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Thanks for the updates on sales figures.
Using the 1/26 and 2/23 figures , you can say that both new and total RXs are growing at > 50% per month.
At that rate of growth , Tyzeka will have the entire nuke market to itself in a year or so.
)
I need to go back to the " Show Board Info " setting . :)
Here's the link to "Feuerstein’s 2007 Biotech Calendar":
http://www.thestreet.com/tsc/common/images/storyimages/022807_feuersteincalendar.html
I just realized , the other link I gave only pertains to upcoming regulatory decisions , not upcoming trial results.
This site has a nice service if you're willing to pay :
http://www.reveredata.com/reports/store/report-type?type=fda
You can look at a sample report at the bottom of the above-linked page.
Also , Adam Feuerstein at thestreet.com recently had a calendar of upcoming biotech events in his column. I don't have the link handy but it's probably easy to find from any of his recent articles.
Astellas Pharmaceutical
OT : The name " Scooter " is not going to serve him well in prison. EOM
Does anyone know offhand if the Provenge synergy with Taxotere was more pronounced in 02a vs. 01 ?
If so , it would make some sense out of the TTP differences between the trials , assuming the 02a patients were in fact 'sicker' than those in 01.
IN Cell Image Competition 2006
( Some cool shots -- worth a look. Like the Hubble pictures but on the other extreme of the size spectrum. )
http://www6.gelifesciences.com/APTRIX/upp01077.nsf/Content/incell_01_07
The IN Cell Analyzer helps you do more complex experiments, on a larger scale, with more replicates and controls in less time. In short, it allows you to discover far more with great image quality.
To illustrate this, GE Healthcare asked IN Cell Analyzer users to submit images to the IN Cell Image Competition 2006. These are the results.
Thank you to everyone who participated in the IN Cell Image Competition. The winning entries are shown below ( link above ), along with all the runners-up. The winners will see their images displayed on the first high definition screen in Times Square, New York, on 10th March 2007.
Cell-Cept and/or ribavirin for HBV
More on immunosuppressants as antivirals :
Antiviral Research
Volume 73, Issue 3 , March 2007, Pages 192-196
http://tinyurl.com/yvazhr
Ribavirin and mycophenolic acid markedly potentiate the anti-hepatitis B virus activity of entecavir
Chunxiao Yinga, Richard Colonnob, Erik De Clercqa and Johan Neytsa, ,
aRega Institute for Medical Research, Faculty of Medicine, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
bBristol-Myers Squibb Pharmaceutical Institute, Wallingford, CT, USA
Received 22 August 2006; revised 4 October 2006; accepted 5 October 2006. Available online 30 October 2006.
Abstract
MPA [the active metabolite of the immuno-suppressive agent CellCept] and ribavirin markedly potentiate the anti-HBV activity of the guanine-based nucleoside analogue entecavir (ETV) against both wild-type HBV and a lamivudine-resistant variant. Ribavirin (in its 5′-monophosphate form) and MPA are inhibitors of IMP-dehydrogenase and cause depletion of intracellular dGTP pools. The active triphosphorylated form of ETV may inhibit more efficiently the priming reaction, reverse transcription and DNA-dependent DNA polymerase activity of the HBV polymerase in the presence of reduced levels of dGTP. The potential for enhanced ETV activity is supported by the observation that exogenously added deoxyguanosine reversed the potentiating effect of ribavirin and MPA. Our observations may have important implications for those (liver) transplant recipients that receive MMF as part of their immunosuppressive regimen and who, because of a de novo or a persistent infection with HBV need antiviral therapy such as ETV. Further studies will need to be conducted to determine if combining ribavirin (a compound used for the treatment of HCV infections) with ETV could have an advantage for the treatment of HBV infections, in particular in patients co-infected with HCV.
OT: Need to find a home for a puppy - any help ?
My next-door neighbor has a puppy he's giving away if he can locate a good home. It's a dachshund , housebroken , and good with kids.
He's getting rid of it because his wife says the dog 'stares' at her when she's undressing , and it freaks her out. LOL! She's a bit of a nutcase , IMO , but that's her story and she won't let the dog stay.
I've got more pets than I can handle already but I'd hate to see the dog go to the pound , so if you have any ideas , let me know .
