AASLD- Idenix Reports On IDX719 and IDX184

Idenix Pharmaceuticals Reports Clinical Data for HCV Drug Candidates - IDX719 and IDX184 - at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting

CAMBRIDGE, Mass., Nov. 10, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced the presentation of safety and antiviral activity results for the Company's clinical-stage hepatitis C virus (HCV) drug candidates - IDX719, a next-generation pan-genotypic NS5A inhibitor, and IDX184, a nucleotide polymerase inhibitor.

Idenix presented updated clinical findings from a three-day proof-of-concept study, which demonstrated that IDX719 was well-tolerated at daily doses up to 100 mg and showed potent antiviral activity across HCV genotypes 1-4, with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL. The Company also presented updated cardiovascular safety and antiviral activity data from the phase IIb study of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV). The IDX719 and IDX184 clinical data are being reported in poster presentations during the 63rd Annual Meeting for the American Association for the Study of Liver Diseases (AASLD) in Boston.

IDX719 three-day proof-of-concept study

Study design

The three-day proof-of-concept study evaluated IDX719 in 64 treatment-naïve, genotype 1, 2, 3 or 4 HCV-infected patients. Genotype 1 patients were randomized to receive placebo, 25 mg QD (once-daily), 50 mg QD, 50 mg BID (twice-daily) or 100 mg QD for three days. Genotype 2, 3 or 4 patients were randomized to receive placebo, 50 mg BID or 100 mg QD for three days.

Study results

• In genotype 1a patients (n=29), mean maximal viral load reductions ranged from 3.2 log10 IU/mL to 3.6 log10 IU/mL across treatment groups.
• In genotype 1b patients (n=5), mean maximal viral load reductions were 3.0 log10 IU/mL in the 25 mg QD arm, and 4.3 log10 IU/mL in the 50 mg QD arm.
• In genotype 2 patients (n=10), the mean maximal viral load reduction was 2.0 log10 IU/mL in both the 50 mg BID and 100 mg QD dose arms with a greater variability in responses among these patients (range: 0.3- 4.1 log10 IU/mL). Four of the genotype 2 patients responded well to IDX719 treatment, and four patients had maximal reductions that were less than 1.0 log10 IU/mL. The decrease in viral load response in genotype 2 patients was associated with the pre-existence or emergence of the M31 polymorphism in the HCV NS5A gene.
• In genotype 3 patients (n=10), mean maximal viral load reductions were 3.3 log10 IU/mL in the 50 mg BID arm and 3.4 log10 IU/mL in the 100 mg QD arm.
• In genotype 4 patients (n=10), mean maximal viral load reductions were 3.9 log10 IU/mL in the 50 mg BID dose arm and 3.6 log10 IU/mL in the 100 mg QD dose arm.

No patients experienced a rebound (> 1.0 log10 IU/mL increase over the lowest viral load) during the treatment period and maximum viral load reductions were typically achieved within 24-72 hours post dose. There were no safety-related discontinuations or serious adverse events. IDX719 was safe and well tolerated at daily doses up to 100 mg for three days. Idenix intends to initiate a phase II clinical trial evaluating IDX719 in combination therapy in 2013.

"To our knowledge, these are the most advanced clinical results validating the robust, pan-genotypic activity of an NS5A inhibitor in HCV," commented Douglas Mayers, M.D., Chief Medical Officer of Idenix. "We look forward to advancing this promising drug candidate into the next phase of clinical testing."

IDX184 phase IIb combination study

Study design

A randomized, double-blind phase IIb clinical trial is evaluating IDX184 in 67 treatment-naive genotype 1 HCV-infected patients. The study features two treatment arms, either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with PegIFN/RBV. Response-guided therapy is used to complete an additional 12 or 36 weeks of PegIFN/RBV treatment.

Study results

All patients had completed treatment with IDX184 when in August 2012, the U.S. Food and Drug Administration (FDA) placed IDX184 on partial clinical hold due to cardiac adverse events seen in a competitor's phase II clinical trial evaluating BMS-986094. The overall safety profile of IDX184 in combination with PegIFN/RBV remains consistent with the known safety profile of PegIFN/RBV alone. In light of the clinical hold, Idenix has evaluated multiple cardiac safety measurements, including electrocardiograms, echocardiograms and two cardiac biomarkers, ultrasensitive troponins and NT-proBNPs, from the ongoing IDX184 phase IIb study and has found no evidence of severe cardiac findings to date.

Similar numbers of patients achieved a complete early virologic response (cEVR; virus levels < 25 IU/mL at 12 weeks) in the 50 mg (26/34; 76%) and in the 100 mg (27/33; 82%) groups. Rates of rapid virologic response (RVR; virus levels < 25 IU/mL at 4 weeks) were also comparable between the 50 mg (18/34; 53%) and the 100 mg (18/33; 55%) groups. The difference in response rates from data previously reported is primarily due to an increased number of genotype 1b patients as well as IL28B CT/TT patients who were enrolled in the second patient cohort. No patient experienced virologic breakthrough during the 12-week IDX184/Peg-IFN/RBV treatment period. The majority of patients are in the ongoing PegIFN/RBV extension treatment phase, and complete sustained virologic response (SVR) results will be available in 2013.

"The IDX184 presentation at AASLD details much of the key clinical data we intend to submit to the FDA in our response package by the end of the year," said Ron Renaud, Idenix's President and Chief Executive Officer. "As always, patient safety is our top priority, and I am pleased with the thoroughness with which our R&D team and the trial investigators have gathered this information and that there have been no treatment-emergent cardiac or renal serious adverse events (SAEs) to date in the ongoing IDX184 study."

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX184 and IDX719; and the likelihood and success of any future clinical trials involving IDX184 or IDX719. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2011 and the quarterly report on Form 10-Q for the quarter ended September 30, 2012, each as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contacts:
         Kelly Barry (617) 995-9033 (media)
         Teri Dahlman (617) 995-9807 (investors)

Idenix Reports Financial Results and HCV Program Update

Idenix Pharmaceuticals Reports Third Quarter and Nine Month 2012 Financial Results and HCV Program Update

CAMBRIDGE, Mass., Nov. 1, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today reported unaudited financial results for the third quarter and nine months ended September 30, 2012 and provided an update of its hepatitis C virus (HCV) development programs.

 

HCV Pipeline and Third Quarter Business Review
IDX719, an NS5A inhibitor

• The Company previously reported early clinical results demonstrating a favorable safety profile and potent pan-genotypic activity for IDX719. Idenix anticipates that a phase II clinical trial evaluating IDX719 in combination therapy will begin in the first half of 2013.

Nucleotide polymerase inhibitor program

• In August 2012, the U.S. Food and Drug Administration (FDA) placed IDX184 on partial clinical hold due to serious cardiac--related adverse events seen with a competitor's nucleotide polymerase inhibitor, BMS-986094 (formerly INX-189). Idenix has obtained cardiac safety measurements from the ongoing phase IIb study of IDX184 in combination with pegylated interferon and ribavirin and has found no evidence of severe cardiac findings to date. Idenix is reviewing additional preclinical and clinical data and conducting further testing . The Company anticipates submitting the complete response package to the FDA by year-end.
• In July 2012, Idenix submitted an investigational new drug (IND) application for IDX19368, a 2'methyl guanosine nucleotide inhibitor. In August 2012, FDA placed IDX19368 on clinical hold due to serious cardiac-related adverse events seen with BMS-986094 and has requested additional toxicology and metabolic preclinical studies for IDX19368 prior to permitting the initiation of clinical studies.
• As part of the ongoing extensive nucleotide discovery effort, the Company is exploring a diverse spectrum of nucleotides with novel bases, prodrugs and sugar moieties. IND-enabling studies have begun for a new nucleotide prodrug and an IND is expected to be filed in 2013.

