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Et tu, biotech values? I guess there is no escape from this today.
I dont understand how/why building these tubes is 10x cheaper than a building rails. My estimate would have been 10x more expansive to build and maintain as the tubes are active and curves need to be smoother (thus substantially more expensive) to accommodate higher speeds.
Otherwise, I thought it contained some clever ideas.
You might be right. However, using the term "substantial improvement" when HR=~0.9 and then "equivalent" when HR=~1.1 for the same endpoint (OS) in the same trial, should be, at least, frowned upon if not the deliberate cause of my confusion.
If the HR for ITT is 0.9 and HR for c-Met- = ~1.0 (no detrimental effect for c-met low patients), the HR for cMet+ needs to be less than amazing no matter what the co hints at this moment.
For ITT, I predict HR=~0.9, p=~0.3.
I had this post a while ago about what I think will be presented for ITT.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=88200973
However, I am quite confused about why Daiichi Sankyo did not let ARQL soften the blow of a failure by presenting a peak to the subset data earlier.
Another real futility analysis.
It seems like this interim analysis was done when two-third of the expected deaths have occurred (426 events). https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-018662-23/GR
p=0.226 is Z=~-1.2. This is right at the the linear boundary at two-third between 0 and -1.96. It's really close.
This new trend of doing real futility analyses support the thesis that OGXI's futility analysis at 1/2 was also a real futility analysis. Same with ARQL.
Also, there was also another OGXI related PR yesterday.
http://finance.yahoo.com/news/oncogenex-announces-multiple-trials-progress-103000378.html
3 of the 7 P2 trials will be presented at ASCO
A) Abstract #TPS4588: The Borealis-2 clinical trial: A randomized phase II study of OGX-427 plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer (June 3, 2013)
B) Abstract #TPS8120: Double-blind randomized phase II trial of carboplatin and pemetrexed with or without OGX-427 in patients with previously untreated stage IV non-squamous non-small-cell lung cancer (NSCLC): The Spruce Clinical Trial (June 1, 2013)
C) Abstract #TPS5101: The Pacific trial: A randomized phase II study of OGX-427 in men with metastatic castration-resistant prostate cancer (mCRPC) and PSA progression while receiving abiraterone acetate (AA) (June 3, 2013)
Also 1 of 3 P3 trials will be presented at ASCO
A) Abstract #TPS5103: Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC) (June 3, 2013)
Re: OGXI
This trial is entirely funded by UK National Cancer Research Network and is entirely within UK. For a reason I am not entirely sure, UK is now pushing cancer trials as part of the treatment. I read somewhere there over 20% of all breast cancer patients are in a cancer trial.
Here I found a reference for the above number. (Correction: 25% not 20%)
http://breast-cancer-research.com/content/12/S4/S20
Thank you.
Assuming that the excluded 555 patients had no inherent bias, the futility analysis of the Marquee trial might have been a real futility analysis as all should be.
The most strict futility boundary I can think of would be a linear one (in z score). Even by assuming the IR person was mistaken (or lied) and the trial protocol was for p<0.01 from the powering info the co supplied (as opposed to p<0.05 as the IR person claimed), at half, that's about p>0.2. At 375 events, that's HR >0.9. Even I assume "substantial" improvement is really close to a statistically significant improvement. At about ~170 events, that's HR >0.8.
Thus, things might not have been as bad as I thought. However, still not so impressive either.
Caravon:
Thanks for sharing this. I also appreciate you giving them hard time as well.
Thanks again.
It seems like the co might have managed to pick the wrong primary endpoint (again). (This time it is not that important.)
I wonder how high the p value was to require its omission.
First, I did not mean that what TEVA is doing is wrong. I believe way too much money is spent on unnecessary trials. Continuing a trial as long is it is deemed unharmful (a la OBF) is not good for the spiraling health care costs. If the p value of the SYNERGY trial, after 250 events, is more than 0.3, it means that the HR is not going to be clinically meaningful. Granted that someone does not save a lot of money by shutting down a trial after the enrollment is complete just 12m earlier that the final analysis. However, these add up.
Second, in this specific case, I think TEVA would dump OGX-011 if the SYNERGY trial fails. So the money TEVA will save is substantial (2 more large trials that are still enrolling).
Third, as we discussed this before (under a general conspiracy theory umbrella). I think TEVA, on purpose, delayed the other two trials. Again, I dont think these were wrong decisions (for TEVA) and I have no proof for this behavior.
PS. Dew: Thanks for the correction.
Here is why I think this is important (rewrite of what I already posted at yahoo). Comments are appreciated.
