Friday, September 2, 2016

Study Explores Marijuana Use and Fibrosis in Women with HIV and Hepatitis C

A study in women coinfected with hepatitis C and HIV found that use of marijuana was not associated with progression to advanced liver fibrosis.

University researchers studied long-term effects of tetrahydrocannabinol (THC) from marijuana on fibrosis progression in women enrolled in the Women’s Interagency HIV Study. Results were published recently in the Oxford Journal of Clinical Infectious Diseases.

The hepatitis C virus (HCV) is a blood-borne disease that, left unchecked, can lead to fibrosis, cirrhosis, liver cancer, or the need for a liver transplant. The authors note that marijuana use has been associated with progression of liver fibrosis in retrospective analyses of patients with chronic hepatitis C and that other studies on the impact of THC use and liver fibrosis progression have reported conflicting results.

“Currently, marijuana has been legalized for medicinal and/or recreational use in 23 US states, as well as the District of Columbia, and its use in HIV/HCV-coinfected patients is common,” the authors stated in the article. “Given that it is becoming more widely available and more regularly consumed, it is critical to assess its clinical effects, including any negative impact of THC use on liver fibrosis progression.”

In this longitudinal analysis, researchers measured marijuana and alcohol use, quantifying it as average exposure per week. Liver fibrosis was categorized according to FIB-4 scores, as none, moderate or significant.

The study followed women who were coinfected with hepatitis C and HIV for an average of 11 years. Out of 575 women, 25% reported less than weekly THC use, 12% reported weekly use and 7% said that they used daily; just over half reported no THC use at all.

There were not many women who were heavy users of THC, but the study’s long follow-up period and study size enabled researchers to conclude that occasional THC is unlikely to contribute to fibrosis progression, according to the article.

“We found no evidence that THC accelerated fibrosis progression in women with HIV-HCV coinfection,” lead author Erin Kelly, MD, assistant professor at the University of Ottawa in Canada, said in an email. “Importantly, daily users were less prevalent in this cohort, therefore our results should not be extrapolated to this group.”

The possibility of underreported THC and alcohol use by the women in the study was noted as a limitation. In addition, liver biopsy was not conducted and fibrosis stage was instead determined using non-invasive tests.

Much like findings from other published studies, predictors of progression of significant fibrosis involving women in the WIHS study included the presence of baseline fibrosis, as well as entry CD4 count and HCV RNA level and ongoing alcohol consumption, according to the article.

“Fibrosis progression was associated with poor HIV control and alcohol use,” the authors concluded. “Clinicians should therefore counsel patients on limiting or excluding alcohol intake, in addition to optimizing medical treatment for HIV and HCV, as these factors are more important than THC use in modulating liver disease,” they advised. - See more at: http://www.hcplive.com/medical-news/study-explores-marijuana-use-and-fibrosis-in-women-with-hiv-and-hepatitis-c#sthash.i3jsMf1w.dpuf
A study in women coinfected with hepatitis C and HIV found that use of marijuana was not associated with progression to advanced liver fibrosis.

University researchers studied long-term effects of tetrahydrocannabinol (THC) from marijuana on fibrosis progression in women enrolled in the Women’s Interagency HIV Study. Results were published recently in the Oxford Journal of Clinical Infectious Diseases.

The hepatitis C virus (HCV) is a blood-borne disease that, left unchecked, can lead to fibrosis, cirrhosis, liver cancer, or the need for a liver transplant. The authors note that marijuana use has been associated with progression of liver fibrosis in retrospective analyses of patients with chronic hepatitis C and that other studies on the impact of THC use and liver fibrosis progression have reported conflicting results.

“Currently, marijuana has been legalized for medicinal and/or recreational use in 23 US states, as well as the District of Columbia, and its use in HIV/HCV-coinfected patients is common,” the authors stated in the article. “Given that it is becoming more widely available and more regularly consumed, it is critical to assess its clinical effects, including any negative impact of THC use on liver fibrosis progression.”

In this longitudinal analysis, researchers measured marijuana and alcohol use, quantifying it as average exposure per week. Liver fibrosis was categorized according to FIB-4 scores, as none, moderate or significant.

