Yes.

For that ASSIST-1 trial, patients need to have failed one of Doxil or Hycamtin in the second line. They are then randomized to receive either Telcyta or one of Doxil / Hycamtin, depending on which of that pair they previously failed. So for example, if a woman failed Doxil in the second line, she would be eligible to receive either Telcyta or Hycamtin.

They also have another phase III in 2nd line ovarian cancer called ASSIST-3. Patients failing first line platinum are randomized to Telcyta + carbo or Doxil. It's basically a resensitization trial. However, this one is still enrolling so it is difficult to have a good estimate for completion. The company has stated that all three ASSIST trials are likely to come to completion under a similar time frame.

Added just one more item to Telik as the ovarian cancer phase III trial is also slated to complete along the timeframe as the NSCLC trial. This list is working out nicely.

ABGX- panitumumab ph III results in ref mCRC expected in Q3;
Ph II combo study with paclitaxel/carboplatin in first line NSCLC in 05. Phase II study results in mRCC

AGEN - Ph iii in RCC 2H05

AGIX - 1H 06 - Ph iii of 1067 on MACE should hit 900+ events for the end of the trial.

AORMF -pivotal AMD3100 results 2nd half 06.

AXCA -pivotal Itax results 2nd half 05.

BOMSF -reporting pivotal MBP8298 results 2 years roughly

CORT - 1H 06 - Results of Ph ii of RU-486 on reversal of Alzheimers functionality
CORT - 1H 06 - Results of Ph iii of RU-486 on Psychotic MD

CRME -pivotal Act3 results this qtr. as well as Phase II oxypurinol CHF results this qtr.

CNVX - Last interim look at melanoma vaccine in Q3/Q4 05

CYAHF -20 patient IDE results 4th qtr, then begin the pivotal phase 1st half 06 as well as commercial launch in Europe later this year.

CYPB - Q3 05 First Ph iii results of Milnacipran in Fibromyalgia

DNA - Rituxan ph III results in RA in Q3 05
DNA - Lucentis phase III results in wet AMD expected July 19th, 05.

DNDN - Q3 05 Survival data for 9902A Ph III of Provenge
DNDN - 1H 06 ttp data for 9902B Provenge Phase III
DNDN - 1H 06 - Results for Ph iii of Provenge efficacy on PSADT in ADPC

GTCB – EMEA opinion on ATryn BLA: Oct 2005

GTOP - 2H 05 (7/25-8/10) - interim look at ttp (very low p value of 0.0002 required for stat sig) for therapeutic vaccine for NHL

IDBE -begin pivotal Fluinsure trials this winter.

ISTKF -report interim Phase III ISA247 psoriasis results August and unblinded results in October.

LBPFF -report Tramadol Phase III U.S. results 2nd half as well as European launch 4th qtr.

LRP -report pivotal viruzulin results later this year.

MCU -reporting some Phase II results late summer.

NABI - ph iii results for vaccine against staph in Q3/Q4 05

ORPH (to become JAZZ?)--2H 05-data from the clinical trial designed to evaluate Xyrem in the treatment of fibromyalgia syndrome

PDLI - Q2 06 volociximab ph II for solid tumors

PTIE - All are 2H05
Oxytrex(TM) Osteoarthritic Pain - Phase III Report top-line results
PTI-901 Irritable Bowel Syndrome - P.III Report top-line results in women
Remoxy Severe Chronic Pain - P.III Initiate second Phase III
Remoxy Severe Chronic Pain - P.III Report top-line results

PTN- Q2 2006 ph.IIb results for PTN-141 in male erectile dysfunction

TH.TO -report ThGrf Phase III Hiv-associated lipodystrophy results late 06.

TELK - Telcyta 3rd line NSCLC and 3rd line Ovarian results 1H06

TRCA - Increlex PDUFA date of August 31.

VSGN - Celacade phase-3 in PAD (SIMPADICO) fiscal 4Q05; phase-3 in chronic HF (ACCLAIM) fiscal 1Q06 (Dec05-Feb 06).

YMI-early 2006?--The pivotal Phase III trial was initiated in March 2004, enrolling 700 patients at 86 sites across 13 countries. The outcome of the trial will be reviewed in light of the Special Protocol Assessment received by YM from the FDA. Because of a subsequent agreement with the FDA to apply a Sequential Analysis to the trial that permits stopping the trial following 192 "events" provided certain criteria are met, YM anticipates that the trial might be completed as early as mid-2006.
YM-report pivotal Tesmilifine breast cancer results possibly 2nd qtr 06.

