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>> Could that be the future corporate tagline? <<
I'd be willing to let them use it for $150K upfront plus 1% of gross sales so yes , why not ?
TNFerade in metastatic disease
Besides the effects on tumors that are directly injected , there may be immune modulating effects that result in action on , and prevention of , distant metastases. There is an ongoing P2 in metastatic melanoma that will shed some light on this , and the only requirement in that trial is for one or more injectable nodules. Animal data also supports the notion of immune stimulation.
GNVC has been working with FUSO on systemic delivery methods but it may turn out that it works systemically as is , at least to a degree.
TNFerade might really be a therapeutic cancer vaccine , not tumor-specific but still specific to tumors.
re: side effects of hep c tx
Thanks for the link. From the article:
" In the registration trials of peginterferon combination
therapy, significant side effects often required dose reductions and occasionally discontinuation of therapy. Because
most of the side effects associated with treatment are
dose related, this strategy has been proven to be a safe and
effective way to decrease adverse events and minimize
serious, life-threatening sequelae. However, recent interest
has focused on the importance of adherence to a prescribed
medication regimen in maximizing response to
antiviral therapy. Decreased adherence due to dose reductions or premature discontinuations could underestimate
the true effect of combination therapy for hepatitis C. "
The above is obviously also true for any new drugs being tried in combination with ifn/riba , and something we should keep in mind when looking at the resulting side effect profiles. I've looked for studies that examined the relationship between SVR and certain AEs and haven't found much , except for one that showed a statsig positive relationship between development of autoimmune hypothyroidism and SVR while on pegifn/riba therapy. Side effects that could be a marker of reversal of immune tolerance might be an early signal of a successful tx. , and it would be a shame if patients ( and docs ) are not made aware of this before treatment begins and encouraged to try to hang in there if at all possible. There is the danger of managing side effects so well that patients enjoy being treated but none of them ever achieve SVR.
More from the paper :
"Future studies should emphasize the importance of developing
additional management strategies that will maximize
adherence to antiviral therapy. Prospective studies
of adherence could evaluate the impact of early versus late
dose reductions and the effects on response in different
genotypes.
Prospective studies of hematopoietic growth factors to
determine their effects on sustained virological response
and quality of life and refining guidelines for dose reduction
for neutropenia may also improve the management
of adverse events during therapy with peginterferon and
ribavirin for chronic hepatitis C."
...
re : AZN narrows focus
AstraZeneca CEO says to cut disease focus -FT
LONDON, Dec 16 (Reuters) - AstraZeneca Plc (AZN.L: Quote, Profile , Research) will cut the number of diseases for which it develops new drugs and concentrate on acquisitions and licensing deals in those areas, its chief executive said in an interview published on Saturday.
David Brennan told the Financial Times the company would withdraw from hypertension, functional gastro-intestinal disorders, inflammatory bowel diseases, Parkinson's disease, multiple sclerosis, addiction, insomnia and stroke.
Its future focus would be to build on the group's strengths in diabetes and obesity, infection, inhalation projects and analgesia, as well as cancer.
"Our primary focus is in areas where we have existing therapies ... (and) are most likely to get a hit. Right now we are much more focused on areas where we are strong, rather than in diversity," Brennan said.
His remarks suggest that acquiring Shire Plc (SHP.L: Quote, Profile , Research) -- Britain's third largest drugmaker -- is not on the cards, since it specialises in attention deficit disorder, gastro-intestinal and renal diseases and human genetic therapies.
Shire was reported to be in AstraZeneca's sights last month, although several industry analysts said at the time they were sceptical of such a deal.
AstraZeneca has suffered a series of late-stage product setbacks, which have shaken confidence in its ability to bring new drugs to market.
Its latest new drug hope, stroke treatment NXY-059, failed in October, following earlier setbacks for anticoagulant Exanta, lung cancer pill Iressa and Galida for diabetes.
Brennan said any further cost-cutting to maintain operating margins at 30 percent would not come from investment in research and development, which he said he would like to increase to 18-20 per cent of sales by 2010.
http://tinyurl.com/ym764s
>> Isn't the above statement a mistatement of the facts as regards the Hepatitis arena? <<
Yes. Twelve week data is not a great predictor of "cure" ( or more properly , SVR ) but it is an excellent predictor of who will fail to achieve SVR. Patients who don't achieve EVR --- at least a 2 log drop in HCV RNA by week 12 --- are not likely to respond to treatment and these patients are often taken off treatment at that time.
