IMUC was taking big risks when they picked OS as PE for a randomized ph2 trial. Had they picked PFS, we'd be looking at a positive trial today.
The ITT population = 124 patients. In a 2:1 randomization, 1/3 went into the placebo-arm, 2/3 got active treatment. To reach the median survival point in each arm 1/2 of the randomized patients have to have died: If 42 patients were assigned to the placebo arm, the median was reached when 21 deaths were recorded, if 82 patients were assigned to receive active treatment, the median survival point was reached at 41 deaths. All in all 62 events on record. The biometric plan was designed such that the study would show a statistically significant mOS difference with this n=124 for a greater difference than the observed 2 to 3 months. For the observed difference to be statistically significant one would have to have made this a much larger (many more patients) and more time consuming and costly trial. That was the risk, IMUC were taking when they launched this protocol. Based on the early clinical experience they could hope for a much larger difference in mOS. The bet was, if (1) the trial comes out positive for the primary endpoint of OS, we have a product to take to the market right away, if (2) we fail on the PE but have proof of this principle being active and effective, we hopefully have enough additional insight to design our phase 3 program for success.
Even with longer follow-up, the mOS endpoint will not become positive. BUT: We will have secondary survival endpoints which in cancer immunotherapies are particularly interesting and important, e.g. 6 months, 1yr, 2yr, 5yr survival rates comparing the two groups. It is an intrinsic problem in running studies with immunotherapies in cancer, that the benefits may only show in patients who survive long enough to enjoy them.
So, on to a much more educated phase 3 trial protocol now with a very active proven principle called ICT-107! But for this, the company needs more $$$..
Yes, it is so obvious that we have an active principle here and long-term survival data are paramount in assessing immunotherapies in cancer, 2yr survival rates, 5 yrs etc. There is no doubt in my mind, that this is an asset that is now severely undervalued because we had too many people invested who thought they would be able to multiply their funds for christmas shopping. The all left in panic through the emergency exit yesterday and laggards today. We'll find a base and it definitely can only get better as data matures.
As so often in biotech, it comes - only much later than expected and potentially much bigger than anticipated.
Sentiment: Strong Buy
Absolutely agree! CLDX has a phenomenal pipeline. Lot's of innovative stuff to be excited about. My intention in this post, however, was only to compare the GBM programs of the two companies (see headline). But thanks, Tyco, for reminding everybody of the richness of CLDX' portfolio (hence, their valuation!).
Target patient population: ICT-107 targets 50-75% of all 1st-line GBM patients. If their Phase 2 results are overwhelmingly positive and since they come first (assuming a breakthrough filing with Phase 2 data), ICT-107 could reduce the market segment for 1st-line rindopepimut significantly (e.g., from 33% down to 8-16% if HLA1/A2 positivity is as frequent in EGFRvIII+ patients as in an all-comer population). Also the 2nd-line GBM population available to rindo should be much smaller as ICT-107 will reduce the prevalent population of recGBM patients very effectively. If then ICT-121 proves to be effective in 2nd-line this (already reduced) market segment will become very competitive, too. But this program is farther behind. So that a positive IMUC development seems to be to the detriment of rindopepimut's market prospects.
In terms of recruitment efficiency, there should be no interference. ACT IV is fully recruited any day now and ICT-121 as a single center Phase 1 should not interfere with all the many reACT trial centers.
Long-term: If both principles (dendritic vaccines ICTxxx and peptide vaccine rindopepimut) are shown to be active principles in GBM, head-to-head or combination trials will be a topic for discussion, also treatment regimen to spare patients from radio chemotherapy. But that discussion is a number of years out into the future.
I disagree. The facts (clinical trial operational performance, clinical endpoints, product features, logistics etc.) do not speak for NWBio. Please, see my post from yesterday under the heading "IMUC vs. NWBio".
People on this Board raised an interesting question: Any interference between these two programs? If so, how?
CLDX' rindopepimut targets EGFRvIII-Marker+ patients, about 1/3 of all 1st-line GBM. It is a peptide vaccine, given intra-dermally. CLDX have an on-going trial in recurrent GBM, called reACT, and a 1st-line trial, called ACT IV. Both trials are actively recruiting. ACT IV is expected to be fully recruited by year end 2013, a first scheduled interim-analysis mid-2014, a second scheduled interim end of 2014. reACT was expanded based on the data presented at SNO. This trial has a tricky design: Group 1 is a randomization of bevacizumab (AVASTIN)-naive patients into rindo+GM-CSF+bev and "placebo"+bev while Group 2 gets rindo+GM-CSF+bev (all bev-failing patients).
IMUC has two GBM-programs: ICT-107 is a dendritic cell vaccine given in conjunction with standard radio chemotherapy, applied intra-dermally, and is in Phase 2. The target patient population has to be HLA1/A2-positive, about 50-75% of 1st-line GBM. The trial completed recruitment in September 2012. Results are due any time now (CEO always speaks of Q4'13 or Q1'14). The company presented these spectacular Phase 1 long-term follow-up results on PFS and OS which seem to bode well for their Phase 2.
