Benitec Biopharma hepatitis C therapeutic pre-clinical results released

Monday, January 09, 2012 by Christine Feary

Benitec Biopharma (ASX: BLT) has received pre-clinical results on the use of the company’s gene silencing technology to develop a therapeutic for hepatitis C viral (HCV) infection.

HCV infection is a leading cause of liver disease, with figures from the World Health Organisation showing that about 170 million people are chronically affected.

The figures showed that there are approximately 350,000 deaths from HCV-related liver disease each year.

At present, therapy typically involves extended dosing of between 24 and 72 weeks duration, with low tolerability and only modest effects.

Results from pre-clinical studies by researchers at Pfizer and Tacere Therapeutics have been published online in the American Society of Microbiology’s journal, Antimicrobial Agents and Chemotherapy.
The pre-clinical trials showed extremely positive results for ddRNAi molecule PF-05095808.

This molecule has been specifically designed to achieve transduction of all liver cells in the liver without causing cell damage.

Importantly, there was no evidence of cytotoxicity nor of induction of the interferon response associated with the administration of the molecule.

It was also shown to be highly effective at inhibiting the commonly circulating clinical isolates of HCV, with the ability to eliminated resistance to the molecule using three shRNA sequences.

The studies indicated that the molecule is able to target commonly circulating strains of HCV.

The report concluded that the molecule represents the prototype of a new approach to HCV therapy, with a single dose that can be administered alone or in combination with other anti-HCV agents.
According to the report, “These studies demonstrated the PF-05095808 delivers sequence-specific antiviral activity in the absence of overt cytotoxicity.”

A clinical trial is expected to follow, with Tacere confirming its commitment to progressing the program, for which it has an exclusive sub-license from Benitec.

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Chronic Liver Disease Hospitalizations Greater for Diabetics

By: SUSAN LONDON, Family Practice News Digital Network

SAN FRANCISCO – Health care providers should be aware that adult patients with diabetes have a sharply increased risk for chronic liver disease and should be counseled accordingly, advised investigators with the Centers for Disease Control and Prevention.

In a U.S. population-based study reported at the annual meeting of the American Association for the Study of Liver Diseases, the investigators found that diabetic adults had four times the rate of hospitalizations related to chronic liver disease, compared with their nondiabetic counterparts. Hepatitis C and "chronic hepatitis and cirrhosis" accounted for most of these hospitalizations in the diabetic group.

"The bottom line is that people with diabetes have associated liver disease, and this is something that providers should be aware of and they should take some sort of preventive measures toward that, [things like] vaccinating against hepatitis B or counseling about decreasing alcohol intake," lead investigator Dr. Kathy K. Byrd of the CDC’s Division of Viral Hepatitis said in an interview.

In fact, the study results provided some of the impetus behind the new recommendation from the Advisory Committee on Immunization Practices that calls for hepatitis B vaccination among diabetic adults aged younger than 60 years, she said.

Dr. Byrd and her colleagues used the Nationwide Inpatient Sample (a nationally representative survey of hospital discharge data) to assess rates of hospitalization related to chronic liver disease for the years 2001-2008. The sample captured information on roughly 7.5-8.2 million hospital discharges per year.

For each hospitalization, the investigators checked for the presence of diagnostic codes for hepatitis B; hepatitis C; chronic hepatitis and cirrhosis; malignancy of the liver or bile ducts; and alcoholic liver disease. They used National Health and Nutrition Examination Survey data to obtain population denominators for adults with and without diabetes.

Study results, reported in a poster session at the meeting, showed that the age-adjusted rate of chronic liver disease–related hospitalization during the entire study period was 1,546 per 100,000 for diabetic adults in the population, roughly fourfold higher than the rate of 398 per 100,000 for nondiabetic adults. For each of the five diagnostic codes, hospitalization rates in diabetic adults were two- to sixfold higher than those in their nondiabetic peers.

Hepatitis C, as well as chronic hepatitis and cirrhosis, were by far the two most common diagnoses within the diabetic group, each seen in about 40% of the hospitalizations, according to Dr. Byrd. Results also showed a temporal trend whereby the rate of chronic liver disease–related hospitalization increased by 34% among diabetic adults between 2001 and 2008 (P = .002). When analyzed by specific diagnosis, there was a 55% increase in the rate for chronic hepatitis and cirrhosis, a 44% increase in the rate for malignancy of the liver and bile ducts, and a 34% increase in the rate for hepatitis C.

