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>>> Although many here seem to refute it, there is some empirical evidence that FastTrack designation provides for improved share price performance versus peers. <<<
I don't think anyone here denies that stocks usually rise on announcement of FT designation , and I don't recall ever seeing a discussion of the merits of holding companies with FT category approved drugs vs. those with non-FT category drugs.
What has been noted here , correctly I believe , is that FT drug candidates have a lower probability of getting approval than non-FT candidates. They're simply operating in a difficult therapeutic area , which is why they get FT designation in the first place.
So , the strategy would be to sell FT drug companies on the FT announcement , then buy and hold those that end up getting their drug approved.
>> autologous (or banked whole-cell) preparations are not able to achieve a concentrated enough DC/antigen ratio to break immune tolerance <<
I'm also curious what you mean by this. Do you mean that they can't generate a sufficient number of Ag-primed DCs to infuse ?
> Why do companies even bother with surrogate endpoints anymore, if all they're going to get is a conditional approval? Sure, the drug may be on the market sooner, but will it have much commercial potential without showing a survival advantage? <
blade ,
I sometimes think the main advantage of the accelerated approval designation accrues to the FDA , who gets to issue a semi-positive ruling while still coverering their own asses , thus making everyone happy.
However , here's an example where the company could benefit substantially. Say you're CEO of a company that runs a trial with an SPA and ends up with AA on a surrogate endpoint with a requirement to demonstrate a survival benefit for full approval. The current trial was powered to give a good shot at the surrogate endpoint , but might be underpowered to demonstrate survival. Thus , you may have to begin enrolling the larger trial to get the full approval , but you're able to sell some drug in the meantime , and you didn't have to risk the full-scale sized trial on the first go. If the first trial gives statsig survival , you're golden. If not ( hopefully it shows a TREND , at least ) , then you have to wait for the big trial to finish.
Depending on the indication , time to enroll , etc ., you might end up with a couple extra years of marketing your drug under the AA designation. If it fails ultimately , you will still likely be better off than if you had run the big trial first , and you almost certainly will have accumulated some extra bonuses and options in the interim ( Not that you would ever let that sort of thing influence your trial design , right ? ).
Re: Study: Virus infection cured molecularly (hep-c)
Some more detail at this link , which reveals that the technique involves IL-10 receptor blockade:
http://www.liai.org/news/releases/oct_06_chronic.htm
They don't mention it but I'd think this might also be applicable to cancer immunotherapy as a more gentle ( compared to , say , anti-CTLA-4 Mabs ) way of overcoming suppression.
Anyone know of any companies looking at IL-10 or IL-10 receptor blockers ?
>>> If unfavorable toxicities evolve from VRTX's ongoing Phase II study, ITMN could gain a lot of attention from physicians, WS etc... <<<
katie ,
I agree. VRTX investors could do worse than holding some ITMN as a hedge against safety issues in the ongoing VRTX P2 trials.
Dew's quiz was only made difficult by our suspicion that there must be a trick , a reasonable assumption considering the source.
The obvious first choice for a doc would seem to be SVR improvement. However , when you consider how tolerability improvements could increase SVR ( through better adherence to dosing schedules ) , as well as bring in more patients ( as those who previously refused treatment due to fear of injections and SEs change their minds ) , it becomes easier to imagine the docs choosing tolerability over SVR.
I don't think those survey results would necessarily translate accurately into real-world sales , but it may excite some investors ( which may have been the intended result in the first place ).
>>> I can't figure out what the walking thing is half-way through the video. It looks cool, though. <<<
It looks like kinesin. Compare it to the video here :
http://www.scripps.edu/cb/milligan/projects.html
>>> Nope! c) is not the most important and there’s a good reason for that if you think about it. <<<
I figured that if biweekly dosing allowed Albuferon to capture a 50% market share with no better efficacy / tolerability , then less frequent dosing is a major driver in determining preference , since you would only expect an even split , all other things being equal , between Pegasys , PegIntron , and Albuferon , i.e. a 33% share for Albuferon.
If the competition is only Pegasys , then I would say b , a , c.
Re: Quiz
I think the order might be different depending on whether they surveyed patients vs. docs. Anyway , my guess : c , b , a .
Re : Biotech P3s
Cabrio03 ,
Nice idea . I'm curious about how you generated the list. Brute force ( my favorite technique ) , or something more clever ?