Usually the efficacy + futility boundaries of a clinical trial are based on O'Brien Fleming which have futility and efficacy at the same time. OBF (and others, such as Pocock or Peto) futility is not a very strict one. It only tells us that the drug cannot be proven to be harmful rather than telling us whether it works or not. However, this situation might be different.
First, the current situation we have in is asymmetrical. We know that passed futility but there was no efficacy analysis. The upside was not limited as other interim analyses. So that's positive #1.
Second, from the powering data, I can calculate that the number of events for the Synergy trial is 500. It seems like my guess of futility+futility+efficacy+final was correct. So we passed a futility at 250 events. That's major because that's a lot of events. That's positive #2.
Third, the most important one for me, I think TEVA required this unusual design for the SYNERGY trial so they could have dumped OGX-011 as quickly as possible. So I'll say the futility boundary was not OBF but something erring on the "saving money" side. It was probably a more strict boundary. I'll say it might even be linear from Z=0 from the start of the trial to Z=-2 at the end of the trial. At half that's Z=-1. That's p=~0.3. So passing futility that might be telling us (at the extreme case) that the OGX-011 is not placebo with a 70% probability.
The last part is a lot of speculation from what I think TEVA would do and from the unusual SYNERGY trial design and the unusual (again) NSCLC trial design.
The truth (the futility boundary) is probably somewhere in between regular OBF and such a strict (unusual) linear boundary. That's positive #3. The most important for me.
I think the pps will appreciate considerably to the interim.
The major question mark I have is that I dont know the reason of the recent selloff. The seller might continue to dump into interim. I also dont know whether there will be dilution before the SYNERGY results.
Re: OGXI
The Synergy trial passed the second and last futility analyses. The efficacy interim analysis has not yet occurred.
http://finance.yahoo.com/news/oncogenex-pharmaceuticals-inc-provides-clinical-200100531.html
Re: OGXI (OGX-011)
I asked the following question to IR. Here is the reply. I thought the answer was very informative. What do you think? Does this answer make sense? (This is related to an long discussion in yahoo message boards whether the current sentiment about the SYNERGY trial is due to lack of (strong) (PFS) response in OGX-011 P2 in mCRPC)
Hi Susan:
What's the company's explanation while Phase 2 OGX-011 trial showed nearly statistical significant OS benefit, it failed to show a (strong) PFS or response benefit? I remember this being discussed 3 years ago but has there been any new information or a new line of reasoning in the last 3 years?
Hi Summer,
“Starting with response rates- classically in oncology we are trained to look at response rates in terms of tumor shrinkage. Response rates are designed to capture treatment sensitive patients whose tumor volume is decreasing as a result of treatment. Since clusterin overexpression is directly related to resistance, one would not expect to see a difference between the two arms (docetaxel vs. docetaxel plus custirsen) because these patients had not yet acquired resistance to treatment.
In our Phase 2, we had essentially the same number of PRs as docetaxel alone, as expected based on the MOA of custirsen. Importantly, we are looking for the lack of disease progression, as opposed to shrinkage, which was demonstrated as more patients on the custirsen arm had stable disease (77% vs 50%) and fewer patients on the custirsen arm had progressive disease (4% vs 17%).
Further, in prostate cancer, only about half of patients have measurable disease, so RECIST RR criteria are of limited value. Prostate cancer typically metastasis to the bone and there are no good means to assess change in bone disease. Scans are good to assess M0 (no bone mets) to M1 or greater (with bone mets). But, once patients have bone disease, scans cannot assess bone lesion shrinkage.
For PFS- Per protocol in the Phase 2 study, we did not treat patients to progression. Treatment was discontinued at 10 cycles or 6.92 months. Looking at the PFS curve, the two arms begin to come together shortly after therapy is stopped, which also corresponds with the natural history of time to progression in prostate cancer and the TTP that was seen with docetaxel alone in this study (6.6months). We can hypothesize that if you stop treatment at the time of natural progression, you are not going to have an effect on PFS, whereas if you treat to progression, you perhaps would see a difference.”
Best, Susan
Susan Specht
Director, Investor Relations
OncoGenex Pharmaceuticals
Re: OGXI (OGX-427)
Any comments on
OncoGenex Announces Plans for the Initiation of the Spruce Clinical Trial Evaluating OGX-427 in Combination with Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer ?
http://ir.oncogenex.com/releasedetail.cfm?ReleaseID=755884
The co now has 3 Phase III and 5 Phase II trials but very low enterprise value.
I remember some people having concerns about a non-targeted therapy. However, I think it is it still the anti anti-sense sentiment.