The rate of chronic liver disease–related hospitalization was consistently higher for men with diabetes than for women with diabetes. This hospitalization rate also increased by a greater extent during the study period among men with diabetes (by 46%; P = .001) than among women with diabetes (by 24%; P = .058).

Dr. Byrd reported that she had no relevant conflicts of interest.

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Vertex Announces Key 2012 Business Objectives as Company Prepares for Planned Global Launch of KALYDECO in Cystic Fibrosis

January 8, 2012

Vertex Announces Key 2012 Business Objectives as Company Prepares for Planned Global Launch of KALYDECO in Cystic Fibrosis

-More than 25,000 people have started treatment for hepatitis C with INCIVEK^®, positioning Vertex for continued growth, earnings and cashflow in 2012-

-Preparations for approval and launch of KALYDECO^TM ongoing; additional studies of KALYDECO planned for mid-2012-

-Nine new medicines in development for serious diseases; multiple proof-of-concept and later-stage studies planned for 2012-

SAN FRANCISCO --(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced its 2012 business objectives in conjunction with the 30th Annual J.P. Morgan Healthcare Conference in San Francisco . Matthew Emmens , Chairman, President and Chief Executive Officer of Vertex, and Jeffrey Leiden , M.D., Ph.D., who will become Vertex's CEO on February 1, 2012 , will discuss these objectives as part of a live presentation, which will be available on Vertex's website, www.vrtx.com, on Monday, January 9 at 11:00 a.m. PT ( 2:00 p.m. ET ).

"In 2011, our team executed a highly successful launch for INCIVEK in hepatitis C, with more than 25,000 people starting treatment since its approval in mid-2011," said Mr. Emmens . "With the strength of the launch for INCIVEK, the submission of our global approval applications for KALYDECO in cystic fibrosis and the advancement of our pipeline programs, we are positioned for significant growth, earnings and cashflow in 2012."

Dr. Leiden commented, "Entering 2012, we are focused on becoming a sustainable business with strong revenues from INCIVEK and the planned global launch of KALYDECO for cystic fibrosis. Importantly, we are pursuing opportunities to further improve treatment with our all-oral regimens in development for hepatitis C and efforts to study our cystic fibrosis medicines in a larger group of people with this devastating disease. As these and other pipeline programs advance, we will manage our business with financial discipline and focused investment to ensure the greatest benefit for patients waiting for new treatments and for our shareholders."

Preparing for Global Launch of KALYDECO^TM in Cystic Fibrosis and Expanding the KALYDECO Development Program

In December, Vertex announced that the U.S. Food and Drug Administration (FDA) accepted the New Drug Application for KALYDECO (ivacaftor) and granted the company's request for six-month Priority Review. A target review date of April 18, 2012 is set under the Prescription Drug User Fee Act for the FDA's approval decision. Vertex's marketing authorization application for KALYDECO has also been validated by the European Medicines Agency , which accepted Vertex's request for accelerated assessment in Europe .

As Vertex prepares for the potential launch of KALYDECO for people with the G551D mutation, the company is also planning to begin additional studies of KALYDECO in children with CF as young as two years of age and in people with CF who have certain mutations that were not evaluated in the previous Phase 3 studies. Pending final feedback from regulatory agencies, the company plans to begin three clinical studies of KALYDECO in mid-2012:

• Pediatric study: A study of KALYDECO in children ages 2 through 5 with gating mutations, including G551D, is expected to evaluate the safety, tolerability and effect on sweat chloride and other measures of clinical activity using a pediatric formulation of KALYDECO.
• Study in people with the R117H mutation: Vertex plans to begin the first clinical study of KALYDECO in people who have at least one copy of the R117H mutation in the CF gene. The R117H mutation causes abnormal function of the CFTR protein at the cell surface. Approximately 3 percent of people with CF in the U.S. have the R117H mutation.
• Study in other gating mutations: Vertex also plans to begin the first clinical study of KALYDECO in other gating mutations where CFTR proteins are present at the cell surface but do not function properly. G551D is the most common gating mutation, present in approximately 4 percent of people with CF in the U.S., and was the focus of previous Phase 3 KALYDECO studies. The remaining gating mutations to be evaluated in this study account for an additional approximately 1 percent of people with CF in the U.S.