You might be able to say that , proportionally , the difference between the treatments might carry thru to SVR data , but I wouldn't bet on that either. For example , ribavirin plus peginterferon gives higher SVR rates than pegifn alone , even when looking at comparable groups of end-of-treatment HCV-negative patients ( i.e. , the addition of riba to the regimen results in a lower rate of relapse after stopping treatment ).
MFs touting VRTX
Vertex: Coming Together Nicely
http://www.fool.com/news/mft/2006/mft06121418.htm
By Brian Lawler
12/14/2006
This has been a productive week for drug developer Vertex Pharmaceuticals(Nasdaq: VRTX). On Monday, it reported positive results from a phase 1 clinical trial for its potential leukemia treatment VX-680, which is partnered with Merck(NYSE: MRK); the drug will now move into phase 2 clinical development. Yesterday, Vertex announced interim results from a phase 2 trial for telaprevir, its developmental candidate for hepatitis C.
The telaprevir results are much more significant to Vertex, since the drug is much further along in development, and being tested in a potentially much larger patient population. Initially, when the clinical trial results were announced, shares dropped nearly 8%. That was surprising, considering that the drug's efficacy in this phase 2 trial was consistent with its performance in earlier but much smaller trials of the drug.
In this interim statistical analysis of one of its pivotal phase 2 trials, telaprevir plus standard care after 12 weeks of treatment left 88% of patients with undetectable levels of the hepatitis C (HCV) virus. The control arm of the trial only saw 52% of patients achieve this result. If these results hold up in the long run (which they usually do -- the pivotal twelfth week of treatment is a great predictor of a longer-term cure), telaprevir would be significantly more efficacious than the approximate 50% long-term cure rates seen for other genotype 1 HCV treatments.
Importantly, this early response in such a large group of patients also holds the potential for those who take telaprevir to endure debilitating HCV drugs for a much shorter amount of time than the 48 weeks of treatment that most patients for genotype 1 HCV must undergo. This alone will provide a huge potential market for telaprevir.
The reason for the negative initial market reaction to the trial results was probably related to the higher dropout rates and adverse events seen in the telaprevir arm of the trial, compared to the placebo arm. A reported 3% of patients taking telaprevir experienced serious adverse events, compared to only 1% of patients in the placebo arm. But with so few patients in the placebo arm, it's way too early to call these results meaningful.
The higher level of adverse events seen in those taking telaprevir is obviously not good news, but given the significantly higher efficacy levels for the drug, they're not even close to stopping telaprevir from becoming one of the dominant forms of treatment for patients with genotype 1 HCV. Considering that as much as 25% of people infected with chronic HCV develop liver cirrhosis or liver cancer within 20 years of being infected, provided the disease progresses unchecked, few patients should have a problem taking their chances with telaprevir.
There's still plenty of time left in the various arms of the telaprevir trials for further light to be shed on the drug's efficacy and safety. If telaprevir continues to show anything like the 80%-90% rate of undetectable HCV virus at end of its trials (and after the important six-month follow-up, after which patients can be considered cured), Vertex shareholders won't be dealing with too many more down days like yesterday.
>> However, results in the test-tube don't always accurately reflect what is happening in a person. <<
I agree with this and thus believe there's a reasonably good chance that NM283 can be effectively combined with riba , in spite of the recent replicon data which showed a negative interaction. Combine good news on the interaction data with today's setback to the most immediate competition and IDIX would be sittin' (sp?) in high cotton.
However , I won't be convinced by drug-drug interaction data showing that plasma AUCs are unaffected or that intracellular phosphorylation is unaffected or that tissue distributions are unaffected , etc. The only thing I want to hear about is antiviral activity --- viral load declines and , ultimately , SVR rates.
Ribavirin seems to do several things that benefit HCV treatment , and one of those is via interaction with the polymerase causing catastrophic error substitutions that result in less fit or nonviable virions. We have to assume that there could be competition for the polymerase active site between NM283 and ribavirin which could act to the detriment of one or both molecule's activities , until this is proven not to be the case by viral load data.
A negative interaction would still leave the option of sequential treatment with a riba + pegifn regimen , though that would be less preferable , obviously.
re : VRTX results
The VRTX phase-2 trials seemed very well-planned and comprehensive when they were first unveiled , but I bet they'd like a do-over about now. The earlier trials with 2-wk and 4-wk durations of VX-950 plus pegifn +/- riba , followed by SOC , may be closer to optimum than 3 months of triple therapy. They do have an arm in Prove-2 using 950 plus pegifn (no riba) that may end up working as well as the triple therapy and could provide valuable insights for the P3 trial design.
