2013 Jun 18
A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients' baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio.
BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonly accepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances.
Seeking Alpha has some serious problems. It also has some reputable contributors well worth reading. I have a few authors I follow on the site.
Intense competition for GBM patients? I'm guessing the immunotherapies are going to be at the forefront. I'm also expecting some competition from the many PD-1 and PD-L1 companies to partner or buyout promising immunotherapies. Roche, BMY and Merck look like the current leaders. Roche's PD-L1 recently got the impressive "breakthrough status". There are many other PD-1 and PD-L1 pipeline drugs in the pipeline that will also be looking for promising immunotherapies to partner. Isn't this the likely goal of ImmunoCellular at this point? Buyout or partnering.
Dendreon's Provenge was not the perfect dendritic cell to train killer T cells and used a very costly manufacturing process. ImmunoCellular likely suffers from the "dendritic cell" legacy of Provenge.
Agree with you on Larrry Smith as being one of the credible Seeking Alpha authors.
Can't find the actual number of patients that were HLA-A2 methylated MGMT? Glioblastoma is lethal fast progressing and painful. How many patients would be needed in a trial so that diagnosed subgroup of patients could look forward to an average of 2 years of PFS to live life. Add in this is an add on therapy that has no adverse side effects.
Is there anyone in this subgroup that when diagnosed would opt out of ICT-107?
FDA agreeing to possible approval for subgroup based on PFS? Adding an extra year of quality of life to late stage terminally ill patients. I really don't see how the FDA could say no to PFS based approval in this case. ImmunoCellular needs to turn this over to Big Pharma and let them use their muscle to fast forward the next stage.
HLA-A2 (non)methylated Gliblastoma
ICT-107 + standard treatment - vs - standard treatment PFS 10.7 - vs - 6
OS 15.8 - vs- 11.8
Phase III Glioblastoma trial
Avastin arm n = 182 (trial for first line, Avastin already approved in second line)
Avastin combined with standard treatment - vs - standard treatment PFS 9.7 - vs - 6
OS 16.6 - vs- 14.8
Avastin did not get first line approval and was associated with a notable downgrade of quality of life and cognitive function.
mehtylated MGMT Glioblastoma - correction to above
Expect ICT-107 arm, guessing OS will be significantly better than 24 months
ICT-107 + standard treatment - vs - standard treatment: PFS 24 months - vs - 8.5 months
OS - not yet reached, so it will be 24 months, guessing significantly as there are 45 patients that have not reached OS point. OS was reached in (non)methylated MGMT arm of trial so how many of remaining patients are ICT-107 methylated MGMT?
Phase III Glioblastoma trial
Cilengitde arm n = 272
Cilengitide combined with standard treatment: PFS 13.5 months - vs - 10.7 months
OS 26.3 months - vs - 26.3 months
Double the PFS is like adding a year of life with no added side effects or pain by adding ICT-107 to standard of care for this subgroup. GLTA, especially the patients.
As long as they have a "pipeline" the management team will likely see huge bonus days when Parson decides the case. They will also have some nice salaries until the money runs out. Management has done a great job of NOT communicating with shareholders during the worst of time.
Regardless, GLTA the small shareholders and traders playing the game management has in store for them. I'm getting the impression dragging this case out is good for many on the management side.
Showing Avastin results as a comparison for what to expect as a response from FDA if/when talks for designing a phase III trial. Lots of nasty side effects with Avastin.
ICT-107, a very different drug:
"ICT-107 targets six cancer-specific peptide antigens (a multi-epitope cancer vaccine targeting the following: HER2, TRP-2, gp100, MAGE-1, IL13R alpha, and AIM-3), including targets that are highly expressed on cancer stem cells."
"multi-epitope (targeting epitopes / specific peptide regions of six tumor-associated antigens) rather than targeting a single cancer-related antigen that results in ICT-107 targeting BOTH cancer cells that comprise the bulk of tumors (daughter cells) AND the much less prevalent / residual cancer stem cell population thought to be responsible for the recurrence and spread of the disease;"
Just speculating on what interested ASCO when they looked at the Phase II trial and bestowed it with an oral presentation.
After ASCO 2014?
Roche and Bristol Myers Squibb have become a big focus with anti-PD-L1 and anti PD-1 Immunotherapy in Cancer. Drugs that overcom the state of immune tolerance that inevitably becomes established in most types of cancer. There are other companies developing similar therapies that are likely looking for promising immunotherapies showing potential.
Buyout potential or partnering with one of these companies that would like to pair with ICT-107 which shows activity with virtually no side effects?
Note the small size of trial needed for Avastin to get accelerated approval for second line use, because of the lack of alternatives.
Avastin failed for first line use in two phase III trials in combination therapy despite improved PFS likely due to quality of life (guess) . OS in trial for Avastin arm and control arm in first line were both averaged 16 months.
On May 5, 2009, the U.S. Food and Drug Administration granted accelerated approval to bevacizumab injection (Avastin®; Genentech, Inc., South San Francisco, CA) as a single agent for patients with glioblastoma multiform (GBM) with progressive disease following prior therapy
(based on 2 trials n=78, n=56)
Found this on Avastin which recently showed almost zero OS improvement, improved PFS with a big disclaimer: "reduced cognitive function and quality of life"
You can google MD Anderson News release:
"Symptoms and quality of life were significantly worse for patients receiving bevacizumab, particularly at weeks 22 and 34. In particular, symptom burden, including treatments, and generalized and affective symptoms were greater, with persistent differences seen in treatment-associated symptoms. Additionally, overall symptom burden, tumor and treatment-related symptoms, as well symptoms that interfered with daily activities, were also worse for those on bevacizumab over the treatment course."
Thinking it was a big surprise ICT-107 got picked for an oral presentation, that is a big deal.
Odds are overall survival will be better than control arm, just not statistical?. This favors a phase III, Strongly favors a phase III trial if the subsets mentioned in the letter to shareholders is what ASCO wants to discuss in the oral presentation. Quality of life will be monitored in OS patients and is something that glioblastoma patients and their support groups will be interested in. Also, will a significant number of longer surviving patients with quality of life show up as an outlier patient subgroup?
Glioblastoma is a horrible disease that is not responding to new therapies. Maybe ASCO is seeing something in the full detail data can communicate to them that couldn't be released to the public due to FDA regulations?
Wild speculation so take this post with a big grain of salt. Anyone else have some negative or positives to add?
Why I'm expecting better results on the late reporting patients.
Importance of HLA
HLA is kind of like blood type. People are born with a certain HLA type (e.g. A1, A2, etc.). About 70% of people in North America have either HLA-type A1 or A2, and ICT-107 is designed to work only in these patients. The vaccine targets six different tumor antigens, but only two (MAGE1 and AIM2) in A1 patients and four (HER2, TRP2, gp100, and IL-13Ra2) in A2 patients. Thus, ICT-107 should only have an effect on A1 patients who have MAGE1 and AIM2 on their cancer cells; it cannot attack the other tumor antigens in A1 patients. For A2 patients, ICT-107 only targets four tumor antigens; A2 patients with tumors only having MAGE1 and AIM2 should see no benefit. ICT-107 is essentially two different products: one for A1 patients and the other for A2 patients.
* Zero benefit for about 30% of patients will show up in early data?
Wall Street has plenty of contacts in the medical press. The Medical Press is fully aware of hundreds of long term therapies than cost well over $100,000/year. Some treatments are in the $500,000 and up range. The articles continue to come out on Gilead's CURE.
Probably a long summer on Gilead price? GLTA, hold tight to your medical stocks with solid cures.