In retrospect , ACOR was the quintessential "Biotech Value" , and , like you , I'd like to be able to define the next one prospectively , if at all possible.
A few on your list , like COLY and IDIX , get discussed here with some regularity. Using IDIX as an example , I can't think of anything that could happen that would result in an overnight 4-banger as happened with ACOR , although it's not hard to envision a similar outcome on a longer timeline.
It might help to focus attention on those companies with a "binary event" in trial results expected in the next , say , 3 or 6 months.
Re: Ariad
>>> I am curious why you think Ariad will lose its legal battle. Is it specific knowledge about weakness of Ariad's patent or is it more general, that the patent was just too broad and should be invalidated? <<<
The latter. Ariad's claim on any drug that acts thru the NF-kB pathway is so sweeping that , given the Rube Goldberg-like connections between biological pathways , it might include ALL drugs.
Actavis ?
>>> I think the neurokinin-B pathway effect on angiogenesis is different than Ariad's IP. But both seem to be active on angiogenesis. If any basic scientists can shed some light, please enlighten us. <<<
You're correct that the NK-B and NF-kB pathways are distinct. It sounds like the role of NK-B is limited to regulation of angiogenesis while NF-kB is involved in regulation of multiple mediators of immune response , some of which also play a role in angiogenesis , as you suggest.
BTW , I think Lilly will win the legal battle , and Ariad's broad claims on NF-kB will be invalidated.
Re: IPO e-mail newsletter
Not a newsletter , but a website that may be of use. I can't vouch for the reliability -- it's just a link I had stuffed in my computer :
http://www.ipohome.com/marketwatch/ondeck.asp
That article is a good one to illustrate the difficulty that SPPI may have in convincing docs to use LFA , unless they can demonstrate a clear reduction in SEs or some other benefit.
To me , it's a lot simpler. I'd rather take a drug that's 99.9% pure than one that's 50% pure.
I don't think drug companies should get INDs for racemic drugs , at least ones that can be resolved easily , unless they've got evidence that the mixture is better than the pure isomer.
Re: SPPI / LFA
>>> What do YOU think of the drug and its sales potential? <<<
Sorry , I don't have much of an opinion one way or another. I had seen the "LFA" acronym before and wondered what it was , thus ending up on SPPI's website.
In general , though , I'm a believer in using optically pure drugs like LFA as opposed to racemic mixtures when the beneficial activity is known to reside in only one isomer. Whether the docs who use the drugs in the U.S. will feel the same is another matter...
Re : SPPI / LFA
(Looks like revenue potential of about $200 million /yr).
Levofolinic Acid (LFA)
Methotrexate rescue therapy in osteogenic sarcoma
Colorectal cancer chemotherapy in both adjuvant and advanced settings
Intravenous and oral
Pure active isomer of Leucovorin (folinic acid)
Potentiate clinical efficacy of 5-FU alone and in combination
NDA pending CMC responses – expected completion Q1 2007
Worldwide LFA sales (outside the U.S.) were $200 Million. LFA is positioned as a premium product and is the unit sales leader in countries where it is promoted.
LFA has similar potential in North America. 2,700 new cases of osteogenic sarcoma are diagnosed per year in the U.S. Colorectal cancer is the 4th most common cancer in the U.S. with 145,000 new cases per year.
Spectrum has licensed the rights to North America.
From:
http://www.spectrumpharm.com/LFA.html
That's true. Someone should crystallize the crap , just in case.
>>> The new study is expected to utilize a new crystalline form of ANA975, developed by Novartis, which will further our understanding of the toxicology profile of ANA975. <<<
I take this to mean: " We've gotten rid of the crap that was contaminating ANA975."
Now they have to pray that the crap wasn't the active part.
>>> IDIX CC... JP refers to a web site where abstracts will be posted on or about Monday.
what web site is he referring to? <<<
AASLD meeting - AKA The Liver Meeting . Abstracts will be searchable ( from Monday on ) via the Itinerary Planner at this link :
http://tinyurl.com/g7z7v
Re : VPHM
I haven't heard them (VPHM) address this , I'm just going by the discussion that's been kicked around here. Have they elaborated on the basis of the claim , or do they just present it as a given?
I suppose you could make the case that when looking for new drug candidates that will likely be used in combo with existing nukes , it might be a better strategy to concentrate on non-nukes ( on the assumption that interference would be less likely).
