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.

BMS formally suspends development of BMS-094...

Posted 8/23/2012 on Fox Business.com.  BMS formally suspends development of nucleoside inhibitor BMS-094/INX-189 due to possible heart and kidney toxicity. One subject died, nine were hospitalized and two remain so at the time of press. The cause of the events has not yet been identified. Ramifications have already been felt through the HCV drug development space, with Idenix's IDX184 clinical trial, a nucleoside inhibitor similar in structure to BMS-094, put on partial clinical hold by the FDA. The FDA hinted in it's letter to Idenix that there were possibilities of similar actions to other nucs in development as well.

Bristol-Myers Discontinues Development of Hepatitis C Drug
Published August 23, 2012

Dow Jones Newswires

Bristol-Myers Squibb Co. (BMY) said Thursday it has discontinued the development of a drug intended to treat the liver disease hepatitis C in the interest of patient safety, after a patient died and others were hospitalized.

Bristol-Myers earlier this month voluntarily suspended a Phase 2 study of BMS-986094, which was formerly known as INX-189, a nucleotide polymerase inhibitor, or "nuke." The initial case of heart failure, which was the basis for halting the study, subsequently resulted in death, the company said Thursday.

Bristol-Myers said it is working with the U.S. Food and Drug Administration and clinical study investigators to conduct ongoing and close follow-ups of all the study's patients. To date, nine patients have been hospitalized, including the initial patient, and two remain hospitalized.

The company said the cause of these unexpected events, which involve heart and kidney toxicity, hasn't been definitively established.

Bristol-Myers decision to halt the study earlier this month raised questions about the experimental drug's potential and the $2.5 billion price tag Bristol paid earlier this year to buy the company that developed it. The suspension was considered a significant setback for the drug maker--already grappling with weak sales of its Plavix anticlotting drug that lost patent protection in May--in the race to develop new hepatitis C treatments.

Bristol-Myers as well as other companies such as Gilead Sciences Inc. (GILD) and Abbott Laboratories (ABT) has been looking to bring the first all-oral hepatitis C regimen to market, hoping to tap what is expected to be a multibillion-dollar market for such a therapy.

To strengthen its hepatitis C position, Bristol-Myers in February shelled out $2.5 billion to buy Inhibitex Inc. at a whopping 163% premium. Bristol was lured primarily by Inhibitex's nuke for hepatitis C, though it did acquire other potential treatments for infectious disease in the deal.

Treatments for hepatitis C are considered lucrative because the disease is prevalent in large sections of the global population. The virus, which can be transmitted sexually or through use of shared needles and at tattoo parlors, affects some 170 million people world-wide.

Separately, Synergy Pharmaceuticals Inc. (SGYP) said it has agreed to acquire the assets related to shingles treatment FV-100 from Bristol-Myers. FV-100 was developed by Inhibitex.

Shares were up by 10 cents to $32.25 after hours. The stock has fallen 8.8% since the start of the year.

-Write to Nathalie Tadena at nathalie.tadena@dowjones.com

Subscribe to WSJ: http://online.wsj.com?mod=djnwires

Copyright © 2012 Dow Jones Newswires

Incivek (telaprevir) product labeling revised...

Posted at FDA.gov on 6/26. The FDA revised the product labeling for Incivek. The changes were a combination of DDI, warnings, clinical trial data revisions and corrections. See below for full list of changes. 

Incivek (telaprevir) product labeling revised

The Incivek (telaprevir) product labeling was recently revised to include the following changes:

1. Update the clinical comment for neuroleptic drug pimozide in Section 4 Contraindications to state: "Potential for serious and/or life-threatening adverse reactions such as cardiac arrhythmias"

2. Update Section 5 Warnings and Precautions subsection 5.4 Anemia to state: "Hemoglobin should be monitored prior to and at least at weeks 2, 4, 8 and 12 during INCIVEK combination treatment and as clinically appropriate."

