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The problem with probabilities assigned to a single incident is that someone can never know whether he/she was right based on the outcome of that incident alone.
I was not surprised to see SYNERGY fail but I was really surprised to see OGXI down this much. If everybody expected the trial to fail, why did it drop this much?
After the detailed analysis, I now expect TEVA drop OGX-011 after a compensation agreement with OGXI ($20-30M). At this valuation, I don't know if that it a good thing or bad thing.
I also expect OGXI partner OGX-427 asap. Something similar to what THLD did.
The co raising money at $60M market cap would be suicide.
EXEL.
In the same exact indication, at similar (but not exact) # of events (387 of 578 vs 305/365 of 511), cabazitaxel pivotal trial which met its study objective by showing a hazard ratio of 0.70 p < 0.0001 but also failed its interim.
OGXI
I agree with the title "Don’t Bank on OncoGeneX Phase III Data".
However, I would have agreed with the opposite title as well. "Don't dismiss/write off Oncogenex Phase III Data".
Even though I do not know the exact mechanism of action, I believe custirsen is an active drug especially after the SATURN trial.
$OGXI. A trial (SATURN) reaches stat. sig. (p=0.032, cox) and the co does not shout it from the rooftops. A first? pic.twitter.com/DOcm0uy8D0
— Summer (@Summer2762) February 5, 2014
ARQL
$ARQL
[Rearranged the post after I answered your questions in the order you asked. However, I think the last question is where the misunderstanding lies. So I moved it to the top.]
$ARQL.
I hope the ARQL and Daiichi can figure out the proper subset of patients for which Tivantinib works. It is not as simple as Met high vs Met low.
Remember that for Met low patients (at Marquee), we had
I havent read all the exchanges on this topic but it seems like the trenches are dug on the HD front and no one will be able to convince the other side through posts here.
To avoid a repeat of the same in AD, can you guys come up with what you would consider success AND failure in the AD trial. Something like, if xyz happens in the AD trial, I accept that PBT2 is active or placebo. Without that, we will see a repeat of HD.
This whole debacle in looking at the same trial results and seeing two different interpretations is the manifestation of a deeper issue in our society (what I called the lack of the Truth classes in the middle schools). Without that politicians will be able to convince public to go additional trillion dollar wars with selective evidence or companies will be able convince investors to waste billions in useless clinical trials.
So please, for your own sake, come up with your own primary end point BEFORE the AD trial results are announced.
Dew: Can you define success (or failure) in AD?
While we are at it, can anyone (especially someone who thinks that the HD was a success), tell me what a failed HD trial would have looked like without introducing safety and tolerability issues?
Maybe. At least I should have listened to my own advice and bought PRAN. Never underestimate the power of data torturing and the desire of a P2 company to stay alive.
I think we need to teach statistics (not the math but the essence) way earlier (middle school) to kids. They need to learn whether to arrive to a conclusion after being "presented" with facts. I would call this class "Truth 101".
I think this is the most important issue we face as a society as marketers (including politicians) now mastered how to present selected facts to convince people. After everyone takes Truth 101, we can then introduce federal level referendum to reduce the power of the congress and thus lobbying.
The funny thing is that PRAN may still continue to go up to AD and even after AD. It's a shame but it might.
Comparing my PR draft to the actual PR. I think I did a good job. :)
Theirs:
- Primary endpoints of safety and tolerability met.
- Secondary endpoint: Statistically significant improvement in a measure of executive function (cognition) in research participants administered 250mg PBT2 daily (p=0.042).
- PBT2 250mg was also associated with a favourable signal in functional capacity.
- Preliminary evidence suggests PBT2 250mg reduced atrophy of brain tissue in areas affected in Huntington disease, seen in a pilot imaging sub-study.
- Company plans to advance PBT2 to a confirmatory Phase 3 clinical trial.
Mine was (after filling the endpoints and p values):
- The primary outcome (safety and tolerability) met. [Near word by word match].
- Also, even though the trial was not powered to show efficacy, <executive function (cognition)> reached statistical significance (<p=0.042>) for <250mg arm>. [Near perfect match again].