Nukes vs. non-nukes
It just occurred to me that the ribavirin interference issue could explain VPHM's assertion that a non-nuke polymerase inhibitor would be preferable.
>>> This abstract would seem to imply that the dose of NM283 ought to be raised when given with ribavirin, but this is not what IDIX and NVS are actually doing. Comments? <<<
I'd like to see the full paper to see what they really did. All the abstract says is that riba interferes with NM283 anti-HCV activity. Is riba competing with NM283 in binding to polymerase ? If so , could NM283 interfere with riba's anti-HCV activity(s) ?
It could be that REDUCED doses of both would be optimum. It all depends on the mechanisms and kinetics of activity vs. inhibition of activity. I think IDIX would be awful lucky to get anything like an optimum protocol out of the first study.
>> Why aren’t more HCV companies talking about this? How much does it cost? Perhaps it’s so good that NVS wants to keep it in house!
p.s. Thanks for the NM283+riba abstract. Next time I talk to IDIX, I will ask them about it. <<
If the mouse model really provides a competitive advantage in HCV R&D , I would think that Chiron would have tried to keep it under wraps.
I'd be interested in IDIX's response to your question about the riba interaction. I wonder if they've known about this for some time , and thus were not terribly excited about pursuing combo studies including riba. It looks like this data could have contributed to the IDIX swoon which started in March , depending on how widely it may have leaked prior to publication. I see it as a bad sign for the riba combo studies , but not conclusive by any means.
Glow-in-the-dark HCV mouse model...
..from Chiron / NVS. Pretty slick.
Novel Robust Hepatitis C Virus Mouse Efficacy Model
Qing Zhu,1* Yoko Oei,1 Dirk B. Mendel,1 Evelyn N. Garrett,2 Montesa B. Patawaran,1 Paul W. Hollenbach,3 Sharon L. Aukerman,1, and Amy J. Weiner4,
Departments of Pharmacology,1 Experimental Pathology,2 Translational Medicine,3 Vaccines, Chiron Corporation, 4560 Horton Street, Emeryville, California 946084
Received 3 April 2006/ Returned for modification 7 June 2006/ Accepted 18 July 2006
The lack of a robust small-animal model for hepatitis C virus (HCV) has hindered the discovery and development of novel drug treatments for HCV infections. We developed a reproducible and easily accessible xenograft mouse efficacy model in which HCV RNA replication is accurately monitored in vivo by real-time, noninvasive whole-body imaging of gamma-irradiated SCID mice implanted with a mouse-adapted luciferase replicon-containing Huh-7 cell line (T7-11). The model was validated by demonstrating that both a small-molecule NS3/4A protease inhibitor (BILN 2061) and human alpha interferon (IFN-) decreased HCV RNA replication and that treatment withdrawal resulted in a rebound in replication, which paralleled clinical outcomes in humans. We further showed that protease inhibitor and IFN- combination therapy was more effective in reducing HCV RNA replication than treatment with each compound alone and supports testing in humans. This robust mouse efficacy model provides a powerful tool for rapid evaluation of potential anti-HCV compounds in vivo as part of aggressive drug discovery efforts.
http://tinyurl.com/p6x5b
Re : IDIX : NM283 plus ribavirin
Just came upon this , coincidentally :
Antimicrobial Agents and Chemotherapy, October 2006, p. 3444-3446, Vol. 50, No. 10
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Ribavirin Antagonizes the In Vitro Anti-Hepatitis C Virus Activity of 2'-C-Methylcytidine, the Active Component of Valopicitabine
Lotte Coelmont,1 Jan Paeshuyse,1 Marc P. Windisch,2 Erik De Clercq,1 Ralf Bartenschlager,2 and Johan Neyts1*
Rega Institute for Medical Research, KULeuven, 3000 Leuven, Belgium,1 Department of Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany2
Received 27 March 2006/ Returned for modification 8 May 2006/ Accepted 31 July 2006
Ribavirin antagonizes the in vitro anti-hepatitis C virus (HCV) activity of the pyrimidine nucleoside analogue 2'-C-methylcytidine, the active component of the experimental anti-HCV drug valopicitabine. In contrast, the combination of ribavirin with either the purine nucleoside analogue 2'-C-methyladenosine or the HCV protease inhibitor VX-950 resulted in an additive antiviral activity. These findings may have implications when planning clinical studies with valopicitabine.
http://tinyurl.com/mxmmd
PPHM patent language...