3. Update Section 5 Warnings and Precautions subsection 5.6 Laboratory Tests to state the following: Use of a sensitive real-time RT-PCR assay for monitoring HCV-RNA levels during treatment is recommended. The assay should have a lower limit of HCV-RNA quantification equal to or less than 25 IU per mL and a limit of HCV-RNA detection of approximately 10-15 IU per mL.

4. Update Section 7 Drug Interactions to remove desipramine from Table 5: Established and Other Potentially Significant Interactions. Also added to Section 7 was a statement that no dose adjustment is needed for Incivek when given with either raltegravir or buprenorphine. The corresponding results from the drug-drug interaction trial with raltegravir and buprenorphine are included in Section 12 Pharmacokinetics.

5. Update Section 14 Clinical Studies to include revisions to the definition of sustained virologic response (SVR) and to correct the SVR rates for African American and Cirrhotic subpopulations as follows:

SVR was defined as HCV RNA less than 25 IU per mL at last observation within the SVR visit window (i.e., weeks 32-78 for patients assigned to 24 weeks of treatment and weeks 56-78 for patients assigned to 48 weeks of treatment).

Trial 108 (ADVANCE)

Twenty-six subjects were Black/African Americans. The overall SVR among Black/African American subjects was 62% (16/26). Among these subjects, 35% (9/26) were assigned to 24 weeks of treatment and of those 89% (8/9)achieved SVR.

Twenty-one subjects had cirrhosis at baseline and the overall SVR in these subjects was 71% (15/21). Among subjects with cirrhosis, 43% (9/21)were assigned to 24 weeks of treatment and of those 78% (7/9)achieved SVR.
Trial 111 (ILLUMINATE)

Sixty-one (11%) of subjects had cirrhosis at baseline. Among subjects with cirrhosis, 30 (49%) achieved an eRVR: 18 were randomized to T12/PR24 and 12 to T12/PR48. The SVR rates were 61% (11/18) for the T12/PR24 group and 92% (11/12) for the T12/PR48 group.
Blacks/African Americans comprised 14% (73/540) of trial subjects. Thirty-four (47%) Black/African American subjects achieved an eRVR and were randomized to T12/PR24 or T12/PR48. The respective SVR rates were 88% (15/17) and 88% (15/17), compared to 92% (244/266) for Caucasians among randomized subjects.
Trial C216

Twenty-six percent (139/530) of INCIVEK-treated subjects had cirrhosis at baseline. SVR rates among cirrhotic subjects who received INCIVEK combination treatment compared to Pbo/PR48 were: 84% (48/57) compared to 7% (1/15) for prior relapsers, 34% (11/32) compared to 20% (1/5) for prior partial responders, and 14% (7/50) compared to 10% (1/10) for prior null responders.
Four percent (19/530) of treatment experienced subjects who received INCIVEK combination treatment were Black/African Americans; the SVR rate for these subjects was 63% (12/19) compared to 66% (328/498) for Caucasians.

The complete revised label can be viewed on the FDA web site at Drugs@FDA.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

Vertex receives FDA warning letter on 'misleading branded story'...

Article posted 5/31/12 on Regulatory Focus.com.  Vertex brushes with the FDA over what the FDA considered to be a 'misleading branded story'.  The timing isn't great as Vertex supposedly is getting ready to amend it's labeling, possibly to include BID dosing. 

‘Misleading’ Patient Perspective Smacked Down by FDA in Untitled Letter
Latest News | Posted: 31 May 2012

By Alexander Gaffney

One pharmaceutical company is learning this week that reproducing a patient’s story to “mentor” other potential patients may not sit well with US regulatory authorities, regardless of whether it represents the patient’s perspective accurately.

Cambridge, Massachusetts-based manufacturer Vertex Pharmaceuticals was sent an Untitled Letter by the US Food and Drug Administration (FDA) warning it about its promotion of Incivek (teleprevir), a Hepatitis C (HCV) drug which FDA said was being marketed using a “misleading” branded story.