Additional Studies in Hepatitis C, CF and Other Serious Diseases

Multiple additional studies of INCIVEK, KALYDECO and Vertex's pipeline medicines in development are ongoing or planned for 2012, including:

Hepatitis C

• Phase 2 ZENITH study: The ongoing Phase 2 ZENITH study is designed to assess the safety, tolerability and efficacy of the polymerase inhibitor VX-222 dosed in combination with INCIVEK and ribavirin, with and without pegylated-interferon, in people with genotype 1a and 1b chronic hepatitis C who were new to treatment. In the first quarter, Vertex expects to announce data, including sustained viral response rates at 4 weeks post-treatment (SVR4), from the two all-oral, interferon-free study arms (Arms E and F) in which patients received VX-222, INCIVEK and ribavirin.
• All-oral, interferon-free studies of the nucleotide analogues ALS-2200 and ALS-2158: Vertex and Alios are currently conducting two Phase 1 studies of the pan-genotypic hepatitis C polymerase inhibitors ALS-2200 and ALS-2158. The studies are evaluating safety and tolerability in healthy volunteers as well as 7-day viral kinetics in people with chronic genotype 1 hepatitis C. Data are expected in the second quarter of 2012, which could enable the initiation of Phase 2 proof-of-concept studies to evaluate multiple all-oral, interferon-free combination regimens in the second half of 2012. These Phase 2 studies are expected to evaluate combination regimens of ALS-2200 or ALS-2158 with INCIVEK or VX-222, potential dual nucleotide regimens (adenosine and uracil) and other interferon-free combination regimens that may also include ribavirin.
• Phase 3 study in people co-infected with hepatitis C and HIV: Enrollment is ongoing in a Phase 3 trial of INCIVEK combination therapy in people co-infected with genotype 1 hepatitis C virus and HIV.
• Phase 3 study of twice-daily dosing of INCIVEK: Enrollment is complete in a Phase 3 clinical trial to evaluate twice-daily dosing of INCIVEK (1,125 mg; BID) compared to three-times-daily dosing of INCIVEK (750 mg; q8h) as part of INCIVEK combination therapy.
• Phase 4 study of INCIVEK combination treatment in African Americans: Vertex plans to begin in the first quarter of 2012 a study of INCIVEK combination therapy in African Americans with hepatitis C who were not cured with a prior treatment of pegylated-interferon and ribavirin.
• Phase 3b study of INCIVEK combination treatment for a total duration of 12 weeks: Enrollment is ongoing in a Phase 3b trial to evaluate the potential for INCIVEK combination therapy to be shortened to 12 weeks in people with genotype 1 chronic hepatitis C who have the 'CC' variation near the IL28B gene.
• Phase 2b and 3b studies in people with hepatitis C following a liver transplant: Enrollment is expected to begin in the first quarter for clinical studies of INCIVEK combination treatment in people who have recurrent hepatitis C following a liver transplant.

Cystic Fibrosis

• Two CFTR correctors in development for people with the most common CF mutation, F508del: Enrollment is ongoing in the second part of a Phase 2 clinical trial of combination regimens of KALYDECO, a CFTR potentiator, and VX-809, a CFTR corrector, in people with the most common mutation in CF, known as F508del. In addition, Vertex plans to begin Phase 2 development of VX-661, a second CFTR corrector, in the first quarter of 2012. Data from the study with VX-809 is expected mid-year, followed by data from the study with VX-661 later in 2012.

Rheumatoid Arthritis (RA)

• 350-patient Phase 2b study of VX-509: A six-month Phase 2b study of the JAK3 inhibitor VX-509 is planned to begin in the first quarter of 2012 for the treatment of moderate to severe rheumatoid arthritis. This study will evaluate once-daily (QD) and twice-daily (BID) doses of VX-509 in combination with methotrexate, a commonly prescribed disease-modifying antirheumatic drug (DMARD) for RA that is frequently used in combination with other RA medicines.