This is an excellent background paper for Vasogen which i highly recommend.

http://www.jci.org/cgi/content/full/101/4/890

If access to the pdf is restricted, please message me with your email and i can forward it.

oh no no... wasn't being snippy. Was just being goofy.

let's try that again:

<goofy> Well, that settles it then! </goofy>

Thank you for the presentation.

But just as a matter of background, i'm familiar with CHF and the literature to define it's etiology.

What I do not understand is how an aliquot of blood that is "stressed" and then injected intramuscularly produces an effect at a distal site, especially with relatively short-lived signaling molecules such as interleukins.

Guess I'll have to look into that.

>You were discussing MOA as a matter of intellectual curiosity. I was discussing MOA as a matter of confirmation that the drug works. The difference is that once I know the drug works I don't care as much how. (Apparently my intellectual curiosity is less than yours -g-) <

Well, that settles it then!

Ok, so now we know the drug works. But weren't we discussing what the moa was? Because I still don't know how it works.

vasg

> have now read the Celacade CHF ph ii paper and in fact it speculates that the mortality efficacy is indeed related to electical improvement - they even weakly cite some evidence that cytokines can negatively impact cardiac electrical activity.<

I've also read that paper. So two questions arise:

1) is the evidence for cytokines affecting the electrical rythmn of the heart a solid one?

2) how do the cytokines get to their place of injection to their place of action? These are not long lived proteins.

Of course, there is no requirement that the moa be clear or explicit for a drug to work or be approved. But it's nice to be able to reason it, if just for intellectual curiosity.

And you're correct that the reasoning along the electrical line gives little evidence to why any aspect of PAD would be resolved. Activated macrophages can actually exacerbate a region of an artery narrowed by plaque buildup.

You also wondered how people with CHF ultimately die. Kidney insufficiency and failure due to underperfusion is a large contributor. Other notables are the risk for arrythmias (as you noted) and pulmonary edema.

As for a previous poster's comment:

>VAS's celecade therapy is not aimed at the heart per se but more at the bodys piping system. CHF is basically when the pumping action of the heart is insufficient to meet the body requirements.<

I believe this is an over-simplification of CHF. The cardiovascular system is highly integrated, and the upstream effects of narrowed arteries can be sensed as an increase in afterload to the heart, forcing it to compensate in a deleterious fashion.

Apparently my skepticism precludes me from liking many biotechs, but I find the post you referred to as a thinly veiled attempt at rationalizing (or showing the added benefits) phenoxodiol's pivotal trial in ovarian cancer.

The company and their mouthpiece message board posters have made a big stink about how their trial is the utmost in rigor because it will take refractory / recurrent ovarian cancer patients and treat them again with their last failed chemo as part of the run-in phase of the clinical trial. And now a poster is coming on saying that the FDA will require such a barbaric practice as part of their clinical development guidelines?

Would you enter any chemo trial that would make you take your last failed chemo again, and risk its mutagen nature, just to try an unproven drug? Especially when you had the results of your last CAT/PET scan in hand showing the cancer advancing while you were taking this chemo?

I think some recent approvals have reinforced the notion that the FDA may be sticky about the proper and clear documentation of the refractory status of a patient (part of imcl's problem), but I refuse to believe that they are in the deliberate business of dreaming up new ways to poison patients.

As an aside: I'd be very suspicious of anything coming from any of the novogen message boards. The referenced applefoot guy is a clear pumper with little insight into the actual FDA process. There are other seemingly solid posters like "sir_wallow" who have gone so far as to lie about a communication with management to bolster their message board position. Buyer beware.

I hack Zhang because he often tosses around comments based on shoddy underlying work.

As cooldrink mentioned, the possibility of Telik stock falling if ASSIST-1 or 2 fail is not informative. Anyone invested in any such biotech needs to be prepared for the possibility of trial failure.

As for his shoddy work, I did read the prudential report. He notes 25% grade 3 or 4 thrombocytopenia and 9% anemia seen at 1000 mg/m2 Telcyta with Tax / Carbo. Tax / Carbo by itself in front line NSCLC gives 12 and 19% thrombocytopenia and anemia, respectively. So on paper, the thrombocytopenia looks higher and the anemia looks lower than the doublet alone (although that could be due to epo use). So perhaps he's right about one of the side effects (thrombocytopenia) being more prevalent in the triplet.