The branded story is told through the eyes of a patient, “JP”, who tells the audience of his struggle with HIV and subsequent—but difficult—success using Vertex’s Incivek, which he claims “cleared the virus” from his body.

FDA explained in its 25 May letter that Vertex has “overstated” the efficacy of Incivek because it suggests the drug is more effective than “substantial evidence or substantial clinical experience” has shown.

“While these claims may be an accurate reflection of James’ own experience with hepatitis C and treatment with Incivek, this branded story misleadingly implies that most or all cirrhotic prior null responders infected with hepatitis C will successfully achieve Sustained Virologic Response (SVR) on Incivek combination therapy,” wrote FDA in the Untitled Letter. “FDA is not aware of substantial evidence or substantial clinical experience to support this implication.”

Put succinctly, “one patient’s treatment response does not constitute substantial evidence,” said FDA. Further, FDA said the testimonial “misleadingly implies removal of HCV from the body, when this is not the case.” Instead, the virus may well have simply become undetectable while continuing to replicate, noted FDA.

The testimonial also minimized important risk information by downplaying the side effects of the drug, explained FDA. The testimonial recounts “JP” receiving the treatment, which caused him to lose significant amounts of hair and develop a rash. “But that was nothing,” said “JP,” referring to the side effects relative to the benefits of the treatment for him. FDA maintains this “minimizes the risk” of both side effects, and particularly the risks of the rash, which the agency called “serious.”

FDA called on Vertex to stop using the branded story and respond to FDA’s Untitled Letter within 15 days.

A Vertex spokeswoman, Nikki Levy, told The Boston Globe the company has never distributed the story and was now working to revise its content in light of FDA’s informal warning.

Untitled letters are different from official FDA Warning Letters in that they do not include a list of potential agency enforcement actions and are generally less serious than are formal Warning Letters.

GSK seeks to expand low-platelet drug Promacta to hepatitis C patients...

Posted on 5/30/12 via MedCityNews.com. GSK seeking to expand drug level to include thrombocytopenia, both pre initiation of therapy for patients with low baseline platelets and  thrombocytopenia as a result of HCV therapy. 

GlaxoSmithKline (NYSE:GSK) wants now wants approval to use its low platelet drug Promacta to treat hepatitis C patients.

GSK has filed regulatory applications in Europe and the United States to add the new indication to the drug. The drug eltrombopag, which is marketed under the brand name Promacta in the United States and Revolade globally, is approved in 88 countires to treat immune thrombocytopenia, a condition in which a patients has low blood counts because the platelets are destroyed by the patient’s own immune system. The condition puts patients at the risk of bleeding. Promacta was co-discovered by GSK predecessor SmithKline Beecham and partner Ligand Pharmaceuticals.

The British pharmaceutical giant, which has its U.S. headquarters in Research Triangle Park, North Carolina, is now seeking to expand approval of the drug to increase platelet counts in patients who have chronic hepatitis C virus infection. The drug would allow them to start interferon-based therapy and could also be used to optimize interferon-based therapy, according to to GSK’s supplemental new drug application.

GSK last year completed a phase 3 study of Promacta in hepatitis C patients whose low platelet levels make them unable to start interferon therapy to treat the virus. The trial met the primary endpoint of improving the sustained virological response.

Promacta does come with some safety risks. Until late last year, the U.S. Food and Drug Administration required doctors and patients to follow a strict regimen in order to watch for adverse effects including liver damage, blood clots and bleeding risks after discontinuing the drug. But the FDA eased those requirements concluding that it was unlikely the safety data collected could determine whether adverse effects were caused by the drug or by the immune thrombocytopenia. While mandatory collection of safety data is no longer required, the agency continues to ask that any adverse events be reported.

FDA advisory panel gives Truvada HIV prophylaxis a thumbs up...

