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Drugs in Development / Clinical Trials—Updated January 12, 2015

Tuesday, January 27, 2015

Low Sodium Levels Increases Liver Transplant Survival Benefit in the Sickest Patients

Researchers report that low levels of sodium in the blood, known as hyponatremia, increase the risk of dying for patients on the liver transplant waiting list. The study published in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, showed an increase in survival benefit for patients with hyponatremia and a Model for End Stage Liver Disease (MELD) score of 12 or more.

The MELD score measures the risk of death on waiting list. It is calculated using patient’s serum bilirubin, creatinine, and prothrombin time and is used by national organ allocation policy to determine the priority for a patient on the transplant waitlist. Patients who are most sick, with a high MELD score, are at the top of the waitlist. Previous research links low serum sodium, in combination with the MELD score, to increased waitlist mortality, prompting Organ and Procurement Transplant Network (OPTN) directors to approve a new policy that gives additional MELD score points (1 to 13 based on serum sodium value) to patients with hyponatremia.

Dr. Pratima Sharma, with University of Michigan Health System in Ann Arbor and lead study author notes, “While the OPTN serum sodium allocation formula may reduce deaths on the waitlist by enhancing access to donor organs, it is not clear if candidates with hyponatremia gain any survival benefit over patients with normal sodium levels. Our study examines if patients with low serum sodium prior to liver transplant have a greater survival benefit than patients without low serum sodium, all other things being equal.”

Using data from the Scientific Registry of Transplant Recipients, researchers identified 69,213 candidates, 18 years of age or older, who were on the waiting list for liver transplant between January 2005 and December 2012. Liver transplant recipients were matched to waitlist candidates with the same MELD score and located in the same donation service area.

Findings indicate that the liver transplant survival benefit increased significantly with decreased serum sodium levels when MELD scores were 12 or more. The survival benefit was not affected by low sodium values for candidates with MELD of 11 or less. Dr. Sharma concludes, “Our results suggest that adjustment based on serum sodium for the purpose of the liver allocation process should be considered for those candidates with low sodium levels and a MELD score of at least 12. Health care providers should also alert liver transplant patients on the waiting list that low sodium levels could increase their mortality risk on the waitlist and may affect the expected survival benefit following liver transplantation."

This research was supported by the National Institutes of Health (NIH, grants DK-088946 and 5R01 DK-70869) along with a research award from the American College of Gastroenterology. 


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Access the full study on the Wiley Press Room here. (To access PDFs and embargoed stories you must be logged in to the Press Room before clicking the link. Request a login here.) Full citation: “Serum Sodium and the Survival Benefit of Liver Transplantation.” Pratima Sharma, Douglas E Schaubel, Nathan P Goodrich and Robert M Merion. Liver Transplantation; (DOI: 10.1002/lt.24063).

URL: http://doi.wiley.com/10.1022/lt.24063

Author Contact: Media wishing to speak with Dr. Sharma may contact Mary F. Masson at University of Michgan at mfmasson@med.umich.edu.

Monday, January 26, 2015

Fish Intake Tied to Liver Cancer Risk

The role of nutrition in liver cancer risk has been underrepresented in research, particularly compared to risk factors such as chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Yet, some studies have indicated that n-3 polyunsaturated fatty acid (n-3 PUFA) may inhibit the promotion and progression stages of carcinogenesis. Fish is a source rich in n-3 PUFA, making it an ideal factor for analysis.

A new study in PLOS ONE reviewed published studies on the role of total fish intake and risk of primary liver cancer in case-control and cohort studies. Ten studies were analyzed, with all but one study hospital-based. A statistically significant inverse association between total fish intake and risk of liver cancer was observed; in comparing high vs. low intake, response models indicated that this risk was reduced by 18% and 6% per one serving/week increase, respectively. Although the exact mechanism of action is unknown, it is proposed that n-3 PUFA may inhibit cancer development via molecular biosynthesis, gene transcription and expression, and signal transduction or through its anti-inflammatory effect.