The study followed women who were coinfected with hepatitis C and HIV for an average of 11 years. Out of 575 women, 25% reported less than weekly THC use, 12% reported weekly use and 7% said that they used daily; just over half reported no THC use at all.

There were not many women who were heavy users of THC, but the study’s long follow-up period and study size enabled researchers to conclude that occasional THC is unlikely to contribute to fibrosis progression, according to the article.

“We found no evidence that THC accelerated fibrosis progression in women with HIV-HCV coinfection,” lead author Erin Kelly, MD, assistant professor at the University of Ottawa in Canada, said in an email. “Importantly, daily users were less prevalent in this cohort, therefore our results should not be extrapolated to this group.”

The possibility of underreported THC and alcohol use by the women in the study was noted as a limitation. In addition, liver biopsy was not conducted and fibrosis stage was instead determined using non-invasive tests.

Much like findings from other published studies, predictors of progression of significant fibrosis involving women in the WIHS study included the presence of baseline fibrosis, as well as entry CD4 count and HCV RNA level and ongoing alcohol consumption, according to the article.

“Fibrosis progression was associated with poor HIV control and alcohol use,” the authors concluded. “Clinicians should therefore counsel patients on limiting or excluding alcohol intake, in addition to optimizing medical treatment for HIV and HCV, as these factors are more important than THC use in modulating liver disease,” they advised. - See more at: http://www.hcplive.com/medical-news/study-explores-marijuana-use-and-fibrosis-in-women-with-hiv-and-hepatitis-c#sthash.i3jsMf1w.dpuf

Gilead to get attorney fees in hepatitis C patent fight with Merck

Aug 11 (Reuters) - Gilead Sciences Inc is entitled to receive the attorney fees it incurred related to hepatitis C patent litigation with drugmaker Merck & Co Inc, a U.S. district judge has ruled.
In June, Gilead was freed from paying up $200 million in damages for infringing two Merck patents related to Gilead's blockbuster drugs Sovaldi and Harvoni, after a U.S. judge found a pattern of misconduct by Merck including lying under oath and other unethical practices.
In a filing on Thursday, U.S. District Judge Beth Labson Freeman said that Gilead was entitled to relief from the fees it incurred while defending the case.
Merck is trying to catch up to Gilead, which dominates the market on a new generation of hepatitis C drugs that can cure well over 90 percent of patients with the liver disease.
The case dates back to 2013 when Gilead and Merck sued each other, claiming ownership of laboratory work underlying sofosbuvir, the active ingredient in Gilead's drugs.

Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) Is Gearing Up For Interim HCV Release Next Month

Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) just reported that it is set to release its latest data from a lead HCV combo trial at the European Association for the Study of the Liver (EASL) Special Conference in September. The trial is a real hot focus in the space right now, with the company’s triple regimen therapy being touted as the next big step in once daily oral maintenance in the condition. We’ve got about a month before the data hits, and chances are we will see plenty of speculative volume ahead of the release. With this in mind, and as we head into the closing month of the quarter, here’s a look at the drug/s in question, and what to keep an eye out for when the data hits press.

So, the drugs. Achillion has developed a triple regimen of three different HPV compounds, odalasvir, AL-335 and simeprevir. The first of these is a compound that Achillion has developed, while the other two are compounds developed by Johnson & Johnson (NYSE:JNJ)’s Janssen subsidiary. Simeprevir is already approved and branded as Olysio, while AL-335 is still investigational. All three of the compounds inhibit a different protease – with each protease being responsible for a different element of viral replication in HCV. The three protease targets are NS5A, NS3, and NS5B. Olysio has already been demonstrated to be effective in this indication. The hope is, however, that by combining the three compounds and administering them as a triple regimen, the treatment can produce what is called a sustained virologic response when taken once daily orally across a comparatively short dosage timeframe (in this instance, around 12 weeks). This short dosing twelve-week regimen is something of a holy grail in HCV treatment, and if these two can get the treatment to market, it could be a real breakthrough for both as far as bringing a first in class candidate to commercialization is concerned.