Posted on 5/8 on Bloomberg.com . Yeah, I know it's not HCV-related, but Truvada is such a triumph of antiviral drug marketing that anything related to it draws me in like a moth to a flame. Gilead's launch and subsequent marketing and promotion of Truvada should be a mandatory case study in any business school worth it's salt. That it got before an FDA advisory panel on a possible indication for HIV prophylaxis is stunning. The fact that the panel gave it a thumbs up knocked me off my chair, over my desk and into the hallway.  Kudos to Gilead. I'll set aside my own reservations on Truvada prophylaxis - misuse leading to possible resistance, kidney toxicity in those predisposed to such and/or a precipitous drop in condom use  - to slap the Gilead marketing machine on the back and buy them whatever's on tap. Truly amazing. Now we'll see if the FDA follows the panels recommendations and see if it actually gets approved and on the market. 

Gilead’s Truvada Pill Is Safe for HIV Prevention
By Ryan Flinn and Shannon Pettypiece - May 8, 2012 6:45 PM PT

Gilead Sciences Inc. (GILD)’s pill Truvada was safe and effective when used to protect uninfected people from getting HIV, U.S. regulators said in a report indicating the main concerns are when and how it should be used.

Truvada was “well tolerated” and its ability to reduce the risk of infection was backed by two studies, the Food and Drug Administration staff said in a report today. Gilead, based in Foster City, California, is seeking to sell the drug as the first pill to keep people from becoming infected.

The FDA asked its advisers to suggest who should get Truvada; what testing would be needed for administration; and what educational material should be used for patients and doctors. The advisers will meet May 10 to discuss the drug, the subject of debates over its appropriate use and cost.

Decisions to prescribe Truvada “should carefully weigh the individual risks for acquiring HIV, their understanding of the importance of adherence to medication, and their potential for development of renal toxicity,” the FDA staff said today in a report on the agency’s website. Education and counseling will be “critically important.”

Gilead fell less than 1 percent to $49.46 at the close of New York trading. The FDA isn’t required to follow what the advisory panel suggests.

Not Expected
Investors aren’t counting on expanded use of Truvada to boost sales much, said Robyn Karnauskas, an analyst with Deutsche Bank in New York. Instead, they are focused on Gilead getting new products to market before facing the loss of half of its revenue from patent expirations beginning in 2018.

“Right now, the company is in a position where they have flat sales and Truvada isn’t going to fix the patent cliff problem,” Karnauskas said.
Truvada sales for prevention are estimated to peak at about $150 million a year, said Tony Butler, an analyst with Barclays Capital in New York. Insurance reimbursement may be a challenge, he said.

Debate over the appropriate use of the drug has divided the AIDS community. Some AIDS advocacy groups say the drug will be a valuable tool for reducing new cases, particularly within stable partnerships where one person has AIDS and the other doesn’t. Others said it may lead to more infections, lower condom use and might build resistance to the medicine.

The population at high risk for contracting the disease includes at least 140,000 individuals whose spouses or partners have the disease, as well as 275,000 gay men who had more than two partners in the past year and didn’t wear condoms during sex, according to the U.S. Centers for Disease Control and Prevention, based in Atlanta.

Three Decades
“Thirty years into the epidemic we can’t dismiss any new options,” James Loduca, a spokesman for the San Francisco AIDS Foundation, said in an interview. “This won’t end AIDS by itself, but we can’t end it without this.”

Loduca said condoms aren’t enough to stem the tide of new infections, and using Truvada as a preventative measure would help if taken correctly.
While the number of people infected with HIV rose to 34 million worldwide in 2009, the virus that leads to AIDS, once a death sentence, can be reduced to low levels in the blood with use of combination antiviral medicines such as Truvada.

Michael Weinstein, president of the AIDS Healthcare Foundation, said approval and prescription of Truvada as a preventative may lead to less condom use and more infections, as well as increased resistance to the drug.