TIA
picture of dog : http://tinyurl.com/29blxt
>>> this begs the question - for pts with high viral loads (and perhaps e ag positivity), should combination therapy be started earlier? <<<
Anna Lok is heading a symposium at EASL on combo therapy in HBV. In areas where cost is not so much of a concern , I think combos of direct antivirals will become SOC for all tx.-naive patients where ifn is contraindicated , and a suitable option even for those that could use ifn. As in HIV , I think it is becoming clear that very long-term suppression without generation of resistance is best achieved by use of effective combos first , rather than sequential single-agent use or add-on therapy. In the case of lam-resistant patients , add-on of adefovir or switching to an all new regimen may be a closer call.
I'm guessing that there are a lot of lam patients out there who are either resistant now or will be before too long and for them adefovir may have the advantage , especially in add-on usage , over other agents because of cross-resistance profiles , but I don't know how cost of that combo compares to other treatment options. I agree that lam monotherapy in naive patients will only occur where cost is paramount , and the cost of lam will probably decline in an attempt to maintain some market share. Where cost is a major concern I'd guess that usage of resistance genotype testing is minimal and docs rely on published cross-resistance info to make tx.decisions , which again would probably favor adefovir in the lam-resistant cohort.
Re : Tyzeka plus immunomodulators
One other thought : With Tyzeka now approved in China , we may see some investigator-initiated studies of combos with ifn or Zadaxin (thymalfasin ) , as well as combos with other direct antivirals. It seems to me that Chinese docs are pretty aggressive in testing new tx. regimens in small groups and then publishing the results , good or bad.
I'd be happy with a qualitative disclosure that made clear what was going on as regards antiviral activity , and maybe we will , in fact , get that. I just got a bad feeling in my gut listening to the Q & A session but that may be related to what was actually in my gut , rather than what was said on the call. Without disclosing details , I'll just say I'm not as pessimistic now.
One abstract that I saw in the EASL program might portend good things for Tyzeka combined with pegifn. The idea was that rapid viral load decline in patients treated with pegifn is associated with higher rates of serocoversion and off-treatment viral suppression , similar to the situation in HCV.
Given the potent antiviral activity of Tyzeka , the combo studies may yield unexpectedly good results if this association holds. There's some evidence that addition of ribavirin might help in this situation as well , though it's scant and not too convincing at this point. Anyway , just a thought that the ifn-combo treatment strategy is one that Tyzeka may be well suited for. Any treatment that significantly boosts HbsAg seroconversion would be big news since that's the HBV equivalent of SVR in HCV , and combos of direct antivirals with ifn or other immunomodulators are the most likely route to get to that outcome , IMO. People are starting to measure sAg levels during treatment , probably as a way to gain insights on the best way to reach that goal.
>> and company plans on releasing full data set, pk and pd, around June. <<
I finally listened to the call this morning , and I got the impression that the data to be released to the public in June could be as little as a simple "yes" or "no" to the question of drug-drug interaction. When asked specifically about whether viral load data would be released then , JP danced around and said maybe , maybe not , because they wanted to save it for a conference presentation. Pretty disconcerting , IMO. I'm sure Piper will provide some insights from their sources , particularly if the news is bad.
I see no near-term catalysts of significance to support share price with the possible exception of SVR data from the nonresponder trial showing hopeful signs , as you suggest , or announcement of an agreement to begin combo protease trials with someone.
Add this to the macroeconomic uncertainty you mentioned and it makes the decision to hold IDIX shares right now a difficult one.
Re: Is a Shotgun Better Than a Silver Bullet?
>>>> The FDA has long held botanical drugs to the same standard as other therapies: Companies applying for regulatory approval had to find the part that works and prove it. <<<<
Except for drugs composed of two or more isomers , some of which may be more active , inactive , or counter-active. In this case , you get approval for the mix first , use up your years of patent protection , then come back later for approval of a purified isomer drug and more years of market exclusivity.
I'm glad to see the FDA opening their eyes to other ways of doing things , but I have my doubts about how rational they will be implementing this new policy , given their history.
If you can now test combos of a hundred compounds in a botanical , it should be no problem testing two or more novel compounds versus hepatitis c.
In a rational world , that is.