"We are working diligently to assemble all of the data requested by the FDA regarding IDX184, and we expect to receive a response from the FDA in early 2013," said Ron Renaud, Idenix's President and Chief Executive Officer. "We also are excited about IDX719, a potentially best-in-class pan-genotypic NS5A inhibitor, and look forward to moving it into phase II clinical development in the near term. Additionally, in 2013 we expect to see the results of our robust discovery efforts focused on next-generation nucleotide inhibitors, with the objective of filing at least one IND next year."
Renaud continued, "Our goal remains to develop an all-oral pan-genotypic regimen that will play a significant role in future HCV treatments. With a strong cash position and the restructured Novartis collaboration, we are able to maximize opportunities for advancing our programs in order to achieve that goal."

Upcoming Meeting
The 63^rd Annual Meeting for the American Association for the Study of Liver Diseases (AASLD) will take place in Boston from November 9 -- November 13, 2012.

• A poster titled "IDX719, HCV NS5A Inhibitor, Demonstrates Pan-Genotypic Activity after Three Days of Monotherapy in Genotype 1, 2, 3 or 4 HCV-Infected Subjects," by D. Mayers, et al, will be presented on November 13 at 8:00 am ET.
• A poster titled "High Rates of Rapid Virologic Response (RVR) and Complete Early Virologic Response (cEVR) with IDX184, Pegylated Interferon and Ribavirin in Genotype 1 HCV-Infected Subjects: Interim Results," by E. Lawitz, et al, will be presented on November 13, 2012 at 8:00 am ET.

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Setbacks in HCV Drug Development Highlight Uncertainties in Treat or Wait Decisions

Setbacks in HCV Drug Development Highlight Uncertainties in Treat or Wait Decisions
Source-
Clinical Care Options

Graham R. Foster FRCP, PhD - 10/22/2012

At the opera, the show isn’t over until the large lady begins her aria. In drug development, licensing and effective treatment of thousands of patients define a successful launch. Following recent problems with emerging drugs for HCV, I am reminded of the difficulties of turning chemicals into drugs and the importance of waiting until the development cycle is complete before claiming success.

I first sensed trouble in April 2012 when it was announced that trials of alisporivir were being suspended. Over 1800 patients had received this cyclophilin antagonist, with impressive virologic responses (Capsule Summary). A phase III trial was moving forward, and I was surprised to learn that a patient receiving alisporivir had died of pancreatitis. The US Food and Drug Administration noted a possible association of pancreatitis with alisporivir and instituted a “clinical hold.” A full evaluation of the alisporivir data set is now under way, and we wait to see whether any possible risks can be managed and whether it is safe to resume testing. Worse news followed in August when unexpected cardiac toxicity was seen with BMS-986094, a nucleotide analogue polymerase inhibitor, leading to the death of a patient and suspension of clinical trials. This nucleotide was just one of a molecular family, and concerns that cardiotoxicity may be a class effect led to studies with related drugs (such as a compound in phase IIb development, IDX184) being placed on full or partial clinical hold. The suspension of this drug family leaves only 1 nucleotide at an advanced stage of development (sofosbuvir, previously known as GS-7977), and I am now crossing my fingers and hoping that its current impressive safety record continues. The failure of drugs in late-stage clinical trials has reminded me that unexpected safety concerns are common, and despite the best efforts of companies and regulators, clinical trials remain challenging.

Safety problems are not restricted to clinical trials. Following the launch of the protease inhibitors telaprevir and boceprevir, data started to accrue in patients with advanced cirrhosis (who were excluded from the clinical trial program). Early results indicate an increase in adverse effects over that seen in clinical trials, particularly with severe anemia and multiple treatment-related deaths, most commonly due to sepsis (Capsule Summary). I certainly find in my practice that patients with advanced cirrhosis are fragile, so it is perhaps not surprising that a small proportion develop serious complications when receiving potent antiviral therapy. However, the unexpected severity of the adverse effects and the associated mortality demonstrate again that a successful phase III trial by no means guarantees the safety of a drug in more challenging patient populations.

The recent concerns with licensed and unlicensed drugs serve as a salutary reminder of the difficulties of drug development. As patients and clinicians who are awaiting the arrival of interferon-free treatment regimes, we should remember that excellent responses in small patient cohorts do not guarantee eventual success. As we wrestle with the decision of whether to treat now or wait for more effective regimens, we need to keep in mind that we still have hurdles to overcome before we can celebrate safe, effective all-oral combination therapy for HCV. In my clinic, I remind my patients that waiting for new drugs is not entirely risk free, and if a decision to wait for better drugs is made, it is important to review the decision in a few months to see if the changing drug development landscape necessitates a review of the original decision. The large lady is on the stage, but the show is not yet over.

Tell me your thoughts: Do these hiccups in drug development alter how you counsel your patients regarding future HCV therapies? Do you discuss the potential safety challenges or focus on the efficacy successes?

Graham R. Foster, FRCP, PhD, is Professor of Hepatology, The Liver Unit, and Consultant Hepatologist, Queen Marys University of London, London, United Kingdom.
 

Graham R. Foster, FRCP, PhD, has disclosed that he has received consulting fees, fees for non-CME services, and funds for research support from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, Novartis, and Roche and has served on the on the safety board with Idenix.

Topics: HCV

 

Idenix Pharma: Guilty By Association

Idenix Pharma: Guilty By Association

 

By Nathan Sadeghi-Nejad

 

Excerpt:

IDX-184 has had no safety issues to date. Nonetheless, structural similarities between Idenix's IDX-184 and Bristol-Myers Squibb's (BMY) BMS-094 were sufficient to warrant concern. Clinical development of the latter drug, which Bristol-Myers acquired in the $2.5 billion takeover of Inhibitex, has been discontinued because of severe cardiovascular toxicity. 

The FDA's clinical hold -- effectively a "stop work" order triggered by unexpected safety issues -- suggests that regulators are also concerned about the safety of IDX-184. In order to get the clinical hold lifted and continue development, Idenix must now convince the FDA that IDX-184 doesn't put patients' lives at unnecessary risk. (At least one patient in the Bristol-Myers study died.)

Let's start with the good news by diving into some chemistry. IDX-184 and BMS-094 are both nucleotide polymerase inhibitors and, structurally speaking, 2′-methylguanosine (2′-MeG) triphosphates. When BMS-094 breaks down in the body, it produces 1-naphthol, a toxic metabolite possibly responsible for the drug's side effects. However, metabolism of IDX-184 does not produce 1-naphthol. Furthermore, while Bristol-Myers' compound showed evidence of mitochondrial toxicity in cell line studies at relatively low concentrations, IDX-184 has a wide margin of cellular level safety......
 

Continue reading @ The Street 

One Bad Apple? Idenix IDX184 Takes the Heat for Competitor's Toxicity Profile

One Bad Apple? Idenix Pharmaceuticals, Inc. (IDIX)' IDX184 Takes the Heat for Competitor's Toxicity Profile
8/20/2012 10:23:07 AM

Their premier drug candidate, IDX184, were put on partial clinical hold by the FDA. The government organization’s decision was based on a recent report of a serious cardiac-related adverse event associated with Bristol-Myers Squibb’s drug, BMS-986094.

Aug 24 Updated -
BMS halts the development of BMS-986094 due to patient death
The original patient subsequently died and eight others suffered from heart and kidney toxicity, the company said in a statement released last night. Two of the patients remain hospitalized.
,
Both drugs are nucleotide polymerase inhibitors being developed to treat Hepatitis C (HCV) infections. Idenix’s IDX184, developed as an orally administered once-a-day therapy, has been tested in combination with other HCV-prescribed treatments such as pegylated interferon and ribavirin. This is not the first time that the company’s leading candidate has been benched due to concerns with the safety and toxicity profile associated with its nucleotide inhibitor related therapy. A partial clinical hold was placed on IDX184 as recently as 2010, due to elevated liver function tests performed on the treatment population. This partial hold was only lifted in February of 2012 after concerns were addressed by company officials.