Really Paranoid
“Why would you take this medication if you intended to use condoms?” he said. “You’ve got to be really paranoid about your pants falling down to wear a belt and suspenders.”

His organization sued the FDA last year after the agency rejected its Freedom of Information act request for correspondence between regulators and Gilead. Weinstein said the studies don’t prove that the pill is effective enough to warrant approval. The AIDS Healthcare Foundation has lined up speakers for the public hearing later this week to oppose its preventative use, Weinstein said.

Barry Zingman, medical director at the AIDS Center at Montefiore hospital in the Bronx, one of the largest treatment centers in New York, said he hopes the drug is approved and plans to offer it to some patients.

$11,000 Cost
He said his big concern is the drug’s more than $11,000 a year price tag.

“People are really interested in the concept, but there have been issue related to insurance coverage,” Zingman said. “Approval would make a significant advance in insurance coverage.”

Aetna Inc. spokeswoman Tammy Arnold and WellPoint Inc. spokeswoman Lori McLaughlin said their companies would consider covering the treatment as a form of prophylaxis if approved by the FDA. UnitedHealth Group Inc. declined to comment.

Medicare, the federal program for the elderly and disabled, and Medicaid, the joint state-federal plan for the poor, typically reimburse for all FDA-approved indications.

If approved, the drug would mostly be given to people at high risk for infection, like men who have sex with men, intravenous drug users and sex workers, said Ken Mayer, medical research director at the Fenway Institute, the largest AIDS treatment center in New England. It would typically be given for a limited period of time, he said.

“I think it would be a mistake for the FDA not to approve this indication,” Mayer said. “If we can figure out how to use this most effectively we can really put a dent in the number of new infections.”

In a study of men who have sex with men, the drug reduced the risk of infection by 42 percent, though adherence in the trail was low, the agency said. In a study of heterosexual couples where one person was infected, the risk was reduced by 75 percent.

To contact the reporters on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net; Shannon Pettypiece in New York at spettypiece@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

NPR: The Race To Create The Best Antiviral Drugs

Radio interview and article with noted viral expert Carl Zimmer posted on NPR.org on 4/17/12.  Not specifically related to just HCV, it gives us a broad overview of some of the science behind creating new therapies to treat a variety of viral-related diseases. Very compelling, in my opinion. 

The Race To Create The Best Antiviral Drugs

If you've ever had a bacterial infection like staph or strep throat, your doctor may have prescribed penicillin. But if you've had the flu or a common cold virus, penicillin won't work. That's because antibacterials only kill bacteria, and both the flu and the common cold are viruses. So for illnesses like the flu, doctors prescribe antiviral drugs, which target the mechanisms that viruses use to reproduce.

"For example, there are antivirals for the flu that interfere with the virus as it tries to get out of its host cell," says science writer Carl Zimmer. "So this molecule latches on to that particular protein that the virus uses to escape, and interferes with it so that the virus is trapped inside."

Zimmer's latest piece for Wired magazine profiles the scientists who are developing antiviral medications, and examines the new ways medicine is working to attack viruses.

"There are some really amazing antivirals that have been invented over the last 40 years," he says. "There are antivirals for herpes. There are antivirals for HIV. ... Now, if you were to get Ebola and you tried to take HIV drugs, they'd do you no good at all because that HIV drug only works for HIV. It's a narrow-spectrum drug, and really, there are no broad-spectrum antivirals, at this point."

But scientists are now working to create a "penicillin-like" drug that will target viruses more broadly. In San Francisco, a company called Prosetta is working on a drug that doesn't affect a virus directly. Instead, it works by affecting the proteins that are naturally in cells that help viruses replicate.

"The basic idea behind it is that viruses need help to build themselves," says Zimmer. "What happens is quite amazing: [Viruses] get lots of different proteins in our cells and cooperate to push their own proteins into place. And so the viruses need these groups of host proteins to form."