Re: OGXI
Today, Oncogenex reached a new 52wk low. The only reasonable explanation I have is that investors might be playing for an interim futility of the Synergy trial (011 mCRPC P3). Since 427 P2 interim data might be before 011 mCRPC P3 data, it's too early to play for a failure of the Synergy trial.
Disclaimer: Long Ogxi (but does not discount an interim futility)
Thanks for clarifying. The last sentence in your original post I replied to sounded to me that you dont anymore think there is any particular reason for MET inhibitors to accelerate disease in MET- patients. Thanks again.
I am slightly confused. Do you share (or do you not share) the reason suggested (by some others on this bboard) why ARQ197 failed the futility at interim for NSCLC and the primary end point for mCRC, which is while ARQ197 being active for c-met+ patients, it is detrimental to c-MET- patients?
Thanks for clarifying.
Congratulations and thanks. I would not have bought (and sold) it without your (and DonShimoda's) recommendation. Thanks again.
The only trial I could find that had a similar design was the PRECISE study.
This had futility, futility, efficacy, final at about 1/4, 2/4, 3/4 and 4/4 #of events.
This seems more logical than futility, efficacy, futility, final than I originally thought SYNERGY would have.
I miss the days OBF seemed complicated.
Re: OGXI / Synergy trial
The CEO today announced that there will be one interim analysis but 2 futility analyses. He refused to give any further info including whether any of these has happened.
I've never encountered such a trial. What would be a good guess for the # of events for each analysis? Any similar trial that comes to your mind?
Could all three be at different dates? Or is that already implied?
If anyone wants to listen, the cc is at http://leerink.metameetings.com/webcasts/healthcare13/directlink.php?p=103
@5:30min
Thanks
Other issues I heard: (1) crowded space: is there room for one more mCRPC drug? (2) obsolete phase 2 data: 4 new drugs got approved since the P2 trial ended (3) unfortunate timing: abi & mdv3100 will probably be used before chemo (4) open label phase 2: can we trust Open label phase 2 data? (5) shifting landscape: will/did the introduction of the new drugs while the trial is running effect the Synergy trial (6) open label phase 3: will/did the patients/doctors declare progression so that the patients can get the new drugs? (7) longer median OS than P2: how much more difficult is it for ogx-011 to show statisticaL significance against 20+m vs 16-m control arm?
Ps. I'm long into interim with the hope that this wont be a repeat of ARQL P3.
IR said that the co does not believe the analyses will be completed and QA’d in time for ASCO. Probably some point in the second half of the year the co will present them.
I was hoping before ASCO but since there was nothing major between now and then, I was assuming ASCO. I did not expect it to be after ASCO.
Re: ARQL
Does anyone have any idea when the co could publish/reveal the full results of the NSCLC trial? ASCO? Thanks.
It seems like you think 60mg will have substantially less AE and dose reductions with similar efficacy?? Tomorrow, I will check the % dose reduction in MTC trial.
PS. Thanks for the link.
You didn't answer my question.
Is it ethical for the patients who achieved PR/CR to be randomized to the placebo arm assuming that they gave consent 12 weeks ago?
From Dew's message, I sense that his answer will be no because he mentioned that PR/CR is strong evidence that the drug works for a specific patient.
From your message, I sense that your answer will be yes because you reduced the ethics question to a logic question and asked "which trial would you join if your goal is to get drug treatment?" Ethics has no role if the patient's goal is to get the drug. So your answer should not matter if I replace "PR/CR" with "SD" in the above question.
The above is my interpretations/guesses from your messages. I might be wrong. However, until you explicitly state your positions, discussing this issue is lost cause for me.
So, is it ethical for the patients who have PR/CR to be randomized 12 weeks later after their consent to the placebo arm?
Also, I agree with Dew. I am not sure about what we will achieve by discussing this in an investment board.
The previous question was a rhetorical/tongue in cheek question. I dont expect you to answer that. (I hope you dont). However, let me ask the following:
Is it ethical for the patients who has PR/CR to be randomized 12 weeks later (assuming that they gave consent)?
I am not asking if it is legal or this changes anything in the statistical powering of the trial. Is it ethical?
Because, at that time, it's the patient's choice.
If a trial requires patients with SD to stop a drug that is perceived by patients as the cause of the SD, it would require the consent from the patients when all the facts are known and not when the SD is not yet established until 12 weeks later.
Asking these patients to consent/commit to that the drug will be stopped 12 weeks before a fact is known is the unethical part especially when PFS is measured in weeks.