Idenix’s shares plummeted almost 30%, to $5.90, after release of the company statement. Certain investors have predicted that this setback will tack on an additional six months to Idenix’s development schedule, but that the company will still be able to deliver on their promise of an HCV cure. It is likely that this setback has done more to damage the momentum of IDX184 than analysts predict. For now, Idenix has stated that they plan to perform cardiac assessments on all patients that have undergone clinical trials with IDX184, in an effort to comply with guidelines set out by the FDA since the events associated with BMS-986094.

As reported earlier, Idenix recently received a fast-track designation for its second candidate, IDX719, which is an NS5A inhibitor capable of providing treatment against multiple genotypes of HCV. Unlike IDX719, IDX184 is directed towards genotype 1 HCV and uses a different Mechanism Of Action (MOA). The adverse events associated with the combinatorial agents have been a driving force for technological innovation in this disease space. Due to the difference in MOAs, it is possible that IDX719 might overtake IDX814 as the company’s leading drug candidate. In this regulated environment, it is possible that a change in corporate strategy might impact the guidelines used to determine the fate of other nucleotide inhibitor drugs.

Currently, the competition for HCV drug development is fierce. Big players such as Bristol-Myers Squibb, Gilead and Abbott stand as stiff competition for Idenix, which can’t compete with these giants on sheer magnitude alone. These companies also benefit from diversified portfolios, - a luxury that a smaller biotech company like Idenix lacks. This might have implications on the company’s ability to weather development delays.

The status of HCV treatment leaves a lot to be desired. Currently, estimates indicate that approximately 3% of the world’s population is infected with HCV. Infected individuals often go on to suffer from exacerbated conditions such as liver cirrhosis and even liver cancer. In this market, treatments such as Idenix’s IDX184 and IDX719 stand out as strong contenders capable of changing the landscape of treatment algorithms on a global scale. With a strong push from global health avenues such as the one from the CDC recommending HCV testing in all baby boomers, one can expect Idenix to rally back and emerge as a real contender in HCV treatment. However, it remains to be seen if this can be achieved with IDX184 instead of its worthy replacement, IDC719.

One Bad Apple? Idenix Pharmaceuticals’ IDX184 Takes the Heat for Competitor’s Toxicity Profile

This expert insight was written by GlobalData's senior healthcare analyst for infectious diseases, Dr. Ramya Kartikeyan. If you would like an analyst comment or to arrange an interview, please contact us on the details below.

-ABOUT GLOBALDATA-

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IDX184 :Heart-related side effects not specifically linked to drug-Have been seen in IDX184 and standard drugs

AP News
Ahead of the Bell: Analyst upgrades Idenix shares

After a huge stock slide this week, shares of Idenix Pharmaceuticals, Stifel Nicolaus advised clients that the company is now fairly valued.

Shares rose more than 5 percent in premarket trading Friday.

The stock slumped by 29 percent Thursday after the Cambridge, Mass., company revealed that placed a hold on testing of its potential hepatitis C drug, IDX184 because of the potential for heart damage in patients.

That puts the stock within the Stifel Nicolaus estimated fair value range of $5 to $6, analyst Stephen Wiley said. Wiley raised his rating on the stock to "hold" from "sell."

The company said no heart-related side effects have been specifically linked to the drug, although some have been seen in patients treated with IDX184 and standard drugs.

Two weeks ago, Bristol-Myers shut down a clinical trial of a similar hepatitis C treatment because a patient suffered heart failure during a clinical trial. That drugmaker has said it was not clear that the side effects in the trial were linked to the drug itself.

The FDA also placed a clinical hold on trials of IDX184 in 2010 because of concerns about the effects of the drug on the liver. It removed that hold in February. Idenix recently completed a mid-stage clinical trial of IDX184 and is preparing to report results from that trial. No patients are currently being treated with the drug.

"We believe this news likely limits additional downside risk over the near-term and, as a result, we are upgrading our rating of (Idenix) shares," Wiley wrote.
Shares of Idenix Pharmaceuticals Inc. sank $2.47 to $5.84 on Thursday, but bounced back above $6 Friday before the market opened.

Stifel Nicolaus makes a market in Idenix securities and expects to receive or intends to seek investment banking services compensation from Idenix.

http://www.businessweek.com/ap/2012-08-17/ahead-of-the-bell-analyst-upgrades-idenix-shares

Related:

Seeking Alpha: Idenix And The High-Stakes Ping-Pong Of Hep C Treatments
Aug 16
It's pretty remarkable just how quickly a hepatitis C (HCV) drug candidate can go from hero to villain in today's market. Investors cheered Gilead's (GILD) bold (and expensive) bid for Pharmasset ... until some concerns about the efficacy of lead drug GS-7977 popped up. Then there was Bristol-Myers Squibb (BMY) making its bold play for Inhibitex, only to see serious safety worries emerge on the key asset (now known as BMS-094).

Now it's the turn of Idenix (IDIX). In a case of what looks to me like guilt by association, the FDA has put lead drug IDX184 on a partial clinical hold due to worries about cardiac safety.

Please click here for more:
Idenix And The High-Stakes Ping-Pong Of Hep C Treatments

Aug 16 press release-

Idenix Provides Update on IDX184 Clinical Development Program

CAMBRIDGE, Mass., Aug. 16, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. /quotes/zigman/90571/quotes/nls/idixIDIX-29.72%, a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that the Company received verbal notice from the U.S. Food and Drug Administration (FDA) that a partial clinical hold has been placed on IDX184, the Company's nucleotide polymerase inhibitor under development for the treatment of hepatitis C virus (HCV).
                              
As a result of the recent occurrence of a serious cardiac-related adverse event encountered with a competitor's nucleotide polymerase inhibitor for the treatment of HCV, the FDA has expressed an interest in further reviewing the safety of IDX184 and has placed IDX184 on partial clinical hold. In previous clinical trials as well as the ongoing phase IIb clinical trial of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV), there has been no evidence to date of cardiotoxicity in patients dosed with IDX184 with PegIFN/RBV beyond that seen with PegIFN/RBV alone. There are currently no patients receiving IDX184 worldwide.
                              
The FDA has requested additional data on patients treated with IDX184. Patient safety is our main concern and Idenix will immediately begin work to comply with the FDA request and expects to submit these data to the FDA in the coming weeks. The Company intends to have an ongoing discussion with the FDA following the submission of this data.

ABOUT IDX184
IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. The Company reported interim data in June 2012 for the first cohort of 31 patients from an ongoing phase IIb clinical trial of IDX184 in combination with PegIFN/RBV. Of the patients who achieved an extended rapid virologic response (undetectable levels of virus at 4 weeks and 12 weeks) and completed an additional 12 weeks of PegIFN/RBV (n=9), 100% of patients (4/4) in the 100 mg arm and 80% of patients (4/5) in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment (SVR4).
                              
In July 2012, an independent data safety monitoring board reviewed the safety data for this study and confirmed that the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegIFN/RBV alone.
                              
ABOUT PARTIAL CLINICAL HOLD
A partial clinical hold is a delay or suspension of only part of the clinical work requested under the investigational new drug (IND) application (e.g., a specific protocol or part of a protocol is not allowed to proceed; however, other protocols or parts of the protocol are allowed to proceed under the IND). Under the partial clinical hold, Idenix cannot enroll patients into additional clinical trials until agreement is reached with the FDA on the next clinical trial design.
ABOUT IDENIX
                              
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com .
                               
