I don't think its mandatory... doesn't affect final outcome. they are doing dsmb reviews every 100 patients. as the poster states, would need to amend protocol with fda...
futility is set for a couple reasons.
1. save dollars if trial going bad
2. possibly stop trial for positive efficacy
3. allow sponsor to add patients to statistically detect smaller os advantage
i don't think 3 is an option for the study. Not defined in the protocol. I would think company could waive the futility and proceed to top line results. Don't see a significant benefit to doing that. Gives them a glimpse at how the study is doing 6-12 months before the end.
it is an interesting question. futility is usually much earlier in the study, where a negative outcome can save the sponsor company significant funds as a percentage of the full cost of the trial.
In this case, enrollment is complete about same time as futility. Not normally the case. They've probably spent 85-90 percent of the funds based on management overhead allocation and funding the trial through full enrollment
Would not performing the futility save significant funds? I would think company would still do futility analysis to get a better view of what's going on in the study.
small caps are in correction mode. Russell off by over 10 percent from highs.
cece has some multinational exposure so fx could impact outside US profits.
I misread thinking they were comparing sap+dac to dac alone at 4 week mortality rate. That is not the case.
it appears to be from a different study. The reference was credited with a 2007 date.
I don't see a 30/60 day mortality data point from daco-016, the k-m curve does not show much separation until about 8 weeks for daco-016 versus control arm and there is a slide that does show 3 month mortality rate at 28% versus sapa+daco at 17%. That's actually huge separation after 3 months.
Have to keep in mind that only 1 cycle was sapa at that point, though.
The curve between pilot data and daco-016 does converge in the middle range (between 6+12 months). sapa+dac always stays better and slighly diverges later... small sample in pilot though can get skewed by just a few patients.
That's where one hopes the older SEAMLESS study group helps the experimental arm separate and diverge.
Full approval was the July approval. Much earlier than expected [note the PDUFA date of Oct 7].
They recd front line approval del17p CLL and second line in CLL/SLL.
Full approval does NOT mean front line approval. Apples/oranges.
Next regulatory feedback is Europe. Which I believe is expected in October.
I saw a slide that said the 30 day mortality rate in pilot was better than daco trial... but 30 day was comparing daco to daco. And that was 30 days with a much older population than daco-016
I do realize that 60 day was better also, but just goes to show that small samples can skew things...
You are right jantham, too small a sample that company converted to 28 day months.
Comparing snss to cycc today, its clear market says they are equal. That's as compelling as anything. if we could get a 300 patient DSMB PR, it might be a nice contrast to the snss p3 failure.
My end of year count down shows 85 days till full enrollment/futility events...
i will say this. cycc did identify the right age group. In daco trial and snss trial, statistical significance of the therapy was much better in older patient subgroup.
Another sad day for AML patients looking for improved therapies.
l2l: the story changed to suit the facts. Plans change... I know. Its called spin. It happens every day at every level of life and business.
Its to the point now where it really doesn't matter. the facts are all unveiled in the next 12 months. First futility within the next 3-6 and then top line data.
Regarding derisk... I would argue it depends on rigorousness of futility criteria. If futility is measuring likelihood of hitting the SPA end point, then it would be a huge derisking event. If a thumbs up by DSMB merely shows that sapa + daco arm is 'trending' towards a better outcome (ie .85 HR is possible or less) then it doesn't really derisk as signficantly. Role of dsmb is always patients' interest, not necessarily regulatory approval... If they see a survival trend without end point being hit, they can recommend the trial continue for the benefit of patients.
I don't know if the criteria for futility is 'knowable'. Or if its a guarded secret.
pre SEAMLESS, i heard CEO say 'post phase 2' is the sweet spot. So don't have to bear the burden of expensive phase 3s. I don't remember him saying post phase 3 futility is the sweet spot.
SEAMLESS has been going for 3.5+ years. futility is 6 months from top line data. That's bearing the the full burden of the cost through phase 3 in my opinion.
With futility being so close to top line read out, I could see a bp waiting the extra 6 months. Then maybe just buying the company if good enough top line data.
If futility were 1-2 years prior to top line data, I'd think partnership after futility is more likely.
the 300 patient review is not looking to stop study for efficacy reasons.
I'm puzzled as to where the 300 patient DSMB is. Did Spiro mention it on last 2 cc's?
200 patient DSMB was in late Nov 2013. And they crossed 300 patient threshold well before the Q2 CC.
