our regimen will provide an important option for patients with hepatitis C.”

With hopeful expectations for U.S. approval of the new regimen by the end of 2014, Bernstein is also looking to the pipeline for future hepatitis C drug development. There, he sees potential next-generation treatments, which have already progressed to Phase 2 at AbbVie, for patients with all genotypes.

“There are other genotypes, genotype 4 and genotype 3 in particular, where there is still significant unmet medical need. We are working on next-generation compounds that will address those needs,” he says. “These compounds include a protease inhibitor and an NS5A inhibitor with activity against all genotypes, as well as activity against many of the resistance-variants that emerge with first-generation therapy use. So, we feel that these will have utility there.”

Yet despite all the excitement surrounding the pharma companies that are developing hepatitis C compounds and regimens, Bernstein adds that it’s important to remember the people who are truly benefitting from these drug discoveries.

“It’s a particularly exciting time for patients in need of improved therapies,” he says. “We’re very, very happy to be contributing to that effort – to improve treatments for hepatitis C.”

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Abbvie TV Commercial -- Hepatitis C Awareness

Abbvie TV Commercial, 'Hepatitis C'

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