Even with these findings, residual or unknown confounding factors cannot be completely ruled out and not all studies controlled for risk factors such as HBV/HCV status. While this study supports a possible relationship between fish intake and liver cancer prevention, future well-designed studies are needed.

READ FULL ARTICLE

Source: http://www.empr.com/fish-intake-tied-to-liver-cancer-risk/article/394500/

Vitale & Codey Take Action to Provide Hepatitis C Screening to All Baby Boomers

Senate Health Committee Advances Legislation to Require Hospitals and Health Care Providers to Offer Testing to Certain High-Risk Patients

TRENTON – A bill sponsored by Senators Joseph F. Vitale and Richard J. Codey that would put New Jersey in line with CDC recommendations to test baby boomers for Hepatitis C was advanced today by the Senate Health, Human Services and Senior Citizens Committee.

“I have seen firsthand the effects that Hepatitis C can have on an individual and their family,” said Senator Vitale, D-Middlesex, Chairman of the Senate Health Committee. “If a patient is screened and made aware of the disease earlier, they can have a real shot at treatment, often so successful as to remove any trace of the disease.  Real lives can be saved with this legislation.”

The issue is close to Senator Vitale’s heart as his father passed away from complications due to Hepatitis C, a disease that he contracted through a tainted blood transfusion. The Senator notes that through this legislation, individuals will be diagnosed earlier, allowing for effective treatment to avoid liver damage, cirrhosis and even cancer.

EnvisionRx and Gilead Sciences Sign Exclusive Agreement to Help in the Fight Against Hepatitis C

TWINSBURG, Ohio, Jan 26, 2015 (BUSINESS WIRE) -- EnvisionRx®, a national, full-service pharmacy benefit management (PBM) company, today announced a partnership with Gilead Sciences Inc., a pioneer in the treatment of the Hepatitis C virus (HCV), to provide availability to HCV infection treatments Sovaldi® and Harvoni™ for EnvisionRx patients on an exclusive basis.

“EnvisionRx is committed to helping patients attain the most effective drugs at affordable prices, and we are proud to be able to offer our patients Sovaldi® and Harvoni™, the market leaders in the treatment of HCV, ” said Dawn Sherman, President of EnvisionRx. “The safety and efficacy profile of Gilead’s HCV products, coupled with the most competitive pricing in the drug class, have solidified EnvisionRx’s choice to place Gilead’s HCV products in an exclusive and preferred formulary position. We believe our comprehensive HCV approach will enable our patients to receive the best available care.”

Consistent with PBM industry practice, exceptions for other hepatitis C drugs will be allowed in some cases. Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg), is the first once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults. Sovaldi™ (sofosbuvir) 400 mg tablets, is a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.

Read more...

Gilead Expands Hepatitis C Generic Licensing Agreements to Include Investigational Pan-Genotypic Agent

–Sofosbuvir/GS-5816 Single Tablet Regimen May Provide Important New Option for Patients in Developing Countries –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Jan. 26, 2015-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the company has expanded its hepatitis C generic licensing agreements to include the investigational NS5A inhibitor GS-5816, which is being evaluated in Phase 3 clinical studies as part of a single tablet regimen that combines the compound and sofosbuvir for the treatment of all six genotypes of hepatitis C. The expanded agreements will allow Gilead’s India-based partners to manufacture GS-5816 and the single tablet regimen of sofosbuvir/GS-5816, once approved, for distribution in 91 developing countries, which together account for 54 percent of the total worldwide population of individuals infected with the hepatitis C virus (HCV).

If approved by regulatory authorities, the sofosbuvir/GS-5816 regimen would become the first pan-genotypic, all-oral single tablet regimen for HCV. A pan-genotypic therapeutic option is particularly important for developing countries, where genotype testing is often unreliable or not readily available.

