Wednesday, July 3, 2013

Liver Cancer-New evidence for the genetic bases

ACRG and BGI report new evidence for the genetic bases of liver cancer

Study published online in genome research provides insights for the diagnosis and treatment of liver cancer

July 1, 2013, Shenzhen, China – The Asian Cancer Research Group (ACRG), an independent, not-for-profit company in collaboration with BGI, the world's largest genomics organization, and The University of Hong Kong (HKU), jointly announced the publication of findings from a study of recurrent mutations in hepatocellular carcinoma (HCC), one of the most deadly cancers worldwide, in the international journal Genome Research. The study provides new insights into potential therapeutic intervention strategies for this common form of liver cancer.

HCC is a primary malignancy of the hepatocytes, generally leading to death within 6-20 months after diagnosis. This type of cancer is more common in parts of Africa and Asia, where the patients with hepatitis B or C are at risk for liver cancer, even if they have not developed cirrhosis. HCC has limited treatment options such as surgical resection of the tumor at its early stage, and the molecular basis of its occurrence and development remains poorly understood.

In this study, researchers used whole genome sequencing (WGS) to survey a cohort of 88 matched HCC tumor and normal samples from Hong Kong for investigating alerted genes and the pathways implicated in HBV-associated HCC. They found that TP53 was the most commonly mutated tumor suppressor gene, accounting for 35.2% in the HCC cohort. Generally, the patients with tumors containing TP53 mutations exhibited poor survival.

The Wnt/β-Catenin signaling pathway is central for liver functions and is frequently abnormal activated in the carcinogenesis of HCC. Researchers in this study found β-catenin maybe the most frequently mutated oncogene. In addition to β-catenin, they found relative high mutation rates in genes in the JAK/STAT pathway, which may act as a major oncogenic driver in HCC tumor progression.

Hancheng Zheng, group leader of this project at BGI, said, "Liver cancer is intractable to nearly all currently available anti-cancer targeted therapies. Our findings in this study provide a better understanding of molecular basis of hepatocarcinogenesis and provide new clues to improving the diagnosis and treatment of liver cancer in the future."

"We detected a series of genes and pathways implicated in HBV-associated HCC using whole genome sequencing, which contribute to a better understanding of the tumor biology and targeted drug screening," said Dr. James Hardwick, Vice President of ACRG, and Director of Informatics & Analysis at Merck, "The ACRG was established to fuel research directed towards improving our understanding of cancers affecting Asian populations. By working together, we are able to generate important breakthroughs that can be transformed to better fight against liver cancer in the future."

"As clinicians, we are very excited about the several prevalent and actionable mutations identified from the study, including activating mutations of JAK1, which warrant testing several existing inhibitors for the treatment of the disease preclinically and clinically," said Dr. Ronnie Poon, Chair Professor and Chief, Division of Hepatobiliary and Pancreatic Surgery, The University of Hong Kong.


About the Asian Cancer Research Group, Inc. (ACRG)

Formed in 2010, ACRG is an independent, not-for-profit company established jointly by Eli Lilly and Company, MSD (known as Merck in the United States and Canada), and Pfizer Inc. to accelerate research and ultimately improve treatment for patients affected with the most commonly-diagnosed cancers in Asia. The goal of ACRG is to improve the knowledge of cancers prevalent in Asia by freely sharing data generated by the ACRG with the scientific community in order to accelerate drug discovery efforts. This collaboration exemplifies a model in which large pharmaceutical companies combine their resources and expertise to more rapidly increase knowledge in the scientific community of underserved diseases with the hope of enabling the discovery of more effective therapies for patients. ACRG is focusing its initial efforts on Asian liver, gastric and lung cancers.

About BGI

BGI was founded in Beijing, China, in 1999 with the mission to become a premier scientific partner for the global research community. The goal of BGI is to make leading-edge genomic science highly accessible, which it achieves through its investment in infrastructure, leveraging the best available technology, economies of scale, and expert bioinformatics resources. BGI, and its affiliates, BGI Americas, headquartered in Cambridge, MA, and BGI Europe, headquartered in Copenhagen, Denmark, have established partnerships and collaborations with leading academic and government research institutions as well as global biotechnology and pharmaceutical companies, supporting a variety of disease, agricultural, environmental, and related applications.