My only problem is that he doesn't give the patient numbers that he based the observations on. There were 4 dose levels of Telcyta in this trial (up to 1000 mg/m2 max). 35 were currently available for safety, up from 13 at interim. With 12% expected to get thrombocytopenia from tax / carbo alone, that's about 1 in 8 patients. If 2/8 had thrombocytopenia for the triplet, that's too small a number to reliably suggest an increase in incidence to an oncologist. However:

Using 9 as a denominator doesn't give you a whole number of patients that rounds the outcome of the fraction to 25%; nor does 10, 11, 13, 14, 15, 17, 18, 19, 21, 22, 23, 25, 26, 27, 29, 30, or 31.

As for the rest:

3/12 = 25%, but then you can't get the 9% incidence for anemia (1/12 = 8.3% and 2/12 = 16.7%)

4/16 = 25%, but then you can't get the 9% incidence for anemia (1/16 = 6.25% and 2/16 = 12.5%)

5/20 is 25%, but then you can't the 9% incidence for anemia (all percentages are multiples of 5)

6/24 is 25%, but then you can't get 9% (2/24 = 8.33% and 3/24 = 12.5%)

7/28 is 25% but then you can't get 9% (2/28 = 7.1% and 3/28 = 10.7%)

The only number possible is 32 evaluable for safety at 1000 mg/m2. That would be 8/32 with thrombocytopenia and 3/32 with anemia. But with a total of 35 evaluable for safety at all 4 doses of Telcyta, that would mean only 1 patient each at the 3 dose levels less than 1000 mg/m2. That sounds unlikely in a dose escalation study.

Something doesn't fit. Maybe i'll contact the hack himself and ask him how many patients went into this observation. I don't trust his numbers or his judgment.

That prudential write-up on Telik doesn't surprise me. Let me guess, was that Jason Zhange that wrote it?

He is an absolute tool.

Zhang previously badmouthed the stock (and tanked his meager reputation) when he polled a few sites and said that ASSIST-1 would not enroll within the timeline that management said it would.

The trial finished enrolling right when management said it would.

Then he said that Telik's data in 3rd line ovarian was not impressive, and buttressed his arguments with comparison of Telik's 3rd line data with other 2nd line data.

His recent comments regarding a dose reduction due to side effects is rather interesting. As a monotherapy, Telcyta does not show serious adverse events. In the triplet, I would hope that Zhang has some data to back up his mouth. His mouth usually runs overtime, however.

I'll see if I can get a look at the Prudential report. But in any case, Zhang is a hack, and I've called him that on every public board after he writes up his useless reports.

re: Telik

See? Would I lie to you about news?

Telik does indeed have SPAs for both their 3rd line ovarian and NSCLC trials, termed ASSIST-1 and 2, respectively.

ASSIST-3 does not have an SPA.

As far as timing for the release of their trial data, I only referred to ASSIST-1 and 2 but not 3 simply because the latter is not yet fully enrolled. However, I concur with your comment that the company expects all three trials to show complete results in a similar time-frame.

A quick comparison of today's update with May's ASCO update:

Triplet: evaluable patients went from 13 to 26 and the response rate went from 62% to 58%

Doublet: evaluable patients went from 25 to 26 and response rate went from 36% to 32%.

The doublet doesn't seem to be enrolling as well as the triplet, mostly because the carbo/taxol in the triplet is the preferred regimen in front line NSCLC. With the triplet, the number of evaluable patients since ASCO have doubled but the response rate has basically stayed the same. Nice to see.

As with any other oncology company with outstanding phase III data, there are obvious risks. But the data that these guys have shown in ovarian and NSCLC cancers have been consistently better than the standard of care (small trial sizes are a concern, of course). They routinely provide thorough disclosure of data, and do not get involved in word games with the investment community.

For oncology, you could do much worse than having a position in Telik. Although many companies toss out the old "our drug resensitized tumours to chemo X", Telik's Telcyta actually appears to be doing it in the clinic.

The triggers for their two enrolled phase III trials will likely hit it 4Q of this year. They have ample cash for a developmental stage company so investors won't have to deal with additional dilution while waiting for phase III results.

Watch for an update of Telcyta doublet and triplet results in a PR tomorrow.

Does simonetti get to keep his outstanding options after he quits? Often execs are forced to forfeit them.