The World Health Organization estimates that around 4% of the global population has HCV – somewhere in the region of 170 million individuals. In the US, estimates put this number  at around 4 million individuals. There are six different genotypes, and this has proved problematic by way of making it difficult to standardize a therapy in a population. At the moment, big Pharma Gilead Sciences, Inc. (NASDAQ:GILD) dominates the space, but if Achillion and Janssen can get this triple regimen approved, it would be able to target multiple genotypes, and as such, could pick up a decent share of the market from Gilead.

So, what are we looking for in the upcoming data?

Well, the trial is split into four different groups, two of which will receive all three drugs, one for six weeks and one for eight weeks, and the other two of which will receive just AL-335 and odalasvir, again, one group for six weeks and one group for eight weeks. The primary endpoint is the percentage of chronic HCV infected subjects who achieve sustained virologic response 12 weeks after the end of treatment, with this response defined as hepatitis C virus (HCV) ribonucleic acid (RNA)<lower limit of quantification (LLOQ =15 IU/mL, detectable or undetectable). This is a pretty standard definition, and we want to see a good portion of patients hit it to consider the endpoint as hit when topline comes out. From this interim data, we will probably see data that relates to SVR at dose completion, since the trial only kicked off a couple months ago. This doesn’t mean we won’t get any insight into efficacy, however. Specifically, we’re looking for a sustained virological response in as many patients as possible, interim. We would consider anything above 50% as statistically significant, and we would also like to see an improvement in the numbers between the two drug regimens and the three drug regimen, as this would support Achilion’s hypothesis.

When should we be watching for the presentation?

The company is set to report the data at the above mentioned conference at the end of September, with September 23 touted as the day to keep an eye on.

Medicare drug spending spike shows need for generics

 An exclusive Associated Press report, which found that Medicare’s spending on certain drugs soared by 85% in two years, emphasizes the government’s need for increasing the use of generics.

The AP report said that Medicare’s spending on high-cost “catastrophic” protection drugs jumped from $27.7 billion in 2013 to $51.3 billion in 2015, primarily due to rising brand-drug costs. AP’s data includes costs to taxpayers, insurers, and beneficiaries, as compiled by Medicare's Office of the Actuary.

The soaring costs were led by hepatitis C drugs Harvoni and Sovaldi (Gilead Sciences). The two drugs accounted for nearly $7.5 billion of Medicare’s catastrophic drug costs in 2015, up from around $3.5 billion in 2014. Other drugs that skyrocketed in price included Gleevec (Novartis) for leukemia and Revlimid (Celgene) for cancer.

“These findings underscore a growing need to make sure that generic drugs are available to hold down public program spending, while increasing patient access to more affordable medicines,” said Chip Davis, president and CEO of the Generic Pharmaceutical Association (GPhA).

In fact, generic medicines saved the U.S. health system $254 billion in 2014, with $33 billion of these savings accrued to Medicare, according to GPhA’s annual Generic Drug Savings in the U.S. report.

And, without generic drugs, Medicare spending would nearly double, according to Davis. “Increasing access to generic drugs for Medicare enrollees translates to significant savings for the program, taxpayers, and patients, and particularly the 12 million Medicare low-income subsidy (LIS) beneficiaries,” he said. The nonpartisan Medicare Payment Advisory Commission (MedPAC) estimates that changing LIS policies to improve generic utilization for this group could save more than $18 billion over 10 years.

One way to realize these savings is for Congress to lower the LIS copay for generic drugs, an effort that can encourage enrollees to choose generic when the option is available, according to Davis.

 Meanwhile, one senator is investigating whether Medicare's prescription drug benefit is vulnerable to manipulation by pharmaceutical companies. After the AP report was published, Sen. Charles Grassley (R-Iowa) asked whether Medicare’s prescription program is being handled correctly in a letter to the agency. "Do you believe there is potential for exploitation of the catastrophic benefit as it is currently framed?" Grassley asked.

Plus, the Congressional Medicare Payment Advisory Commission recently warned that spending on the prescription program is rising at an "unsustainable" rate, singling out specialty drugs covered under Medicare's catastrophic protection.

GPhA suggests several additional measures for increasing access to generics and reducing Medicare drug spending. Policymakers should ensure that “a fully-resourced [FDA] can address the backlog of more than 3,100 generic drug applications and shorten FDA median generic drug approval timelines,” Davis said.