BGI has a proven track record of excellence, delivering results with high efficiency and accuracy for innovative, high-profile research: research that has generated over 200 publications in top-tier journals such as Nature and Science. BGI's many accomplishments include: sequencing one percent of the human genome for the International Human Genome Project, contributing 10 percent to the International Human HapMap Project, carrying out research to combat SARS and German deadly E. coli, playing a key role in the Sino-British Chicken Genome Project, and completing the sequence of the rice genome, the silkworm genome, the first Asian diploid genome, the potato genome, and, more recently, have sequenced the human Gut Metagenome, and a significant proportion of the genomes for the1000 Genomes Project. For more information about BGI, please visit

Media Contacts

For BGI:

Bicheng Yang
Public Communication Officer

For the Asian Cancer Research Group:

Eva Groves

NPR - Doctors Recommend Baby Boomers Get Tested For Hepatitis C

Hepatitis C affects more than 3 million adults, most baby boomers. New York has passed legislation to become the first state to require doctors to offer the test to this age group. But some doctors are opposed to it, and it's unclear whether Governor Cuomo will sign the measure.

Stem Cell Transplants Clear HIV in Two Patients in Study

Stem Cell Transplants Clear HIV in Two Patients in Study

By Simeon Bennett - Jul 3, 2013 4:30 AM ET

Two HIV patients in Boston who received stem-cell transplants for cancer had no trace of the AIDS-causing virus after the procedure, suggesting they may have been cured.

The two patients, treated at Brigham and Women’s Hospital, stopped HIV treatment after the transplants, which in other patients has opened the door for the virus to come roaring back. In one patient there was no sign of the virus 15 weeks after stopping treatment, while the other has gone seven weeks without HIV rebounding, according to results presented today at the International AIDS Society’s meeting in Kuala Lumpur....

Read more..........

AIDS: Stem Cell Transplant Leads to HIV Remission

Published: Jul 3, 2013

By Michael Smith, North American Correspondent, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

KUALA LUMPUR -- Two HIV-positive men who got a stem cell transplant to treat blood cancers have now been off antiretroviral drugs for several weeks without evidence of the virus rebounding, a researcher said here.

The apparent HIV remissions are exciting developments, but it is too early to say the men have been cured, according to Timothy Henrich, MD, of Brigham and Women's Hospital in Boston.
"It is possible that the virus could come back next week," Henrich told reporters before his late-breaker presentation at the 7th International AIDS Society meeting on HIV pathogenesis, treatment, and prevention.

But researchers have been unable to find evidence of HIV replication or of HIV DNA integrated into inactive immune cells, although the men have been off HIV therapy for 8 and 15 weeks, respectively, Henrich reported.

If that state persists, he said, it might offer clues to a more widely applicable approach to inducing HIV remission, since stem cell transplant is "not a practical strategy" to cure the 34 million people with HIV worldwide.

Outside experts also cautioned against hyping the findings.

"The next step is to confirm this in larger numbers," said Sharon Lewin, MD, of Monash University in Melbourne, Australia. That might be possible because stem cell transplants are performed relatively often around the world, some of them in people with HIV.

But she echoed Henrich's view that stem cell transplant will not be widely useful in curing HIV, if only because of the expense and risk of the procedure.

But, she told reporters, such cases are "absolutely instrumental in moving the science forward."
Indeed, Henrich said, so far investigators don't know what aspect of the stem cell transplant and subsequent therapy led to the disappearance of the virus.

The best guess at the moment, Henrich said, is that graft-versus-host disease -- a common sequel to allogeneic stem cell transplant -- eliminated HIV-bearing host cells while the donor cells were protected from infection by antiretroviral therapy.

The finding is reminiscent of the case of Timothy Brown, the "Berlin patient," who was the first person to have an apparently curative stem cell transplant.

But in that case, doctors sought a donor whose immune cells carried a mutation -- the delta32 variant of the CCR5 gene -- that rendered them resistant to HIV infection.

Brown had what is called myoablative conditioning to completely destroy his own immune system before getting the donor cells and was not on antiretroviral drugs after the transplant.
In the 2 cases in Boston, both men had minimal conditioning with chemotherapeutic drugs, so their own immune systems were not completely destroyed. And they got donor cells that -- in principle -- were susceptible to HIV.

During and after the transplant, both patients remained on antiretroviral therapy for 2.7 and 4.5 years of follow-up before stopping therapy, Henrich said.

