Idenix suffers another FDA-mandated clinical hold...

Posted 8/27/12 on Fierce Biotech.com. Idenix suffers another setback as the FDA puts its NS5B inhibitor, IDX19368 on clinical hold as the fallout from the AE's from BMS-094 continue. Both IDX184 and IDX19368 are in the same class of nucs as the ill-fated BMS-094 and share the same active metabolite. Idenix CEO Ron Renaud feels there is enough differentiation between BMS-094 and the Idenix compounds to put safety concerns to rest, but the company is doing its due diligence in terms of ensuring the safety of the patients enrolled in its trials. The clinical holds certainly slow down the development of Idenix's nucs, but hopefully Mr. Renaud is right and the Idenix compounds still hold market potential. 

Idenix plunges after FDA puts another hep C treatment on hold

August 27, 2012 | By John Carroll

Idenix already faces a partial clinical hold on its top hepatitis C program. Now the FDA has stepped in to add a clinical hold on its preclinical therapy IDX19368, another nucleotide polymerase inhibitor, or "nuc," in the pipeline. The biotech ($IDIX) also spelled out some added safety checks for its lead hep C treatment, which the company says can be completed in a matter of weeks. But its shares swiftly plunged on the fresh round of troubling news.

"Based on our discussions with the FDA, we understand the clinical hold is a precautionary decision made by the FDA in light of the adverse events seen with BMS-986094," said Idenix CEO Ron Renaud. "Both IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094. However, there are many attributes of our compounds, particularly the prodrug approach, that we believe favorably differentiate the toxicity profiles from that of BMS-986094."

Idenix's FDA woes were triggered by the abrupt failure of BMS-094, a once sizzling-hot hep C treatment which raised alarms after one patient died and 8 others in a study were hospitalized, just 8 months after Bristol-Myers Squibb paid $2.5 billion to acquire Inhibitex. Bristol ($BMY) announced on Thursday that it was writing off $1.8 billion and scrapping the drug entirely. Idenix added today that BMS is lending a hand in resolving the holds.

Idenix also reported that it has lined up ethocardiograms for 50 patients enrolled in its IDX184 study. A few done so far have not revealed any safety concerns and the developer says that it should be able to complete this process in a few weeks.

A lingering concern for Idenix, though, is whether the company can regain the glow that had enveloped it after some big deals in the hepatitis C space made the company a prime takeover target, with analysts speculating about the prospect for a big premium. The Cambridge, MA-based company 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.

Idenix shares plunged 40% on news of the partial hold 11 days ago. This morning the stock plunged another 16% in premarket trading. Both of these programs are unpartnered, which leaves Idenix holding the bag now for any long-term loss in value.

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

Posted on 8/19/12 on Seeking Alpha.com. Commentary by Tiran Rothman from Bioassociate Consulting on the current state of affairs in HCV drug development. His feeling is that the troubles with the NS5A inhibitors may give formerly dark horse companies developing drugs with differing approaches to tackle the virus (mentioned are BioLineRx with it's BL-8020 entry inhibitor and Transgene's TG4040 therapeutic vaccine) a chance to shine. 

Is The Hep C Drug Pipeline Beginning To Crack?

By Tiran Rothman

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 II trial.

A different approach is taken by BioLineRx (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 others' 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.

IDX184 suffers setback in clinical trial....

Posted 8/16/12 on MarketWatch.com. Ouch. This makes Novartis look almost prescient in it's restructuring of it's relationship to Idenix. BMS-094, PSI-938 and IDX184 all share the same chemical structure - even if the cardiac event is unrelated to BMS-094 (hard to tell) I think the market will be wary regarding nucs sharing this structure.  

Idenix plunges 30% on HCV drug setback       08/16 10:43 AM

 BOSTON (MarketWatch) -- Shares of Idenix Pharmaceuticals (IDIX:$5.93,00$-2.38,00-28.64%) plunged 30% to $5.96 Thursday on news that the U.S. Food and Drug Administration has partially halted a Phase II clinical trial for its drug IDX184 over safety concerns. Idenix has been testing the product for the treatment of the hepatitis C virus, or HCV. The FDA placed a 'partial hold' on the trial pending the evaluation of reports that one of the patients taking the treatment had suffered a severe cardiac event. The FDA has also requested that Idenix provide additional patient data to help the agency with its evaluation. IDX184 belongs to a newer class of HCV drugs known as nucleotides. Earlier this month, shares of rival Bristol-Myers Squibb (BMY:$31.95,00$0.07,000.22%) slid almost 10% after the company announced it had suspended a Phase II study of its HCV nucleotide agent due to concerns that a patient had developed heart failure.