Influenza

• Proof-of-concept study planned for mid-2012 with VX-787: A Phase 1 study is ongoing for VX-787, an investigational medicine that is designed to treat influenza A, including recent H1 (pandemic) and H5 (avian) influenza strains. Following the completion of this Phase 1 study, Vertex plans to initiate a proof-of-concept study for VX-787 in the second quarter of 2012.

Epilepsy

• Enrollment is ongoing in a Phase 2 study of VX-765 in people with treatment-resistant epilepsy.

Continued Productivity in Research

Vertex continues to focus its research efforts in the areas of infectious diseases, including viral infections - such as influenza - and bacterial infections, inflammatory diseases, cancer and neurological disorders, including pain. Vertex expects additional development candidates for the treatment of one or more of these diseases to emerge from research in 2012.

The company will report full-year 2011 financial results and financial guidance on February 2, 2012 .

Webcast

Vertex Pharmaceuticals will webcast its corporate presentation at the 30th Annual J.P. Morgan Healthcare Conference on January 9, 2012 at 11:00 a.m. PT ( 2:00 p.m. ET ). A link to the live webcast will be available via Vertex's website, www.vrtx.com, in the Events & Presentations section. An archived webcast of the presentation will be available on Vertex's website through January 23, 2012 .

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA , we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada . Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.

Safe Harbor Statement

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including the statements made by Mr. Emmens and Dr. Leiden in the second and third paragraphs of the press release, and statements regarding (i) Vertex being positioned for continued growth, earnings and cashflow in 2012; (ii) regulatory timelines for KALYDECO; (iii) Vertex's preparations for the potential launch of KALYDECO; (iv) proof-of-concept studies and later-stage studies planned for 2012; (v) planned and ongoing studies of INCIVEK, KALYDECO and the company's drug candidates and the expected timelines for initiating and announcing data from these studies and (vi) the expectation that additional development candidates will emerge from the company's research programs in 2012. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes for each of Vertex's planned clinical trials and studies may not be favorable, that regulatory authorities may require supplemental clinical trials in order to support the registration of KALYDECO, that planned or potential clinical trials may be delayed or may not be conducted, that the company may not be able to successfully develop its drug candidates, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. The company disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX - GEN)

Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge , 617-444-6108
or
Lora Pike , 617-444-6755
or
Media:
Zachry Barber , 617-444-6992 (at J.P. Morgan Healthcare Conference : 617-767-9533

Source: Vertex Pharmaceuticals Incorporated

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Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: NHANES 2001-08

Hepatology. 2011 Dec 27. doi: 10.1002/hep.25556. [Epub ahead of print]

Denniston MM, Monina KR, McQuillan GM, Jiles RB.

Source

Epidemiology and Surveillance Branch, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA. mmd1@cdc.gov.

Abstract

Many persons infected with hepatitis C virus (HCV) are unknown to the healthcare system because they may be asymptomatic for years, have not been tested for HCV infection, and only seek medical care when they develop liver-related complications. We analyzed data from persons who tested positive for past or current HCV infection during participation in the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2008. A Follow-up Survey was conducted six months after examination to determine: 1) how many participants testing positive for HCV infection were aware of their HCV status before being notified by NHANES, 2) what actions participants took after becoming aware of their first positive test, and 3) participants' knowledge about hepatitis C. Of 30,140 participants tested, 393 (1.3%) had evidence of past or current HCV infection; 170 (43%) could be contacted during the follow-up survey and interviewed. Only 49.7% were aware of their positive HCV infection status before being notified by NHANES, and only 3.7% of these respondents reported that they had first been tested for HCV because they or their doctor thought they were at risk for infection. Overall, 85.4% had heard of hepatitis C; correct responses to questions about hepatitis C were higher among persons aged 40-59 years, white non-Hispanics, and respondents who saw a physician after their first positive HCV test. Eighty percent of respondents indicated they had seen a doctor about their first positive HCV test result. CONCLUSION: These data indicate that fewer than half of those infected with HCV may be aware of their infection. The findings suggest that more intensive efforts are needed to identify and test persons at risk for HCV infection. (HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

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Many benefits go along with vitamin D

Article posted: 1/8/2012 6:00 AM

There is a lot of research going on with vitamin D. Vitamin D use is associated with significant reductions in the risk of a number of cancers, diabetes, coronary heart disease, high blood pressure, multiple sclerosis, autoimmune disease. Vitamin D has been shown to be a biologically important compound binding at over 2,000 sites on DNA and influencing over 200 different genes. Despite this information, there has been little research directly showing that specific levels of vitamin D affect disease and mortality. A recent study in the American Journal of Cardiology showed that better serum levels of vitamin D were directly linked to better health and survival.