Davis is also urging Congress to repeal Section 602 of the Bipartisan Budget Act of 2015. “The Medicaid rebate increase for generic drugs in the budget deal is bad for Medicaid and its beneficiaries, bad for taxpayers, and it should be immediately repealed,” he said.

Davis is also urging Congress to pass the bipartisan CREATES Act, the FAST Generics Act, to curb some brand-drug company abuses of FDA safety programs such as Risk Evaluation and Mitigation Strategies (REMS). This would result in an estimated savings of $2.4 billion to $3.2 billion over 10 years, he said.

Finally, Davis believes Congress should work closely with industry and regulatory partners to ensure that the framework for biosimilar drugs expands and expedites patient access. Savings to the U.S. healthcare system from biosimilars are projected to reach between $57 and $110 billion from 2015 through 2020, according to the IMS Institute for Healthcare Informatics.

Community pharmacy helps diagnose people with hepatitis C infection, study shows

Pilot project involved community pharmacists in the Isle of Wight testing at-risk adults for hepatitis C virus, hepatitis B, HIV and syphilis.

Winners of the 2015 Care Awards Audience Choice Awards. From left, Ryan Buchanan, Pembe Hassan-Hicks and Kevin Noble

Source: Simon Wright Photography / The Pharmaceutical Journal

A project looking at the role of community pharmacy in identifying people with hepatitis was the 2015 Pharmaceutical Care Awards Audience Choice Awards winners. From left, Ryan Buchanan, Pembe Hassan-Hicks and Kevin Noble

Community pharmacists have the potential to identify people with undiagnosed hepatitis C infection, according to research published in Clinical Pharmacist[1] (online, 5 August 2016).

In 22 pharmacies on the Isle of Wight, community pharmacists were trained to offer dry blood spot tests to anyone attending needle exchange and opiate substitution therapy. People were also encouraged to self-refer for the service by a publicity campaign.

The pilot project performed tests on 88 at-risk adults for hepatitis C virus (HCV), hepatitis B (HBV), HIV and syphilis over a nine-month period from September 2014 to May 2015.

The researchers found that 39 of the 88 adults were drug users. Of these, 17 users had not accessed the island’s drug support centre – the recovery integrated service – and were also less likely to have had a previous test compared with those who were registered with mainstream drug support services (77% versus 41%, P=0.04).

“The provision of pharmacy-based testing more than trebled the number of tests for HCV undertaken in community open access settings during the pilot period and provides additional capacity for testing in the future,” the researchers say.

“Pharmacy-based testing has the potential to reach at-risk individuals who are not tested for HCV elsewhere. When combined with integrated specialist referral, it has the potential to reduce the burden of undiagnosed HCV and engage new diagnoses directly with specialist care.”

Individuals who had a positive test for HBV surface antigen or HCV RNA were given a point-of-diagnosis consultation with a member of the specialist hepatology team in the pharmacy at an arranged date, which involved further tests and examinations.

People were referred for liver imaging and HCV treatment as necessary; adults with positive tests for HIV and syphilis were referred to the local sexual health service.

During the same time period, the recovery integrated service performed similar dry blood tests on 34 patients, of whom 85% had a history of injecting drugs and 56% had been tested previously.

Some 7% of tests carried out in the pharmacy and 9% of those carried out at the island’s recovery integrated service were positive for HCV RNA.

The average age of people screened by the pharmacist was 40 years and 54% of those screened were men. Around 18% (16 people) of tested individuals presented as a result of a publicity campaign while the remainder were recruited directly by pharmacists.

“We have demonstrated that pharmacies are able to reach patients with more diverse risk factors, who are not engaged with, and are therefore less likely to have been tested at, other services,” the researchers say. “This may be because of the inherently non-stigmatising nature of community pharmacies and the co-provision of a range of other services, such as routine prescriptions and needle exchange.

The pilot, they say, also illustrates successful collaboration between pharmacists and hepatologists to provide “readily accessible, community services for patients with HCV and thereby secure patient engagement at the beginning of their care pathway”. Researchers believe that if the pilot was rolled out it would have the potential to identify many patients with HCV across the UK.