It was only recently -- after consultation with ethics boards, the patients themselves, and their doctors -- that Henrich and colleagues "felt justified" in stopping the anti-HIV medications.
The decision to undertake an "analytical treatment interruption" was based on the continuing inability to find HIV in the two men, Henrich said.

Because of the effectiveness of current anti-HIV therapy, the investigators thought stopping treatment entailed "minimal risk" to the patients, senior investigator Dan Kuritzkes, MD, also of Brigham and Women's, told MedPage Today.

Such treatment interruptions have been tested several times in patients who have suppressed virus under anti-retroviral therapy, and usually result in HIV rebound within days.

But there are several cases -- including a cohort in France -- where such interruptions have led to durable control of the virus without the need to resume anti-HIV therapy.

And U.S. researchers are following up the case of an HIV-positive infant, treated within hours of birth, who currently has no evidence of the virus although she was lost to follow-up and did not receive treatment for several months.

In the months and years to come, Lewin said, it's extremely likely that more such individual cases of HIV remission will be found, which might raise "false hope" for a cure.
"We want a much larger, scalable cure" to treat 34 million people, she said, "and that is going to be quite a challenge."

Primary source: International AIDS Society
Source reference:
Henrich T, et al. "In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation" IAS 2013; Abstract WELBA05.

Tuesday, July 2, 2013

Health-related QOL poorer during early HCV treatment with addition of telaprevir

Health-related QOL poorer during early HCV treatment with addition of telaprevir
Vera-Llonch M. Aliment Pharmacol Ther. 2013;38:124-133.
July 1, 2013
Patients with chronic hepatitis C experienced a temporary decrease to health-related quality of life during interferon-based therapy that was more pronounced with the addition of telaprevir in a recent study.
Researchers evaluated the health-related quality of life (HRQOL) of 722 patients with chronic HCV genotype 1 enrolled in the multicenter, phase 3, placebo-controlled, double blind ADVANCE study. All patients were treatment-naive and received either 48 weeks of therapy with pegylated interferon alpha-2a and ribavirin (PR; n=359), or 12 weeks of telaprevir with either 24 (T12PR24; n=210) or 48 weeks (T12PR48; n=153) of PR.
Read more....
Preliminary results suggest safety, efficacy of tremelimumab as HCC, HCV therapy
Sangro B. J Hepatol. 2013;59:81-88.
July 2, 2013
Patients with hepatocellular carcinoma and chronic hepatitis C may experience antiviral and antitumoral benefits from treatment with tremelimumab, according to results of a recent pilot study.
In the phase 2, noncontrolled, multicenter, open-label trial, researchers administered 15 mg/kg tremelimumab intravenously daily to 21 adult patients with chronic HCV genotype 1b and hepatocellular carcinoma (HCC) for 90 days for a maximum of four cycles or until severe toxicity or tumor progression occurred. Toxicity was evaluable in 20 participants and tumor response was measurable in 17 cases.
Read more....

Ex-Vegas MD guilty of murder in wide Hepatitis C outbreak

8 News NOW

Former prominent Las Vegas doctor and endoscopy clinic owner Dipak Desai in court July 1, 2013 after being convicted of second-degree murder, among 27 counts stemming from what's considered one of largest Hepatitis C outbreaks in U.S. history / KLAS-TV

Read more....

Achillion Hepatitis C Drug Trial on Hold on Liver Concern

Achillion Hepatitis C Drug Trial on Hold on Liver Concern

By Mary Camille Izlar & Robert Langreth - Jul 2, 2013 4:09 PM ET

Achillion Hepatitis C Drug Trial on Hold on Liver Concern U.S. regulators put the hepatitis C drug trial on hold after some patients experienced elevated liver enzymes, Achillion said in a statement yesterday. 

The elevations were observed in healthy patients when Achillion’s sovaprevir was combined with two medicines used to treat HIV infections in order to test for possible drug interactions. The combination may have resulted in a drug interaction that produced higher-than-expected blood levels of the therapies, Achillion said.

“Achillion voluntarily stopped further dosing” and “promptly notified” the Food and Drug Administration of the finding in the early-stage trial involving sovaprevir, the New Haven, Connecticut-based company said. The hold doesn’t affect a current second-stage study of the drug in hepatitis C patients.

Achillion has three drugs in clinical testing for hepatitis C, a liver disease that affects 170 million people worldwide. The company said April 23 that one of the treatments, ACH-3102, appeared effective in five out of eight patients, reducing the amount of the liver-destroying virus in their bloodstream to undetectable levels after 12 weeks of treatment.