Novartis restructures HCV licensing deal with Idenix...

Posted on 8/1/2012 on PharmaTimes.com. It seems like subtle change is afoot in the HCV drug development field. Gilead announced that it would co-formulate GS-5855 and GS-7977 into one pill with an expected launch date of 2014 and Vertex posted earnings well below expectations of Wall Street on lower-than-anticipated sales of Incivek. Now, Novartis announces it is restructuring it's licensing deal with Idenix, giving the latter company back it's development rights for it's HCV pipeline. We can only speculate on why the rights were handed back to Idenix, but I'm sure Gilead's bold announcement and the post-EASL dampening of the current marketplace and it's chilling effect on the life cycles of the first generation of anti-HCV drugs didn't offer any remedy for cold feet.


Idenix gets rights back to pipeline from Novartis
WORLD NEWS | AUGUST 01, 2012

KEVIN GROGAN

Idenix Pharmaceuticals has regained the rights to hepatitis C compounds that were partnered with Novartis and announced plans to raise $150 million.

The US firm and the Swiss major first teamed up in May 2003 when the latter purchased a 54% stake in Idenix and licensed the hepatitis B treatment Tyzeka/Sebivo (telbivudine). Under the original agreement, Novartis had the option to license any of Idenix' candidates after proof-of-concept, so long as it maintained at least a 30% stake.

Novartis currently has a 31% holding but the pact has now been restructured. The option to license Idenix's development-stage drug candidates in any therapeutic area has been terminated and Novartis will be entitled to royalties on future hepatitis C virus drugs.

Novartis will have a non-exclusive option to conduct trials evaluating a combination of any of its and Idenix' HCV drug candidates, and the latter firm will no longer receive royalty or milestone payments from Tyzeka/Sebivo sales. The Basel-headquartered group will retain the right to designate one member to Idenix's board, reduced from two, as long as it continues to own at least a 15% stake.

Ron Renaud, Idenix chief executive, said the new agreement gives the firm "increased flexibility to optimise the value of our pipeline". By regaining the worldwide rights to all its drug candidates, "we believe Idenix will be well-positioned to develop pan-genotypic all-oral direct-acting antiviral combination treatments with potential collaborators," he added.

As the restructured deal was being announced, Idenix noted that it has commenced an underwritten registered public offering of $150 million of its common stock.

The proceeds will be used to develop combination Phase IIb trials of its HCV drugs IDX184 and IDX719, and Phase IIa studies with IDX19368 in combination with ribavirin. The funds may also be used to "potential acquisitions of new businesses, technologies or products that Idenix believes complements or expands its business".

Guru Focus: Idenix Pharmaceuticals Lagging Behind In Breakthrough Hepatitis C Drug Development

Posted on 7/13/12 on www.gurufocus.com. The author is worried about Idenix's pan-genotype nuc, IDX184. I'm not as worried, but Idenix definitely needs other drugs beside it's own to pair IDX184 with - preferably those well into Phase IIb or Phase III studies.  Those are drugs that are most likely to make it to market first, barring any errant new safety signals that would gum up the works and put pinholes in the dreams of investors everywhere. A good example to follow is Medivr/Janssen's protease inhibitor TMC435. That partnership has done an outstanding job of partnering with every company with a drug that looks hopeful, expanding their status as the 'preferred partner' drug in every combination that looks effective and safe.  On the other hand, we've learned in HIV that a good, potent, well-tolerated nuc (preferably ones with a unique resistance profile) will always come in handy. A good drug never has to worry. Only the company developing it does. 

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

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.

Idenix hep C polymerase inhibtor shows promise in mid-stage study...

Posted 6/19/2012 on the Chicago Tribune website. Not a whole lot of info in this bare-bones press release, but it looks like Idenix's HCV polymerase inhibitor IDX184 is faring pretty well, at least with an n=31 in this mid-stage clinical trial in combo with P/R. More info to follow as soon as I can dig some up. 