Maybe the increased severity of rash and other SEs resulted in reduced treatment compliance and , therefore , efficacy. Ironically the SEs may be largely due to immune mechanisms that could beneficially contribute to SVR , but if the patient drops out you never find out if this is true.
I wonder if the '9% discontinued' means they are also lost to follow-up , or did some go on SOC and could still contribute to SVR rates , assuming they received at least some VX-950 tx.
If not it means the absolute upper limit on SVR is 91% , and that assumes no more dropouts and 100% SVR rates for the rest , which ain't gonna happen.
New guesses....
Per protocol basis : 77 and 75
ITT basis : 70 and 68
The large numbers of dropouts relative to placebo makes it necessary to specify the basis , IMO , but for simplicity's sake you can choose whichever pair above you wish.
There is one thing about this data that bothers me more than any other : Why didn't I get to see it two days ago like everyone else ? Is there some kind of filter on my PC that holds data releases for 48 hrs. ? Am I in the " Biotech Investing Twilight Zone" ?
I don't know whether to assume the 12 wk. negs were also neg at 4 wks. , or what ? All in all , a crappy data release by VRTX , probably because it was hastened by the obviousness of the leakage. The SEC should make everyone who had access to the VRTX data wear Pampers for a week , on the outside where everyone can see.
...
>> The phase-3 program for Albuferon includes a whole 900-patient trial just for genotype-2/3 <<
The added bonus is you get to see your results 6 months earlier in the gen2/3 trial.
I've seen studies in which gen-2 patients who achieved RVR ( HCV-neg @ 4wks. ) could be treated for only 12 or 16 wks. and achieve similar SVR rates as those treated for 24 wks. It will be interesting to see if add-ons to SOC can reduce this treatment time even further.
>> just suppose NM283 and ribavirin do not "mix" well...
what do you see P3 looking like w/o riba
and w/ riba? <<
If they can't use them concurrently then they will probably try to use them sequentially , e.g., 24wks. on pegifn plus NM283 followed by 24 wks. on riba plus pegifn. This would still fit within the trial design proposed by Dew.
>> Treatment for non-genotype-1 HCV is a major unmet medical need in its own right, but it has been all but ignored by Wall Street amid the buzz surrounding the larger market for genotype-1. <<
I agree that the Street is not making much of an attempt to model the entire HCV marketplace , with all of the potential niches that could end up supporting several second-tier drugs even if a single superior drug pulls ahead initially. Other genotypes , coinfection , intolerance to ifn and/or riba , various categories of nonresponders , etc. , are all areas that might be exploited by 'second-best' candidates.
I'd like to know what the triggers are that cause a CEO to decide to run , say , non-gen1 or HIV coinfection trials as a development strategy as opposed to what seems to be the current standard of going for the gen1 , monoinfected group first. I guess they all want to go for the biggest brass ring until it's no longer out there to grab.
In the case of VRTX , they've stated that they'll run non-gen1 and coinfection studies in '07. I think it makes sense for them to optimize ritonavir boosting before doing so since they may get a higher sustained circulating VX-950 level that could help make up for the lower binding to non-gen1 proteases.
Some good data on the NM283-riba interaction study would awaken the Street People , IMO , since they've probably already priced in bad results and would thus have to rethink the competitive landscape.
And , as dewophile pointed out , if no single addition to SOC results in dramatic improvements in SVR rates , then the possibility exists for multiple players grabbing multiple , smaller , brass rings even in the gen1 space.
re : What is this?
Valtorcitabine.
>> I’ve semi-seriously wondered if VRTX made the design of PROVE-1 and PROVE-2 unduly complicated so that investors and analysts wouldn’t be able to keep track of what is supposed to be reported when. <<
If that's true they might be looking for a way to silence you.
Watch your back !
>> This IS for real money if you've got positions in the hep C marketplace! <<
dew ,
I should be hoping for a VX-950 failure since my only position in this space is IDIX ( though I might consider some mad-money option bets on the upcoming VRTX data release ).
Your points are all well-taken and my relatively optimistic outlook is driven mainly by a srong desire to see pegifn and/or riba relegated to the scrapheap ASAP. We need better tx. regimens for the patients' sake and Roche and SGP need an attitude adjustment.
The "accordian effect" in HCV treatment is well known and I think I've even heard VRTX use the term in their CCs. This effect being the success of short tx. regimens when HCV-negativity occurs early and is maintained for "X" period of time before stopping tx. , compared to HCV-negativity occuring later and maintained for ">>X" before stopping tx. , in order to achieve the same SVR rates. In terms of generation of resistant mutants, the strategy of hitting the virus hard and fast with multiple MOAs is the method of choice until proven otherwise with real data , IMO , based on general principles derived from other antiviral and antibacterial txs. I wince when I hear IDIX sing the praises of the 'slow but steady' effects of NM283 without any more justification than the story about " The Tortoise and The Hare".