Achillion is competing with drugmakers including AbbVie Inc. (ABBV) and Gilead Sciences Inc. (GILD) to develop new treatments for the disease, a market analysts’ estimate may be $20 billion.

To resolve the hold, the regulatory agency has asked for data from two drug interaction studies as well as a safety analysis of continuing sovaprevir studies, which the company said it plans to provide in about six weeks.

Achillion shares had gained 35 percent in the past 12 months through yesterday.

To contact the reporters on this story: Mary Camille Izlar in New York at; Robert Langreth in New York at

To contact the editor responsible for this story: Reg Gale at

Liver toxins delay CT Achillion's hep C trial
July 2, 2013
Achillion Pharmaceuticals Inc. got a dose of bad news about its efforts to develop a treatment for hepatitis C.

The New Haven biopharmaceutical company said Monday the U.S. Food & Drug Administration suspended one of its clinical trials for its hepatitis C drug sovaprevir after a trial subject built up an unusually high amount of toxic liver enzymes.

Despite the setback, however, the FDA is allowing Achillion to continue enrollment and the 12-week treatment of patients in Phase 2 trials involving sovaprevir and Achillion's ACH-3102 formulation, the company said.

The company was due to elaborate on the FDA notification and other clinical-trial data during a Monday afternoon conference call with financial analysts and reporters.

UPDATE 1-FDA places clinical hold on Achillion's hep C drug, shares plunge

Mon Jul 1, 2013 6:27pm EDT

* Co says liver enzymes elevated in drug interaction with HIV drug
* Co says hold does not affect mid-stage study
* Co could potentially lose access to market for HIV patients - analysts
* Shares fall 22 percent in extended trading

By Vrinda Manocha
July 1 (Reuters) - Achillion Pharmaceuticals Inc said the U.S. Food and Drug Administration had placed a clinical hold on its hepatitis C drug sovaprevir after elevations in liver enzymes were noted in an early-stage study of the drug's interaction with an HIV drug.
Shares of the company fell 22 percent in extended trading.

The company said the FDA had asked for study reports from two drug-drug interaction studies involving the drug and a safety analysis of ongoing trials.

Achillion was testing sovaprevir's interaction with an antiretroviral drug atazanavir, which was boosted by another drug called ritonavir.

The company said it had detected elevations in liver enzymes, an indication of liver damage, in multiple subjects, but none of the elevations met the criteria of a serious adverse event.
"We don't know what's going on. What we know is that when Achillion's drug is evaluated with a pretty typical HIV drug, we get a toxic combination," Maxim Group analyst Jason Kolbert told Reuters.

"Clearly now the profile of this drug is not perfect at a time when the market wants to see drugs with a very clean profile."

William Blair analyst Katherine Xu said if the drug-drug interaction was real, then the company may not be able to target patients taking atazanavir.

"I think about 20 percent of hepatitis C patients are infected with HIV, and then within these HIV patients, probably 10 percent are taking atazanavir. It's not that much, it's more a perception. It might be a nuisance for doctors to prescribe", she said.

Maxim's Kolbert also said that some people had thought that Achillion was positioning itself to be sold, and the news would hurt their chances that a buyer would want to acquire the entire company.
The company said none of its other drug-drug interaction studies had showed such elevations in liver enzymes.

The FDA issues clinical holds to delay the clinical investigation of a drug, or to suspend an ongoing investigation. Companies may not recruit new subjects when an ongoing study is placed on a clinical hold.

The clinical hold does not affect the company's mid-stage trial testing sovepravir in combination with another of its hepatitis C drugs and a standard therapy ribavirin.
The company said it expected to provide the information to the FDA within about six weeks.
Shares of the company, which were halted prior to the news, closed at $8.36 on Monday on the Nasdaq.

July 1, 2013
Achillion Provides Update on Sovaprevir Development Program
Following Phase 1 drug-drug interaction study with ritonavir-boosted atazanavir showing elevated liver enzymes, sovaprevir placed on clinical hold by FDA
Ongoing enrollment and treatment of patients remains unaffected in Phase 2 -007 combination trial evaluating 12-weeks of sovaprevir and ACH-3102 for treatment-naive genotype 1 patients
Conference call and webcast to be hosted today at 4:15 p.m. EDT
NEW HAVEN, Conn., July 1, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that the Company has received notice from the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on sovaprevir after elevations in liver enzymes associated with significantly higher than anticipated exposures to atazanivir and sovaprevir were noted in a Phase 1 healthy subject drug-drug interaction (DDI) study evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. The FDA has allowed continued enrollment and treatment of patients in the Phase 2 -007 clinical trial evaluating 12-weeks of sovaprevir in combination with ACH-3102 and ribavirin for patients with treatment-naive genotype 1 hepatitis C viral infection (HCV).