“Today’s announcement marks an important milestone in Gilead’s effort to make effective hepatitis C treatment accessible to as many patients, in as many places, as quickly as possible,” said Gregg H. Alton, Executive Vice President, Corporate and Medical Affairs, Gilead Sciences. “Developing countries are home to a diverse mix of hepatitis C genotypes, and the development of a medicine that has the potential to cure any patient, regardless of genotype, could help accelerate access to treatment.”

Professor Abhijit Chowdhury, Head of Hepatology, Institute of Post Graduate Medical Education and Research, Kolkata, commented: “Pan-genotypic hepatitis C treatments have the potential to radically change the treatment landscape in developing countries, removing the need for patients to undergo burdensome laboratory tests. Even if testing facilities are available, their cost is a barrier to treatment access, so a regimen that can be used for any genotype is going to be a real attribute in tackling this disease on a global level.”

The amended agreements expand on Gilead’s existing generic licensing partnerships for hepatitis C, announced in September 2014, under which partners may produce sofosbuvir and the single tablet regimen of ledipasvir/sofosbuvir. Eight Indian-based generic manufacturers now hold licenses to manufacture Gilead’s HCV medicines – Biocon Ltd., Cadila Healthcare Ltd., Cipla Ltd., Hetero Labs Ltd., Mylan Laboratories Ltd., Ranbaxy Laboratories Ltd., Sequent Scientific Ltd. and Strides Arcolab Ltd.

Sofosbuvir recently received regulatory approval in India (January 2015), and regulatory submissions have been completed in additional countries, including Pakistan, Thailand, Brazil, Uganda, South Africa and Nigeria.

About GS-5816
The single tablet regimen of sofosbuvir/GS-5816 is an investigational agent and its safety and efficacy have not been established. Phase 3 studies evaluating the combination of GS-5816 and sofosbuvir are currently underway, with data anticipated in the second half of 2015.

Gilead’s Approach to Treatment Access in Developing Countries
Gilead makes it a priority to increase access to its medicines for people who can benefit from them, regardless of where they live or their economic means. In developing countries, Gilead’s treatment access strategies include tiered pricing, voluntary generic licensing (often in advance of U.S./EU regulatory approval), negotiation with national governments, regional business partnerships, product registration, medical education and partnerships with non-profit organizations. This approach has been successfully applied to Gilead’s humanitarian program in HIV over the past 10 years, where seven million patients are now receiving Gilead-based HIV medicines in developing countries.


For more information on Gilead Sciences, please visit the company’s website at www.Gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

- See more at: http://gilead.com/news/press-releases/2015/1/gilead-expands-hepatitis-c-generic-licensing-agreements-to-include-investigational-pangenotypic-agent#sthash.XNY7QWgP.dpuf

Saturday, January 24, 2015

Hepatitis C: What Therapy this Week?

“We really have entered this new era of direct acting antivirals, and as of this fall, we’ve finally laid to rest Interferon in the grave that we’ve all been wanting to put it in, for more than 2 decades,” opened Jacqueline G. O’Leary, MD, MPH, AGAF during her presentation at the 2015 AGA Clinical Congress of Gastroenterology & Hepatology.

According to O’Leary, sofosbuvir certainly changed everything – a truly pangenotypic polymerase inhibitor (NSSB) prescribed as 400 mg daily, never modified with no significant food effect reported. It had recently been co-formulated with ledipasvir, the first in class NSSA inhibitor, once daily dose, and also with no existing food effect.

Switching gears, O’Leary discussed the other FDA approved all oral regiment of paritapevir with ombitasvir and dasabuvir, for their genotype 1 patients. “This is a trick from HIV that allows lower dosing in medication, a dramatic increase in half-life, which adds an additional protection. This is binding against the thumb blood site, which definitely gets two thumbs up, because it allows you to give the finger to hepatitis C.”

- See more at: http://www.hcplive.com/conferences/aga-2015/Hepatitis-C-What-Therapy-this-Week#sthash.XnTiU8TC.dpuf

Genotype 1: VIEKIRA PAK Therapy

Be sure to check out our new HCSP fact sheet on Genotype 1: VIEKIRA PAK Therapy