But it's also plausible that if his outstanding options expire with his termination, then he may have wanted to exercise what he can now prior to his departure, and then he can sell after he leaves the company. I assume that at that time, he would no longer be an insider and could sell without bringing attention to the company?

>Anyone know of a good list of trials coming due over the next year or so?<

Might be nice to put one together here. Controlled phase II and III studies would be of interest to me. The list could be updated as more data become available.

Some that I follow out of interest / curiosity:

DNDN in Q3 05: summer!

TELK in 1H 06: The company will announce earlier, in a PR, when the triggering events for the two fully enrolled phase III trials have occured. They will also then provide a timeframe for official data release.

CTIC in 4Q 05 to 1Q 06: There should be an interim review of their phase III trial for pixantrone.

re: gnta

For melanoma, they did not show an increase in overall survival, but did show a statistically significant increase in side effects.

For CLL, they routinely omit from their PRs that the time to progression for the Genasense arm was numerically inferior to the control arm. Luckily for them, the difference wasn't statistically significant. Again, they did show a statistically significant increase in side effects.

I think the melanoma application has a zero percent chance of approval. CLL has a 2% chance of approval, in my opinion. To top it all off, on a scale of 1 to 10, management rates a zero.

yes, it is poorly written.

however, i'm quite confident that they tested ~13K people and about a 1000 came up positive by the test, and 194 ended up actually having an ischemic stroke during the follow up period.

Here's the original work on it. GSK / HGSI have a couple of compounds in clinicals against this target.

N Engl J Med. 2000 Oct 19;343(16):1148-55. Related Articles, Links

Comment in:
N Engl J Med. 2000 Oct 19;343(16):1179-82.

Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group.

Packard CJ, O'Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GD.

Department of Pathological Biochemistry, Glasgow Royal Infirmary, Scotland. chris.packard@clinmed.gla.ac.uk

BACKGROUND: Chronic inflammation is believed to increase the risk of coronary events by making atherosclerotic plaques in coronary vessels prone to rupture. We examined blood constituents potentially affected by inflammation as predictors of risk in men with hypercholesterolemia who were enrolled in the West of Scotland Coronary Prevention Study, a trial that evaluated the value of pravastatin in the prevention of coronary events. METHODS: A total of 580 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or a revascularization procedure) were each matched for age and smoking status with 2 control subjects (total, 1160) from the same cohort who had not had a coronary event. Lipoprotein-associated phospholipase A2, C-reactive protein, and fibrinogen levels, and the white-cell count were measured at base line, along with other traditional risk factors. The association of these variables with the risk of coronary events was tested in regression models and by dividing the range of values according to quintiles. RESULTS: Levels of C-reactive protein, the white-cell count, and fibrinogen levels were strong predictors of the risk of coronary events; the risk in the highest quintile of the study cohort for each variable was approximately twice that in the lowest quintile. However, the association of these variables with risk was markedly attenuated when age, systolic blood pressure, and lipoprotein levels were included in multivariate models. Levels of lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase), the expression of which is regulated by mediators of inflammation, had a strong, positive association with risk that was not confounded by other factors. It was associated with almost a doubling of the risk in the highest quintile as compared with the lowest quintile. CONCLUSIONS: Inflammatory markers are predictors of the risk of coronary events, but their predictive ability is attenuated by associations with other coronary risk factors. Elevated levels of lipoprotein-associated phospholipase A2 appear to be a strong risk factor for coronary heart disease, a finding that has implications for atherogenesis and the assessment of risk.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_...

It's probably because the test gave 1006 "positives", and 194 of those positives had the predicted ischemic stroke at follow up. The remaining 812 did not have such an episode during the follow up period. They later went on to correlate the levels of lp-lpa2 in the 1006 patients and saw that the lucky 194 had generally higher levels than the 812.

I used to own inkp. I think that is one of the better examples of management putting their money where their mouth is... when their initial sales of Visicol lagged due to proctor & gamble's lolly-gagging, the stock took a major hit. But the CEO and a few other upper management types put hundreds of thousands into market purchases and told investors they would right the ship. They're now profitable, if I'm not mistaken. They don't get much a valuation premium from the market because they have absolutely no pipeline to speak of because their only other developmental drug is designed to cannabilize their existing seller.

and so it goes...

OT: Microbe!

I guess the net is relatively small after all.