Martek in burger business
Martek Announces Veggie Patch(TM) All Natural California Veggie Burgers Featuring life'sDHA(TM)
COLUMBIA, Md., March 1 /PRNewswire-FirstCall/ -- DHA omega-3 innovator Martek Biosciences Corporation (Nasdaq: MATK) announced today that Food Tech International has added life'sDHA(TM) to their already successful line of Veggie Patch(TM) All Natural California Veggie Burgers. The Veggie Patch(TM) line of vegetarian food selections offers consumers a variety of
meatless and vegetable-based products with nutritional value. The new California Veggie Burgers will now feature 42 mg of vegetarian DHA omega-3, an omega-3 fatty acid important for brain, eye and heart health, along with other key nutrients for the health conscience consumer. Each package contains 16 burgers individually wrapped at approximately 1/4 lb. each.
Currently available in the frozen food department at Costco Wholesale Food Markets, in their Southeast region, the new burgers are currently certified by the American Heart Association as a healthy heart food option.
Continued at :http://tinyurl.com/2d5kkc
>> JP Sommadossi Co-Chair @ HepDART 2007
HepDART 2007 (9 - 13 December)
Co-Chairs: Drs. Schinazi, Sommadossi, Rice
Ritz Carlton Kapalua, Maui, Hawaii <<
Rough life.
Idenix Pharmaceuticals "buy"
Wednesday, February 28, 2007 8:55:19 AM ET
Morgan Joseph & Co
NEW YORK, February 28 (newratings.com) - Analyst Eugene Trogan of Morgan Joseph reiterates his "buy" rating on Idenix Pharmaceuticals Inc (IDIX.NAS). The target price is set to $13.
In a research note published this morning, the analyst mentions that the company is expected to report its 4Q06 and FY06 EPS at -$0.34 and -$1.22, representing, representing a y/y decline. Idenix Pharmaceuticals is expected to announce positive data for its NM283 drug this week and initiate Phase III trials for the drug by mid-2H07, the analyst says.
http://www.newratings.com/analyst_news/article_1484393.html
I'm imagining a conversation about funding between an administrator and a research director:
Admin : " I'm increasing your budget for PSADT studies but I'm cutting your DKK. "
Researcher : " You're cutting my DKK ?? How much ? "
Admin : " To the bone. "
Researcher : " ( Sobbing sounds ) "
No comment
Serum dickkopf-1 in men with advanced prostate cancer.
Sub-category: Tumor & cell biology
Category: Biology of Prostate Cancer
Meeting: 2007 Prostate Cancer Symposium
Abstract No: 67
Author(s): D. A. Bradley, C. Hall, S. Daignault, J. Friedman, K. Ignatoski, J. Escara-Wilke, D. C. Smith, E. T. Keller
Abstract: Introduction: The Wnt signaling pathway and its key player, B-catenin have recently been implicated in the development and progression of prostate cancer (PCa). Wnt activity is antagonized by endogenous proteins including dickkopf-1 (DKK-1). We have demonstrated that DKK-1 modulates the ability of PCa cells to promote bone osteoblastic activity in a murine model. Therefore, we hypothesize that DKK-1 modulates osteoblastic lesions in men with PCa. DKK-1 has never been measured from human serum. We therefore investigated whether DKK-1 could be measured from serum in men with metastatic hormone refractory prostate cancer (HRPCa). Methods: Utilizing blood samples from men with HRPCa and bone metastasis who were enrolled in a prospective, randomized trial and treated with zoledronic acid (Z) or estramustine/docetaxel (ED) for the first cycle and combination ZED for all subsequent cycles, we examined whether DKK-1 could be measured in serum. We then investigated whether serum DKK-1 levels were affected by therapy and whether there was a correlation between treatment response and change in DKK-1 levels. DKK-1 was quantified from serum samples utilizing a sandwich ELISA developed in our laboratory from a DKK-1 Duoset ELISA development kit (R&D Systems, Inc, Minneapolis, MN). Results: We successfully quantified DKK-1 serum levels from 13 men on the Z arm and 14 men on the ED arm. Baseline serum levels of DKK-1 were 98-1,650 pg/ml. No significant difference was seen between baseline and post cycle 1 serum DKK-1 levels in the Z arm (p = 0.8466) or the ED arm (p = 0.4592). In an exploratory analysis, no significant difference in the relative difference of quantitative serum DKK-1 was seen between responders and nonresponders as determined by a 50% decrease in PSA after 3 cycles of therapy (p = 0.8062). Conclusions: DKK-1 can be measured from serum in men with metastatic HRPCa and confirmed bone metastasis; however, it does not appear to be prognostic for therapeutic response. The small sample size may have not provided enough power to determine a significant difference. Based on preclinical observations, further investigation into the role of DKK-1 in prostate cancer metastasis is warranted.