The other thing VX-950 may have going for it , in terms of shorter tx. durations , is the corrective effect on ifn signalling of protease inhibition. This might result in a faster 'turnaround' of the immune response after HCV-negativity is attained , and more rapid achievement of a stable , serum-sterilizing immune response. No evidence for this yet , of course , just one possibility among many.
>> Dr. Payson has more than 30 years of experience in the health care industry, currently as chairman of the board at Concentra Inc. Prior to joining the board of directors at Concentra in 2005, Dr. Payson served as the chairman and chief executive officer at Oxford Health Plans from 1998 to 2002 where he led Oxford's successful turnaround. <<
A basher on the YMB is saying : " Oh oh! A turnaround specialist! They must be in trouble! "
LOL
Sounds like a good addition to the board to me.
BTW , thanks for getting me sraight on the VRTX data release schedule. I printed a copy this time so I don't have to ask again , but I'm not making any promises.
>> I'm banking on fact that svrs go way down for gen-1 with short (24 wks) vs long (48 wks)duration of therapy for those who are undetectable at end of tx, and that 10 weeks is just inadequate. <<
dew,
I believe that the current SOC for gen 1 patients who are hcv-neg at wk.4 and remain so is 24wks. of treatment , because additional tx. does not significantly raise the SVR rate. This is more comparable to the situation here rather than just looking at end-of-treatment hcv-negativity. I agree that the 12-wk. tx. length may well be too short to be effective , and my WAG is relying on the extended length of triple therapy , versus the 2 or 4 wks. in the earlier studies , to make up for the reduced overall tx. time. As I said , I won't be too surprised regardless because there are no precedents for 3-month treatments like this. Even if your guess of 60% SVR turns out to be correct , it will still be a dramatic result considering the shorter tx. , but it probably wouldn't impress the Street too much.
>> I'll also guess there is an appreciable spread between svr 12 and 24 with such a short duration of tx, although this difference may disappear with longer treatment duration. <<
I haven't seen much data on time-to-relapse after stopping treatment , but what I've seen suggests that the bulk of patients become hcv-pos. in the first month , and virtually all by 3 months. I'm making the assumption that high-sensitivity testing (10 IU/ml) will capture virtually all relapsers by 3 months off-treatment. Of course , when you start to get higher ranges of SVR , as VX-950 is almost certain to do , then by definition the differences between SVR12 and SVR24 will become smaller on an absolute basis. So whatever regimen VRTX settles on , if it results in high SVRs , will likely result in the replacement of SVR with SVR12 sooner or later. JMHO/WAG.
BTW , if this bet was for real money I'd bet on your numbers , not mine.
SVR guesses
My WAGs :
TMA-neg at both 4 and 10 wks: 19/20 (95%)
SVR12 : 18/20 (90%) or 18 of the 19 who stopped tx. @12 wks.
SVR : 17/20 (85%) or 17 of the 19 " " "
It wouldn't surprise me to see 100% for all three figures , however , and I'd only be mildly surprised to see mediocre results. The only thing we can really go by is the earlier results which were from patients in Europe and Puerto Rico , and we also don't know if the viral loads or gen 1 subtypes will be similar in this study.
I have a pretty strong hunch that SVR12 will be essentially the same as SVR , with the loss of no more that a few percent , if any , that relapse between SVR12 and SVR , so change my SVR guess above to 17.5/20. I think the VX-950 studies may lead to a new definition of SVR.
The results in the next few months may tell us a lot about what to expect from the nonresponder studies , as well. If they get , say , 90% SVR in naive gen 1 patients , then about half of those responders are patients who would have failed to respond to SOC. You could then be pretty certain that there would be no difficulty in designing a successful trial in nonresponders. Of course , some of the nonresponder pool consists of patients who will be much more difficult to treat ( cirrhotics, multiple treatment failures , etc. ) , but overall it would still be clear , IMO , that VX-950 would add significantly to SOC results.
When do we see the results from the other arms of Prove 1 ? For some reason I thought we would get the first 20 patients from each arm at the same time.