CONFERENCE CALL AND WEBCAST INFORMATION
Idenix will hold a conference call today at 8:30 a.m. ET. To access the call, please dial (877) 640-9809 (U.S./Canada) or (914) 495-8528 (International) and enter passcode 22005490. A slide presentation will accompany the conference call and can be accessed on the Investor section of the Idenix website at www.idenix.com . Please log on approximately 10 minutes prior to the start of the call to ensure adequate time for any downloads that may be necessary.
A replay of the conference call and webcast will be available until August 27, 2012, by dialing (855) 859-2056 (U.S./Canada) or (404) 537-3406 (International) and enter the passcode 22005490.

http://www.marketwatch.com/story/idenix-provides-update-on-idx184-clinical-development-program-2012-08-16

Is The Hep C Drug Pipeline Beginning To Crack?

Aug 24 Updated - BMS halts the development of BMS-986094 due to patient death
The original patient subsequently died and eight others suffered from heart and kidney toxicity, the company said in a statement released last night. Two of the patients remain hospitalized.

Is The Hep C Drug Pipeline Beginning To Crack?
Tiran Rothman
Seeking Alpha

Another crack appeared today in the ultra-hype of next generation Hep C drugs.

Idenix Pharmaceuticals (IDIX) released news that its Phase IIb trial with IDX184 was put on partial clinical hold by the FDA due to the recent cardiovascular toxicity experienced by a patient treated with a similar treatment developed by Bristol-Myers Squibb (BMY). Idenix's investors were quick to pull the trigger, sending the stock for a 40% nosedive.

Both Idenix's IDX184 and BMS's 094 are NS5 family inhibitors, which are the front line of Hep C drug candidates, destined to be part of an oral therapy regimen that will make the current use of interferon injections redundant. Even though there has been no evidence of cardiotoxicity in patients treated with IDX184, the FDA has expressed a concern regarding potential safety problems of the drug.

Gilead (GILD), the current leader in the next-gen Hep C drugs, is planning a Phase III study with a combination therapy of its NS5A and NS5B inhibitors. The FDA's recent caution regarding NS5 inhibitors might also affect Gilead's sprint toward the finish line. Novartis (NVS), which has recently joined the Hep C crowded waters with the $440m Enanta Pharmaceuticals deal, might also suffer from this new NS5-related safety issues.

About 180 million people worldwide are chronically infected with HCV. The global Hepatitis market was estimated at $6 billion in 2011 and is forecasted to grow to $20 billion until the end of the decade. The combination of this huge and growing market and insufficient efficacy of the current treatments has generated an immense interest among drug developers and quite a few deals.

The recent holdups in the NS5-related treatments suggest that the Hep C pipeline might need some variations. Several companies are developing alternative, non-NS5 inhibitor-related, Hep C treatments. Examples for such technologies are Transgene's (TRGNF.PK) TG4040 - a therapeutic Hep C vaccine based on a virus carrying and expressing three of the major Hepatitis C virus's non-structural proteins (NS3, NS4 and NS5B). TG4040 is currently in a phase 2 trial.

A different approach is taken by Bioline Rx (BLRX) that develops BL-8020, an orally available treatment with a unique mechanism of action - inhibition of Hepatitis C virus-induced autophagy. In other words, BL-8020 acts on the host cell rather than the virus itself, thus greatly differentiating it from current and pipeline Hep C drugs. Preclinical studies have shown a synergistic effect of BL-8020, when combined with other anti-Hep C agents, which is likely to increase these agents' potency and reduce any adverse effects by enabling utilization of lower dosages.

With the current setbacks seen among Hep C pipeline frontrunners, additional rounds of licensing and acquisition deals in this area are expected, and companies that develop new and different approaches for Hep C treatment may greatly benefit from other's failures and should be closely watched by investors that follow this therapeutic field.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

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IDX184-Idenix hepatitis C drug put on partial hold

.WSJ-The biopharmaceutical company in February said the FDA lifted a prior partial hold issued in September 2010 after three cases of elevated liver function tests were observed in the Phase 2B study.

Aug 16 (Reuters) - Idenix Pharmaceuticals Inc's experimental hepatitis C drug was placed on a partial hold by the U.S. health regulator, barely two weeks after Bristol-Myers Squibb Co's hepatitis C treatment encountered a heart-related safety issue.

Aug 24 Updated -
BMS halts the development of BMS-986094 due to patient death
The original patient subsequently died and eight others suffered from heart and kidney toxicity, the company said in a statement released last night. Two of the patients remain hospitalized.

Idenix shares dropped 24 percent in premarket trade.

 

The U.S. Food and Drug Administration wanted to further review its drug, called IDX184, citing the serious heart-related adverse event seen in a competitor's drug, Idenix said in a statement.

Idenix did not name the competitor but Idenix's IDX184 and Bristol's drug BMS-986094 were both being tested in mid-stage trials and both belong to a promising new class of hepatitis C medicines known as nucleotide polymerase inhibitors.

The FDA has requested additional data on patients treated with IDX184 and Idenix said in a statement it plans to have an ongoing discussion with the FDA following the data submission.

Nucleotide polymerase inhibitors work by targeting polymerase -- an enzyme essential for the replication of the hepatitis C virus -- and are expected to be the game changer for both patients and physicians.

Most hepatitis C drugs used today are combination therapies that include interferon. This causes unpleasant flu-like symptoms and other side effects, leading many patients to discontinue or delay treatment.

The new nucleotides, or nucs as they are commonly called, do not require the use of interferon.

The hepatitis C virus is the most common cause of viral hepatitis, an inflammation of the liver.

Idenix shares traded at $6.30 premarket after closing at $8.31 on Wednesday on the Nasdaq.

(Reporting by Esha Dey in Bangalore; Editing by Rodney Joyce)

((esha.dey@thomsonreuters.com; within U.S. +1 646 223 8780, outside U.S. +91 80 4135 5800; Reuters Messaging: esha.dey.thomsonreuters.com@reuters.net))

Keywords: IDENIX FDA/HEPATITISC

(C) Reuters 2012. All rights reserved. Republication or redistribution of Reuters content, including by caching, framing or similar means, is expressly prohibited without the prior written consent of Reuters.

UPDATED: Idenix craters as clinical hold spurs tox jitters for hot hep C drug
August 16, 2012 | By John Carroll

Idenix Pharmaceuticals ($IDIX) went into free fall this morning, tumbling about 40% on the news that its nucleotide polymerase inhibitor IDX184 was put on partial clinical hold as the FDA studies whether a recent cardiac event that may well have spiked a similar treatment at Bristol-Myers Squibb ($BMY) raises similar toxicity issues for Idenix.

"In previous clinical trials as well as the ongoing Phase IIb clinical trial of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV), there has been no evidence to date of cardiotoxicity in patients dosed with IDX184 with PegIFN/RBV beyond that seen with PegIFN/RBV alone," Idenix cautioned this morning in a short statement. But even a whiff of this kind of trouble is enough to spook investors who have bid up shares in hopes of cashing in on new treatments.

Cambridge, MA-based Idenix has been among the leaders in the mad scramble to advance new "nucs" and NS5A inhibitors that can be combined with ribavirin into an all-oral regimen with megamarket potential. But the quest for the new holy grail in biotech has been slowed by a cardiac event that has halted work on BMS-094. Analysts have pointed to a somewhat similar chemical structure between BMS-094--formerly INX-189 before Bristol bought Inhibitex in a $2.5 billion deal--and IDX184, which has sent shivers down investors' spines

Bernstein's Geoffrey Porges, though, think the differences outweigh the similarities of the two therapies. "This event is likely to raise concerns about the risks of nuke programs across the spectrum, but we believe it is important to understand the difference among the assets," he notes, according to Bloomberg.