Rachel Halford, deputy chief executive of charity The Hepatitis C Trust, welcomes the report. “It adds to the evidence that community pharmacies could be playing a key role in finding the 100,000 people thought to be living unknowingly with hepatitis C in the UK and ensuring those newly diagnosed are on the path to treatment,” she says.

“The proposed cut to community pharmacy funding is concerning, it will likely limit the impact pharmacists would be able to play in the UK’s commitment to the elimination of this disease as a threat to public health.”

Kevin Noble, a community pharmacist who was involved in the study, says an NHS culture change is needed to allow the model to reach its potential nationally.

“The idea [behind this service] isn’t rocket science. Community pharmacists are running needle exchange services already and needle exchange users are a primary risk of HCV,” he says.

Ryan Buchanan, hepatology research fellow at the University of Southampton who was also involved in the project, says community pharmacy was “a really nice environment to work in and was much better from the perspective of the patient”.

“The only downside was that only two of the pharmacies had beds in the treatment rooms so potentially examinations were quite limited,” says Buchanan. “But these pharmacists have a fantastic relationship with these patients who are really quite chaotic. The pharmacists are well known to them and have their confidence and trust.”

Merck not only loses hep C case against Gilead, it gets stuck with the bill

Merck & Co. was sitting pretty earlier this year after winning a legal dispute over sofosbuvir, the active ingredient in Gilead's multibillion-dollar babies Sovaldi and Harvoni. But all of that turned around when a judge threw out the victory and snatched back the $200 million Merck had been awarded. Now, to add insult to injury, Merck has been handed a $200 million bill for Gilead’s legal fees.

In a filing on Thursday, U.S. District Judge Beth Labson Freeman said that Gilead was entitled to relief from the fees it incurred while defending the case, Reuters reports.

Merck had won the case in March, but then in June, Labson Freeman reversed the decision, saying she found “a pervasive pattern of misconduct” by Merck ($MRK) in the patent fight. A retired Merck scientist and lawyer “intentionally fabricated testimony” about early discoveries that led to the development of next-generation hepatitis C drugs, including Gilead’s blockbuster duo, Harvoni and Sovaldi, the ruling states. And Merck supported the “bad faith conduct,” the judge said.

Merck, which has trailed Gilead in the lucrative hep C market, had hoped to capture a piece of Gilead’s enormous revenue stream from Harvoni and Sovaldi. The earlier jury verdict delivered only a $200 million award but also opened the way for Merck to pursue royalties from the two blockbuster drugs’ ongoing sales. Merck’s rival hep C cocktail, Zepatier, recently won FDA approval, but Gilead’s meds have an enormous head start in the market, with more than $23 billion in combined sales since their launches.

Merck said earlier that it intended to appeal, saying the judge’s ruling “does not reflect the facts of the case.”

A Cure For Hepatitis C: Bringing Medication Within Reach For All

Here's the promise: There is a cure, a complete cure in a short 12 weeks, for hepatitis C virus (HCV), which the Centers for Disease Control and Prevention estimates afflicts between 2.7 and 3.9 million Americans, and which is a leading cause of liver cancer and other devastating health complications. This new class of HCV drugs, which are much easier on the human body and virtually free of side effects, attacks the virus directly and can reduce the viral load to zero when taken correctly.

As with so many things in healthcare, this promise comes with challenges. First, the price tag can be steep--nearly $100,000 for a full 12-week course. But weigh this against the down-the-line medical and lost-productivity costs, not to mention human toll, associated with hepatitis C (HCV) infection, which can cause chronic liver infection, cirrhosis, cancer and the need for a liver transplant. In 2014, there were nearly 20,000 deaths in the U.S. with HCV infection as an underlying or contributing cause.

And, although treatment often comes in the form of a single pill taken once a day--simple, right?--people's lives are complicated. Medicine is only as effective as an individual's ability to take it properly, and Americans in general have a poor record here. Nearly three out of four people in the U.S. report that they do not always take their medication as directed. If the HCV regimen is started and abandoned, a great deal of money is being wasted--something the healthcare industry can ill afford.


For those suffering from HCV infection, many obstacles can stand in the way of taking medications as directed. What if you don't have stable housing and have nowhere to store the pills? What if you are elderly, asthmatic, live in a fourth-floor walk-up and cannot get to the pharmacy to fill your prescription? What if the medication interacts poorly with the HIV medication that is sustaining your life? Or, what if, fearing stigma of a disease often contracted by sharing needles, you secret the medication away and fail to refill it?