Halozyme Therapeutics / Roche deal
( HTI should get a nice boost tomorrow. The buying by Randall Kirk was the tip-off. Wish I owned some. )
Halozyme and Roche Enter Agreement for the Application of Enhanze, A Novel Technology to Improve Drug Delivery
Tuesday December 5, 5:48 pm ET
BASEL, Switzerland and SAN DIEGO, Dec. 5 /PRNewswire/ -- Halozyme Therapeutics, Inc. (Amex: HTI - News) and Roche today announced they have entered into an agreement to apply Halozyme's proprietary Enhanze(TM) Technology to Roche's biological therapeutic compounds. Enhanze Technology is Halozyme's proprietary drug delivery technology based on its recombinant human hyaluronidase (rHuPH20). rHuPH20 is an analogue of a human enzyme that temporarily clears space in the matrix of tissues such as skin. This clearing activity should allow rHuPH20 to improve drug delivery by enhancing the entry of therapeutic molecules through the subcutaneous space.
Under the terms of the agreement, Roche will pay Halozyme $20 million as an initial upfront payment for the application of rHuPH20 to three pre-defined Roche biologic targets. Over the next ten years, Roche will also have the option to exclusively develop and commercialize rHuPH20 with an additional ten targets. Pending the successful completion of a series of clinical, regulatory, and sales events, Roche may pay Halozyme further milestones which could potentially reach a value of up to $111 million as well as royalties on potential product sales for the first three targets. For each of the additional ten targets, Roche may pay Halozyme further upfront and milestone payments of up to $47 million per target. In addition, the Roche Venture Fund will make an $11 million equity investment, representing approximately 5% of Halozyme's outstanding common stock.
Under the collaboration, Roche will also obtain access to Halozyme's expertise in developing and applying rHuPH20 to Roche targets. Roche will obtain a worldwide, exclusive license to develop and commercialize product combinations of rHuPH20 and Roche target compounds resulting from the collaboration.
http://tinyurl.com/y7tmsy
Resverlogix / ApoA-1
Resverlogix Corp.: RVX208 Unique MOA Positions it as a Leader in ApoA-I/HDL Marketplace
Hundreds of thousands of patients in key landmark trials demonstrate that enhanced ApoA-I significantly reduces cardiovascular disease risk
CALGARY, ALBERTA -- (MARKET WIRE) -- 12/05/2006 -- Resverlogix Corp. ("Resverlogix") (TSX: RVX), announced that the Company's lead drug candidate RVX208 unique mechanism of action (MOA) is well positioned in the emerging HDL therapeutic market segment for reducing atherosclerosis and heart disease. Given recent events in the marketplace regarding cholesterol management drugs, Resverlogix verifies that its lead candidate will be tested in humans Q1 2007. It is imperative to understand that one of the most important factors for a successful drug target is to have large bodies of clinical evidence to support it, which Resverlogix does. More than 200,000 subjects have participated in the landmark Esperion trial and other major epidemiology trials such as AMORIS and INTERHEART. These clinical studies have built a very compelling body of evidence that ApoA-I, not other targets such as CETP or PPAR, has the most robust clinical validation demonstrating a reduction in cardiovascular disease risk.
"As confirmed in epidemiological and mechanistic studies and expressed at our Clinical Advisory Board meeting in November at the American Heart meeting in Chicago, increasing ApoA-I production is undoubtedly associated with CVD protection," said Dr. Jan Johansson, M.D., Ph.D., SVP Clinical Affairs, Resverlogix. "Resverlogix is in the unique position of having a small molecule drug that in animal studies increases the natural synthesis of ApoA-I. The enhancement of ApoA-I by RVX208 has the potential to become a first in class therapeutic for the treatment of atherosclerosis and cardiovascular disease," said Dr. Johansson.
Mr. Donald McCaffrey, President & CEO, Resverlogix stated, "Resverlogix's repeated success in the rapid onset of ApoA-I production is pointing to a definite pattern of predictability in our data. This intriguing pattern will likely provide Resverlogix with multiple opportunities in the marketplace including acute, chronic and combination therapies thus permitting us to treat patients across several categories."
Additionally Dr. Johansson stated, "As a point of clarification, there is no known link between ApoA-I metabolism per se and blood pressure. Epidemiological data consistently demonstrates that subjects who have a high plasma ApoA-I concentration also have low-normal blood pressure. Presently it is not known if the lower blood pressure in subjects with high ApoA-I is because of their cleaner and less atherosclerotic blood vessels or because of hereditary and/or life style reasons."
http://tinyurl.com/ylpq87
re : AGIX
If you buy , think about selling some covered calls. If you sold the Jan 15s @ $1.50 , your net cost on your shares would be reduced to about $10.50. At that point I'd be thrilled if my shares were called away at $15.00. If not , I'd then sell
more calls if prices are still comparable to current levels.