- Furthermore, <functional capacity, reduced atrophy of brain tissue> were close to reaching statistical significance for <250mg> <insert the p values less than 0.2>. [I thought there would be 3 or 4 such endpoints. They PR'ed only 2 endpoints]
- We are very excited. These results show that Pbt2 is an amazing drug. [I seriously thought they'll say that they are taking PBT2 to phase 3, but I just laughed at the thought. So not a complete match but close.]
OGXI. Not publicized ASCO GU Paper.
At ASCO GU, there was a paper about the canceled SATURN trial.
http://abstracts.asco.org/142/AbstView_142_124097.html
There were a total of 14 patients and
> Their only cost for the complete purchase would have their LT tax liability for the sold shares.
Aren't they in the hook for the tax liability this year (not when they sell)?
>I would wager that it’s less than 2%
That would have been my guess. However, about 2/3 of exercised & held options are options that would not have expired for another 4yrs. See table 5 in the same paper.
Furthermore, time-value or how much the option was in the money is not strongly correlated to positive insider info. However, the opposite seems to be true for negative insider info in case of a exercise & sell.
The authors of that paper also have the following interesting discussion about why someone would exercise and hold:
Re: ENTA. How long does an executive have to report a sale?
Does anyone know if the following statement is correct?
"by selling within a month an executive need only file one report of trades with the SEC" **
Incidentally, that paper agrees with the sentiment that this is a bullish sign.
About 30 percent of option exercises are followed by no share sales within thirty days. Partitioning the option exercises on whether the shares are sold within thirty days, “keep-all” if no shares are sold and “sell-all” if all shares are sold, we found strong evidence that the keep-all sub-sample is associated with positive private information, and weaker evidence that the sell-all sub-sample is associated with negative private information.
** http://www.anderson.ucla.edu/faculty/david.aboody/AbHuLiSu.pdf
>Regardless of Luly’s motivations
Can this indicate that there will be a proxy fight and he needs the share count even though 250K is not a lot?
I think you misunderstood my point. What you describe is one definition of success. It is not the only definition. With 7 endpoints and 3 arms and no clear definition of success, how can this trial fail? If it cannot fail, how can it succeed?
Try to write a failure PR. You'll see that it will morph into one of two cases I wrote.
From investment point, investing for the HD trial seems to be a good idea just because the trial "cannot" fail. 21 nearly independent chances of statistical significance for the price of one is a good gamble. I think.
If Pbt2 is/were placebo, the probability of the Huntington trial "succeeding" is 41%.
I can visualize the first paragraph of the PR announcing the results of the trial: Either
a) [>41% probability] The primary outcome (safety and tolerability) met. Also, even though the trial was not powered to show efficacy, <insert a secondary endpoint> reached statistical significance (insert the p value) for <100mg or 250mg arm or "when both arms combined">. Furthermore, <insert 3-4 secondary endpoints> were close to reaching statistical significance (or also reached statistical significance) for <insert arms> (insert the p values less than 0.2). We are very excited. These results show that Pbt2 is an amazing drug.
b) [<59% probability] The primary outcome met. Also, even though the trial was not powered to show efficacy, <insert 2-3 secondary endpoints> were close to reaching statistical significance for <insert arms> (insert the p values less than 0.2). Furthermore, for subgroup of patients, <insert subgroup such as those younger than than 70yrs>, <insert a secondary endpoint> reached statistical significance (insert the p value) for <insert arm>. We are very excited. This result shows that Pbt2 is an amazing drug. However, we wish we had more more secondary endpoints and/or arms so that we could issue a PR like the first.
In my limited experience, Phase 2 trials from single drug companies very seldom fail.
PS. My estimate of 41% is based on 21 independent trials (7 x 3) assuming placebo vs placebo each with 2.5% chance of success. In actuality, it is slightly less as "both arms combined" is somewhat dependent to the chance of success in each arm.
Congratulations. Thanks for doing the research and recommending ENTA.
I know I will most probably regret this but I sold most my holdings today. Hopefully, it will reach or exceed your $66 target.
Thanks again.
Was it ever revealed why/how DNDN got away after disclosing the interim HR? Was there a non business related reason to disclose the interim HR?
Tracking the clonal origin of lethal prostate cancer
Even though the processes and the conclusions are hard to generalize, this is a very intriguing paper.
http://www.jci.org/articles/view/70354?key=4f436390394081ee2a50
Especially the following result
Re: MDVN HR vs Median
The page to which you refer puts the OS medians of the prechemo Zytiga trial as 35.3m vs 30.1m. That's a reminder that we (as investors) should always look at the KM graphs.