Things are fine. Will be moving in August to start a new position. I hope the south is treating you well!

The new Iressa label (or should I say "no label") basically weans patients off the drug. If you've been taking Iressa, then you're allowed to receive refills; otherwise no on-label Iressa for you. The door is left open for clinical trials. Although some point to Iressa as an example of the FDA's failure to properly police drugs, I think it is a textbook example of how subpart H should and does work.



AstraZeneca Announces US Label Change for IRESSA(R) (gefitinib) and New Distribution Program
Friday June 17, 10:29 am ET

WILMINGTON, Del., June 17 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE: AZN - News) announced today that after discussions with the U.S. Food and Drug Administration (FDA), the company is making a labeling change to IRESSA® (gefitinib tablets). Based on the FDA's assessment of currently available data, including the lack of survival benefit in the Phase III Trial 709 (ISEL) comparing IRESSA to placebo in advanced recurrent non-small-cell lung cancer (NSCLC), and the availability of other treatment options in the United States that do prolong life, the revised label indicates that IRESSA is only to be used in patients who have previously taken IRESSA and are benefiting or have benefited from IRESSA. In addition, IRESSA will continue to be available for use in clinical trials approved by an Institutional Review Board (IRB) prior to June 17, 2005. Clinical trials approved by an IRB after June 17, 2005, must be conducted under an investigational new drug application (IND). To implement the new label, as of September 15, 2005, AstraZeneca will initiate the IRESSA Access Program to fill renewal prescriptions for IRESSA through a single mail order pharmacy for patients meeting the criteria set forth by the label. IRESSA will remain available in the United States, through the IRESSA Access Program, for patients who are currently benefiting or who have benefited, pending availability of new data that would support an additional revision to the label, or possible future withdrawal. Approximately 4,000 patients currently are taking IRESSA in the United States.

"AstraZeneca and the FDA have worked diligently to ensure uninterrupted access for existing patients in the United States who are benefiting from IRESSA. Current patients should be assured that their access to IRESSA will continue with this program," said Dr. Judith Ochs, oncologist and Senior Medical Director for IRESSA in the United States. "The label change now clarifies which patients the FDA believes should receive this drug and the IRESSA Access Program ensures that only those patients will be able to get the medication."

Patients taking IRESSA as of September 15, 2005 may continue to receive IRESSA and will fill prescription refills through the IRESSA Access Program after required patient and physician forms are filed. After September 15, 2005, no new patients will be allowed access to IRESSA unless they are part of a clinical study approved by an IRB prior to June 17, 2005 or they are part of a clinical study approved by an IRB after June 17, 2005 that is conducted under an IND. The updated label and information on the IRESSA Access Program, including enrollment forms, are available by calling AstraZeneca at 1-800-601-8933 or via the web at http://www.Iressa-access.com

IRESSA is approved in the United States under accelerated approval by the FDA (sub-part H) that enabled the drug to be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product had an effect on a surrogate end point likely to predict clinical benefit in a serious or life threatening illness for which there is an unmet medical need. The Phase III study called ISEL, or trial 709, released in December showed that IRESSA did not produce a statistically significant survival advantage over placebo in patients with advanced NSCLC.

AstraZeneca is continuing to evaluate potential predictive biomarkers to better identify more readily those patients who are most likely to benefit from IRESSA. AstraZeneca is committed to continuing IRESSA research and to validating the emerging science in controlled clinical trials.

About IRESSA

IRESSA is currently approved in 36 countries. IRESSA is approved in the United States under sub-part H for use as monotherapy for the continued treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after failure of both platinum-based and docetaxel chemotherapies who are benefiting or have benefited from IRESSA. For other patients, in light of positive survival data with other agents, physicians should use other treatment options. The effectiveness of IRESSA was initially based on objective response rates. Subsequent studies intended to demonstrate an increase in survival have been unsuccessful.