Not a rec to buy , BTW. I don't know anything about AGIX.
Pfizer Scientist Faces Ethics Charge
( Oops , I meant GOVERNMENT Scientist. It's hard to tell the difference , sometimes. )
Government Scientist Faces Ethics Charge
With a rare criminal case against a senior federal researcher, prosecutors are sending a message to scientists on the government payroll: Making money from companies on the side can land you in big trouble.
Dr. Trey Sunderland, a leading expert on Alzheimer's disease at the National Institutes of Health, found that there was no wiggle room in his outside work for a pharmaceutical company, even in a time when rules were far more lax than today.
The U.S. attorney in Baltimore charged Sunderland with felony conflict of interest Monday for his private consulting with Pfizer Inc., that earned him $285,000 and improperly overlapped his official duties.
Sunderland was researching early indicators of Alzheimer's both as an NIH collaborator with Pfizer and a paid Pfizer consultant on work "directly related" to his government job, according to the court papers filed with U.S. District Court in Baltimore.
The scientist failed to obtain the proper approvals from his supervisors or disclose the work to NIH as was required, the prosecutors said.
Last year, NIH banned such outside work for drug and biotechnology companies following its own internal probe that was prompted by congressional investigations and disclosures in the Los Angeles Times. The probes revealed some researchers took advantage of a permissive environment which was designed to encourage public-private collaborations that might speed disease cures.
Lucrative moonlighting was still allowed during Sunderland's 1998-2003 deal with Pfizer, but the prosecutors allege his consulting gave him a financial interest in the work he did at taxpayer expense.
"This should put other federal officials on notice that you can't disregard the rules," said Vera Sharav, president of the nonprofit Alliance for Human Research Protection.
She and other critics contend that weak enforcement feeds conflicts even when ethics rules are in place.
After NIH's internal investigation, most of the 44 researchers found to have breached ethics rules got written or verbal reprimands or were permitted to retire. An agency survey found that many scientists consider the new rules so restrictive that they are considering leaving NIH.
The felony charge against Sunderland, with a maximum sentence of one year in prison and a $100,000 fine, was contained in a criminal information rather than indictment, a route that often precedes a plea deal.
Sunderland did not return a telephone message and his attorney, Robert Muse, declined comment Monday.
He remains on the government payroll although he asked to retire after House investigators began unraveling his Pfizer financial ties two years ago.
Members of the House Energy and Commerce Committee which launched the probe called Monday for Sunderland's dismissal from his post at the NIH's National Institute of Mental Health. Otherwise, Rep. Bart Stupak, D-Mich., said in a statement, "We can only conclude that no one is being held accountable, the system is broken and the public trust has been violated."
"Will a criminal conviction for conflict of interest be enough to get someone fired from NIH?" said Rep. John Dingell, D-Mich.
NIH officials declined to comment.
The court documents allege Sunderland participated as a government employee "in a particular matter in which, to the defendant's knowledge, he had a financial interest."
The conflict began in 1998 when Sunderland was making arrangements for NIH to work with Pfizer on Alzheimer's research. At the same time, he began negotiations to be a paid consultant on the same project, prosecutors allege.
Sunderland, 55, is to appear Friday for arraignment.
The case is believed to be the first conflict prosecution against a federal scientist since 1992 when NIH researcher Prem Sarin was convicted of embezzling a drug company payment to NIH that was intended to help with AIDS research.
http://tinyurl.com/yf2hz3
>> Are you impressed with how similar Viread and Hepsera are? They are almost as similar as Tyzeka and Clevudine. <<
It is amazing when you think about the specificity of biological systems. In 2D many of these molecules are absolutely identical , but in the real 3D world the differences are sufficient to make them behave like unrelated compounds. It must make modelling of drug-protein interactions a nightmare when you start combining two or more of these drugs.
>> You cheated? <<
Bingo !!
I assumed misdirection so I checked the structures first , but you have to admit it makes for an easy quiz.
I didn't answer so you would have time to edit the filenames so others could still take a stab at it. I guess it might be too late for that , but at least next time you'll check those filenames first.:)
Wrong , wrong , and VERY wrong !
Try again.
re : Structure quiz
A quiz for Dew :
Why is your structure quiz so easy to answer correctly ?
>> "There is still value, but not value as a blockbuster," she added. <<
LOL. I bet there's never been a drug with annual sales of $999 million --- the EOY sales incentives , for drug reps and customers alike , must be humongous when they approach the magic $1 billion figure.
What would a drug with a trillion in sales be called ? A 'ballbuster' ?