Idenix hep C drug shows promise in mid-stage study
 
Reuters
4:34 p.m. CDT, June 19, 2012

(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)

JMP Securites upgrades Idenix stock on HCV pipeline...

Posted on 4/30/12 on CBSNews.com. JMP Securities analyst Lisa Bayko doesn't think much of Idenix's nucleotide inhibitor IDX 184 (recently given the green light from the FDA after a clinical hold) but has higher hopes for compounds deeper in the Idenix pipeline. Specifically, she mentions NS5A inhibitor IDX 719 which Idenix currently retains ownership of.  

April 30, 2012 3:15 PM

Idenix Pharmaceuticals rises on analyst upgrade

NEW YORK — Shares of Idenix Pharmaceuticals Inc. rose Monday after a JMP Securities analyst upgraded the stock, saying it should trade higher as Idenix reports new data on its experimental hepatitis C drugs.

THE SPARK: Analyst Liisa Bayko upgraded the shares to "Market Perform" from "Market Underperform." Bayko said she doesn't think the company's most advanced drug candidate is effective enough to be the basis of a new treatment for the virus, but had a more optimistic view of some of Idenix's other drug candidates.

"We expect a steady flow of news from Idenix's hepatitis C pipeline in the second half of 2012 to generate increased interest in the stock," she wrote.

THE BIG PICTURE: Idenix is paid royalties on sales of the hepatitis B drug Tyzeka, which is marketed by Swiss drugmaker and Idenix shareholder Novartis AG. Idenix's most advanced drug candidate is designated IDX184. That drug is currently in mid-stage clinical testing. In January, the company started an early-stage trials of a drug candidate called IDX719.

Novartis has an option to license IDX719, but Bayko said she thinks Novartis will decline. That would give Idenix full control of the drug, and it would be able to combine IDX719 with other experimental drugs and look for another development partner.

SHARE ACTION: Idenix stock rose 29 cents, or 3.4 percent, to $8.84 in afternoon trading, after peaking at $9.21 during the session. The shares are down 44 percent from their 52-week high of $15.25, which they set Jan 19.

The Street - "Winners, Losers From EASL Hep C Data Dump"

Article posted on 4-4-12 on The Street.com. The author is right - the data people really want to see (tx-naive arm of ELECTRON; QUANTUM and GS-7977 + daclatasvir) won't be available until 4-21 after the Late Breaker sessions. After all, EASL has to fill seats for five days and Barcelona isn't just up the street for most of us. These leaves room for speculation - LOTS of speculation in the case of Idenix, which saw it's market cap take a hit after an analyst speculated that because nuc mericitabine (RG7128) under-performed in the JUMP-C study, it's distant cousin IDX184 would likely do the same.  The Idenix CEO quickly retorted that such comparisons are unfounded. We'll see - amazing the power of the Wall Street analyst in this market place. 

Adam Feuerstein
04/04/12 - 03:20 PM EDT
Updated with new information, including comments from the CEO of Idenix Pharmaceuticals.

BOSTON (TheStreet) -- The European Association for the Study of the Liver (EASL) finally released hepatitis C drug research abstracts Wednesday ahead of its closely followed conference in two weeks. But investors looking for clear winners and losers in the race to develop new all-oral hepatitis therapies came away disappointed.

As with all things hepatitis C, the EASL abstract "data dump" raised more questions than provided answers, in part because a lot of the data investors most wanted to see remains under wraps.

Still, Wall Street loves to make snap judgments, so Abbott(ABT) shares rose less than 1% to $61.60 on strong results from a small mid-stage study of a three-drug, all-oral regimen, which resulted in hepatitis C cure rates greater than 90%.

Abbott's gain was Gilead Science's(GILD) pain, causing the latter's shares to fall 2% to $47.13. Further hurting Gilead Wednesday was the absence of new data on GS-7977, the hepatitis C drug acquired in the $11 billion Pharmasset purchase. EASL chose not to make GS-7977 data available Tuesday, withholding for presentation at the meeting itself.

EASL also kept under wraps data from an important study combining Bristol-Myers Squibb's(BMY) daclatasvir with Gilead's GS-7977. A Bristol spokesperson did confirm, however, that interim results tracking early cure rates from this study will be presented at the EASL meeting.