Bristol-Myers hasn't written off its once-hot hep C drug, but it is pondering the move. Cardiovascular side effects have triggered the demise of many therapies and regulators have no tolerance for subjecting patients to potential risks in the clinic. Novartis ($NVS) recently relinquished its hep C partnership with Idenix, though most analysts have seen that as a positive move for the developer--at least until now.

- here's the press release
- here's the Bloomberg report
Read more
Subscribe: http://www.fiercebiotech.com/signup?sourceform=Viral-Tynt-FierceBiotech-FierceBiotech

Idenix held a conference to discuss IDX184's recent partial clinical hold

Idenix announced that the US FDA has put a partial hold on the phase II trial evaluating IDX184 for the treatment of hepatitis C.

The partial hold was in place due to the recent occurrence of a serious cardiac-related adverse event encountered with the company's competitor's nucleotide polymerase inhibitor for the treatment of HCV. Per the company, previous clinical trials conducted with IDX184, cardiotoxicity in patients dosed with IDX184 with PegIFN/RBV was not beyond what was observed in patients treated with PegIFN/RBV alone.

Idenix said the company will work with the FDA to supply the Agency's requests for additional data on patients treated with IDX184. It plans to submit the data in the coming weeks.

IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine. The medication was developed using the company's proprietary liver-targeting technology which enables the delivery of nucleoside monophosphate to the liver. This will lead an increase in the formation of high levels of nucleoside triphosphate, maximizing the drug efficacy, and limiting systemic side effects with low, once-daily dosing.

The agent is currently being studied in the
phase II trial. The interim reports analyzing data from the first cohort of 31 patients showed:

10 patients achieved an extended rapid virologic response and completed an additional 12 weeks of PegIFN/RBV. 5 of these patients received 100 mg and 5 received 50 mg of IDX184 once daily.

100% patients in the 100 mg and 80% of patients in the 50 mg arm achieved a sustained virologic response four weeks after the study's completion.

.
The independent data safety monitoring board confirmed the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegIFN/RBV alone in July 2012.

The company held a conference call which took place at 8:30 Eastern Time on 16-August-2012 to discuss the clinical hold.

Idenix will hold a conference call today at 8:30 a.m. ET. To access the call, please dial (877) 640-9809 (U.S./Canada) or (914) 495-8528 (International) and enter passcode 22005490. A slide presentation will accompany the conference call and can be accessed on the Investor section of the Idenix website at www.idenix.com. Please log on approximately 10 minutes prior to the start of the call to ensure adequate time for any downloads that may be necessary.

A replay of the conference call and webcast will be available until August 27, 2012, by dialing (855) 859-2056 (U.S./Canada) or (404) 537-3406 (International) and enter the passcode 22005490.

About Partial Clinical hold:

• A partial clinical hold is a delay or suspension of only part of the clinical work requested under the investigational new drug (IND) application (e.g., a specific protocol or part of a protocol is not allowed to proceed; however, other protocols or parts of the protocol are allowed to proceed under the IND). Under the partial clinical hold, Idenix cannot enroll patients into additional clinical trials until agreement is reached with the FDA on the next clinical trial design

http://blog.pharmapodia.com/2012/08/idenix-held-conference-to-discuss.html

Idenix: New HCV Treatment Could Be A Game Changer

Investing Commentary

Author's Profile

Idenix Pharma (IDIX): New HCV Treatment Could Be A Game Changer

Excerpt:

The company's candidate IDX184 is the principle value driver at this point. Although IDX184 is considered to be less potent than the leading HCV nuclear clinical candidate (Gilead Sciences' GS-7977), the available data suggest that IDX184 would be successfully developed, thereby unlocking significant value in Idenix shares...

"While the wholly-owned key asset IDX184 is not a best-in-class nucleotide ("nuc") polymerase inhibitor, we think its high barrier to resistance will confer value in alternative DAA combos, with data in 2013 driving estimates higher and solidifying its scarcity among late-stage nucs," UBS analyst Matthew Roden wrote in a note to clients...

Idenix has the only unencumbered nuc in late-stage clinical development, as well as IDX719, a potentially best-in-class pan-genotypic NS5a inhibitor in phase-1 trials as well. IDX719 targets the HCV non-structural 5A (NS5A) protein presents a second clinical stage asset, and could be differentiated among the NS5a class in terms of potency and pan-genotypic activity.

The company has also planned to begin trials with a combination of IDX 719 and IDX 184 towards the end of this year. "Given the potential for both classes to become backbone therapies in HCV (and potentially form an all-IDIX pan-genotypic combo), we believe the Idenix pipeline has considerable scarcity value, and will attract large pharma or biotech partners," the analyst noted. In addition, Idenix holds significant intellectual property in nuc chemistry, and may have rights to other nucs in HCV.....

Continue Reading....

Related - Published July 14 at gurufocus.com
IDX184-Idenix Pharmaceuticals Lagging Behind In Breakthrough Hepatitis C Drug Development

IDX184-Idenix Pharmaceuticals Lagging Behind In Breakthrough Hepatitis C Drug Development

Idenix Pharmaceuticals Lagging Behind In Breakthrough Hepatitis C Drug Development
July 13, 2012
Muhammad Bazil

Idenix Pharmaceuticals (IDIX) is one of the biopharmaceutical companies focused on discovering, developing and commercializing drugs for the treatment of life-threatening human viral diseases such as Hepatitis C. Hepatitis C is a form of liver disease that is passed on from one person to another through contact of bodily fluids. The Hepatitis C virus can severely damage the liver as it is asymptomatic and therefore, the effects are slowly felt over a long period of time. Hepatitis C has the potential to kill if not detected early enough.

It is estimated that 75% to 85% of Hepatitis C infections become chronic, leading to serious liver disease such as cirrhosis and may even causing liver cancer. Researchers at the Centers for Disease Control and Prevention estimate that about 50% of the 3.2 million Americans who have chronic Hepatitis C do not know about it. This is frightening to say the least, given that Hepatitis C is now estimated to be killing more Americans than HIV, the virus that causes AIDS. The Hepatitis C virus has also been found to be more prevalent in the "baby boomer" generation born between 1945 and 1964. This was a time when casual sharing of needles and drug use was the norm. I was floored to discover that the current worldwide figure of persons considered to be living with chronic viral hepatitis stands at between 480 million and 540 million, with approximately 130 million to 170 million of them infected with the Hepatitis C virus.

IDX184 is a pan-genotypic oral nucleotide polymerase inhibitor and Idenix Pharmaceutical’s lead product for the treatment of Hepatitis C. It is Idenix’s belief that the Hepatitis C treatment paradigm will evolve rapidly within the next three to five years as various companies continue to develop direct-acting antivirals (DAAs) from different drug classes. The treatments would potentially reduce the duration of treatment from one year to six months or less, increase the sustained virologic response rates and improve drug tolerability. It would also be extremely convenient as patients would be able to take all the drugs orally. I believe this is significant as the side effects associated with the combination of Interferon and Ribaravin during treatment disqualify many Hepatitis C-infected candidates from undergoing the treatment. Therefore, a breakthrough in this area would be a huge stride for Idenix and has the potential to affect its share price positively. Idenix Pharmaceuticals has also co-developed a Hepatitis B drug candidate, telbivudine, with Norvatis Pharma AG (NVS). The product is commercially sold as Tyzeka®, and Idenix Pharmaceuticals earns royalties from the product sales.