(courtesy rdh19869 : http://tinyurl.com/2rwopq )
Pfizer says maraviroc suppresses AIDS virus
http://biz.yahoo.com/rb/070227/pfizer_aids.html?.v=2
Tuesday February 27, 9:41 pm ET
By Deena Beasley
LOS ANGELES (Reuters) - Pfizer Inc. (NYSE:PFE - News) said on Tuesday pivotal-stage trials found that adding its experimental HIV drug maraviroc to a regimen of the best-available drugs resulted in twice as many patients achieving suppression of the virus.
If approved by regulators, maraviroc would be the first in a new class of oral HIV drugs since the introduction of protease inhibitors about 10 years ago, said Dr. Howard Mayer, a Pfizer executive in charge of the drug's development.
Maraviroc is designed to block the human immunodeficiency virus from taking up residence in T cells, a type of white blood cell vital to the immune system, by jamming receptors -- or docking stations -- that dot the surface of T cells and act as doorways in. If HIV cannot enter, it cannot replicate.
As the receptors are made of a protein called CCR5, maraviroc and others in this new crop of drugs are called CCR5 inhibitors.
About 80 percent of recently infected HIV patients and 50 percent of treatment-experienced patients have so-called CCR5-tropic virus, said Chris Petropoulos, chief scientific officer at Monogram Biosciences, which makes a CCR5 test.
Over time, the virus in most patients develops the ability to use an alternate pathway known as CXCR4, he explained.
Pfizer, the world's top drugmaker, unveiled 24-week results of two Phase III trials involving patients with CCR5-tropic HIV who had stopped responding to other treatments at the 14th Conference on Retroviruses and Opportunistic Infections.
The first trial of 601 patients showed 60.4 percent of those who took maraviroc twice a day along with a background regimen of current HIV drugs achieved a level of less than 400 HIV copies per milliliter of blood, compared to 54.7 percent on a once-daily dose and 31.4 percent on just background therapy.
The second trial, involving 475 patients, found that 61.3 percent of twice-daily maraviroc patients achieved target HIV levels, compared with 55.5 percent on once-daily therapy and 23.1 percent treated only with other drugs.
Mayer said even though maraviroc patients were on therapy for longer -- because most did not become resistant -- side effect profiles were similar between both arms of the trials.
"We are not seeing any evidence of hepatotoxicity ... there has been no evidence of increased risk of lymphoma or other malignancies," he said, referring to side effects such as liver damage seen with other CCR5 inhibitors under development.
The Pfizer executive said the company has not observed any increased infection risk in patients treated with maraviroc.
Because CCR5 inhibitors do not attack the virus itself, as with existing HIV treatment classes, Mayer said HIV might be less likely to develop ways of resisting their effects.
The virus that causes AIDS infects more than 1 million people in the United States and nearly 40 million worldwide.
Resistance is a problem as HIV can mutate, particularly if patients fail to rigorously follow complicated drug regimens.
About a tenth of newly diagnosed HIV patients are infected with a virus resistant to at least one of the three main types of AIDS drugs, the U.S. Centers for Disease Control and Prevention said on Monday.
The Food and Drug Administration has convened for April 24 an advisory panel to review Pfizer's maraviroc application.
Mayer said the trials in heavily treated patients are ongoing and the company expects to have results later this year of the drug's effectiveness in newly diagnosed AIDS patients.
Poor compliance / dose modifications due to AEs ?
>>> I'm looking forward to info out of the bavi HCV trial on any difference in cytokines from the bavi therapy. <<<
The cytokine data could go a long way towards alleviating any doubts about bavi efficacy , IMO , especially as regards the HCV data to date. When the viral load declines seen are in the range of a log or so , people start worrying about random variability and other factors that may be clouding the picture. Showing an increase in Th1 cytokines that correlates with the antiviral data would present a much more compelling case for bavi.
LOL. I may have already read them , in that case. That's OK , I'll look at them again.
Everything I read goes in one eye and out the other.
Thanks , jazz. I'll add those to the reading pile )
Humira for Crohn's
( just saw this posted by cattoes on the DNDN board )
"The labeling of Humira includes a boxed warning, the strongest type of label warning, that use of this product has been associated with serious, sometimes fatal, infections, including cases of tuberculosis, opportunistic infections, and sepsis. Before initiating Humira treatment, patients should be evaluated for tuberculosis risk factors and tested for latent tuberculosis infection. Other serious adverse events reported by Humira users include lymphoma, a type of cancer. The most frequent adverse events included upper respiratory infections, sinusitis, and nausea."