Prosetta created a drug that prevents the host proteins from performing their cooperative jobs and helping the viruses out. Preliminary studies have shown that targeting these host proteins — and not the virus itself — can stop Ebola, influenza, rabies and other viruses.

Other researchers are working to replace or help interferons, our body's own natural virus-fighting system. Eleanor Fish, a researcher at the University of Toronto, is heading a project to create synthetic interferon, in order to accelerate the body's virus-fighting response.

"Today, people with Hepatitis C can get interferon treatment, but it doesn't work all that well. It has some benefit, but not as much as Eleanor Fish would like," says Zimmer. "So she has been essentially tweaking the interferon molecule to make it more effective, to make it last longer, to make it safe and to make it cheap. Because what she wants to do is deploy interferon all over the world where there isn't fancy refrigeration. She wants to help people who are dealing with viruses in very remote places."

A third approach, says Zimmer, involves creating an artificial protein that would latch onto viruses and then instruct them to literally self-destruct. Spearheaded by Todd Rider at MIT, the project has been tested in cells and in mice.

"Rider's basically hot-wiring your cells so that as soon as they get infected by a virus, that trips a switch," says Zimmer. "This doesn't exist naturally, but if you were to take a pill, the thinking is, then this molecule would go into your infected cells, and as soon as it detected the virus, it would kill the infected cell, and you would recover from your disease."

But successfully eradicating viruses may bring a host of other problems, says Zimmer. He points to broad-spectrum antibiotics, which wipe out good bacteria in addition to bad bacteria.

"Eventually your body may recover, and it can take awhile, and there may be some bad consequences of the antibiotics themselves," he says. "So it's going to be interesting to see what happens in the future if we are, in fact, knocking out lots of viruses. Because we don't understand the full ecology of the viruses that get into our bodies."

There are trillions of viruses that live in our bodies, even when we're not sick, says Zimmer.

"Some are harmful, some may not be harmful," he says. "Some may even help us defend against other viruses. It's very complicated in there, and we don't really understand it very well yet."

hysicians are now using bacteria to combat other diseases. Zimmer points to an example of a patient infected with the Clostridium difficile bacteria, which causes severe diarrhea and can frequently return, even when treated with antibiotics. The patient was treated with a transfusion of gut microbials from a healthy individual's fecal material to restore the bacterial flora in her intestinal tract.

"Literally two days later she started feeling better, and a couple weeks later, when they went to sample the bacteria that was there, they couldn't find the C. difficile anymore. It was just gone," he says. "The only thing they had done was essentially restore her ecology, essentially like restoring a wetland."

Zimmer says fecal transplants have only been performed on patients when all other options fail — but they are seemingly quite effective.

"The problem is, as some other journalists have reported, is that the FDA has a very difficult time figuring out how to come up with regulations for this," he says. "Before it's going to become a widespread practice, the FDA is going to have to move beyond its old paradigm of giving people regular drugs to being able to give people tailored concoctions of living things — of bacteria, of maybe even viruses — as medical treatments."

These bacteria and viruses work in conjunction with other bacteria and viruses in the body, but scientists still know very little about their mechanisms, says Zimmer.

"There's this whole ecosystem of interactions going on inside our own bodies that we do not understand — barely at all," he says. "Scientists are just starting to figure it out with very big projects where they're sequencing all the genes these microbes have. But they're just at the beginning of understanding it."

Pharmasset awarded fast track status for polymerase inhibitor PSI-938...