Idenix Pharmaceuticals stock began trading on July 2004 with an initial public offering of 5.8 million shares at $14 per share. On 23 April, 2012 Idenix Pharmaceuticals gained 6.5% to even out at slightly below $9. Earlier in March 2012 the share price had traded at an average of $12. Idenix Pharmaceuticals released its fourth quarter and financial results for the year ending Dec. 31, 2011 in February. Its total revenue was $7 million compared to 10.2 million in the year ending Dec. 31, 2010. The company recorded a net loss of $52 million on Dec. 31, 2011 as compared to $61.6 million on Dec. 31, 2010. The share price seems to fluctuate a lot so if you’re looking to trade in stock it is probably advisable to consider day-trading or swing-trading as compared to making a long-term investment.

Another competitor, Gilead Sciences (GILD) made astronomical progress in April 2012, when a mid-stage clinical trial revealed that a combination of the GS-7977 drug and the antiviral Ribaravin cleared the virus in approximately 88% of the patients. The GS-7977 drug was administered together with Ribaravin, completely eliminating the need for the injectable interferon. Gilead Sciences is the world’s largest HIV drug maker, so this news comes as no surprise.

Gilead’s shares have evened out at an average of $51 after they jumped from about $47 to an average of $53. These developments have clearly placed Gilead Sciences ahead of the pack, and I would not hesitate to recommend trading its shares.

Vertex Pharmaceuticals (VRTX) is also in the process of carrying out a study to evaluate the effectiveness of a Hepatitis C treatment on patients who are not on antiretroviral therapy for HIV versus those who are on a Atripla- or Reyataz-based treatment for HIV. Vertex Pharmaceuticals is carrying out the study in collaboration with Janssen, one of Johnson & Johnson (JNJ)'s pharmaceutical companies. The study is intended to evaluate the safety and tolerability of the Incivek drug combination therapy in patients infected with both the Hepatitis C virus and HIV. The drug is marketed in the U.S. and Canada and is also available in the Far East and Japan.

Vertex Pharmaceuticals stock is trading at an average of $37. January 2012 was a terrible month for Vertex with their share price dipping to $34 after an analyst at Leerink Swann reduced the sales forecast for Incivek from $2.3 billion to $1.5 billion this year, citing recent developments of interferon-free regimens and the possibility of more aggressive developments. There is a great need for Hepatitis C treatment and more so amongst those infected with HIV. If Vertex Pharmaceuticals manages to develop a drug that can be safely used to treat those co-infected with Hepatitis C and HIV then it is safe to say that it will be worth your while to invest in Vertex Pharmaceuticals.

Victrelis, a product of Merck & Co. (MRK), was approved for the U.S. market by the Food and Drug Administration just last year for the treatment of Hepatitis C. It is surprising therefore when I learned from my research that the drug’s effectiveness is lowered when used in combination with some antiretroviral therapy drugs. It’s not all bad news though. Merck recently agreed to pay Endocyte (ECYT) up to $1 billion to develop and commercially market Vintafolide, an experimental cancer drug. Merck will own all the global rights meaning that a surge in sales will push its share price upwards. Merck is currently trading at an average of $28 and its future outlook does not look very promising at the moment.

Abbot Laboratories (ABT)'s main line of business is in the discovery, development, manufacture and sale of a wide range of health care products. Abbot Laboratories released data earlier in April 2012 from a mid-stage clinical trial that indicated combining ABT-450 boosted by an antiviral, Ritonavir, along with Ribaravin and a polymerase inhibitor achieved a 95% cure rate. Deutsche Bank consequently boosted Abbot Laboratories rating to “Buy” in March 2012 with a price target of $70. The share price is currently trading at slightly under $60. I’d say this is pretty close to what analysts at Deutsche Bank projected. Abbot Laboratories is in the process of separating into two healthcare companies by the end of the year, so it is advisable to carry out day trading and keep a close eye on the share price.

http://www.gurufocus.com/news/182519/idenix-pharmaceuticals-lagging-behind-in-breakthrough-hepatitis-c-drug-development

Idenix: New HCV Drug Could Be A Blockbuster

Idenix: New HCV Drug Could Be A Blockbuster

Cris Frangold

Seeking Alpha

Idenix Pharmaceuticals, Inc. (IDIX) recently announced encouraging initial results from Phase IIb results for the treatment - namely, IDX184 and IDX719 - of the hepatitis C virus (HCV). Some reports about HCV say that it affects more than 170 million people globally, including over 4 million Americans. The global market for an effective treatment could reach as high as $100 billion by the year 2020.

HCV infects people who come in contact with contaminated blood that carries the virus, and is one of the main causes of chronic liver disease, which may end up as liver cancer. The result is also an increase in the number of liver transplants for people who contract the disease. The present treatment, which includes injections of the drug interferon alpha, cannot be tolerated by some patients, and can result in side-effects such as fever and depression.

Experts in the field say that this is a landmark moment in the treatment of HCV, because these results show that it is possible to treat the disease without using interferon. There is potential that these two drugs, with complementary profiles, can be given orally and eradicate the virus. The stage has been set for devising a treatment for effecting a complete cure among a large number of people. Experts also feel that the IDX 184 drug from Idenix can be used as a patch, and may overcome its deficiencies if it is combined with another potent drug such as Merck's (MRK) MK-5172/Victrelis (boceprevir), which has already been approved by the FDA.

With so many companies developing and testing treatments for HCV, it is worth our time to briefly survey the current developments. Idenix itself has produced some encouraging news about clinical trials for one of its new hepatitis C drug treatments, IDX719. The study measured a number of things, including the interaction between patient safety and food, and the effectiveness of the drug treatment.

In all, 40 volunteer patients took part in the trial, of which eight were given IDX 719. The volunteers reacted well to the drug, and have provided the company with positive feedback so that the trials can be continued. The company has also planned to begin trials with a combination of IDX 719 and IDX 184 towards the end of this year. Meanwhile, clinical trials on both drugs will continue to enable the company to gather as much data as possible before applying for FDA approval.

So many big companies are now involved in developing and testing drugs for HCV, that investors are asking whether they should invest in smaller companies, like Idenix, or look to larger pharmaceutical companies. Obviously, with the successful clinical trials to date, Idenix has to be taken seriously, but it may be appropriate to examine what the competition is doing. HCV drugs have recently become popular with investors because of the size of the potential market and the problems with the existing treatments for the disease. A successful treatment that would kill the virus, or at least keep it dormant, will help millions of people, and be extremely profitable for the company concerned.

Abbott Laboratories (ABT) has recently provided information on its pipeline drugs. Two short studies have shown recovery rates that are significant among the participants. The studies showed cure rates of 95% and 93%, respectively, for patients taking other HCV treatments, and 47% of patients not taking any other treatments. A cure rate refers to stopping or slowing down the spread of the virus, though the damage the virus has already caused cannot be reversed with these drugs. The company has started Phase II clinical trials, and will proceed to Phase III clinical trials before applying for FDA approval to manufacture and sell the drug treatment.

Gilead Sciences (GILD) also has a drug called GS-7977, which it took over when it acquired Pharmasset in late 2011. Gilead, is best known for its HIV drug treatments, Truvada and Viread. This HCV drug could become formidable competition for Index and other companies if it performs well in upcoming clinical trials. Gilead is under pressure, however, as its HIV drug treatments will lose patent protection by the end of the decade, and become vulnerable to low-cost generic producers.

Vertex Pharmaceuticals (VRTX) and Merck, two other companies developing new drug treatments for Hepatitis C, are also powerful competitors, and the recent problems that Vertex has had in respect of its data on Incivek do not take away from the effectiveness of the treatment. Finally, Medivir (MVIRB), working with Johnson & Johnson (JNJ), has reported good results with its drug TMC435. The company conducted a trial that resulted in an 80% 'cure' rate for volunteers who took the drug for 48 weeks and, within 24-weeks post-treatment, the virus disappeared.