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01572.html
I find the above warning particularly ironic. A close relative of the TB bacterium called Mycobacterium avium has been long suspected by many researchers to be causative for at least some cases of Crohn's. This theory is largely pooh-poohed by the establishment in the U.S. , in a way that reminds me of the H.pylori / ulcer / gastric cancer story. As with H.pylori , if some cases of Crohn's were curable with a course of cheap antibiotics ( or even expensive ones ) it would severely impact the bottom line on many internist practices.
The M.avium correlation has been around for decades in animal models ( Johne's disease of cattle ) in the same way that the H.pylori connection to ulcers was. In recent years Crohn's has been associated with defects in the NOD / CARD genes which code for , guess what , immune pattern recognition receptors for mycobacterial antigens.
plus ça change...
>>> In this study, CD4(+)CD25(-) T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring T(reg) cells, including expression of Foxp3, a crucial transcription factor of T(reg) cells, production of low levels of IL-2, high levels of IL-10 and TGF-beta, and the ability to suppress CD4(+)CD25(-) T cell proliferation. <<<
jazz ,
What am I missing here ? This seems like it would be bad news for bavi , since it suggests that tumor cells can generate the immunosuppressive signals independently of any immune cell interactions. It also suggests that selection pressures would favor tumor cells producing more TGF-beta as a counter to any immune response mounted by the host.
BTW , thanks for your continued posting of abstracts and such , much of which I find interesting.
Re : THLD
Why did they go after the 2nd-line indication first ? Toxicity concerns ?
The P2 trial in 1rst-line sounds like a better bet.
100 day median survivals -- wow , tough crowd to treat.
Assuming the tx. effect was real , and the effect size as described , anybody know offhand how many patients they would have needed to get the p from .19 to .05 ?
TIA
New Directions in Drug Safety
( Sorry , no link. From a Bio-IT World email newsletter )
Agrawal: New Directions in Drug Safety
By Deborah Borfitz
The drug safety departments of most pharmaceutical companies have become too burdened with operations to effectively manage risk. A new approach is needed to detect problems earlier, communicate clear benefits, and prevent a risk-averse public from potentially blocking important advances.
So says Sanket Agrawal, chief strategy officer of Irvine, CA-based Relsys International (see below). At the moment, safety departments end up placing 80 percent of their focus on single adverse event (AE) management and aggregate reporting, and the remainder on risk and signal management. For instance, over one-third of many companies' core safety staff currently supports the "non-value-added function" of AE intake. "It could be the other way around, as intended, through a sustained drive to simplify processes, integrate underlying systems, and perhaps even some regulatory assistance."
Passive monitoring of products is an outdated notion, given the complexity of today's medical products, says Agrawal. "Some studies show that as few as 1 percent of AEs even get reported by physicians." Beyond "being a good citizen," they have no incentive to do so.
By contrast, doctors in the U.K. are required by regulation to report any AE on the first 10,000 prescriptions of a newly released drug, says Agrawal. In Japan, pharmaceutical companies voluntarily pay physicians to track every patient prescribed a new drug for up to a year after its release. New product distribution is also limited to specific providers. The Japanese approach "seems to be more effective than passive reporting in surfacing abnormalities."
A few years ago, a pharmaceutical company launching a product in Europe limited distribution to providers willing to actively collect patient safety information, says Agrawal. "The company got three times as many quality reports than they would have otherwise."
Were physicians in the U.S. to become more conscientious about reporting AEs, "the industry would collapse" in a deluge of data. The public needs constant education about the realities of drug development, says Agrawal. Consumers want risk-free products, unrestricted access, and a speedier drug approval process. But they will also litigate if approvals come too fast or products are abused or misused.
Relsys uses the image of an iceberg in its educational efforts with lay people. "No matter how good the science is," Agrawal says, "when a drug is released we can see only a percentage of the risks. If we want to know everything, it means we would never release a drug." The message should be that "all drugs are chemicals and come with side effects, known and unknown. Pharmaceutical companies need to communicate the benefits [correlated to price] versus the risks...and let people make informed decisions."
The focus has been disproportionately on risk, says Agrawal, "which is understandable given the human propensity to weigh risks higher than rewards. For example, direct-to-consumer ads read through a list of risks, leaving consumers confused about the benefits of a product. Clearly, there's a lot of room for improvement in the educational aspect."