(Good news for Pharmasset, as the FDA awards it's polymerase inhibitor PSI-938 fast track status, which would shorten the review period from 10 months to six months. Pharmasset also announces the start of an interferon-free, dual polymerase inhibitor trial of PSI-938 in combination with it's PSI-7977 compound in the Q3 of this year)

PSI-938 Receives Fast Track Designation from the FDA for the Treatment of Chronic Hepatitis C Infection

PRINCETON, N.J., Aug. 24, 2011 /PRNewswire via COMTEX/ -- Pharmasset, Inc. /quotes/zigman/101019/quotes/nls/vrus VRUS +0.02% has received fast track designation from the U.S. Food and Drug Administration (FDA) for PSI-938 for the treatment of chronic hepatitis C virus (HCV) infection. PSI-938 is an oral guanosine nucleotide analog polymerase inhibitor of HCV.

In March 2011, Pharmasset presented data from the NUCLEAR study demonstrating that PSI-938 has potent antiviral activity and is generally safe and well tolerated, both as monotherapy and in combination with Pharmasset's lead nucleotide analog, PSI-7977. The NUCLEAR study was conducted in treatment naive subjects with genotype 1 HCV who were treated for 14 days with either PSI-938 or a combination of PSI-938 and PSI-7977 with 92% achieving HCV RNA <15IU/mL, the limit of detection, in the combination arms. Pharmasset plans to initiate QUANTUM, an interferon-free combination trial with PSI-938 and PSI-7977 in the third quarter of 2011.

Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious and life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. PSI-938 was granted the fast track designation primarily due to the need for HCV treatments with improved tolerability, safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in four Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.

For full press release, click on the attached link.

Boceprevir labeling highlights...

View approved label for Boceprevir here: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf

FDA issues draft guidelines for STAT-C/DAA development ...

The FDA has just issued a draft of potential guidelines for companies developing STAT-C / DAA drugs for Hepatitis C.  This is for comment only, the FDA will issue their final guidelines toward the end of the year.  The draft can be viewed on the FDA website.

FDA Commissioner discusses "Regulatory Science" to speed evaluation of new drugs and medical procdures...

WASHINGTON, June 11 -- The American Association for the Advancement of Science issued the following news release:

Universities, industry, and government must join to develop state-of-the-art "regulatory science" that can speed evaluation of new drugs and medical procedures and bring them more quickly to patients, Dr. Margaret Hamburg, commissioner of the U.S. Food and Drug Administration, told a AAAS audience.

Advanced research and technology are driving remarkable new discoveries, Hamburg said, but the United States' current process of evaluating and approving them for use dates to an earlier era. The resulting gap between new discoveries and older treatments already on the market--some have termed it the "valley of death"--brings risk not only to patients, but to the nation's economy and innovation culture, she said.

"We live in a time when science and technology are changing our world in dramatic ways," Hamburg said. "We are seeing an explosion of knowledge and capabilities emerging from many domains of research and from around the globe. And with that comes a fundamental question of how do we make sure that we fully translate the potential and promise of that research into real-world products and programs that really matter.

"A big part of the answer is by strengthening regulatory science. This is a component of the overall scientific enterprise that is really essential, and yet has been underappreciated and underdeveloped."

Hamburg delivered a luncheon address at the 2010 AAAS Forum on Science and Technology Policy. The Forum celebrated its 35th year on 13-14 May with a selection of programs and events that included talks by John P. Holdren, assistant to the president for science and technology and director of the White House Office of Science and Technology Policy; U.S. Representative Vernon J. Ehlers (R-Michigan); Douglas W. Elmendorf, director of the Congressional Budget Office; Sabine Herlitschka, director of European and International Programmes for the Austrian Research Promotion Agency; and Patrick Gallagher, director of the National Institute of Standards and Technology.

Hamburg has had broad experience, and her influence has ranged from bioterrorism to infectious disease control and U.S. health policy. While New York City health commissioner from 1991 to 1997, she advanced innovative programs for controlling the spread of tuberculosis and AIDS. Between 1992 and 1997, the TB rate for New York City fell by 46%, and by 86% for the most resistant strains.