Dr. Nissen of Cleveland Clinic on Torcetrapib
A reasonable summary of the current situation , IMO , though nothing new for most here. A 5 min. interview at the link on the right-hand side of this Bloomberg page :
http://tinyurl.com/ykverr
Take your pick : Tyzeka , Sebivo , or telbivudine.
Re: CC for DVAX HBV vaccine
Thanks for the report. I wasn't aware of the IP conflicts. The 10Q suggests they might have a problem with COLY as well. ( I didn't see any mention of conflicts with ARIA IP but that seems like a possibility also , pending the outcome of the current ARIA patent dustup ) :
" Two of our potential competitors relative to HEPLISAV, Merck & Co., Inc., or Merck, and GlaxoSmithKline Plc, or GSK, are exclusive licensees of broad patents covering hepatitis B surface antigen. In addition, the Institute Pasteur also owns or has exclusive licenses to patents covering hepatitis B surface antigen. While some of these patents have expired or will soon expire outside of the United States, they remain in force in the United States and are likely to be in force when we commercialize HEPLISAV or a similar product in the United States. To the extent we were to commercialize HEPLISAV in the United States, Merck and/or GSK or the Institute Pasteur may bring claims against us.
If we are unsuccessful , yada , yada , ...
Another of our potential competitors, Coley Pharmaceutical Group, or Coley, has issued U.S. patent claims, as well as patent claims pending with the U.S. Patent and Trademark Office, or PTO. If these claims are held to be valid, Coley may seek to enforce its rights under these claims, including, for example, by suing us for patent infringement. Consequently, we may need to obtain a license to one or more of these claims held by Coley by paying cash, granting royalties on sales of our products or offering rights to our own proprietary technologies in order to commercialize one or more of our formulations of ISS in the U.S., including TOLAMBA and HEPLISAV. Such a license may not be available to us on acceptable terms, if at all, which could preclude or limit out ability to commercialize products. "
>> Could it be that they will file
for approval of the 3-dose regimen in Asia while
aiming for a 2-dose regimen in the West? <<
I bet it's something like that. For the first P3 , it made sense to do a head-to-head 3-dose comparison study , and in many countries this single trial may be sufficient for registration. In the EU and US they'll need a 2nd trial , and they may as well go for the 2-dose regimen as it will be an added marketing tool. The just completed trial will be supportive of the upcoming P3 using only two doses.
I wonder how that goose is doing -- Ok , I hope.
Sort of a BV board mascot. I guess we may as well name her 'Diane'. :)
After just a quick look , the ANGO / RITA combo looks like a good fit that could result in a positive synergy. Are you looking at the new company as a possible investment ?
Dynavax says Hep B vaccine meets study goal
(A good PR for all the TLR drug cos.)
Tue Nov 28, 2006 4:24 PM ET
CHICAGO, Nov 28 (Reuters) - Dynavax Technologies Corp. <DVAX.O> on Tuesday said its investigational vaccine for Hepatitis B met its goal of providing better protection against the virus compared to a rival vaccine, pushing shares up 31 percent in after-hours trade.
The company said its late-stage trial found its vaccine, called Heplisav, provided protection against the virus in 100 percent of subjects, compared with 73.1 percent of subjects receiving another vaccine called Engerix-B, made by GlaxoSmithKline Plc <GSK.L>.
Dynavax said the results of the 400-person trial were statistically significant.
http://tinyurl.com/w4ff6
More detail in Yahoo PR :
http://tinyurl.com/y5llny
re : IDIX / Susquehanna
" Jason Kolbert, the first member of what will ultimately be a several member team covering a broad group of biotechnology companies, comes to SFG from Darby Capital Group, an affiliate of Susquehanna International Group , where he had been a healthcare portfolio manager for the past four years.
Prior to joining Darby, Mr. Kolbert was a senior analyst and healthcare equity strategist for Citigroup. Previously, Mr. Kolbert was an analyst for Schering- Plough in Japan and an engineer at Biotage, Inc."
http://tinyurl.com/ykbwtb
>> What the difference between an inefficient market and a reverse efficient market? <<
A reverse efficient market accurately predicts past stock prices.
HCV : Th1 vs. Th2 immune response
( A new paper on an old concept. Ribavirin is believed to help promote a Th1 bias. )
1: J Gastroenterol Hepatol. 2006 Dec;21(12):1789-93.
Changes of soluble CD26 and CD30 levels correlate with response to interferon plus ribavirin therapy in patients with chronic hepatitis C.