Companies could also more actively communicate to the public all they do to monitor known and unknown drug risks, says Agrawal. "If you go back any more than five years, you will see that companies are doing much more now, but are not getting credit for their efforts."
Proactive Surveillance
On the other side, "clinical trials will never expose risks the way real-world usage does," says Agrawal. More proactive post-marketing surveillance is required. At the moment, communications between product manufacturers and health care providers is "almost a one-way dialogue, focused on getting drugs on a formulary or approved list."
Growing acceptance of active surveillance is behind the exponential growth in Phase IV clinical studies and the desire to tightly integrate eClinical and safety tools, says Agrawal. Seamless electronic integration has yet to happen, in part because drug development is a multi-departmental, multi-IT-system process at most companies. "Vendors are just starting to offer that capability." Some vendors are acquiring complementary technology and integrating in-house, while others like Relsys are pushing for a standards-based open integration through "best-of-breed" alliances.
Risk management, from pre-clinical to post-marketing, needs to be a "holistic discipline," Agrawal says. Technology is needed in such areas as signal management, regulatory communications, and label update tracking. The U.S., which has separate guidances for risk assessment and risk minimization, is philosophically a bit behind Europe.
The FDA is taking steps in the right direction, including its recently announced plans to do a comprehensive assessment of the safety of drugs 18 months after introduction and to collaborate with the Veterans Health Administration to track how real patients fare after taking drugs, says Agrawal. The FDA has also announced its intentions to "take into account some of the recommendations of the IOM [Institute of Medicine]. There are now budget requests for this, to hire additional people at CDER [Center for Drug Evaluation and Research] and acquire new electronic tools [to facilitate reporting and analysis of AEs]."
The FDA stresses that it wants to "use the strength of science" to support its safety monitoring work, says Agrawal. The agency probably doesn't have the infrastructure to independently conduct research, as it once did. More likely, the FDA will be "a more active participant in clinical trials" and "make public all clinical trial results," as is currently being pushed in Congress.
Agrawal's "holy grail" is to find signals, in real time, directly from physicians' medical records. "Healthcare systems have the data in a structured format," he says, but privacy concerns remain a critical barrier.
---
Relsys International is the leading global provider of drug safety and pharmacovigilance solutions that help pharmaceutical, biotech and medical device companies ensure regulatory compliance, streamline operations, and improve product safety. Argus Safety™, the company"s flagship product, is the world"s best selling adverse event reporting system, used by more leading pharmaceutical companies than any other solution.
Re : China
Some exerpts from a more recent (12/05) Datamonitor report TOC :
Datamonitor insight into the Chinese Hepatitis B & C market
China is undergoing an economic boom, generating 12% of global economic trade, and it is currently the leading recipient of foreign investment. Since 34% of the world's chronic hepatitis B patients and 24% of the world's chronic hepatitis C patients live in China, the Chinese hepatitis B (HBV) and C (HCV) markets have historically represented a significant growth opportunity, with a realistic current valuation of $1.0 billion (HBV) and $0.9 billion (HCV). However, the Chinese healthcare system has been ranked 144th out of 191 by the WHO, prompting it to be denounced as one of the most unfair systems in the world. These problems, together with the inability of many patients to afford these drugs and concerns over their efficacy in Asian patients, are retarding Western pharmaceutical penetration.
Chinese physicians indicated that HBV incidence is decreasing and is set to continue to fall. In contrast to the seven major markets, where most patients acquire HBV sexually, the dominant route of HBV transmission in China is perinatal transmission, which increases the likelihood of becoming immune tolerant and impacts on HBV disease progression and the effectiveness of drug therapy. In China, physicians do not consider any of the currently available therapies a gold-standard, although lamivudine is the most prescribed first-line therapy, while adefovir is the most prescribed second-line therapy.
Chinese physicians indicated that HCV incidence may be increasing. Blood transfusion is thought to be the dominant HCV transmission route in China, while in the seven major markets, HCV is mainly acquired through intravenous drug use. The Chinese HCV treatment market is highly fragmented, with treatment differing significantly between regions. For example, in Hong Kong, all HCV patients receive pegylated interferon/ribavirin combination therapy, currently considered the global standard of care. However, across mainland China, unmodified interferons are more commonly prescribed than pegylated interferons, and interferon monotherapy is more frequently used than interferon/ribavirin combination therapy.
