If I were a bit more cynical, I would have said J&J's early unblinding has a little bit to do with trying to avoid introducing a confounding variable, (off-label) cabazitaxel usage, which introduces an unknown to the trial (like the discussion we are having here).
However, I know that pharmaceutical companies are like angels. So I know that early unblinding had nothing to do with that.
Good post. I don't expect huge advantage in OS from abiraterone either due to the size of the study - they didn't expect huge advantage by designing such a big trial. Cabazitaxel trial has active comparator chemo mitoxantrone and prednisone while abiraterone trial comparator is prednisone only. Thus same number of MOS advantage is not equal.
Closely watch both MOS data and AE profile as well.
About abiraterone: I thought a little bit more about the interaction of OGX-011 (first line) and abiraterone.
Since the abiraterone trial got unblinded early, the p value is <0.0096. The trial got unblinded about 16 months after the last patient got enrolled. So the trial did not get unblinded that early. Cabazitaxel detected about 2.4 months difference in a similar (not the same) patient population with lower p value. http://products.sanofi-aventis.us/jevtana/jevtana.pdf . Since this trial was 50% larger (powered to detect even smaller differences than cabazitaxel trial), I dont expect the OS difference to be that different.
I expect 50% of the patients in the OGX-011 study to have ketoconazole before taxotere. (This figure was 50%+ in abiraterone phase 2 trials) which reduces the OS advantage of abiraterone.
So even if the OS advantages of OGX-011 and abiraterone are exclusive (for which I see no reason) or there is an inbalance (for which I see no reason as well) of post study usages, based on phase 2 data, OGX-011 might compete head-to-head with abiraterone making it still a solid investment.
We'll learn more about it in October.
About NSCLC: I agree. However, the Phase 2 NSCLC was not randomized. Even though as you said there would be fewer enrollment and marketing uncertainties, it's a riskier investment.
I still believe in 2-3 years, before the results are announced, the market cap of ogxi will be substantially higher based just on CRPC. In the meantime, let's see how low this will go.
It was a good format, and he did spend a lot of time talking about how OGX-011 should work well in combination with Abiraterone. Now if only Teva would commit to running a trial like that after Abiraterone is approved it would give OGXI's pps a much-needed boost. I assume they'd have to do a P2 trial initially, but if it's big enough and randomized maybe it could be a P2b trial and qualify for registration.
Meanwhile it would be nice if Cormack could report some progress in developing the protocol for the lung cancer trial. We haven't heard much about that in awhile. I don't think there have been as many new breakthrough drugs in that indication as in prostate, so there would be fewer enrollment and marketing uncertainties. Presumably we'll get an update before the end of the year.
>Hopefully, Cormack can address this concern head on
He did. mr_ssssamsa was right about preclinical OGX-011 studies in this regard.
He also addressed (not to my 100% satisfaction; but this was the best explanation I ever heard) how we can reconcile lack of response, tumor shrinkage, PFS with OS advantage.
The format of this conference was much superior to other conferences. The replay of this conference is highly recommended.
You make some good comments.
1. Every organization - public or private - needs confidentiality to carry on its competitive activities. Hopefully, Cormack can address this concern head on, and that doesn't mean getting into specifics if competitive risks are involved. It may be simple enough to say JNJ's tests do not represent a challenge to the tests that are being conducted by OGXI, or, if so, plans have been put into place which won't jeopardize the results or timelines.
2. All businesses to some extent are tax funded - look at the payments by the State for education. Companies profit from these expenditures. Biotech is a good example of the synergies of government and private funding - look at OGXI for example. It is a spin of from UBC.
Maybe the new economy is less about private v. public and more about how the two systems can work together to produce a better quality of life. Or maybe I'm just a Canadian.
But HP isn't taxpayer-funded. Although it probably is, to some degree -- the Defense Dept seems to throw money at almost every major high-tech industry and then just lets them keep the profits from whatever products result.
Biotech is a perfect example of how the "free market" usually functions when it comes to new technology. Taxpayers fund most far-out biotech R&D, either directly through agencies like NIH or through grants to universities and small companies. The few compounds that show enough promise to get into phase 1 and 2 are then funded by more government grants and by small investors like us. The small subset of those products that make it into phase 3, where the risk is substantially reduced, are then scooped up by big pharma which reaps most of the profits. The taxpayers get a tiny royalty, if that.