The most frequent drug-related adverse events associated with IRESSA were diarrhea (48%) sometimes associated with dehydration, rash (43%), acne (25%), dry skin (13%), nausea (13%), and vomiting (12%). These events generally occurred within the first month of therapy and usually were mild to moderate. 2% of patients stopped taking IRESSA due to an adverse drug reaction. Infrequent cases (about 1%) of interstitial lung disease (ILD - described as interstitial pneumonia, pneumonitis, and alveolitis) have been observed in patients receiving IRESSA. Approximately 1/3 of the ILD cases were fatal. When ILD occurred, it was often accompanied by acute onset of breathing difficulty with cough or low-grade fever requiring hospitalization. IRESSA may cause fetal harm if administered to a pregnant woman. Asymptomatic increases in liver enzymes and eye irritation have also been observed in patients receiving IRESSA. Increases in bleeding events have been observed in cancer patients taking warfarin and IRESSA.

http://biz.yahoo.com/prnews/050617/phf011.html?.v=14

> a biotech company focusing on oxidized glutathione for use in fighting cancer and hepatitis<

This is an absolute scam. Oxidized glutathione will just react with proteins in the blood stream and be neutralized. Or if it gets into the cell, it will simply be reduced by the equivalents that are abundantly available. Plus, the downstream effects of oxidized glutathione is often to impair normal protein function, and it is rather nonspecific.

>But seriously, what do you do when a biotech rises by 80% in just 2 weeks on no news<

Makes me think there is a financing coming. Do they need cash imminently?

DNDN's advantage over AGEN is at the leukapheresis vs. tumour resection stage. The latter can obviously be problematic. If that step goes swimmingly, then AGEN's technology becomes easier to produce / replicate.

But since both require that you re-introduce a biological that has been processed ex vivo back into the patient, both have equal QC hurdles, in my opinion. Perhaps DNDN has just a slightly higher hurdle at reinjection time since they're reinjecting relatively larger volume compared to AGEN and have to pay closer attention to pH / salinity; but it's far from an insurmountable task.

In my opinion, CEGE's GVAX is the easiest to prepare and ensure QC.

You have to wonder that if the onset of the vaccine's effect is slower than competing antibody / small molecule drugs, then do the vaccine's have any shot at treating cancers other than prostate and breast?

To briefly add to Dew's comments:

Stay away from ISIS.

>If I'm 50 years old, and I know that with a simple blood test I can determine whether I have a predisposition to develop AD based on a test that is 90% accurate, would I "elect" to have the test performed?

I know what my answer would be.<

And what if it gives you a false positive?

Unfortunately I've not had any interaction with Dr. Young, so I can't offer an insight into his particular interest in this therapy. I do notice that he has not been the type to indiscriminately run trials for any drug that hits his desk... so maybe he personally sees something very worthwhile in Vasogen's approach?

i have the JACC paper on celacade if anyone wants it.

poorgradstudent@yahoo.com

oh wait... you guys aren't subscribers are you? Maybe I can't share...



j/k

It's an integrated effect.

One of the hypothesized downstream consequences of the inflammation can be a remodeling of the heart. CHF patients tend to undergo a gradual remodeling, so the ability of this therapy to shut that off would have a discernible effect on the EF.

But otherwise you're correct insofar as the therapy having an effect to reduce plaque rupture. The premise being that the plaque sites offer a pro-inflammatory signal that can recruit additional macrophages which tend to eat up oxidized lipoproteins, swell and sit in the vessel as a fatty streak.

I think the authors may have been thinking along the lines of an integrated cardiovascular response to this therapy because the primary endpoints were treadmill and New York Heart Association classification; both are reflective of overall cardiovascular health (vessels + heart). All cause mortality and hospitalization were secondary endpoints, presumably because the study was not large enough to reasonably predict, beforehand, that a statistically significant outcome in these endpoints could be obtained. My bet is that they were relatively surprised with the mortality outcome

Well, the paper admits that the method is a little haphazard. The concept that you can get a homogenous response from whole blood exposed to UV rays and oxidative stress may be a point of discussion.

Theoretically, the technique suggests that you can create an anti-inflammatory cytokine response using this method. However, in the JACC paper none of the cytokines that they measured in this trial were significant between the treatment and placebo arm. So that raises the question whether or not the method is working in practice as they think it is in *theory*.

The paper defends the absence of a specific effect on the circulating cytokine levels by suggesting that the levels in the blood are not reflective of the levels in the tissue (where the action is). However, using an intramuscular injection, it is hard to see how the cytokines take a purely tissue route to get to the vessels and the heart itself.

The concept of inflammation being important in the etiology of heart disease relates more to the infiltrating cells in the myocardium releasing pro-inflammatory cytokines. This method would not stop that signaling, as far as I understand. Also, the absence of an effect on the ejection fraction is troubling. The ejection fraction along with the treadmill test (not different between groups) were the two measures that best reflected a direct treatment effect in this trial.