Due to the high cost of pharmaceuticals and the cost-conscious nature of the Chinese healthcare system, the hepatitis market faces a number of threats, including TCMs, generic drugs and counterfeit drugs.
Similar to the seven major markets, efficacy is the most important factor driving HBV and HCV pharmaceutical prescription in China, with cost and reimbursement in second place. Interestingly, the side-effect profile ranked third in China, while this factor ranked second in the seven major markets.
http://www.the-infoshop.com/study/dc35273-hepatitis-china_toc.html
Re : China
I think China has a middle class of 30 or 40 mill., and growing , that has an income > $10K. SCLN sells about $30 mill./yr of Zadaxin there , mostly for HBV. It's probably important to get on the gov't-approved formulary for optimum success there ,and this approval may be as much based on politics as on science.
Here's a somewhat dated factsheet on the China hep mkt.:
"Massive growth potential in China's untapped hepatitis market"
http://www.the-infoshop.com/press/dc23166_en.shtml
>>> Isn’t that’s a strong assumption for the follow-up (non-treatment) period of a phase-2 clinical trial? As these patients are not permitted to switch to another therapy during the six-month follow-up period, what information of practical use would be gained by conducting a blood test every month? <<<
I really don't know how extensively patients are tested during or after the dosing period. It's just that PJ seems to have some information that probably should be blinded to them and everyone else. That being the case , and given the statements made in the report , I speculated on a data collection protocol that could hypothetically provide that sort of data. We know that VRTX looks at 3-month SVR data. Both companies may collect more data than is revealed publicly , as a means to try to understand what's going on with treatment failures , or in the interest of patient safety ( to detect hepatic flares , for example ).
The other possibility , though less likely , is that patients get tested off-site.
My main point is that if we assume PJ can get SVR data then we have to assume they can get other data as well , and to the extent that any off-treatment data is collected , it could provide a measure of SVR in advance of the final SVR time point.
>> What is rational for the IDIX's p2 study comparing NM283/PEG when the more important issue is NM283/PEG/RBV.? <<
IDIX would like to have a label that shows that NM283 / PEG is at least as effective as PEG / RBV , so as to capture those patients that would like to avoid taking RBV. The triple combo would then show superiority to SOC on the same label.
In an ideal world , anyway.
Re : PJ report
I do worry about the reports of relapse. The question is one of reliability of the sources , not whether enough patients could have been surveyed , IMO.
If you assume that viral load measurements are continued at regular intervals after treatment stops , say monthly , then you could get a good feel for the final results very quickly if relapse rates are indeed high. Patients with detectable virus at EOT or any time after EOT are unlikely to achieve SVR , so one need not wait the entire 24 wks. post-treatment to know what's up.
Of course , her 'contacts' may be posters on internet patient forums , in which case the info is suspect , at the least.
>>> In other words, McMinn does not depict any scenario in which the two drugs are fully additive or more than fully additive, which is the usual meaning of synergy. <<<
Yes, and it makes me suspicious of the entire analysis. I think she had a good basis for her argument - the replicon studies which showed antagonism between NM283 and riba - but she went too far with it in her 'scenarios'.
#3 , which was based on no antagonism , should have assumed at least a modest benefit to NM283 addition to SOC. Instead it showed a detriment.
And in #4 , just to cover her butt re: Murphy's Law , she should have assumed a significant , true synergism.
That way ,if the trial results are unexpectedly good , she would be covered. As it is now , if the combo shines , her cred will be shot.
What a shame that would be , eh ?
Re : SGP + WYE/VPHM?
'Last call' is approaching and the couples ( and triples ) are hooking up. Here's a new abstract on the same topic :
http://jvi.asm.org/cgi/content/abstract/81/6/3005?etoc
Journal of Virology, March 2007, p. 3005-3008, Vol. 81, No. 6
Copyright © 2007, American Society for Microbiology.
Synergy of Small Molecular Inhibitors of Hepatitis C Virus Replication Directed at Multiple Viral Targets
David L. Wyles,1* Kelly A. Kaihara,1 Florin Vaida,2 and Robert T. Schooley1
Department of Medicine, Division of Infectious Diseases,1 Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, California2
Received 22 September 2006/ Accepted 10 December 2006
Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.