From iHub PPHM :
http://tinyurl.com/krru7
The newly issued patent covers the therapeutic use of all regimens that combine agents specifically targeting tumor blood vessels with other anti-cancer agents, such as chemotherapy drugs.
"We believe that the breadth of this patent's allowed claims make it relevant to many of the researchers pursuing targeted combination therapy approaches based on destroying the essential blood supply of tumors," said F. David King, vice president of business development for Peregrine. "Sub-licenses to our VTA intellectual property will provide them with freedom to operate in this area, and this new patent should therefore be a valuable addition to our business development initiatives."
Is this claim likely to hold up to challenge ?
It seems to me that it fails the "obviousness test " by a wide margin. Is PPHM really the first company to propose targeting tumor blood vessels specifically , and even if they are , would it not be an obvious extension of prior art in the field to combine that specific targeting with the delivery of chemotherapeutic agents ?
JMO , but I don't see much chance of a royalty stream flowing in PPHM's direction as a result of this claim.
Re : >> [OT] gofishmarko: Did you know the quiz answer because:
a) You googled it;
b) You listened to Pharming’s webcast today; or
c) You knew it already? <<
A quiz about the quiz ?
The correct answer is b). I figured it had to be in the UBS webcast when you made the comment about not being able to get it by googling . Luckily the answer was revealed early in the webcast because I was losing interest pretty fast.
Re : Quiz
Pharming gave away their employees , along with mfg. facilities and other goodies , to Genzyme and Crucell , with a money-back guarantee. Apparently the employees were pretty good , since none got returned.
Re : Quiz
Avastin?
Sorry , guys. I was composing mine while you were having the " short VRX" discussion.
Great minds think alike ?
Re : VRX / Viramidine
If they're interested , I bet ITMN could buy back the Infergen franchise at a good discount right now.
VRX can probably get past the FDA eventually in a non-inferiority trial using a sufficient weight-based dosing , but the anemia SEs will be back along with the antiHCV activity , I suspect. Not much to market there against cheap generic riba.
Here's a quote from less than a year ago to add to their sad story :
"The acquisition of Infergen will have an immediate sales impact on Valeant and provide us with a valuable addition to one of our core therapeutic areas," said Timothy C. Tyson, Valeant's president and chief executive officer. "In addition, we intend to hire up to 50 of InterMune's sales and marketing force, which will help to provide Valeant with an immediate presence in the hepatitis C market and position us for the anticipated launch of Viramidine(R)." Viramidine, which is currently in Phase 3 clinical trials, is expected to be launched in 2007. "
Maybe VRX is a good short ?
>>> Dosing will be adjusted on the fly—up to a maximum of twice the loading dose—using the EGFR-induced rash as a proxy for efficacy. <<<
"RASH" :
Old definition : Side effect.
New definition : Dosimeter.
>>> A handy rule of thumb <<<
But one that's probably only valid in the worldwide context , since genotypes vary so much in different regions ( for both HBV and HCV ) and genotypes probably influence the rates of cirrhosis / HCC significantly.
I'd also guess that regional variables like diet , incidence of other diseases , etc. , affect the rates.
Contributions of Hepatitis B and C to Cirrhosis and Primary Liver Cancer Worldwide
( Provides some updated figures relevant to past discussions here on the impact of preventative HBV vaccination on HCC occurrence. )
http://www.hivandhepatitis.com/hep_c/news/2006/091206_a.html
It is well known that a proportion of individuals with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection will go on to develop advanced liver disease, including cirrhosis and hepatocellular carcinoma (HCC, a form of primary liver cancer). It is estimated that end-stage liver disease accounts for 1 in 40 deaths worldwide.
As reported in the October 2006 Journal of Hepatology, researchers from the U.S. Centers for Disease Control and Prevention (CDC) attempted to quantify the global contribution of HBV and HCV to cirrhosis and liver cancer.
The researchers obtained data from representative samples of published reports on the prevalence of serologic markers for HBV and HCV infection among patients diagnosed with cirrhosis or HCC. Attributable fractions of cirrhosis and HCC due to HBV and/or HCV were then estimated for 11 World Health Organization regions.
Results
Globally, 57% of cirrhosis cases were attributable to either HBV (30%) or HCV (27%).
78% of HCC cases were attributable to either HBV (53%) or HCV (25%).