Vitamin D is a hormone that begins in the skin with light and cholesterol and is further processed into active vitamin D by the liver and kidney. It is not commonly found in foods and, in Chicago, the sun is inadequate to generate enough vitamin D throughout the year.

The commonly held idea of vitamin D is keeping bones strong. It stimulates calcium absorption from foods and encourages the cells that make bone, osteoblasts, to use the calcium to make bone. It is common knowledge that vitamin D prevents rickets in children and osteoporosis in adults.

Vitamin D, through its binding to DNA affects cell growth, nerve and muscle function, stimulate the immune system and reduce inflammation. It also helps to regulate cell division, differentiation and even has a role in cell death.

There really is no recommended daily dose of vitamin D. Some people need a lot, some just a little. The best way to evaluate vitamin D status is to measure the serum concentration of vitamin D. One of the failings of medical studies is that serum vitamin D is rarely measured. It makes it difficult to interpret results of studies, both positive and negative, unless you know the blood level of vitamin D in each participant.

A recent study in the American Journal of Cardiology did it right. They followed the serum levels of vitamin D in 10,899 participants for over five years and correlated the vitamin D levels to the development of several illnesses and death. Interestingly, a whopping 70 percent of the participants were consistently vitamin D deficient. Vitamin D deficiency was directly associated with hypertension, coronary artery disease, cardiomyopathy and type II diabetes.

Vitamin D deficiencies, over the five years, also were strongly correlated with death from any cause. These data indicated that supplementation with vitamin D conferred a considerably positive impact on health, survival and probably would lower medical costs.

Wouldn’t it be wonderful if a drug was discovered that prevented disease, promoted wellness, increased survival, was inexpensive, lowered medical costs, was universally available and almost nontoxic?

Well, it may be that this new wonder “drug” does not come from a pharmaceutical company … it comes from the combination of sun, cholesterol, skin, liver and kidney … vitamin D.

• Patrick B. Massey, M.D., Ph.D is medical director for complementary and alternative medicine for the Alexian Brothers Hospital Network. His website is alt-med.org

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Bristol-Myers buying Inhibitex for $2.5 billion

Jan. 8, 2012, 11:05 a.m. EST

By Russ Britt, MarketWatch

LOS ANGELES (MarketWatch) — Pharmaceutical giant Bristol-Myers Squibb is purchasing Inhibitex Inc., a specialist in hepatitis C treatments, in a cash tender offer for $2.5 billion.

In a deal announced late Saturday, Bristol-Myers  will pay $26 a share for Inhibitex  based in Alpharetta, Ga., a suburb of Atlanta.

Inhibitex shares ended Friday trading at $9.87, up 24 cents, or 2.5%. New York-based Bristol-Myers was up marginally to $34.22.

While Inhibitex describes itself as dedicated to developing treatments for all serious infections, it’s now focused primarily on the treatment of hepatitis C. Its lead product in that realm is called INX-189, an oral treatment which it says has exhibited potent antiviral activity. INX-189 is in Phase II development.

“This transaction puts INX-189 and the company’s other infectious disease assets in the hands of an organization that can more optimally develop them, and which believes as strongly as we do in INX-189’s potential in the treatment of chronic [hepatitis C],” Russell Plumb, Inhibitex’s chief executive said in a prepared statement.

“There is significant unmet medical need in hepatitis C. This acquisition represents an important investment in the long-term growth of the company,” Lamberto Andreotti, Bristol-Myers Squibb’s chief executive said in the same statement.

Bristol-Myers said the deal should be dilutive to earnings through 2016, with an impact of 4 cents a share in 2012 and 5 cents a share in 2013.

Russ Britt is the Los Angeles bureau chief for MarketWatch.