In a Phase 1 drug-drug interaction study, Achillion was evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. While conducting this study, Achillion detected unanticipated elevations in ALT liver enzymes (grade 3 or 4) in multiple subjects, although none of these met the criteria for a serious adverse event (SAE). Achillion voluntarily stopped further dosing in the DDI study and promptly notified the FDA of these findings. Preliminary pharmacokinetic results indicate a metabolic interaction whereby plasma concentrations of both atazanavir and sovaprevir were substantially increased upon co-administration. Such ALT elevations have not been seen in the 12-week combination -007 trial, the 12-week combination -005 trial with ACH-3102 and ribavirin, or in any other drug-drug interaction studies completed with sovaprevir to date.

With the preliminary draft data on hand at the time of notification, the FDA placed sovaprevir on clinical hold. In order to resolve the clinical hold, the FDA has asked for study reports from two drug-drug interaction studies and an integrated safety analysis of on-going sovaprevir trials, each of which Achillion expects to provide to the FDA within approximately six weeks.
With respect to the ongoing -007 Phase 2 clinical trial, Achillion is treating patients in the first segment of the study and plans to release interim clinical trial results, including rapid virologic response (RVR) during the third quarter and sustained viral response (SVR) during the fourth quarter, as previously anticipated. To date, patients enrolled in the trial have received up to six weeks of combination treatment with no safety issues noted.

Conference Call
The Company will host a conference call and simultaneous webcast on Monday, July 1, 2013 at 4:15 p.m. Eastern time. To participate in the conference call, please dial (877) 266-0482 in the U.S. or (631) 291-4567 for international callers. A live audio webcast of the call will be accessible at or Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

A replay of the webcast will be available on Alternatively, a replay of the conference call will be available starting at 7:15 p.m. Eastern time on July 1, 2013, through 11:59 p.m. Eastern time on July 7, 2013 by dialing (855) 859-2056 or (404) 537-3406. The replay passcode is 14259844.

About Achillion Pharmaceuticals
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit or call 1-203-624-7000.

Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potential causative factors for the unexpected results in Achillion's Phase 1 drug-drug interaction study of sovaprevir and ritonavir; Achillion's expectations regarding timing for the completion and reporting of results of its clinical trial of ACH-3102 in combination with sovaprevir and ribavirin; and Achillion's expectations regarding timelines for submitting additional data to FDA in response to the clinical hold. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," " estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: satisfactorily respond to regulatory actions with regard to its clinical development programs, including the FDA's request for further information and data regarding the Phase 1 drug-drug interaction study; successfully resolve the partial clinical hold with regard to sovaprevir; continue to advance sovaprevir in clinical trials; replicate in later clinical trials positive results found in preclinical and earlier stage clinical trials of sovaprevir, ACH-3102, and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2013 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

Monday, July 1, 2013

Lawmakers to NY Docs: Screen All Baby Boomers for Deadly Liver Disease

Lawmakers to NY Docs: Screen All Baby Boomers for Deadly Liver Disease

Monday, July 01, 2013    


Hepatitis C News Team Launch New Online Hep C TV Channel

 (PRWEB) July 01, 2013

The team behind, an online community for those living with hepatitis C, has launched Hep C TV, a weekly online news channel.

Hep C TV from will feature news, views and updates on hep C from around the world. Also on offer is a regular Ask the Expert slot fronted by Dr Matthew Foxton, consultant hepatologist with London’s Chelsea & Westminster Hospital, as well as regular interviews with key figures from leading patient organisations and support groups, real-life stories from those living with hep C and updates on treatment advancements.

Hepatitis C is a liver disease that affects around 150 million people worldwide. Often referred to as a silent disease, as in most cases it does not result in any symptoms, hepatitis C is most commonly transmitted through contact with an infected person’s blood. The hepatitis C virus can cause serious damage to the liver and, if left untreated, can result in scarring of the liver, liver disease or even death.

Launched in December 2012, offers those living with hepatitis C the opportunity to share their real-life experiences and tips with each other.

For further information, visit or