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* Corresponding author. Mailing address: 9500 Gilman Drive, MC 0711, La Jolla, CA 92093. Phone: (858) 822-1779. Fax: (858) 822-5362. E-mail: dwyles@ucsd.edu.
Published ahead of print on 20 December 2006.
More on HIV / HCV coinfection
"As a result of common routes of transmission of HIV and hepatitis C virus (HCV), a substantial proportion of HIV-infected persons in the developed world are coinfected with both viruses. Coinfection rates are relatively low at 8% in The Netherlands(1) and 13% in Australia,(2) but they are 33% in the EuroSIDA study,(3) 38% among US military veterans receiving antiretroviral therapy (ART),(4) 45% in patients attending the Johns Hopkins Hospital HIV Clinic,(5) 46% in the Italian Cohort of Patients Naive from Antiretrovirals (ICONA) study,(6) and 51% in persons receiving ART in British Columbia.(7) It is interesting to note that the prevalence of HCV infection in participants in the 2 major US HIV clinical trials organizations, the AIDS Clinical Trials Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA), is only 16%(8) and 17%,(9) respectively, suggesting that the clinical trials populations are not broadly representative of the HIV-infected population in the United States...."
and
"Anti-HCV therapy with pegylated interferon plus ribavirin can cure HCV infection in up to 40% of coinfected patients; however, only approximately 10% of coinfected patients are considered candidates. "
from : Early Initiation of Antiretroviral Therapy:
The Current Best Way to Reduce Liver-Related Deaths in HIV/Hepatitis C Virus-Coinfected Patients
http://www.natap.org/2007/HIV/012307_01.htm
Good.
Now it's officially a blemish.
He could have added : " I know a lot of people in the drug development business , and they all admit they just throw a bunch of crap at a wall , then see which crap sticks. Or they steal someone else's crap."
"Quips Novartis research head Mark Fishman: "Some of my best friends run systems biology departments. They still haven't been able to explain to me what it means."
http://www.forbes.com/free_forbes/2007/0312/072.html?partner=yahoomag
GNTA Fri. afternoon PR
Phase 2 Results of Genasense(R) Plus Chemotherapy in Advanced Prostate Cancer Reported at Cancer Conference
Friday February 23, 4:01 pm ET
BERKELEY HEIGHTS, N.J., Feb. 23 /PRNewswire-FirstCall/ -- Genta Incorporated (Nasdaq: GNTA - News) announced preliminary results from a Phase 2 study of Genasense® (oblimersen sodium) Injection plus chemotherapy in patients with advanced prostate cancer. This randomized open-label trial was conducted by the European Organisation for Research and Treatment of Cancer (EORTC). Dr. Cora N. Sternberg, from the San Camillo Forlanini Hospital in Rome, Italy, presented the data this afternoon at The Prostate Cancer Symposium, a joint meeting of the American Society of Clinical Oncology, the Society of Urologic Oncology and the American Society for Therapeutic Radiology and Oncology, which is being held this week in Orlando, Florida.
Of 111 patients who were evaluable in this study, 24% had previously received estramustine (a combination of estrogen plus a chemotherapy agent), 26% had pretreatment elevation of serum lactate dehydrogenase (LDH), and 41% had previously progressed in each of three clinical parameters including prostate specific antigen (PSA), bone, and viscera. At baseline, more than 90% of patients had widely metastatic disease to bone and/or viscera. Following randomization, patients were treated with docetaxel (Taxotere®; sanofi aventis) either with (N= 54) or without Genasense (N=57).
For patients who received Genasense plus docetaxel versus docetaxel alone, there were similar response rates as measured by RECIST criteria in patients with measurable disease (24% vs. 19%) or by PSA (37% vs. 46%). Neither progression-free nor overall survival has yet been reported. Occurrence of Grade 3-4 neutropenia (80% vs. 83%) and febrile neutropenia (11% vs. 9%) was similar, whereas Genasense was associated with an increase in Grade 3 thrombocytopenia (9% vs. 0%).
"A patient population with metastases to bone and viscera, elevated LDH, and prior chemotherapy may not have been ideally suited for study", noted Dr. Sternberg.( MAY not have been?? ) "Data that support the activity of Genasense in earlier-stage disease were not known when this study was designed, and this information probably would have substantially impacted its design. Further study with Genasense may (good choice here though) be warranted in patients with hormone-refractory prostate cancer whose disease is limited to a rising PSA."
http://biz.yahoo.com/prnews/070223/aqf037.html?.v=1