The biggest loser Wednesday appears to be Idenix Pharmaceuticals(IDIX), with shares down 12% to $8.99 but not because of any new information released on its hepatitis C drugs. Instead, investors appear to be worried about the future of Idenix's lead drug IDX184 based on poor results released today on a similar drug being developed by Roche.

EASL's International Liver Congress is being held April 18-22.

More details on the hepatitis C research abstracts made public Wednesday:

Abbott: Today's results come from a phase II study of its own all-oral Hep C regimen consisting of protease inhibitor ABT-450, a ritonavir booster and the non-nuke polymerase inhibitor ABT-333. The study enrolled treatment naive genotype 1 patients as well as treatment-experienced non-responders. Patients were treated for 12 weeks.

In the treatment-naive patients, SVR12 or hepatitis C "cure" rates were 93% and 95% for the low- and high-dose arms, respectively. These are some of the strongest cure rates seen for new hepatitis C therapies, particularly for regimens that exclude injectable interferon. The high cure rates are even more impressive given that a majority of the patients enrolled were diagnosed with the more difficult-to-treat genotype 1A subtype.

In patients who failed to respond to previous treatment, the Abbott all-oral regimen resulted in a cure rate of 47%.

One looming concern about the Abbott hepatitis C regimen is convenience. As formulated now, patients must take one pill once per day and another two pills twice per day. For a relatively short treatment duration of 12 weeks, remembering to take a total of five pills per day may not be a problem, unless competing companies develop equally effective and simpler therapies.

Idenix: A Roche study combining the nucleoside polymerase inhibitor mericitabine, a protease inhibitor danoprevir and ribavirin proved to be relatively unsuccessful, with a cure rate of 41% overall (71% in genotype 1b patients and just 26% in the harder-to-treat genotype 1a patients.)

This study has nothing to with Idenix except that the company's own nucleoside polymerase inhibitor IDX184 is perceived by some investors to be similar to that of Roche's mericitabine. This raises concerns that any future combination regimen pairing IDX184 with a protease inhibitor may result in similarly poor cure rates.

Idenix CEO Ron Renaud calls comparisons between IDX184 and mericitabine "ridiculous," adding that data already presented shows '184 to be more like GS-7977 than mericitabine. "Comparing '184 to mericitabine, I don't know where that comes from," says Renaud. "It's just conjecture and assumptions being made by some… All we can do is continue to generate good data. We remain as optimistic about '184 as we've ever been." Hepatitis C data not yet released by EASL but expected at the meeting:

Gilead Sciences: Data from two separate but similar studies (ELECTRON and QUANTUM), both involving the two-drug combination of GS-7977 plus ribavirin in treatment-naive genotype 1 patients.

Gilead has said results from the QUANTUM study could be announced in a press release early in the second quarter i.e. before the start of the EASL meeting. Investors are sure to scour the EASL web site Thursday for any early patient data that may give a hint about the later '7977 results. Much is riding on the outcomes from these treatment-naive patient studies because '7977's potency was cast in doubt due to poor results in so-called "null responder" patients.

Bristol-Myers Squibb: Interim results from a phase II study combining Bristol's NS5a inhibitor daclatasvir (BMS-52) with Gilead's GS-7977 in genotypes 1, 2, and 3 is the most highly anticipated data presentation at the EASL meeting this year. The study is important because it will be one of the first glimpses at the Hep C-killing potency of these two classes of direct-acting antivirals combined into a single, all-oral therapy.

If this study is successful, Bristol is expected to swap out GS-7977 for its newly acquired nuke INX-189, gained from the Inhibitex acquisition. Gilead may also capitalize on the study by combining GS-7977 with its own NS5a inhibitor.

--Written by Adam Feuerstein in Boston.

Idenix seeks a partner for IDX184...

From Bloomberg News:  Idenix CEO Ron Renaud announces they need a protease inhibitor or NS5A inhibitor-weilding partner for their HCV nuc, IDX184. Analysts speculate that Tibotec or Merck may be attractive partners.

Idenix Seeks Partner for Hepatitis C Combination Drug, CEO Renaud Says

By Sasha Damouni - Jan 13, 2012 1:05 PM PT .
...
Idenix Pharmaceuticals Inc. (IDIX), the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.