For example, the 35.3m median in that trial is due to a single patient. See page 21:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202379s007lbl.pdf
The issue is the way the median is calculated from the KM curves. IMO, KM curves, from which Hazard Ratios are also derived, do not estimate the true shape of the curve when the number of patients is limited which is usually the case towards the maximum followup period because the method that derives the KM curve is memoryless. It does not remember the shape of the curve on the left to estimate the right side and then uses linear lines to fit the curve. For example, based on that KM, @36m the ratio of patients to be alive on both arms is 0% which is most probably not correct at all.
A non linear curve fitting before numbers are extracted should generate better estimates for medians or any other derived data. For example, a better estimate for the median OS for both arms would be 29m vs 33m for the Zytiga trial.
IMO, Hazard Ratios are also inadequate (for patients) for yet another reason. HR puts as much emphasis to early survival as late survival. This is going to be speculative but, IMO, late survival (tail end) is more important than the median or HR (e.g., the ratio of patients alive after say x years should carry more weight than what happened early in the trial).
Anyway this is not yet another philosophical post but a reminder that we (as investors) should always look at the KM curves before investing using data derived from those curves.
Probably you are right.
However, prednisone in prechemo setting might be slightly more beneficial than we believe it is. Here is one trial that I'm familiar with.
http://files.shareholder.com/downloads/SNUS/2298119926x0x602114/836c4017-26fd-4180-bbfd-c25ef8ed6681/ESMO%202012%20Poster%20FINAL%20OGX427%20CRPC.pdf
The control (prednisone only) patients in that trial:
21% had >50% PSA response
41% had >5 to <5 CTC change
For post chemo, the effects seem less. In the post chemo Zytiga trial, 10% (6%) of the prednisone patients had >50% PSA (confirmed) response vs 4% (2%) for placebo in enzalutamide post chemo trial.
However, based on the info in the CC and other factors you and others identified, I think it is due to the combination of both factors and not prednisone alone.
Re: MDVN
I just listened to the CC. I still cannot believe that some of the analysts on the call do not have basic statistics knowledge (e.g., how the median is calculated even though 1/2 of the patients are still alive).
I always believed that some of these guys were "fraud" but I never thought they would be this clueless as well.
Based on the CC, another contributing factor of the the lower control arm rPFS is the inclusion/exclusion criteria related to visceral disease.
Re: MDVN rPFS
I'm confused about why being able to assess the MET status has a positive impact on HR.
Considering that HR of MET status not assessable is near stat significant (lower CI = 0.92), I would like to see the HR of MET status assessable vs MET status non assessable.
I can think of various reasons why not being to assess the MET status might be associated with lower OS but I could not think of an obvious correlation to justify the bias in favor of Tivantinib.
Any idea?
Thanks for the link. Do you have a link to the other critics of this trial?
Also, as I just posted to twitter, I do not understand how on earth did they came up with 35% after they state they assume HR=0.8. A 2:1 trial with 578 events with HR=0.8 is 75% powered. Did they just assume 50-50 after all the calculations? Very scientific.
20% dropout in an OS trial? How?
Re: ICAD
Does anyone follow this co? A radiation oncologist friend is excited about the potential of Xoft eBx system for the treatment of certain types of skin cancer.
I never invested into device companies before. So I am a little bit reluctant.
Any insight?
Yet the pps manages to lose ~5% on this news (of yet another (investigator sponsored) trial).
If my math is correct, Fidelity, which was liquidating its OGXI holding for the last year, is done (today) or about to be done (later this week).
It was depressing to be an OGXI investor for the last two years. Hopefully, this is the bottom.
I still do not understand why the stock prices go up before the trial data. I had a working theory related to interaction of the stock price and options. However, PRAN does snot have options.
The only other theory I have remaining is that this is a positive feedback loop that has something to do with human psychology.
I know I asked this before before but I cannot be the only one interested in finding the cause of this phenomenon. You guys have way more experience than I do. I am sure you also wondered why this happens.
Or did you guys find the reason and silently caching it?
Dew: Thanks for the recommendation. I pulled the trigger on Friday. I appreciate the time and effort you put into this. Thanks again.