A little news: they've recently decided to expand enrollment in the SYNERGY trial from 800 to 1,000 patients. That obviously increases the statistical power and presumably Teva will pick up the added cost since (assuming they're not amending the partnership deal) OGXI's obligation for all 011 trials is limited to the $30mm they had already committed to spending. He said they still expect to complete enrollment this year.
He said they expect to begin enrollment in the P3 lung cancer trial for 011 "later this year."
He said they expect to provide updated data on the 427 P2 trial in prostate and P1 trial in bladder by year-end. I think Dr. Gleave in the recent ASCO panel discussion said they'd update at ASCO in the summer. I'm not sure either statement was intended as formal guidance so I don't know if anything has changed.
He reiterated that they plan to start a P2 trial of 427 in combination with abiraterone. He said they're often asked why they don't pair 427 or 011 with MDV3100 and said the reason is that it's not approved yet.
He said they have enough cash to last through 2013. In the past they've said it would last into mid-2014. I don't know if this is just a more conservative estimate or is meant to take into account the new 427 trial with abiraterone, which is partially but not completely grant-funded.
Another conference call tomorrow so maybe we'll learn a bit more about all of the above.
Thanks for explaining that. I thought Scott said they wanted to increase the "n" (as in number of patients) not the "end" of the trial. Which still begs the question of why they want to do it and raises the issue as you say of whether p needs to be less than .05.
I'd be very interested in whatever you hear from IR so please share if you can.
>Different topic: does the expansion of the SYNERGY trial from 800 to 1,000 patients change the likelihood that the trial will be halted at interim? I don't know if you have enough information to answer that, and there's no rush.
There are 3 primary reasons why the number of patients in a trial is increased midway through the trial.
1. DMC informs that the # dropouts is higher than expected (I doubt that's the case here).
2. to end the trial earlier than originally planned. If the co doesn't change the number of events (deaths in this case) required to end the trial (407) or reach the interim (271, my guess), then 1000 patients would reach the required number of events faster.
3. Increase the power (the probability that the trial will show statistically significant results) while keeping the trail duration the same. To do that the co actually needs to change the number of events required to end the trial not the number of patients in the trial. Say the co increased the number of events from 407 to 500. The trial duration would probably stay the same but the power would go up from 90% to ~94%). That also lowers the achieved alpha about which FDA cares a lot.
If that's the case and they might also the trick that MDVN did, the probability that the trial will be halted at interim goes up.
Scott's explanation @8:20 at BIO-CEO CC "increase (stutter) the end of the trial (and everything he says after)" is confusing. Actually, the "single trial" reference is simply scary. This is the second time he is hinting that that simply achieving p<0.05 would not be sufficient. I dont like this part at all.
I am planning to send an email to IR before the CC about this.
I'm still having trouble envisioning a 427+abi P3 when the safety and efficacy of the two drugs in combination have never been tested in a clinical trial. Who knows, maybe combining two agents that act on the androgen receptor will produce some unexpected negative effect, instead of the enhanced efficacy you'd think would result. But I suppose the same concerns would apply to running a P2 trial of 427+abi and OGXI plans to go forward with that. So maybe you're right, the main obstacle is cost. Is it worth it to J&J to spend $60mm or more on a P3 when the extent, if any, to which 427 adds to abi's efficacy and/or side effects is completely unknown? Maybe it is, since if the outcome is positive abi gets a nice competitive edge on MDV3100.
But as you point out, until the results of the abi prechemo P3 are known, you have a problem determining what the control arm should be. And say abi fails the prechemo P3 (which seems unlikely). In that event, you propose that the trial should pit 427+abi+prednisone against just prednisone. I'm pretty sure the FDA won't allow a trial of more than unapproved agent at a time (e.g., if abi had failed in postchemo and wasn't approved at all you couldn't do a trial of abi+427 vs. placebo). What I don't know is whether it will allow a trial of two agents, one of which (427) is unapproved and the other of which (abi) is approved but only for a different indication (postchemo). Maybe it will.
Anyway, thanks for raising this possibility. Maybe once the abi prechemo results are known OGXI and J&J will pleasantly surprise us and initiate a P3. It certainly would raise the profile of 427 in a hurry.
Different topic: does the expansion of the SYNERGY trial from 800 to 1,000 patients change the likelihood that the trial will be halted at interim? I don't know if you have enough information to answer that, and there's no rush.
To run a trial, you dont need the other drug approved.
The barriers against a prechemo 427+abi P3 at this moment are 1) cost/risk 2) the choice of the control arm. If abi fails prechemo P3, the control arm should be prednisone. Else, it should be abi+prednisone. Either case benefits J&J.
There is nothing (except cost) that prevents a 427+prednisone vs prednisone P3 at this moment.
I trust that they spend more time about these possibilities than we do. I also hope they know better than we do as well.
Given the pre-lim data we have seen with 427 and given the full patient data set will read-out late this year.
If that data is as good or better does OGXI have a drug that it can partner early 2013?
To me 427 looks like a cancer drug pipeline within a single molecule.
Agree that it makes sense for J&J to get behind the 427 + abi trial to help abi compete with MDV3100. It might even make sense for J&J to fund a P3 without getting a stake in sales of 427 since if successful the trial would boost sales of abi.
But would the FDA approve a P3 trial when neither the safety nor the efficacy of the abi/427 combo has been established? Maybe instead of a P2 they could do a P1 study of the PK/PD effects of the combo similar to what is apparently being planned for the 011/paclitaxel combination in connection with the 011 lung trial. But that would still take at least a year so they might as well just do their randomized P2 to evaluate efficacy.
I think abi is already being used off-label in the prechemo setting. That may allow enrollment in the 427 P2 trial to proceed fairly quickly, though I agree it will probably be at least 2 years before results are in. Since the trial is partially grant-funded they don't need J&J's help with it, and by the time it's done they'll have the results of the 011 SYNERGY trial. If that's successful, the milestones and royalties would allow them to fund the P3 for 427 themselves. Not that they're likely to take their chances on the SYNERGY outcome -- they'll probably do a financing well ahead of it (unless they decide to partner 427 -- curious that nothing has been said about their plans in that regard in the panel discussion or either of this week's CCs).
Maybe the plan is that if the P2 trial for 427 succeeds and SYNERGY does as well, OGXI becomes a prime takeover target that would be of particular interest to J&J.
All that said, if there's no FDA barrier to going directly to a P3 427 + abi trial then I agree they should approach J&J and try to work out a deal. The fact that that doesn't seem to be happening suggests to me that for whatever reason it's not an option.
Just looked at the slide presentation that accompanied the BioCEO CC, which is archived on the website. According to slide 16, the planned P2 study of 427 + abiraterone will be in the prechemo space. I thought I heard Dr. Gleave say in the ASCO panel discussion that it would be in the post-chemo space where abiraterone has already been approved. I realize that J&J is trying to get abi approved for prechemo patients. I don't know how far along they are but now I'm confused. Of course, the prechemo patient population is larger so I hope the slide is accurate.
Thanks. It seems like the webcast of the cc is removed from the website.
The increase from 800 to 1000 is good news. The most important news as always is that the co expects to finish the enrollment this year.
I am also confused about prechemo vs postchemo.
The focus on abi might be an indication that J&J is interested in 427 to stay competitive against mdv3100.