In most regions, these infections accounted for more than 50% of HCC and cirrhosis cases.
Applied to 2002 worldwide mortality estimates, these fractions represent 929,000 deaths due to chronic HBV and HCV infections, including:
- 446,000 cirrhosis deaths (HBV 235,000; HCV 211,000);
- 483,000 liver cancer deaths (HBV 328,000; HCV 155,000).
( Given that there are roughly twice as many people worldwide with chronic HBV vs. chronic HCV , it looks like the RATES of developing cirrhosis are about twice as high for HCV vs. HBV , and about equal rates as regards HCC. )
Conclusion
The authors concluded that, "HBV and HCV infections account for the majority of cirrhosis and primary liver cancer throughout most of the world, highlighting the need for programs to prevent new infections and provide medical management and treatment for those already infected."
9/12/06
Reference
J F Perz, G L Armstrong, L A Farrington, and others. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of Hepatology 45(4): 529-538. October 2006.
Good freebies in today's NEJM ....
...focused around T-cell costimulation and the P1 trial results of Tegenero's anti-CD28 superagonist MAB , from March of this year , that came close to killing the 6 trial participants. The data they collected probably comes as close as you could get to a model of sepsis in a healthy , uninfected patient.
There are 3 related articles , all free , at :
http://content.nejm.org/current.shtml
1)Focus on Research: T-Cell Costimulation — Biology, Therapeutic Potential, and Challenges
A. H. Sharpe and A. K. Abbas
2)Brief Report: Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412
G. Suntharalingam and Others
( also a good audio interview with Dr. Sunthalralingam )
3)Volunteers at Risk
J. M. Drazen
GNVC - Malaria vaccine
Double whammy vaccine targets malaria
09 September 2006
A TWO-for-one vaccine may offer a cheaper, more effective way to protect against malaria.
Biotechnology company GenVec of Gaithersburg, Maryland, modified an adenovirus to express fragments of two proteins called CSP and LSA1, which are normally produced by the malaria parasite Plasmodium falciparum. Once injected into people, the virus should churn out both these antigens, priming the immune system to target the parasite.
Tests in mice have shown a vaccine containing the modified virus triggers 5 to 10 per cent of the "killer T" immune cells in mice to recognise and stop the malaria infection, a change in immunity sufficient to protect mice against the parasite.
From issue 2568 of New Scientist magazine, 09 September 2006, page 19
http://tinyurl.com/h488m
( posted by heldnova at iVillage )
Gottleib on CNBC tomorrow A.M. ....
....Squawk Box 6:00 AM - 9:00 AM ET
( per Tunes on iVillage DNDN board http://tinyurl.com/op7cp )
>>> Results and guidance from CSCO are modestly bullish for the economy: <<<
I'd settle for a modestly bullish economy going forward , so I hope the CSCO gauge is still in calibration.
A few years ago someone proposed that a good gauge for predicting recessions in the U.S. is the volume of mass mailings of deeply-discounted magazine subscription offers , on the assumption that it provides a read on consumer discretionary spending power.
Based on the offers I've been receiving in my mailbox , the outlook must be pretty dim. I've subscribed to all kinds of junk I'll never read because I couldn't pass up the great deals !
>I was briefly thrown in iHub Jail for unknown reasons…<
Are you sharing a PC or internet connection with other iHub users?
No. I have no idea what triggered it. I'm probably just collateral damage , as you suggest. I sent Matt an email and he didn't suggest that I'd broken any laws. Earlier today when I tried to post I was still incarcerated , so I dumped all my iHub cache and re-logged in , which seemed to fix it.
Re : VRTX et al.
Thanks , katie , for your comments on treatment of HIV/HCV coinfected patients.
I recall , maybe incorrectly , that IDIX talked of plans for studies in coinfected patients during an earlier CC. I remember thinking at the time that it might be a strategy to address a patient population that VRTX will not be targeting initially.
The ANDS animal studies are more ominous now that we know the effect was seen in monkeys as well as rats. Did they give any more detail on the nature of the "severe immune response " observed ?
( I haven't had time to listen to any CCs lately , as I'm trying to get ready for a 2-week vacation starting this weekend. A fishing vacation , as you may have guessed.
Also , I was briefly thrown in iHub Jail , for unknown reasons , but managed to bail myself out by tossing my cookies , or else Matt set me free.
None too soon , either. It was scary in there.