“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”

The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.

The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”

Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.

Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. (BMY) said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. (GILD) for $10.8 billion.

Safer Treatments
As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.

On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.

“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.

While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.

Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world’s biggest health-care products company, also may have an interest because of its hepatitis C research program.

To contact the reporter on this story: Sasha Damouni in New York at sdamouni2@bloomberg.net
To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net; Brad Skillman at bskillman1@bloomberg.net

Wedbush analyst Duane Nash talks, people listen... Idenix stock rises.

(I wish I had that kind of power. Wedbush analyst Duane Nash recommends Idenix stock. He feels that Idenix's nucleotide inhibitor IDX184 is currently ripe for partnership and cites Pharmasset's partnership with BMS and J&J with PSI-7977 as a prime example of small pharma partnering with Big Pharma to leverage economies of scale on the development and commercialization front.)

Idenix rises as analyst looks to partnerships

NEW YORK

Shares of Idenix Pharmaceuticals Inc. rose Tuesday after an analyst upgraded the stock, saying the company's experimental hepatitis C drug may become a hot commodity in 2012.

THE SPARK: Wedbush analyst Duane Nash raised his rating on Idenix shares to "Outperform" from "Neutral." Nash said big drugmakers will be interested in the heptatitis drug, now called IDX184. After Idenix reports more data on the drug candidate, he said, it could find a marketing partner or a company interested in acquiring the drug outright. He raised his price target on Idenix shares to $11 from $6.

The company plans to report early results from a mid-stage trial of IDX184 during the first quarter of 2012.

THE BIG PICTURE: Throughout this year, companies like Pharmasset Inc. have been reporting strong clinical trial data for new hepatitis C drugs. Some of those drugs, including Pharmasset's PSI-7977 and Idenix's IDX184, are nucleotide drugs designed to prevent the hepatitis C virus from making copies of itself. Vertex Pharmaceuticals Inc.'s new hepatitis C drug Incivek also stops the virus from replicating, but it attacks a different part of the virus' genome and is not a nucleotide drug.

Nash said the data will get large pharmaceutical companies interested in nucleotide drugs. However there are not many of them available: Pharmasset already has development partnerships with Bristol-Myers Squibb Co. and Johnson & Johnson, and several other drug companies have similar partnerships.

Nash said only two companies are running clinical trials of a nucleotide drug that is not already partnered: Idenix and Inhibitex Inc.

"Due to the growing likelihood that (nucleotide drugs) will be essential for interferon-free therapy, and combined with the scarcity value of available nucs, we are increasingly optimistic that IDX184 will be partnered or acquired in 2012," Nash wrote.

Idenix spokeswoman Kelly Barry said the company has "multiple ongoing discussions with potential partners."

SHARE ACTION: Shares of the Cambridge, Mass., company picked up 26 cents, or 3.9 percent, to $7 in afternoon trading. Earlier in the session, the stock reached a three-year high of $7.38.

Idenix compounds put on 'clinical hold' after three serious adverse events...

CAMBRIDGE, Mass., Sept. 7 /PRNewswire-FirstCall/ -- 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 that the company received verbal notice on Friday, September 3, 2010 from the U.S. Food and Drug Administration (FDA) that the IDX184 and IDX320 programs have been placed on clinical hold. A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. This decision was made after Idenix notified the FDA of three serious adverse events that occurred during a drug-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers. These observed serious adverse events were elevated liver function tests detected in three subjects during post exposure safety visits. The liver function tests have returned to nearly normal levels in all three subjects during follow-up. All planned studies of IDX184 and IDX320 to date have been completed and there are currently no healthy volunteers or patients receiving IDX184 or IDX320. Idenix will submit full data to the FDA from recently completed preclinical and clinical studies, including 3-month chronic toxicology studies of IDX184, a 14-day study of IDX184 in combination with pegylated interferon/ribavirin (PegIFN/RBV), a 3-day proof-of-concept study of IDX320 in hepatitis C (HCV) infected patients, and the IDX184 and IDX320 drug-drug interaction study in healthy volunteers in order to assess next steps in the development of both compounds.