Second IMUC GBM-program is with a CD133 targeted dendritic cell vaccine, ICT-121, in Phase 1, recruiting since mid-year, n=20, single-center. This target is particularly frequent in rec/ref GBM-patients, and the study is in 2nd-line patients only. I don't know (anybody?) whether also this trial is only in HLA1/A2-positive patients and whether that will be a selection criteria for further development and what the frequency of this biomarker is in 2nd-line GBM (same as 1st-line? different? how different?).
Target patient population: ICT-107 targets 50-75% of all 1st-line GBM patients. If their Phase 2 results are overwhelmingly positive and since they
IMUC has the potential of a game changer and if ICT-107 ph2 is positive it will make recruitment into the NWBio even more sluggish. NWBio would have to take their trial from Western Europe further east - with all the costs and risks this entails.
Again: I would not bet my money on NWBio...
It's excellent and - let's not forget - it was deemed spectacular enough to be given an oral presentation by the SNO program committee. Cheers to all longs!
If effective in such late stage patient population (reACT, bev-refractory), it is nearly guaranteed to be highly effective in first-line, too. Good news for CLDX !!
"Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer" - here is in short what I could gather from all press releases pertaining to this trial and from SEC filings by NWBio:
Q4 2006: Trial starts as an open, randomized phase II, n=140; first IRB approval at Henry Ford Hospital, Detroit in Nov 2006. Study start date (acc. to clinicaltrialsdotgov): Dec 2006.
Q1 2007: First two patients enrolled undergo surgery in Detroit; UCLA joins as the second trial center
2008: Trial halted, because too many patients randomized to the control arm (no active treatment) withdraw. NWBio designs a placebo procedure in response.
Q1 2009: Trial re-starts as a randomized, placebo-controlled phase II trial; n=240
Q1 2011: 31 US sites open and active; 33 patients enrolled. May 2011: co re-confirms the number 33.
May 2012: 41 US sites open and active; no new patient numbers. Trial is up-graded to a phase III, n increased to "up to" 300 patients. Planned expansion to Europe and an interim analysis for efficacy (no mention of the trigger for this analysis).
Oct 31, 2012: S1 SEC filing, 41 US sites open and active, plan to open a total of "80 or more sites in both the US and Europe". No up-date of patient numbers.
Feb, 2013: Still - only - 41 sites open, "poised to begin recruiting in the UK"… Finally, PAREXEL engaged as global CRO to manage the trial
Sep, 2013: German authority (PEI) approves trial to start recruiting in Germany with substantial changes to the protocol.
You may consider IMUC a speculative investment and I wouldn't argue against that. However, their randomized, placebo-controlled phase II trial is fully recruited since early Sept 2012 and we simply have to wait for it to mature and produce the overall survival data sometime soon (Q4'13, Q1'14). NWBio keep everyone in the dark about the true performance of their trial, true accrual numbers. It seems fair, however, to infer from their public statements that they are far from completing recruitment, left aside producing meaningful results….
IMUC may be speculative, but, at least, we reach the value inflection point any day now. With NWBio, you don't know where they stand at present and results from this trial are out into indefinite future. IMUC, if positive, runs a fair chance even to go straight into filing.
Nothing to be taken for granted in drug development, Whippersnapper. But good reasons to be optimistic about CLDX. Cheers!
Agree. Sell out or organic growth should both result in multiples of today's MC. ...provided clinical results keep up with or exeed expectations.
I, too, wonder. I have seen oncology products approved by FDA based on single-arm phase II trials, but larger n (e.g., crizotinib in 2011). Thus: Not impossible but not very likely either. Let's begin to speculate when we see/hear what they have to tell at SNO in November.
The cohort getting expanded to a total of 100 patients is the only unblinded cohort in the trial and the cohort with the worst prognosis. Many if not most (all) of these patients are likely 2nd relapse at the time of enrollment. They had SoC radio-chemo 1st line and Avastin 2nd line and progressed under Avastin. They enrolled and continued on Avastin plus rindopepimut. What the announcement tells us is, that in this open-label cohort we have "preliminary evidence that rindopepimut may have activity", meaning in this desperate group of patients they saw a few (or more) with either stabilization of disease or even regression.
What's the buzz? Well, if rindopepimut works in this very unfavorable group of patients, it will very likely be superior also in the blinded part of reACT (adding to the effects of Avastin in Avastin-naive patients) in probably mostly 2nd line patients - and if it is effective in 2nd line it should also be superior in addition to 1st line SoC compared to SoC alone in the ACT IV phase III trial. The news today can be taken as a first indication that the rindopepimut program odds are beginning to lean towards BINGO!! Addt'l upside: The publication of the first 25 patients at SNO later this year will facilitate and accelerate enrollment into reACT and ACT IV (and thus may bring the ACT IV read-out forward somewhat). Downside: It'll take longer before we see the final results of reACT.
...and where is the read-out of the reACT trial on your smart list? Rindopepimut is supposed to show results in recurrent glioblastoma before the year is over. And if that happens to be positive the on-going ACTIV phase III trial in first-line will start to appear like a slam dunk. AND: reACT could be filable for approval in 2o14 even though a phase II. That could really drive the share price, don't you agree?
you're wrong, Jaks. Goldie is 99 and has only one holding (that explains his 991) which is in XOM. He is holding on to it since decades, cause he still drives around in his 1949 Ford Pick-up that gives him about 7 miles to a gallon. Can't wait to see his final post AFTER he passes away. All the wisdom of a century ...