Collaborating Towards a Cure

Here's a question: How can we ensure that if we use such a costly medicine to treat people with HCV infection, including some of society's most vulnerable, they will follow the regimen day in and day out--and emerge disease-free? A novel partnership in New York City, where an estimated 150,000 people have HCV infection, is aiming to find out and provide a blueprint for others.

The effort, called Project INSPIRE* NYC, is funded by an almost $10 million Health Care Innovation Award from the Centers for Medicare & Medicaid Services (CMS). It focuses on collaboration, integrated care and care coordination that is so crucial for a population often burdened with other chronic illnesses and medications, and living without a strong social or family safety net. Now in the second year of a three-year HCIA award, the project reaches out to patients at risk for HCV infection in the Bronx and Manhattan, using an integrated model of care in which primary care providers collaborate with specialized care coordinators, and peer navigators to enroll people with HCV infection, then educate and guide them through the treatment process.

This government-provider-payer collaboration is a terrific example of what needs to be done to sustain comprehensive and effective care for a vulnerable population. The New York City Department of Health and Mental Hygiene developed this project to target communities with the highest prevalence of HCV infection. The Health Department is working in partnership with Montefiore and the Mount Sinai Health System, which administer the treatments and provide care coordination, to implement the project. Partners also include two not-for-profit health insurance companies--including my organization, VNSNY CHOICE Health Plans, through its SelectHealth Special Needs Plan--which cover the cost of treatment, recognizing that the true value of the treatment lies not just in delivering the medication but in ensuring that it is taken appropriately.

Those covered by our plan, SelectHealth, are Medicaid-eligible New Yorkers with HIV, and, while they are used to being compliant with therapy regimens, they are often living in vulnerable circumstances and can be overwhelmed by adding another medicine to their already long list. "Our Medicaid population includes a sizeable number of people with psychosocial challenges that make it difficult to stick to a three-month medication protocol," explains Dr. Jay Dobkin, SelectHealth's Medical Director.

SelectHealth has already had over 400 of its members successfully complete treatment with new HCV drugs. These successes are made possible by care coordination and other supportive services, as is being demonstrated by Project INSPIRE. Our Pharmacy Services program actively encourages robust communication among the patient, care provider and the patient's dispensing pharmacy to ensure that prescriptions are being filled and refilled in a timely manner and that contraindications (including with certain HIV and OTC medications) are observed. For homebound patients, we encourage and monitor home delivery. We have fielded questions from patients accustomed to older HCV therapies that had to be refrigerated, on how to store new meds (answer: at room temperature). And, we recognize the need for patient education, including for patients who have tried older, injectable medications, and fear that regimen's same tremendous commitment and wide array of difficult-to-manage side effects.

Creating a Sustainable Model

Project INSPIRE offers a model that is right for the times in this era of value-based purchasing in healthcare--focusing the financial equation on health outcomes rather than individual encounters. The cure's $100,000 price tag, then, must be justified by the outcomes determined and achieved by Project INSPIRE. That includes making sure each person who begins the treatment completes it, , and carefully studying the costs offset by achieving a complete cure--including the considerable costs of liver transplants and treatments for liver cancer and end-stage liver failure.

"Paying for medical and pharmacy costs is a good investment in the long-term health of our members--and also a Medicaid requirement," says Eli Camhi, Vice President & General Manager of SelectHealth. "We're modeling a new way of reimbursing that pays not only for the medication, but also helps the patient with medication adherence and provides the care coordination services needed to support this vulnerable population. The HCIA dollars get you off the ground and allow evaluation of the intervention, but when the award funding goes away, CMS doesn't want to see the initiative end. They want to know that there's a financial commitment through understanding what this partnership has learned, in order to make sure that the model can be sustained."

Eli notes that if the project's positive early reports hold up, it can lead the way on a model that may eventually be adopted across the country. CMS could recommend that Medicare and Medicaid plans cover the cost of care coordination for patients undergoing treatment for HCV infection.

"We know the new treatments work," he notes. "Our goal is to be sure our members complete the treatment and get cured."