"We have not yet received a formal letter from the FDA, nor has the Agency had an opportunity to review the safety and efficacy data from recently completed clinical trials with IDX184 and IDX320. Based upon our discussions with the Agency, we are primarily focused on three cases of elevated liver function tests observed during our drug-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers," said Jean-Pierre Sommadossi, Ph.D., Idenix Chairman and Chief Executive Officer. "Based upon the safety and antiviral activity we observed in the IDX184 14-day study and the IDX320 3-day proof-of-concept study, both in HCV-infected patients, we remain committed to the future potential of these drug candidates. We will work closely with independent experts and our external safety committee to better understand the cause of these serious adverse events in the combination study of IDX184 and IDX320 and to provide the FDA with more information in order to expedite their review and resolve this matter as quickly as possible."
Full data presentations of IDX184, IDX320 and IDX375 studies will be presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD), which will be held at the end of October in Boston.

Phase I: IDX184/IDX320 Combination
Idenix completed a two-week Phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetic drug-drug interaction between IDX320 and IDX184 in healthy volunteers. Two cohorts were evaluated in the study with 10 subjects in each cohort randomized eight to active drug and two to placebo. Subjects in the first cohort received 400 mg once-daily of IDX320 for the first week, subsequently adding 100 mg once-daily of IDX184 for the second week. Subjects in the second cohort received 100 mg once-daily of IDX184 plus placebo for the first week, subsequently adding 400 mg once-daily of IDX320 for the second week. The combination of IDX184 and IDX320 was generally safe and well tolerated during the 14 days of treatment. Liver function abnormalities deemed to be serious adverse events were detected in three subjects during the post exposure safety visits. Liver function tests in these subjects have returned to nearly normal during follow-up. Pharmacokinetic drug-drug interactions between IDX184 and IDX320 were not considered to be clinically significant. Neither the plasma exposure of IDX184 and its metabolite, 2'-methylguanosine, nor IDX320 plasma exposure explain these three serious adverse events.

Phase IIa: IDX184, a liver-targeted HCV nucleotide prodrug
This 14-day, Phase IIa clinical trial evaluated 50 to 200 mg doses of IDX184 in combination with PegIFN/RBV in treatment-naive HCV genotype 1-infected patients. At Day 14, mean (+/- standard deviation) viral load reductions were 1.5 (+/- 1.3) logs for placebo (n=16), 2.7 (+/- 1.3) logs for 50 mg IDX184 QD (n=16), 4.0 (+/- 1.7) logs for 50 mg IDX184 BID (n=8), 4.2 (+/- 1.9) logs for 100 mg QD (n=8), 4.1 (+/- 1.2), for 150 mg QD (n=15), 4.1 (+/-1.4) logs for 100 mg BID (n=8) and 3.7 (+/- 1.2) logs for 200 mg QD (n=8). In the cohorts of 100 mg, 150 mg, and 200 mg daily doses in combination with PegIFN/RBV, 50%, 40% and 25%, respectively, of patients achieved undetectable virus levels (<15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved with all doses of IDX184. The side effect profile of the three drug combination was consistent with the known side effect profile of PegIFN/RBV alone. The most common adverse events reported were fatigue, myalgia, headache and nausea.
Phase I/II: IDX 320, an HCV protease inhibitor

This randomized, parallel-arm, double-blind, placebo-controlled proof-of-concept trial evaluated the safety, tolerability, antiviral activity and pharmacokinetics of IDX320 in treatment-naive HCV genotype 1-infected patients. Thirty patients were randomized equally and received placebo, 50, 100, 200 or 400 mg of IDX320 orally once-a-day for three days. One cohort of eight patients was randomized to receive 200 mg IDX320 BID or placebo. At Day 3, mean (+/- standard deviation) viral load reductions were 0.1 (+/- 0.15) logs for placebo (n=5), 2.6 (+/-0.49) logs for 50 mg IDX320 QD (n=5), 3.1 (+/- 0.29) logs for 100 mg QD (n=6), 3.1 (+/- 0.41) logs for 200 mg QD (n=6) and 3.3 (+/- 0.28) logs for 400 mg QD (n=7). At daily doses of placebo, 50, 100, 200, and 400 mg, 0%, 20%, 67%, 67% and 86%, respectively, of patients achieved greater than or equal to 3 log reduction in HCV RNA at the end of treatment. In the 200 mg IDX 320 BID cohort at Day 3, mean (+/- standard deviation) viral load reductions were 3.8 (+/- 0.52) logs and all patients (100%) achieved greater than or equal to 3 log reduction in HCV RNA. In the 3-day proof-of-concept study, IDX320 was generally safe, well tolerated, and demonstrated potent, dose-related HCV antiviral activity.