Some things drive me nuts...

>The study showed a significant reduction in mean QTc interval of 18 milliseconds (msec) among assessable patients in the Celacade™ group (n=20), compared to an increase of 12 msec in the placebo group (n=15), resulting in a significant between-group difference at the end of the study (429±45 vs. 463±45 msec, p=0.035).<

Ok, so a total of 73 patients in the trial, yet only 35 were assessable on an EKG? Only 35 of the 73 patients had chests?

Makes you wonder...

>this vaccine is directed against not a tumor but against a hormone; and, it is derived from a bacterial host (think maybe goats ? - no?) not a chemical synthesis.<

The Aphton product was directed against GnRH, just as the YMI product.

As for its origin, I don't think it matters much if it is bacterial or chemical synthesis. Both would be highly purified and neither would be post-translationally modified.

Hey, perhaps they got this from Aphton? Biotech garage sale?

I'd be careful with this vaccine for a couple of reasons:

1) They don't provide any indication of the magnitude of the immune response. I've been a broken record over this point, but a company saying that the patients have developed anti-vaccine antibodies isn't useful without a titre (an indication of the magnitude of the response).

My personal belief is that companies don't regularly provide these data because, when available, they are demonstrably weak when compared to the immune responses seen for conventional vaccines.

2) Aphton tried this anti-GnRH vaccine strategy but they dumped it in favor of their gastrin vaccine... which flopped monumentally. Hard to see a fundamental reason why the vaccine would work much better this time around.

No prob! Since I don't follow dndn too closely, I thought it was something that I missed yet again.

Time to listen to Telik's earlier CC...

I didn't catch anything in the dndn press release that suggested an actual reduction in PSA. Was it in the UAU abstract itself?

>2) As many patients (5) showed an increase in PSADT >12 months as showed no response.<

I thought this was a curious sentence in the PR regarding PSADT > 12 months. I guess 12 months is just a landmark timepoint that DNDN chose to emphasize. However, this 12 month metric is not that useful when we don't know what the number was at the start... did they go from PSADT of 6 months to 12 months or from 10 months to 12 months?

Also, the 5.2 to 7.9 months values I presume are medians, but I can't be sure. Anybody have further details?

I was just adding some color to the discussion about the benefit guidelines that are used to model trials.

I'd suspect that oncology trials with HRs less than 1.2 will garner ODAC discussion at the least, regardless of statistical significance.

The FDA generally doesn't like to design pivotal oncology trials around a HR less than 1.30-1.33.

Can you name anymore?

Couple of thoughts in this regard:

1) For the trial looking at first line use of Tarceva in any stage IIIB / IV patient, i think the results look good and comparable to the front line Taxol / carbo doublet (disregarding Avastin at this time). Taxol / carbo offers ~25% response rate with 10 months PFS and 4.5 months TTP. The Tarceva data's response rate compares, but the TTP / PFS (let's assume they're the same thing) comparison appears to favor the doublet. The nice thing is that this Tarceva trial hasn't reached median survival yet with a minimum follow up of 10 months. That suggests to me that you have equivalence with a large safety margin.

They need to get on Roche to run this trial in Europe. Doesn't sound like you could run this in the US.

It also looks from this data that schedule of administration for EGF-R inhibitors with chemo in front line is very important (stating the obvious). The median survival in this trial, albeit a small trial, looks no different than the standard doublet or the failed tar + taxol + carbo triplet. I hope that has raised some flags at OSI.

2) For the front line data in 70+ year old patients, I think they need to push this hard by themselves. I know from personal experience that for this age group, chemotherapy for some is absolutely no option. They can ethically run this trial in the US for older patients who refuse chemo, probably against a best-supportive care arm. The results from this trial would also give them an angle to support their filing in the front line setting for an unselected population of first line NSCLC patients. If you can show a large data set of 70+ year olds (200-300 patients) on monotherapy Tarceva that have the same median survival as unselected NSCLC patients on Taxol / carbo, then a good clinical development team should be able to get a green light, or at least a very clear road map to approval from the FDA powers-that-be.

In the near term, I think Goddard needs to do a better job of spelling out their strategy to the investment community. I think he sounds somewhat childish in these CCs where he's always telling investors how Tarceva's results are better than this or that trial. They're seeing good penetration in 2nd line NSCLC, and they have 2 strong partners that they need to take advantage of when communicating the Tarceva development plan.