My count down clock shows 90 days till end of year and the big futility/full enrollment milestones.
Need the 300 patient DSMB first. Spiro? Judy? Open the mail!!!!!!!
to summarize my points/purpose re: AGIO/AG221/AG120
Partnership very early in development even though INITIAL market for medicines is small is beneficial to company/shareholders/business partner.
I don't buy the argument that the CYCC CEO gives of not partnering sapa due to its smaller market size in initial indication. AGIO is a great counter argument with initial development in areas that are subsets of sapa's targets.
I agree that AG221/AG120/sapa could all be approved and garner market share. If I were a patient IDH1 or IDH2 positive, I'd certainly seriously consider AG221/120 based on what I know. If I were a patient not IDH1 and not IDH2 positive, I would look to a therapy like sapa+daco.
my reasoning is interest in another player in AML gaining a partner super early in their development, with extremely favorable terms addressing a subset of patients that have AML (and MDS).
They have a novel approach and is worth dialog.
It also is counter to Mr. Rambotis saying that elderly AML was too small to partner. AGIO is a $2B market cap with phase 1 therapies, so I think that flies counter to that theory.
my 100 day counter is down to about 95 for full enrollment!!! Let's go team!
I think this is your summary stmt.
1. are you asserting that only 5 patients are on still on AG-221 as of June? if so that is not the case... The PR said 14 responses and 5 stable disease. The follow on cc asserted that no patients had relapsed from their response and were continuing to take the medicine OR moving to transplant due to CR.
2. you give a lot of stats. from other sources... what is your opinion? At $2B you seem to be saying the market is wrong but you don't say that explicitly, so not sure. There was a recent piece in the New Yorker about from an md, describing the mechanism / approach. Its a short / good read.
3. Along with desire to have open discussion about other companies in AML/MDS space, I see a company like AGIO as an example of how an early bp CAN move things forward quickly. AGIO has presented 2 times at medical conferences and will present at 2 more before end of year. There's a benefit to their relationship with CELG. Thus far it has been a win/win.
4. Your message imply this targets a smaller subset of patients than sapa- if this is the case, would this not fly in the face of ability to partner it at such an early stage. If their target was so small, why would CELG take such a great interest and partner for LARGE upfront payments/equity stakes/etc... ? CYCC's claim was that frontline elderly AML is too small to partner by itself, but AGIO partnered with 2 medicines that target a SUBSET of these patients (IDH1 and 2 mutations). Something seems amiss in the logic for NOT partnering.
5. Finally, my view of the universe is simple. If I'm a patient NOT IDH1 and 2, and not eligible for intense chemo, I'd find an AML study like SEAMLESS. If I was IDH1 or 2 positive, I'd probably try to join the AGIO phase 1. That means the two can live in harmony together...
Again, bottom line. Success of either company or both means more live saving therapies for patients.
are you following AGIO, l2l? AML and blood cancer malignancy therapies in the clinic.
I posted here a few times about it earlier this year and you I know you were not impressed. Market sees it otherwise...
They are going to be reporting data on their second therapy which just launched phase 1 during Q1 - AG-120. Already reporting data in November.
They'll also have updated data at ASH on their first therapy. AG-221.
One of my issues with CYCC has been the pace and AGIO has a large partner early on to accelerate their development.
In the end, all of it means better news for patients. A partner could have helped accelerate CYCC's pipeline across all 'promising' therapies.
jantham: there wasn't much really planned for 2014 anyway. A pre study feasibility survey was one of the key milestones. There will be a lead in study that would be conducted if phase 2b or 3, so I think the official 2b will be launched well after futility, imo.
30 day mortality rate in SEAMLESS. Do you know if the first cycle of SEAMLESS is daco or sapa? What I've read indicates cycle number 1 is daco. So I would expect 30 day mortality to compare evenly.
Do you see the trial running daco then sapa starting out or vice versa?
don't forget the 300 patient dsmb safety check.
I have got my 100 day count down clock going on futility and full enrollment...
good times... there a comin...
i thought maybe they were holding the 300 patient DSMB pr for the R&R presentation...
l2l: I think we talked about September being absolute latest that we'd expect to see the PR for this. Are you expecting this literally any day?
I'd be surprised if not in the next few weeks.
'news flow picks up alot from here'.
could not agree more. Seriously, l2l, we are in complete sync on this one.
I am uber confident also that the news from CYCC going forward to be greater than what we've seen lately.
Anyone going against that statement is not following the storyline.
bring on the news flow!!!!!!!