Yang SS, Fu LS, Chang CS, Yeh HZ, Chen GH, Kao JH.
Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Background: Clearance of hepatitis C virus (HCV) is attributed to host cellular immune responses, in which T helper cells play a critical role. The purpose of the present paper was therefore to study the serial changes of serum soluble markers released from T helper 1 (Th1) and 2 (Th2) and their correlations with treatment responses in chronic hepatitis C patients receiving interferon-alpha plus ribavirin for 24 weeks. Methods: Serum markers (soluble CD26 and CD30 levels) of T helper cells were quantified before and 6 months after combination therapy in 33 chronic hepatitis C patients and in 20 healthy controls. Results: Compared to healthy controls, chronic hepatitis C patients had significantly lower serum soluble CD26 levels before (140.4 +/- 63.9 ng/mL vs 200.6 +/- 60.3 ng/mL, P < 0.0001) and after (115.9 +/- 32.9 ng/mL vs 200.6 +/- 60.3 ng/mL, P < 0.0001) combination therapy. The level was even lower in those with non-sustained virologic response (non-SVR; 139.0 +/- 50.9 ng/mL vs 117.7 +/- 40.3 ng/mL, P = 0.039). In contrast, soluble CD30 levels at 6 months after combination therapy were significantly lower in patients with SVR than those with non-SVR (6.4 +/- 3.5 U/mL vs 10.4 +/- 5.4 U/mL, P = 0.021). Conclusion: Chronic hepatitis C patients have a weak Th1 response as reflected by lower soluble CD26 levels and the levels are even lower in non-sustained responders. In sharp contrast, downregulation of Th2 response with serial changes of soluble CD30 level is associated with successful treatment of HCV infection.
http://tinyurl.com/yx93ut
...
PMID: 17074015 [PubMed - in process]
re : IDIX / VRTX
I think the VRTX Prove 2 study has a VX950 plus pegifn-only arm but I think this was done for label-enhancing purposes only , to help capture the riba-intolerant crowd.
re : IDIX
Were any of the patients treated to date with NM283 plus pegifn given the option to continue treatment with SOC ( minus NM283 ) at some point ? If so , IDIX might already have a good feel about the feasiblity of the two stage approach , since the models for predicting SVR are probably pretty reliable once the patient has been switched over to SOC for a couple months.
re: idix and smith barney
>> latest data show disparity in undetectable viral load of 15% between nm-283+peg vs peg-ribavirin (favoring nm-283). We have yet to know how this spread will translate to differences in svr, but i figure should be mroe or less the same. <<
I hope you're right about this but I won't feel confident till I see some SVR data , even if only 3-month , that supports the notion that on-treatment HCV-negativity translates to eventual SVR at similar rates for NM283 plus pegifn as it does for riba plus pegifn. In order for end-of-treatment HCV-negativity to result in SVR , it's generally believed that the immune response must be functioning properly and many think that riba contributes to the necessary 'resetting' of the immune response , something that hasn't been suggested for NM283. VX950 might have a better shot in a riba-free tx. , since it does presumably help correct the disruption in ifn signalling caused by the HCV protease.
Assuming the in-vivo studies do show a significant negative interaction between riba and NM283 , I think they should try a two-stage tx. regimen to avoid the total loss of riba's benefit. For example , 24 weeks of NM283 plus pegifn followed by 24 wks of pegifn plus riba ( +/- NM283 , depending on whether they believe NM283 would add any benefit in the second stage ). This might complicate a P3 trial , since I assume the FDA would want to see the corresponding placebo control arm , in addition to the regular SOC control arm. Ideally this would have been examined in P2 trials ; maybe the current studies have some arms like this.
Although I agree with the gist of the SB report as regards NM283 , I don't agree with this :
>> We caution that the stock could be volatile to downside if this interaction is shown in the current 90-patient clinical study when data is released in Q1:07 since this could lead to termination of further development efforts of NM283 <<
NM283 can still make a splash if it's the first polymerase inhibitor to market , even if it's way behind VX950 in efficacy. The reason is that there will be the opportunity to try combos of the two drugs (NM283 and VX950 ) , each with new and different MOAs , with the potential to greatly reduce or eliminate the need for BOTH riba and pegifn. I don't think NVS / IDIX will give up on NM283 , even in the face of unfavorable drug-drug interaction results with riba ( as long as they think they can design a successful P3 ).
...
>> There are some iHubbers whose daily output is in the hundreds. Of course, most of those are the one-line throwaway variety. <<
Indeed. Here at BV , we much prefer the multi-line throwaway variety.
)
Kidding , of course. Have a good weekend , all.