Idenix has a robust drug pipeline centered on treatments for HCV. The company is investigating three separate classes of drugs. It has already been successful in developing and launching the licensed hepatitis B drug candidate, Telbivudine. The company has collaborations with other well-known companies, such as Novartis (NVS) and GlaxoSmithKline (GSK). These collaborations have produced several drugs such as IDX375 and IDX136. The company's best chance for a blockbuster is IDX184.

I have never believed that promising biotech investments can be identified with the use of conventional techniques and ratios involving past financial performance. A new blockbuster drug can be a complete game changer for a company. The kind of returns that are possible can easily outweigh the high risk and the process of waiting on FDA approvals. Idenix has a good track record, as well as a stellar product that could be a breakthrough in the potentially enormous HCV treatment market. If you can tolerate the risk of biotech investments, I would strongly recommend buying Idenix now.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

Source

Idenix HCV Drug IDX184-Good Data. Good Enough for a Partner?

Related-HCV Drug Candidates IDX184 and IDX719-Idenix Announces Positive Clinical Data

By Brian Graney, The Motley Fool

Posted 3:37PM 06/20/12 Posted under: Investing

On the surface, Idenix Pharmaceuticals' (NAS: IDIX) hepatitis C data looks pretty good. A solid 100% of patients taking the high dose of its nucleotide inhibitor IDX184, and 80% of the patients taking the low dose of the drug, were rid of the virus four weeks after treatment was completed. Combine those for an 89% early cure rate.

Dig a little deeper and you'll see there's a little more to the story.
First, between both doses, there are only nine patients. Hepatitis C drugs tend to perform fairly consistently as trials progress, so solid early data shouldn't be dismissed. With just nine patients, though, it isn't clear whether the data will be closer to 80% -- a ho-hum result -- or 100%, which would obviously be very competitive.

More important, those nine patients were from a subset of patients that responded well to the initial treatment with a combination of IDX184, pegylated interferon, and ribavirin. Of the 31 patients that entered the trial, only 18 had undetectable virus levels four weeks and 12 weeks after treatment. Nine of those patients were given 12 additional weeks of pegylated interferon and ribavirin, which is the interim data we have now. The other nine were given the combo for an additional 36 weeks.

Presumably those patients that stay on the drugs for 36 weeks will perform as well or better than those that were given the drugs for just 12 weeks. But what about the 13 patients that weren't randomized to get either 12 or 36 weeks of additional treatment? One achieved a quick response like the other 18, but dropped out of the study before the randomization began. The other 12 didn't achieve a quick response and were put on the longer 36-week treatment, so it isn't known how many will eventually come up positive. Keep in mind that group represents 40% of those known to still be enrolled in the trial, which could drag down the overall cure rate.

Not that the combo of IDX184, pegylated interferon, and ribavirin will ever see the light of day. Pegylated interferons -- Roche's Pegasys and Merck's (NYS: MRK) PegIntron -- have to be injected and have nasty side effects. Idenix ran this trial simply to gauge IDX184's efficacy, which seems fairly good for now, but it'll need to combine it with (an)other oral drug(s) to compete with all oral regimens being developed by Gilead Sciences (NAS: GILD) , Bristol-Myers Squibb (NYS: BMY) , Abbott Labs (NYS: ABT) , and others.

Which drug(s)? Management didn't say.

It likely depends on who owns IDX184. If Bristol's BMS-986094, which it got from the acquisition of Inhibitex, is a failure -- hints of that here -- the pharma might be interested in picking up IDX184 to combine with its daclatasvir, which has already been shown to work well with Gilead's nucleotide inhibitor.

If Idenix has to go it alone, the biotech has an NS5A inhibitor, same class as daclatasvir, a little behind IDX184. That seems like a less than ideal scenario for investors, but certainly an option if no one is interested in picking up IDX184 or the whole company.

David Gardner and his team at Rule Breakers aren't counting on an acquisition to get solid returns from one of their recent health-care picks. Find out what it is and why they like it in the Fool's free report "Discover the Next Rule-Breaking Multibagger."

http://www.dailyfinance.com/2012/06/20/good-data-good-enough-for-a-partner/

The article Good Data. Good Enough for a Partner? originally appeared on Fool.com.

HCV Drug Candidates IDX184 and IDX719-Idenix Announces Positive Clinical Data

Idenix hep C drug shows promise in mid-stage study (Reuters)

Idenix Pharmaceuticals Inc said interim data from a mid-stage trial on its experimental hepatitis C drug showed promise, sending its shares up 12 percent.

The drug, IDX184, was given to 31 patients in combination with the standard hep C treatments pegylated interferon and ribavirin.

Nine patients received the combination therapy for 12 extended weeks and were checked four weeks later for signs of the virus in the blood to determine if there was a sustained virologic response, or SVR.

All four patients in the 100 mg arm and four out of five patients in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment.

Patients who did not have undetectable levels of virus at 4 weeks and 12 weeks automatically entered the 36-week combination therapy extended treatment phase which is ongoing, the company said.
Idenix shares rose 12 percent to $10.45 in extended trade, after closing at $9.37 on Tuesday on the Nasdaq.

(Reporting by Shailesh Kuber in Bangalore; Editing by Saumyadeb Chakrabarty)
http://www.reuters.com/article/2012/06/19/us-idenixpharmaceuticals-brief-idUSBRE85I1N220120619
Source: Idenix Pharmaceuticals
Date: June 19, 2012 16:06 ET

Idenix Announces Positive Clinical Data for HCV Drug Candidates IDX184 and IDX719

In an Interim Analysis From an Ongoing Phase IIb Clinical Trial of IDX184, an HCV Nucleotide Inhibitor, 89% of Patients Who Completed an Additional 12 Weeks of Pegylated Interferon Plus Ribavirin Treatment Achieved SVR4; 100% (4/4) in 100 mg Arm and 80% (4/5) in 50 mg Arm

IDX719, an HCV NS5A Inhibitor, Achieves Potent Pan-Genotypic Activity in Three-Day Proof-of-Concept Clinical Trial

CAMBRIDGE, Mass., June 19, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced results from an ongoing phase IIb study of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV). Of the first cohort of 31 patients enrolled in the study, those who achieved an eRVR (n=18), defined as having undetectable levels of virus at 4 weeks and 12 weeks, were randomized to stop treatment after either an additional 12 weeks (n=9) or 36 weeks (n=9) of PegIFN/RBV. Of the nine patients who completed their 12-week PegIFN/RBV extended treatment phase, 100% of patients (4/4) in the 100 mg arm and 80% of patients (4/5) in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment (SVR4). Patients who did not achieve an eRVR automatically entered the 36-week PegIFN/RBV extended treatment phase which is ongoing. To date, the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegIFN/RBV alone.

"We are encouraged by the initial SVR results from the phase IIb program, which have confirmed previous data showing that IDX184 is a potent nucleotide inhibitor with a profile supporting its potential role as a key component of all-oral direct-acting antiviral (DAA) combination regimens for HCV," stated Ron Renaud, President and Chief Executive Officer of Idenix. "We look forward to initiating interferon-free DAA combination studies in the near term."

IDX184 Phase IIb Study Design

In July 2011, the company initiated enrollment of treatment-naive genotype 1 HCV-infected patients into a randomized, double-blind, parallel group phase IIb clinical trial of IDX184. The study features two treatment arms, either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with PegIFN/RBV. Response-guided therapy was used to complete an additional 12 or 36 weeks of PegIFN/RBV treatment. Study objectives include safety and tolerability, and antiviral activity endpoints.