In 1997, she was selected by President Bill Clinton to be assistant secretary for policy and evaluation at the U.S. Department of Health and Human Services. Beginning in 2001, she served as vice president for biological programs at the Nuclear Threat Initiative, which is dedicated to reducing the threat from nuclear, chemical, and biological weapons. By unanimous voice vote in the U.S. Senate, she was confirmed as President Barack Obama's FDA commissioner in May 2009.

She took charge as the FDA was under broad criticism for its handling of U.S. food safety oversight, its approval of drugs that later were found to pose dangers to some patients, and ties with the pharmaceutical industry that were, in the view of critics, too close.

While the FDA's regulation extends over a quarter of the U.S. economy, regulatory science as discussed by Hamburg at the AAAS Forum is not widely-known. Where research scientists may take years to discover a new drug, regulatory science generally seeks to do its work more quickly; if research scientists develop a new cancer therapy, it is the goal of regulatory science to establish a mechanism that allows for effective evaluation of the therapy, and, if it is safe, allows its use by patients.

Generally, it is a tool used by government, and it is shaped by elected officials and other policy-makers. It is multi-disciplinary, often involving clinical research, epidemiology, statistics, and other fields. It closely overlaps with a growing field of initiatives in translational medicine, which seeks to translate cutting-edge discoveries into regular medical practice. [AAAS and Science last year launched a new weekly journal, Science Translational Medicine (http://stm.sciencemag.org/)]

Hamburg conceded that regulatory science lacks the allure of "discovery science." But without the best possible regulatory science, she suggested, a too-lengthy time may pass before the benefits of discovery find practical use for patients.

"Americans cannot take full advantage of the breakneck speed of biomedical research unless we also emphasize innovation in regulatory science," Hamburg said. "Just as biomedical research has evolved over the past few decades, regulatory science must also evolve in important and powerful ways."

She cited several fields of medical research where regulatory science will be critical for supporting clinical research--in studies of emerging stem cell and cancer treatments, for example, or in the effort to more tightly control tuberculosis, or TB.

But, she said, TB is a complex challenge. A cure requires multiple drugs administered over many months, and if a TB infection is not eradicated, the disease can evolve so that it's resistant to drugs.

"Fighting TB effectively requires combination products," Hamburg explained. "It will take forever if we have to approve each new drug independently and then look at how they work in combination. But that is how the process would traditionally work. Instead, we have embarked on a new initiative to work with researchers and companies interested in developing combination products which will be reviewed as such."

That's "much more complicated for FDA scientifically," she added, "but it is what patients need and what public health demands."

The effort to develop a more robust regulatory science requires the FDA to build its in-house science capacity, Hamburg said. And, she added, it will seek close collaboration with allied medical and regulatory agencies, such as the National Institutes of Health (NIH). Already, she said, the FDA and NIH recently launched "an important and broad collaboration" in translational and regulatory science.

She said that FDA will continue and expand relationships with academic groups, patient advocacy groups, and industry. International collaboration also could play a critical role in advancing regulatory science.

"There are enormous opportunities to collaborate with scientific colleagues around the world on matters of regulatory science, and also to engage with international sister regulatory agencies to address issues of common concern, share information, and to harmonize standards and approaches," Hamburg said.

"Outreach and collaboration are central to regulatory science efforts. When successful, these collaborative efforts will help predict more swiftly and effectively which discoveries will succeed or fail as actual products, thereby reducing product-development costs and getting better products to patients faster."

President Obama has backed an overhaul of the agency, and Hamburg said that the FDA already is benefiting from renewed attention and new resources. But given the precarious state of the U.S. economy, she predicted that the agency faces a significant challenge in meeting its regulatory science goals in the near future.

"A robust, state-of-the-art regulatory science is essential to the work of the FDA," she insisted in her conclusion. "But more than that, it represents an important driver of our nation's health, the health of our health care industry, and the health of our economy. ... It's vital to our nation's global competitiveness. It is a field of endeavor that must be fully embraced by academia, industry, and government."