Phase I: IDX375, an HCV non-nucleoside polymerase inhibitor
Idenix has an ongoing Phase I clinical trial in healthy volunteers evaluating single doses of the free acid form of IDX375 ranging from 200 to 1200 mg per day. Overall, IDX375 achieved pharmacologically relevant drug exposure and was well tolerated for doses up to 1200 mg for one day in healthy subjects. In the fourth quarter of 2010, Idenix plans to initiate a 3-day proof-of-concept trial in treatment-naive genotype 1 HCV-infected patients.

Conference Call Information
Idenix will hold a conference call today at 8:30 a.m. ET. To access the call please dial (800) 471-3635 U.S./Canada or (706) 758-9475 International and enter passcode 99538089. A replay of the conference call and webcast will be available until September 21, 2010. To access the replay, please dial (800) 642-1687 U.S./Canada or (706) 645-9291 International and enter the passcode 99538089.
About HCV

Idenix starts recruiting for drug-drug interaction study evaluating the combination of IDX320 and IDX184 in healthy subjects

Idenix, Inc starts recruiting phase I, double-blind, multiple-dose study to evaluate the pharmacokinetic drug-drug interaction between it's protease inhibitior IDX320 and it's polymerase inhibitor IDX184 in healthy subjects
More info here: http://bit.ly/dlDQdC

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

PR Newswire US - Jun. 10, 2010

CAMBRIDGE, Mass., June 10 /PRNewswire-FirstCall/ -- 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 that it has initiated a 3-day proof-of-concept study of IDX320, a protease inhibitor for the treatment of hepatitis C virus (HCV) infection, under a Clinical Trial Application (CTA). The study is evaluating IDX320 in treatment-naive hepatitis C genotype 1-infected patients.

"The potent and multi-genotypic activity demonstrated in vitro, as well as the favorable pharmacokinetics observed in healthy volunteers, suggests a promising profile for further development of IDX320," said Jean-Pierre Sommadossi, Ph.D., chief executive officer of Idenix. "The landscape for combination development in HCV is evolving quickly. Assuming favorable results from the IDX320 proof-of-concept study, we plan to discuss with regulatory agencies a direct-acting antiviral combination strategy with IDX320 and IDX184, our HCV nucleotide polymerase inhibitor."

Douglas Mayers, M.D., Idenix's chief medical officer commented, "We are encouraged by the results seen to date with IDX320 and are hopeful that future clinical studies will allow us to continue advancing this program with the ultimate goal of treating a wide range of patients infected with HCV."

The proof-of-concept trial in HCV-infected patients is a Phase I/II randomized, parallel-arm, double-blind, placebo-controlled study evaluating the safety and antiviral activity of IDX320 in treatment-naive adult patients infected with chronic hepatitis C. The study will evaluate four doses of IDX320, ranging from 50 to 400 mg once-per-day, administered for three days. Each cohort of the study will evaluate eight patients randomized six to IDX320 and two to placebo. 

About IDX320

IDX320, a macrocyclic HCV protease inhibitor, is an inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC50 values from 0.8 to 1.9 nM), as well as from genotype 3a (IC50=23 nM). IDX320 did not inhibit nine tested cellular proteases (IC50 > 10 uM) in vitro, suggesting high selectivity. IDX320 bound tightly to the HCV protease enzyme with a long dissociation half-life (> 9 hours). After single 2 mg/kg oral doses of IDX320 in two animal species, favorable bioavailability and a long plasma half-life were observed, with substantial plasma concentrations 24 hours post dose. Comparable drug exposure was confirmed in healthy volunteers (n=6) receiving a single 200 mg oral dose. Further, no significant in vitro inhibition of human drug metabolizing enzymes, CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions in patients.

About IDX184

IDX184 is a novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine monophosphate, 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. IDX184 in combination with pegylated interferon and ribavirin has demonstrated a generally favorable safety profile and potent antiviral activity in an ongoing Phase IIa study.