IDX719 Proof-of-Concept Clinical Trial Data and Study Design

Idenix also announced today positive data from a three-day proof-of-concept study evaluating IDX719, an NS5A inhibitor, in 64 treatment-naïve, genotype 1, 2, 3 or 4 HCV-infected patients. Genotype 1 patients were randomized to receive placebo, 25 mg QD (once-daily), 50 mg QD, 50 mg BID (twice-daily) or 100 mg QD for three days. Genotype 2, 3 or 4 patients were randomized to receive placebo, 50 mg BID or 100 mg QD for three days.

IDX719 was well tolerated with no serious adverse events reported. Treatment with IDX719 exhibited potent pan-genotypic activity across genotypes:

In genotype 1 patients (n=28), mean maximal viral load reductions were 3.2 log10 IU/mL in the 25 mg QD arm, 3.7 log10 IU/mL in the 50 mg QD arm, 3.2 log10 IU/mL in the 50 mg BID arm and 3.5 log10 IU/mL in the 100 mg QD arm.
In genotype 2 patients (n=8), the mean maximal viral load reduction was 2.0 log10 IU/mL in both the 50 mg BID and 100 mg QD dose arms with a greater variability in responses among these patients (range: 0.3 – 4.1 log10 IU/mL). The company is currently conducting pharmacokinetic and sequencing analyses to further characterize these results.
In genotype 3 patients (n=8), mean maximal viral load reductions were 3.3 log10 IU/mL in the 50 mg BID arm and 3.4 log10 IU/mL in the 100 mg QD arm.
In genotype 4 patients (n=7), mean maximal viral load reductions were 3.9 log10 IU/mL in the 50 mg BID dose arm and 3.4 log10 IU/mL in the 100 mg QD dose arm.
More detailed findings are expected to be presented at a scientific meeting in the second half of 2012.

"We are pleased to demonstrate the first clinical validation of IDX719 in patients in a multiple-dose study with robust activity across multiple HCV genotypes," commented Douglas Mayers, M.D., Chief Medical Officer of Idenix. "Given these promising findings, we look forward to initiating a phase II combination study of IDX719 with IDX184 by the end of this year."

ABOUT IDX184

IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. In the ongoing phase IIb clinical trial, IDX184 has been well tolerated with a side effect profile similar to that of PegIFN/RBV. In the first cohort of 31 patients, at 12 weeks in an intent-to-treat analysis, the complete early virologic response (< 25 IU/mL at 12 weeks) was 93% for the 100 mg IDX184 arm (n=15) and 81% for the 50 mg IDX184 arm (n=16) of the study. The company completed enrollment of a second cohort of 36 additional patients in May 2012.

ABOUT IDX719

IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. In 36 healthy volunteers, IDX719 was safe and well tolerated at single doses of 5-100 mg as well as multiple doses of 100 mg for 7 days. Single doses of IDX719 demonstrated potent pan-genotypic antiviral activity in 18 genotype 1, 2 or 3 HCV-infected patients, with greater than 3 log10 viral load reductions achieved in the 100 mg dose arm.

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with HCV. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX184 or IDX719 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; the likelihood and success of any future clinical trials involving our drug candidates; and expectations with respect to future milestone or royalty payments, funding of operations and future cash balances. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the Company's dependence on its collaboration with Novartis; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2011 and quarterly report on Form 10-Q for the quarter ended March 31, 2012, each as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contacts:
Kelly Barry (617) 995-9033 (media)
Teri Dahlman (617) 995-9807 (investors)

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Idenix Pharmaceuticals Provides Update on Hepatitis C Clinical Development Programs

April 19, 2012

Idenix Pharmaceuticals Provides Update on Hepatitis C Clinical Development Programs

IDX719 Demonstrates Pan-Genotypic Activity at Single Doses in HCV-Infected Patients Achieving Greater Than 3 log10 Viral Load Reductions in the 100 mg Dose Group Across Genotypes 1, 2 and 3; Three-Day Proof-of-Concept Study Underway

IDX184/PegIFN/RBV Phase IIb Study Fully Enrolled

CAMBRIDGE, Mass., April 19, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced data from a phase I clinical trial of IDX719, an NS5A inhibitor for the treatment of hepatitis C virus (HCV) infection, demonstrating potent pan-genotypic antiviral activity with single doses.

In January 2012, Idenix initiated a phase I clinical study of IDX719. The first part of the study evaluated the safety, pharmacokinetics and food effect of IDX719 in 40 healthy volunteers at single doses ranging from 5 to 100 mg. Eight healthy volunteers received 100 mg of IDX719 daily for seven days. All doses were well tolerated and pharmacokinetic data supports once-daily dosing in future studies. In the second part of the phase I study, single-ascending doses of IDX719 achieved substantial viral load reductions in the following cohorts of HCV-infected patients:

• A cohort of 12 HCV genotype 1-infected patients received single IDX719 doses of 1, 5, 10, 25, 50 or 100 mg (2 patients per dose). Mean maximal viral load reductions were 1.9 log10, 2.6 log10, 3.3 log10, 3.7 log10, 2.8 log10 and 3.5 log10, respectively;

• A cohort of three HCV genotype 2-infected patients received single IDX719 doses of 25, 50 or 100 mg (1 patient per dose). Maximal viral load reductions were 0.4 log10, 3.2 log10 and 3.5 log10, respectively; and

• A cohort of three HCV genotype 3-infected patients received single IDX719 doses of 25, 50 or 100 mg (1 patient per dose). Maximal viral load reductions were 2.2 log10, 3.7 log10 and 3.3 log10, respectively.

The single-dose data were presented at the Cambridge Healthtech Institute's 5th Annual HCV Drug Discovery meeting this week in San Diego, California. A three-day proof-of-concept study has initiated dosing and is designed to evaluate 64 treatment-naïve genotype 1, 2, 3 or 4 HCV-infected patients.

"These single-dose IDX719 data show potent viral load reductions, with some patients maintaining viral suppression out to three days," said Douglas Mayers, Chief Medical Officer of Idenix Pharmaceuticals. "We are pleased with the promising antiviral activity in genotypes 1, 2 and 3, and we look forward to seeing multiple-dose data in a larger number of patients from the ongoing three-day proof-of-concept study."

Additionally, Idenix has completed enrollment of the second cohort of 30 patients in the ongoing 12-week phase IIb study of IDX184, an HCV nucleotide inhibitor, in combination with pegylated interferon and ribavirin (PegIFN/RBV). IDX184 continues to be safe and well tolerated with no treatment-emergent serious adverse events reported and a side effect profile similar to that of PegIFN/RBV. As the study currently remains blinded, further data from the ongoing clinical trial will be available in the second half of 2012.

"Idenix's clinical programs have made significant progress in the past few months. For IDX184, we are looking forward to initiating a combination study with a protease inhibitor and ribavirin in the near-term to establish the safety and potency of an all-oral IDX184-containing regimen, and, if successful, potentially support a phase III clinical program," said Ron Renaud, Idenix's President and Chief Executive Officer. "We are also very pleased with the early viral load reduction data for IDX719. Our ultimate goal is to advance a proprietary, pan-genotypic HCV treatment regimen. We intend to evaluate the combination of IDX184 and IDX719 in a clinical trial that is planned to begin by the end of this year."

ABOUT IDENIX
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com .

FORWARD-LOOKING STATEMENTS
This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX184 or IDX719 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; the likelihood and success of any future clinical trials involving our drug candidates; and expectations with respect to future milestone or royalty payments, funding of operations and future cash balances. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the Company's dependence on its collaboration with Novartis; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2011, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contacts:
Kelly Barry (617) 995-9033 (media)
Teri Dahlman (617) 995-9807 (investors) Source: Idenix Pharmaceuticals

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