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Hep C Takeover Speculation Rains Down on Idenix and Achillion

By Adam Feuerstein 01/08/12 - 01:48 PM EST

SAN FRANCISCO (TheStreet) -- Three independent hepatitis C drug developers bought, two more -- Idenix Pharmaceuticals(IDIX_) and Achillion Pharmaceuticals(ACHN_) -- waiting at the altar.

Bristol-Myers Squibb(BMY_) snatches up Inhibitex(INHX_) for $2.5 billion in a deal announced Saturday night as the entire biopharmaceutical industry travels here for the start of the J.P. Morgan Healthcare Conference on Monday morning. [Is there any better way to kick off a closely watched investor confab like this than a blockbuster buyout? I think not.]

Gilead Sciences(GILD_) is expected to close on its $11 billion acquisition of Pharmasset(VRUS_) this week or no later than before the end of the month.

It seems teeny by comparison, but let's not forget that Roche(RHHBY) bought Anadys Pharmaceuticals for $230 million in October.

All three buyouts were done to achieve the same goal: Develop the next generation of highly potent hepatitis C therapies composed entirely of pills so patients no longer need to endure weekly shots of interferon. The prize for the companies that can cobble together the two or three drugs (perhaps just one) necessary to create this all-oral regimen is about $10 billion or more in expected future hepatitis C revenue.

The pace of hepatitis C deal activity is breathtaking if not unprecedented. Takeover speculation will certainly rain down Monday on Idenix and Achillion given their status as the last two independent Hep C drug developers.

Idenix's lead drug, IDX184, belongs to the same "nucleoside" or "nuc" class of oral Hep C drugs as Pharmasset's PSI-7977 and Inhibitex's INX-189.

The Food and Drug Administration has a partial clinical hold on IDX184 due to liver toxicity that cropped up in a study that combined '184 with another Idenix Hep C drug known as IDX320. Idenix believes this safety signal was caused by '320, and development of that drug was shelved.

To remove '184 from the Hep C safety doghouse and clear it for future combination studies, Idenix is conducting a short phase IIb study with interim data expected imminently, perhaps even this week. If the safety profile of '184 comes back clean, the FDA should be persuaded to lift the partial clinical hold and potential suitors may move quickly to snatch up Idenix.

Idenix executives will be presenting at the J.P. Morgan conference on Wednesday at 5 p.m. EST.

Achillion expects to release proof-of-concept data from studies of three experimental hepatitis C drugs -- ACH-1625, ACH-2684 and ACH-2928 -- in the first half of the year. ACH-1625 is a once-daily protease inhibitor (the same Hep C drug class as Vertex Pharma's Incivek and Merck's Victrelis) that is being combined with interferon and ribavirin.

Achillion is not scheduled to present at the J.P. Morgan conference this week, but the company's CEO Michael Kishbauch has not been shy about letting investors (and potential suitors) know that his company is for sale.

Additional thoughts and questions on the rapidly evolving (and consolidating) hepatitis C drug landscape:

Who are the potential buyers still out there? Merck(MRK_) , Johnson & Johnson(JNJ_) and Abbott(ABT_) are all invested heavily in hepatitis C drug development already, so each could step up as potential acquirers. Merck may have the most to lose because its approved Hep C drugs PEG-Intron and Victrelis are threatened by the push to develop new all-oral therapies.

This is actually the second time that Bristol-Myers has made a hepatitis-related deal in the midst of the J.P. Morgan Healthcare Conference. In January 2009, Bristol licensed a long-acting interferon from Zymogenetics. In September 2010, Bristol bought Zymogenetics for $885 million. The payoff on this deal now has to be questioned given the drive to do away with long-acting interferons in hepatitis C in favor of developing all-oral regimens.

How many, if any, of these experimental oral Hep C drugs will ultimately fail clinical trials or be shelved due to safety problems? It's hard to believe that all will ultimately be successful, given the typical failure rate seen in drug development.

What happens if either Idenix or Achillion are not acquired? Can these small companies survive on their own? If Hep C turns out to be anything like HIV, the answer is no.

Inhibitex shares have been very volatile recently due to worries about the safety of INX-189. It's not known whether Bristol is protecting itself with an exit clause in its tender offer if INX-189 does run into safety issues.

-- Written by Adam Feuerstein.

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