But that's a discussion for a different message board. Let's hope Cormack doesn't invoke state secrecy tomorrow when discussing how abiraterone will affect the P3 trials for OGX-011.
So what does this mean for OGX-O11? JQ? Summer? Anyone?
My own layman's take is that it could make it harder to recruit patients for the second-line pain palliation trial, since the patient population -- people who've progressed following treatment with docetaxel -- is the same as the one in the Abiraterone trial, and that population may now prefer being treated with Abiraterone to enrolling in the OGX-011 trial. Enrollment in the 0GX-011 trial began a few months ago and Abiraterone probably won't be on the market for at least 6 months and probably longer, but still, Cormack said awhile back that enrollment in this trial was likely to be slow. Maybe he'll say in the presentation this Wednesday that OGXI had made contingency plans for this, as MDVN claims to have according to that statement Jet posted.
In theory, Abiraterone's success shouldn't have a big impact on the size of OGX-011's market if its second-line trial succeeds, since Abiraterone isn't a cure and patients eventually stop responding to it, so at that point their only option may be another cycle of chemo accompanied by OGX-011. But after a first round of chemo followed by Abiraterone, who knows how many patients will want to undergo another round of chemo?
The Abiraterone result doesn't seem to have a direct impact on the OGX-011 first-line trial, since Abiraterone won't be available (at least initially, unless it's used off-label) for that patient population. I suppose it could complicate the survival analysis, if the number of the patients in the OGX-011 + docetaxel arm who later go on to use Abiraterone is different from the number in the docetaxel only arm who do.
Again, thoughts anyone?
Good questions. I dont know the answers as we have little info about abiraterone and it doesnt seem like this will change till October.
>that population may now prefer being treated with Abiraterone to enrolling in the OGX-011 trial
Correct. However, my understanding is that patients after failing docetaxel, will unfortunately fail following Abiraterone as well.
>it could make it harder to recruit patients for the second-line pain palliation trial
This may not be true. Since Abiraterone, as opposed to cabazitaxel, is not chemo, I see no exclusion criteria in teh second line trial of OGX-011 for the patients who failed Abiraterone to become eligible again (after 28 days) for trial. Thus, I am not sure if availability and approval of abiraterone would effect the enrollment of the second line trial significantly.
>But after a first round of chemo followed by Abiraterone, who knows how many patients will want to undergo another round of chemo?
Possible pain palliation (with potential OS advantage) is a major incentive for a patient who ran out of options.
>The Abiraterone result doesn't seem to have a direct impact on the OGX-011 first-line trial, since Abiraterone won't be available (at least initially, unless it's used off-label) for that patient population.
Assuming http://clinicaltrials.gov/ct2/show/NCT00887198 also succeeds, the correct course of action for the patients seems to try all antiandrogen therapies including Abiraterone before chemo. Thus in the long term, availability of abiraterone should not impact OGX-011.
>I suppose it could complicate the survival analysis, if the number of the patients in the OGX-011 + docetaxel arm who later go on to use Abiraterone is different from the number in the docetaxel only arm who do.
As an investor, as the study is open label, that's also my major concern.
However, abiraterone is just an antiandrogen therapy. Ketoconazole, a drug that is currently widely used off-label as a hormonal therapy, was a major exclusion criteria for Abiraterone trial and Phase 2 studies of abiraterone showed significantly less effect if the patients were treated with ketoconazole first. Would the abiraterone trial have succeeded if it were head to head against ketoconazole? I dont know. So what percentage of the the patients who sign up for the first line trial would have Ketoconazole first? I dont know. I am sure they have this data from the Phase 2 trial. Phase 2 trial required the patients to discontinue antiandrogens. Will they add a similar clause to phase 3 study? I dont know.
>Maybe he'll say in the presentation this Wednesday that OGXI had made contingency plans for this
Im also sure they are at least aware of the issue. Taking corrective measures for a trial not yet started should be easier to take than for a trial already underway. However, I dont know what corrective measure they can take (if there is a need) except for praying the first line abiraterone trial to succeed as soon as possible.
I am sure we will hear a good discussion of this soon in the CCs. If I am not satisfied with the answer, I will reduce the rate of my accumulation of this stock or I would stop it. Till then, I trust that they are clever people who think about this more than I do and they want these trials to succeed at least as much as I want.
I would expect that OGXI anticipated positive results for Abiraterone and proceeded with trial design based on assumption that such positive results would not impact on chemo combo trials. But you may be right and Cormack might address that issue this week in Boston.